Superbug

If you came here from Bittman's Opinionator at the New York Times...

2011-11-19T21:23:00.000-06:00

I'm thrilled to see you! But I'd love even more for you to join the conversation at this blog's new home at Wired:

http://www.wired.com/wiredscience/superbug

-- Maryn

Gone. (Again.) And it's really exciting. (And some NDM-1, too.)

2010-09-14T12:15:00.000-05:00

Constant readers, cast your minds back to early summer, when SUPERBUG briefly bugged out of here to Scienceblogs. Scienceblogs was a great community, but not quite the right fit, and so I ended up happily back here, doing my own thing, and you very kindly followed me. And it's been an exciting few months back here, with lots of news on NDM-1 (look here for the archive), and flu and C. diff and HAIs.

And now, some real news. SUPERBUG is moving again. And this is going to be great.

I'm thrilled to be one of seven launch bloggers in a new network set up at Wired.com: Wired Science. It's an amazing, diverse group, high-performance and hyper-cool: Frontal Cortex, Neuron Culture, Laelaps, Dot Physics, Clastic Detritus, Genetic Future, and me. I'm beyond flattered to be among them.

Our launch announcement is here. My new page is here. (The complete addy, which may change in a few weeks after a tweak, but keep it for now:
http://www.wired.com/wiredscience/superbug/)

My inaugural post is the latest news, from the ICAAC meeting, on NDM-1.

We're having some issues with the archives, so I'll be leaving this site up as a resource. But I'd love to see you there as well as here. Please come check us out. And thank you, so much, for your loyalty, interest and attention over these years.

Antibiotic resistance: Scandinavia gets it

2010-09-08T09:57:00.000-05:00

Odd but interesting fact: Scandinavia takes antibiotic resistance incredibly seriously. Denmark has one of the most thorough programs for preventing antibiotic misuse in agriculture; Norway has very tough regulations regarding antibiotic stewardship in hospitals (as captured in this AP story last year). Sweden has pressed the issue as well; drug resistance was a major issue for the Swedish Presidency of the European Union in the last half of 2009 and led to a major conference there on creating incentives to bring antibiotic manufacturers back into the market.

The presidency has since been relinquished to more southern countries (Spain in the first half of this year and now Belgium) but the Swedish focus on resistance persists, pushed along by the nonprofit organization ReAct, based at Uppsala University. Earlier this week, ReAct hosted a three-day international conference on antibiotic resistance in Uppsala. They haven't posted the full conference report yet, but they have come out with a closing press release, which says some interesting things (emphases mine):

At a historic three day conference at Uppsala University, Sweden, 190 delegates representing 45 countries and many leading stake holders – civil society, academia, industry, governments, authorities, supranational organizations – agreed on Wednesday to turn a new page and move towards concerted action on antibiotic resistance...
The new signals from the Uppsala meeting include:
- A shared conviction that antibiotic resistance is a universal problem. Like global warming, it requires joint action, not least by governmental alliances.
- A clear signal from the pharmaceutical industry that return of investment on research and development of new antibiotics and diagnostic tools will have to be de-linked from market sales in order to boost necessary innovation while yet limiting the use of antibiotics. This requires a new business model where private and public sectors cooperate.
- A strong recommendation to all stakeholders to speed up the efforts to limit unnecessary use of antibiotics, while at the same time making the medicines affordable and accessible in developing countries.
- A commitment to improve the monitoring of antibiotic resistance across the world, through shared data and increased efforts. A global network of surveillance will require common methods, and is crucial for both prudent use and needs driven development of new agents.

The release also mentions some promising events coming next year:

- A final report from TATFAR, The Transatlantic Task Force on Antibiotic Resistance.
- A policy meeting on antibiotic resistance in Delhi, India.
- A WHO Action Plan on Antibiotic Resistance.
- A number of regional initiatives, including in Southeast Asia, Africa and The Middle East.

(Hmm. Surely it is time for me to go back to India...)

People who've worked in this field for a long time will know, of course, that up-front commitments are easy to make; it's downstream action, carried out over the long term, that makes a difference. But this looks like a promising start: Even just stimulating international recognition of the program is an encouraging beginning.

Until the final conference report is posted, you can see video of the opening and final sessions here.

Every once in a while: Some stuff about me

2010-09-02T06:20:00.000-05:00

Drowning in work here, folks, which is a pity because there's lots of news to talk about. Back soon. Meanwhile: I try not to do this very often, because most of what we have to talk about is so much more interesting than me — but my week at UGA, which is capped by an appearance at the Decatur Book Festival, has generated some ink. So here's some amusements for your morning coffee:

A very kind Q&A with me, done by excellent pal Barth Anderson, operator of the feisty food-policy site Fair Food Fight
Another Q&A by my former colleague Phil Kloer, for the great arts blog Arts Critic ATL
And a video about one of my speeches at UGa, done by student TV station WNEG-TV. (The last line of the report? I didn't say that. But otherwise, well done.)

On the road this week, and a reading rec

2010-08-31T08:36:00.000-05:00

Constant readers, I'm teaching this week at the University of Georgia's Grady College of Journalism and New Media Institute, so blogging will be light. If you're in the Athens or Atlanta area, please come say hello, I'll also be speaking publicly:

Tuesday: 4 p.m., Room 175 of the University of Georgia's Coverdell Center for Biomedical and Health Sciences, Athens.
Wednesday: 6 p.m., the Vaccine Dinner Club of Emory University (Whitehead Health Science Center Administration Building), Atlanta.
Thursday: 4:15 p.m., Athens-Clarke County Library, Baxter Street, Athens.

Here's a press release that UGa kindly put out about the events.

Meanwhile, some reading: When we're talking about MRSA control, we often talk, somewhat lightly, about isolating people within a hospital or nursing home in order to control MRSA's spread. For instance, isolation is the key technique on which "search and destroy" hinges.

In today's New York Times, Dr. Abigail Zuger writes a thoughtful column on the historic roots and present-day challenges of putting patients into isolation. It's very much worth reading, particularly for understanding why tending to patients in isolation is such a time-burden for health care staff. Also, her description of how C. diff spreads will make you want to wash your hands immediately.

More soon.

New CDC flu numbers: This may not go well

2010-08-26T19:13:00.001-05:00

(Constant readers: Apologies for the slow blogging. Casa Superbug's little medical crisis from a week ago has recurred, and things are a bit distracting. Back to normal soon, I hope.)

In public health, one of the numbers you hear most often — and especially so the past few years — is 36,000. That's the number of deaths that the CDC estimates occur in an average year from influenza.

Or rather, estimated. Because today, in its weekly bulletin MMWR and also in a teleconference for the press, the CDC announced that it is discarding that widely used number, in favor of newer numbers from newer studies that take into account the wide variation in illness and death from one flu season to the next.

The new estimate is: 23,607. Or, a range that goes from 3,349 to 48,614. Or, in the language recommended by a CDC scientist and a communications specialist in the press call, "tens of thousands of people [who] may die each year in an average flu season."

If that sounds difficult to communicate in a concise manner, well, the reporters on the CDC call today clearly thought so too. And while reporting study results forthrightly is transparent, and more precise numbers are almost always better, I can't help but wonder whether this attempt at precision and transparency will not be received well. After all, we are only a few months (or a few weeks, depending whose end date you accept) away from the dribbling conclusion of a worldwide pandemic that was taken so not-seriously by the public that, in the US, 71 million doses of H1N1 vaccine went unused — and in Europe, some public representatives alleged that the entire emergency was a concoction by pharmaceutical companies.

Given that history, putting out a public message that flu kills fewer people than we thought — but is, still, a serious disease that should be planned for and vaccinated against — sounds like a hard sell.

Here's how today's new numbers came about:

The mortality rate from flu has always been difficult to assess: People die of influenza directly, but they also die of underlying conditions — heart disease or chronic obstructive pulmonary disease, among others — that might not kill the person if influenza were not putting an extra strain on the system. In either case, but especially in the latter, the death may not be attributed to flu, particularly if the victim has not been tested for the presence of the flu virus.

So, to arrive at an estimate, the CDC has used a statistical model. As explained in the briefing today by Dr. David Shay of the CDC's Influenza Division:

We have two categories that we look at... One is death certificates that have an underlying diagnosis of pneumonia or influenza. 99% of those deaths are actually coded as pneumonia. So, that's to make an estimate of deaths in a particular season from pneumonia that are associated with flu. And typically, that's about 8.5% of deaths over the time period that we looked at... The broader category of respiratory and circulatory deaths we think encompasses the full picture of influenza-associated deaths, including things such as people who might die because of worsening chronic obstructive pulmonary disease or worsening congestive heart failure that results in death after an infection. And we estimate that about 2% of that broader category in any typical year is associated with influenza.

One other factor affects flu mortality: Which flu strain type is dominant in the season being measures. Flu is generally taken to cause the most severe disease, and the greatest number of deaths, in the elderly; but some strains cause more severe disease than others, and some (H1N1 "swine" flu, for instance) attack the young, who are healthier and less likely to die, more than they do the old. Again, Shay:

[I]t's important to keep in context, which we don't really describe in this article because of space, that there's at least four factors that affect sort of flu mortality in any particular year, and those four would be the specific strain or influenza strains that are in circulation, sort of the length of the season or how long influenza is circulating in the united states, how many people get sick, because of course, the more people get sick, there is more likely to be more serious outcomes, and finally, who gets sick.

In the study released today, the CDC did two things: It broadened the range of flu seasons from which it took data to feed into the statistical model, and it took a second look at the years on which the previous model, the one that produced the 36,000-death estimate, was based.

When the range of years was broadened to 31 flu seasons (1976-77 to 2006-07), here's what shook out:

For deaths from influenza and pneumonia: from 961 in 1986-87 to 14,715 in 2003-04, an average of 6,309
For deaths from respiratory and circulatory complications: from 3,349 in 1986-87 to 48,614 in 2003-04, an average of 23,607.

(When asked which number should be used for shorthand, Shay said: "The broader category of respiratory and circulatory deaths we think encompasses the full picture of influenza-associated deaths.")

When the 36,000-death estimate was re-examined, Shay said:

The 36,000 number that's often used pertains to a very specific time period from 1990 to 1999. And in that decade, where we had prominent circulation of H3N2 viruses, they were prominent in eight of the nine seasons that are contained within the data that were used to make that estimate, and those are, as you know, typically more severe seasons. We had a high mortality for that nine-year period.

According to the MMWR analysis, mortality rates in the H3N2 years were 2.7 times higher than in years when other types were dominant.

So that's the rationale behind today's dialed-down numbers. Here's the potential problem with it: It just took me about 1,000 words to (somewhat talkily) explain. It requires patience and detail to impart, which in the current media environment are in very short supply. As one of the participants on the call said today:

I'm really scratching my head here wondering what I'm going to use, because we really don't have a lot of time ... to present a lot of numbers, and I think in a sense to say that the range is 3,000 or 3,300 to 49,000 raises a lot of questions, and I think we don't have time to answer those questions in every report. And I also wonder if it's not a bit misleading to use 3,300 as the bottom number since it's been 20 years since it was that low, and even in the last 20 years, the mortality has never been much below 12,000.

You see the problem.

To repeat: This is an effort at transparency and accountability; those are worth applauding. But it's also a nuanced and difficult health-communication message, launched into a zeitgeist already tuned toward conspiracy theories and a media marketplace with little time or expertise to counter them.

Pessimistically, I wonder how long it will be before this message gets transformed into something like, "See? I told you so. Flu isn't that big a deal after all." I hope the CDC is prepared when it does.

(Here's today's MMWR article, the transcript of the press briefing, and a Q&A on the new calculation. The cite is: Morbidity and Mortality Weekly Report, "Estimates of Deaths Associated with Seasonal Influenza --- United States, 1976--2007." August 27, 2010. 59(33);1057-1062)

Friday comic relief

2010-08-20T16:31:00.000-05:00

I give you: the Singing Doctors! (via damagedcare.com):

NDM-1: The World Health Organization warns governments

2010-08-20T14:16:00.001-05:00

The World Health Organization released a statement this afternoon, prompted by news of the NDM-1 multi-resistance gene. It's worth taking a look: The agency recommends that countries around the world pay serious attention to the emergence of this resistance factor.

WHO calls for broad action within countries, from hospital infection-control and antibiotic-stewardship programs, to increased surveillance for the emergence of resistance, to legislative control of over-the-counter sales. Those sound like (and are) minimal and rational suggestions — but they have the potential to be quite controversial in some countries, from India where OTC antibiotic purchases are a major economic sector, to the US where best practices for hospital control of resistant organisms continue to be, umm, vociferously debated.

The WHO says:

Those called upon to be alert to the problem of antimicrobial resistance and take appropriate action include consumers, prescribers and dispensers, veterinarians, managers of hospitals and diagnostic laboratories, patients and visitors to healthcare facilities, as well as national governments, the pharmaceutical industry, professional societies, and international agencies.

WHO strongly recommends that governments focus control and prevention efforts in four main areas:
surveillance for antimicrobial resistance;
rational antibiotic use, including education of healthcare workers and the public in the appropriate use of antibiotics;
introducing or enforcing legislation related to stopping the selling of antibiotics without prescription; and
strict adherence to infection prevention and control measures, including the use of hand-washing measures, particularly in healthcare facilities.

The WHO has been working on antibiotic resistance for a while now, though the effort seems to be continually obscured by urgent news of outbreaks such as SARS, H5N1, H1N1 and so on. Here's their short fact sheet, detailed program page, and Global Strategy for Containment of Antibiotic Resistance (sadly 9 years old, so it predates the emergence of community MRSA, not to mention NDM-1).

NDM-1: The early warnings

2010-08-18T10:30:00.004-05:00

Sorry to drop out of sight, constant readers; a little medical emergency at Casa Superbug, but all better now. There are some new developments regarding the novel resistance factor NDM-1, which renders Gram-negative bacteria resistant to almost all antibiotics:

Germany has announced its first identifications — plural, apparently. (Bloomberg News)
Vietnam says it has also recorded its presence. (Thanh Nien Daily, h/t H5N1)
And France says that it will begin testing for the gene's presence in bacteria carried by patients being admitted to hospitals, in hopes of keeping the plasmid from transferring to other bacterial species and creating a wider resistance problem. (Agence France Presse) This is a reasonable fear; it is analogous to the process by which MRSA became vancomycin-resistant (VRSA), by acquiring the gene for vancomycin resistance from VRE, vancomycin-resistant Enterococcus. But there's much more to be said about what it will take for a hospital to keep this bug from entering or spreading; more on that in a future post.

Before we get too much further from the initial news, I want to go back over the history of NDM-1's discovery — because, as with so many superbugs that take the public by surprise (recall the furor when the CDC's estimate of 19,000 MRSA deaths a year was published in late 2007), it turns out that there have actually been alarm bells ringing on this for a while. Largely, of course, unheard.

The first finding was in an older man of South Asian origin, living in Sweden, who went back to India in 2007, was hospitalized in New Delhi as a result of longstanding health problems, returned to his new home, was hospitalized there also in January 2008, and was discovered there to be carrying this resistance factor. The first public description of his case was made in October 2008, during a poster session at the annual ICAAC meeting (Interscience Conference on Antimicrobial Agents and Chemotherapy). That was later expanded to a journal article that was published in Antimicrobial Agents and Chemotherapy in December 2009; the full text is online in PubMed Central.

In the interim, though, the UK's Health Protection Agency published its first alert, in July 2009, describing 19 patients carrying this resistance in 2008 and the first half of 2009, 9 of whom had received medical care in South Asia:

One UK patient, who developed a bloodstream infection with an E. coli that produced NDM-1 enzyme had received treatment for a haematological malignancy in both India and the UK; two others had undergone cosmetic surgery in India and one of these presented to a UK hospital with a wound infection that grew a mixed microbial flora including K. pneumoniae with NDM-1 enzyme; others had received renal or liver transplantation in Pakistan.

Meanwhile, other researchers in Europe were becoming alert to the threat that NDM-1 posed if it were to spread widely; English researchers warned of it in September 2009, and Scandinavian researchers did the same in November 2009.

And in June 2010, the CDC published its first report and warning of NDM-1 in patients in the US, noting that all three, who lived in different states, had received medical care in India.

But what's important to note is that, despite the surprise and indignation coming from South Asia after the publication of last week's Lancet Infectious Diseases papers (article, editorial) describing the spread of NDM-1, the existence of that resistance factor has been discussed in Indian medicine since sometime last year.

From August to November 2009. a team of physicians at the Hinduja National Hospital and Medical Research Centre in Mumbai surveyed their ICU patients, and found 22 isolates carrying NDM-1. Their paper was submitted very quickly, in December 2009, and published in March 2010 in the Journal of the Association of Physicians of India:

We sought to identify NDM-1 positive strains among the carbapenem resistant Enterobacteriaceae isolates at our tertiary care centre. In a short span of 3 months, we identified 22 such organisms. The physicians at our institute follow the hospital antibiotic policy and do not indiscriminately use carbapenems. However being a tertiary centre we receive transfer in cases / referrals from other hospitals... The identification of NDM-1 in 22 of 24 isolates is a worrisome development indeed. NDM-1 being present among Enterobacteriaceae has the potential for further dissemination in the community. Such dissemination may endanger patients undergoing major treatment at centres in India and this may have adverse implications for medical tourism. Besides stringent infection control in hospitals, good sanitation in the community is also needed to contain the spread of such clones. (Deshpande et al., JAPI 2010)

News of their finding must have percolated through Indian medicine, because in January 2010 — before their paper was published — a worried letter discussing NDM-1, by a South Asian scientist working at the Royal Infirmary of Edinburgh, was published in the Indian Journal of Medical Microbiology:

The virtual nonexistence of antibiotic policies and guidelines in India to help doctors make rational choices with regard to antibiotic treatment is a major driver of the emergence and spread of multidrug resistance in India. This is augmented by the unethical and irresponsible marketing practices of the pharmaceutical industry, and encouraged by the silence and apathy of the regulating authorities. Poor microbiology services in most parts of the country add to the problem. (Krishna, IJMM 2010, DOI: 10.4103/0255-0857.66477)

And in March 2010, Dr. K. Abdul Ghafur of the Apollo Hospital in Chennai published a passionate and despairing call to arms ("An obituary — on the death of antibiotics!") alongside the Mumbai team's findings. The full text is online and it is worth reading in its entirety:

Our country, India, is the world leader in antibiotic resistance, in no other country antibiotics been misused to such an extent. Microbes are the ultimate warriors. They have sophisticated weapons and use ingenious methods of attacks. They have always been many steps ahead of us. Even in the twenty first century with all the developments in the modern medicine, when we face microbes, we feel helpless. Whatever weapons we had in the form of antibiotics, we ourselves have ruined them. Indian medical community has to be ashamed of the NDM-1 (“New Delhi Metallo-1”) gene. Even though we have not contributed to carbapenem development, we have contributed a resistance gene with a glamorous name. The overuse of antibiotics is embedded in our Indian gene. It is an Indian tradition. (Ghafur, JAPI 2010)

That Ghafur's plea went unheard is all the more striking — because for almost a decade, Indian researchers had been reporting, in their own journals, a steady and troubling expansion of carbapenem resistance in Indian hospitals. More on that when I post next.

More on NDM-1

2010-08-13T12:03:00.002-05:00

One of the frustrations of being a working journalist and a blogger is that, when a big blog-story breaks, you're likely already to be working on something else. And so it is, unfortunately, with NDM-1: I'm on a magazine assignment and will be off interviewing people when I should be blogging.

(This s a great time to recommend that, for any breaking infectious disease news, you follow Crof at H5N1 (@crof) and Michael Coston at Avian Flu Diary (@Fla_Medic), who are dedicated, thoughtful, nimble and smart.)

Since I last posted, there's been lots of additional coverage of the "Indian superbug." Much of it, blog and media, is just echo chamber cannibalizing of the earliest reports (including but certainly not only mine), but there are some important new developments worth noting, which I'll list below.

There are also some important points that are getting lost in the echo-chamber bounce: First, it is not correct to say that every person who acquired this was seeking cheap medical care or engaged in medical tourism; a few of them were treated on an emergency basis while traveling, and a few have no apparent healthcare tie. So this is not a situation of people seeking to save money and, as some commenters seem to be suggesting, receiving their karmic payback. (C'mon: Seriously?) Second, it is also not correct to say that every case of this has been linked to a hospital — it's quite clear in the Lancet ID paper that in South Asia, a number of the cases were community infections. So it is not just a case of hospitals that are dirty or have poor infection control (which by the way is a problem in the US as well, right?); NDM-1 is already a community bug, which will make detection and defense much more complex.

OK, curated list:

First, if you're interested in more from me, CNBC asked me to write up a piece about NDM-1, which ran Thursday; and Friday morning I was on the WNYC-FM (and nationally syndicated) radio show The Takeaway.

Second, the list of potential victims of NDM-1 is growing. Most of them have survived, so marking their cases is really a way of measuring the resistance factor's previously undetected spread:

The UK has released a new statement, updating its earlier warning, and says it has found "around 50" cases carrying NDM-1, an update from the Lancet ID paper. (Side note: This statement, and the earlier warnings, came from the UK's Health Protection Agency. The UK has just announced that it will be shutting down that agency in a cost-cutting measure. Great timing.)

The government of Hong Kong has announced that it has seen one case of NDM-1, but the patient recovered.

Canada has disclosed that it has had two cases, not the one mentioned in the Lancet ID editorial, in two different provinces.

Australia says that it has had three cases scattered across the country.

Belgium has announced one death.

And finally — sadly but probably not surprisingly — India is objecting to the stigma of being characterized as the source of NDM-1. The study's first author has disassociated himself from the paper and members of the government are claiming a "pharma conspiracy." Medical tourism has become a significant industry in India, and it is true some of these reports cast doubt on its safety. But still, I find this reaction disappointing.

Evading the stigma of an emerging disease is not a new impulse: Recall how the government of China suppressed for 6 months the news of the start of the SARS epidemic. They did not stop the epidemic, of course — it eventually sicked more than 8000 people across the globe and killed about 775 — but their suppression of the details of its spread kept other jurisdictions from mounting a defense in time. From my teaching gigs in Hong Kong I can testify how much bitterness endures in Hong Kong over this.

China's actions in 2002-03 led to the enactment of the new International Health Regulations by the WHO, which specify that, because expanding epidemics take no notice of borders, it is inappropriate for any government to attempt to impede the free flow of information about their spread. India is a signatory to the IHRs.

I am not suggesting that India is attempting any suppression of news about NDM-1 — there's no evidence of that — but the volatile language being used does concern me. I acknowledge that India is an extremely open society, with degrees of political expression that can sound surprising from this distance. But let's hope the government takes its commitment to the IHRs as seriously as any signatory should.

NDM-1: Novel, global, complex and a serious threat

2010-08-11T18:07:00.002-05:00

There's news today in the journal Lancet Infectious Diseases of the further spread of a troubling new resistance problem that I first talked about in June: Gram-negative bacteria carrying a novel resistance factor that has been dubbed New Delhi metallo-beta-lactamase, or NDM-1.

In writing about resistant bacteria, it's difficult to avoid overusing superlatives — but this resistance mechanism has spread widely, been transported globally, and brings common bacteria up to the brink of untreatable. It already has been found in India and Pakistan, Sweden, the Netherlands, Australia, Canada and the US, and has been distributed not just by travel but specifically by medical tourism. It has the potential to become an extremely serious global threat.

Necessary background: One major way that microbiologists classify bacteria is on the basis of the organisms' cell membranes; some have a single membrane, and others have two separated by fluid. The groups are identified by their response to a 4-step staining process, called Gram stain for the Danish physician who invented it in the 1880s. Cells that pick up the first stain applied, which is usually violet but sometimes blue, are single-walled; cells that resist the bath of the first stain, but pick up a lighter tint from another chemical in a later step, are double-walled. The single-membrane, dark-stained organisms are dubbed Gram-positive; the double-membrane organisms are known as Gram-negative.

Here's why that distinction is so important for understanding antibiotic resistance: Most of the drugs that kill or control bacteria act by attaching to or penetrating through cell membrane. The double membrane of the Gram-negatives presents a greater obstacle to drug-molecule interference than the single membrane of the Gram-positives — and thus makes developing drugs that can control Gram-negatives a more complex task. Hence, while there's abundant concern about the narrowing drug pipeline for Gram-positives including MRSA, there is even more alarm about the dearth of new drugs for Gram-negatives (as captured last year in this article from Clinical Infectious Diseases).

The novel resistance factor that is described today in Lancet ID appears only in Gram-negatives, primarily in E. coli and K. pneumoniae but also in other species. Bacteria that have acquired this mechanism are resistant to multiple classes of drugs commonly used against Gram-negatives: beta-lactams, fluoroquinolones, aminoglycosides, and most troublingly carbapenems, generally considered the drug class of last resort for those organisms. Several of the isolates found in the study were susceptible only to colistin, a drug that dates back to the 1960s and is considered toxic to the kidneys, and tigecycline, which was only licensed in the US in 2005. Several responded only to aztreonam. One was susceptible to nothing.

The real threat in today's news, though, is not only how resistant these organisms have become; it is also how they got that way, and how and by what means they are spreading.

As the Lancet ID paper reports, NDM-1 resides on a plasmid — a snippet of DNA, not on a chromosome, that reproduces on its own and can move freely between organisms. Intuitively, you would think that bacteria either inherit resistance from their progenitors or develop it on their own when they encounter a drug. Plasmids short-circuit both those processes, allowing resistance to spread rapidly within a single bacterial generation to organisms that have never experienced the drug they are acquiring defenses against. And as the paper testifies, NDM-1 has spread: The authors surveyed for NDM-1 in India, Pakistan and the UK, and found it both widely distributed in South Asia, and also present in UK residents who had family or business ties to South Asia, or had gone to the subcontinent for medical care. And unlike some resistant organisms, the bacteria carrying NDM-1 were not confined to the bug-friendly environment of hospitals or the the debilitated systems of hospital patients. Instead, it was out in the community, causing common illnesses such as urinary tract infections.

There are a couple of points embedded in that report that bear unpicking because they are so foreboding.

First, that this is happening in India, which not only harbors some of the world's largest manufacturers of generics, but also (and possibly synergistically) has some of the world's highest rates of antibiotic use. Some Indian researchers have been warning for years that the subcontinent is on the verge of a homebrewed crisis of drug resistance (Indian Journal of Bioscience, Indian Journal of Medical Microbiology, Indian Journal of Medical Ethics).

Second, that it is linked to medical care, and especially to medical tourism — which has become a booming international industry, not only for elective options such as cosmetic surgery, but because it offers an inexpensive way to perform major procedures that health systems might once have wanted to have done close to the patient's home. A study covered last January by The Independent in London recommended shipping UK patients to India for care, suggesting it could save the beleaguered health service more than $200 million.

And third, that these isolates were found in community infections caused by common organisms such as E. coli. That testifies not only to their wide distribution, but also to how difficult it might be to conduct surveillance for their presence — or, put another way, how easily they could evade detection while they continue to spread. It is not likely that physicians are going to culture every UTI that comes their way, either in the resource-poor developing world or in the overstressed conditions of Western medicine.

One example of the importance of surveillance: That's how NDM-1's first appearance in the United States was detected, via three isolates from three states that were tested at the CDC's national labs in the first half of this year. In a bulletin in June (the subject of my first post on NDM-1), the CDC urged clinicians to be alert for resistant infections in any patients who reported receiving medical care in India or Pakistan.

Unfortunately, given the drought of new drugs for Gram-negatives, surveillance may be the best bet for controlling or at least slowing NDM-1's further spread. It's the urgent recommendation of the author of a companion Lancet ID editorial, also published today (and who appears to have seen Canada's first case):

The spread of these multiresistant bacteria merits very close monitoring and worldwide, internationally funded, multicentre surveillance studies, especially in countries that actively promote medical tourism. Patients who have had medical procedures in India should be actively screened for multiresistant bacteria before they receive medical care in their home country. ...The consequences will be serious if family doctors have to treat infections caused by these multiresistant bacteria on a daily basis.

Cites:
Kumarasamy KK, Toleman MA, Walsh TR et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. The Lancet Infectious Diseases, early online publication, 11 August 2010doi:10.1016/S1473-3099(10)70143-2
Pitout JDD, The latest threat in the war on antimicrobial resistance. The Lancet Infectious Diseases, early online publication, 11 August 2010. doi:10.1016/S1473-3099(10)70168-7

News break: Hospital-acquired MRSA trending down - but why?

2010-08-10T20:01:00.000-05:00

There's good news today in the Journal of the American Medical Association: A 4-year study by the CDC and its partners in the Active Bacterial Core Surveillance System reports significant declines in invasive MRSA infections contracted in hospitals. The study, which covers 2005 through 2008, finds a decline of 9.4% per year among infections that were contracted in hospitals and also diagnosed there, and a parallel decline of 5.7% per year in what the CDC calls "hospital-acquired community-onset" infections, ones that were acquired in the hospital but didn't become evident until after the patient was discharged. Overall, the decline over the study period of hospital-onset infections was 28%, and the decline in hospital-acquired community-onset infections was 17%.

MRSA is the leading organism in the vast national epidemic of hospital-acquired infections (HAIs), which conservatively sicken 1.7 million Americans per year and kills 99,000 of them. (Those numbers date back a decade to an Institute of Medicine report, and have been challenged by Consumers' Union as an underestimate.) So any solid indication that the epidemic is decreasing is good news. And the CDC study is a solid indication, built on a population-based survey that covers about 15 million people in 9 geographical areas.

So it's a great pity that we don't really know why MRSA has declined in this fashion. The study can't tell us. And because we don't know, we'll find it harder than it ought to be to keep the trend going in the appropriate direction.

Here's the problem: Though it is about healthcare infections, this study doesn't use data from hospitals. The study itself says: "National data describing changes in incidence in US healthcare institutions are not available." The data that hospitals report on infections that occur within their walls or result from their actions, contained in the CDC's National Healthcare Safety Network, is voluntary, partial and anonymous; in fact, to participate, hospitals are guaranteed confidentiality. The only surveillance systems in the US where hospitals are not anonymous are the various states where legislators, out of exasperation or in response to citizen pressure, have passed laws mandating that infections be reported.

So the declines in MRSA incidence that are reported in this study can't be linked to specific practices — and that's important, because for more than a decade, American healthcare has been locked in a ferocious argument over the best way to reduce MRSA and other HAIs in hospitals.

On the one hand, there are institutions such as the Pittsburgh VA (in a project partially funded by the CDC and since adopted across the entire VA) and Evanston Northwestern Healthcare (now called Northshore University Health System) that follow some variant of "active surveillance and testing" or simply "search and destroy," which tests incoming patients for MRSA carriage and isolates and treats them until they are clear. On the other hand, there are institutions that reject "search and destroy" as too MRSA-specific (and too dependent on expensive rapid-test technology) and opt instead for broader infection-control programs with special emphasis on hand hygiene and antibiotic stewardship. (This paper by physicians from Virginia Commonwealth University summarizes the issues well.) The patients whose data ended up in the JAMA CDC study might have attended hospitals that followed either of these paths, or neither. There's no way to know.

In addition, a significant proportion of the decline in the CDC study fell into the category of bloodstream infections — which are now also being targeted by the checklist approach espoused by Macarthur Fellow Dr. Peter Pronovost and New Yorker writer and surgeon Dr. Atul Gawande, and adopted patchily across the US. Plus, there's a further confounder: Since 2009, the Center for Medicare and Medicaid Services has been applying a carrot-and-stick approach — refusal to reimburse for the extra care needed — to certain preventable hospital-caused conditions, including central-line associated bloodstream infections (which are caused by a variety of organisms including MRSA). How successful that has been, or how much influence it has exerted, has not been assessed.

So, to recap: MRSA appears to be declining in hospitals; that's good. From this study, we can't say why: That's frustrating. And, one more point: If we had truly accountable, truly transparent hospital reporting for preventable infections and other medical errors, we would not be in this data fog. Surely it's past time to clear the air.

Cite:
Kallen AJ, Mu Y, Bulens S et al. Health Care–Associated Invasive MRSA Infections, 2005-2008. JAMA. 2010;304(6):641-647. doi:10.1001/jama.2010.1115
Accompanying editorial:
Perencevich EN, Diekema DJ. Decline in Invasive MRSA Infection: Where to Go From Here? JAMA. 2010;304(6):687-689. doi:10.1001/jama.2010.1125

Unintended consequences: C. diff death after extended Lyme treatment

2010-08-04T17:15:00.001-05:00

The ongoing fight over long-term Lyme disease treatment has to be one of the most ferocious in health care. If you don't live in the Northeast or upper Midwest, Lyme disease may not be on your radar, so here's a super-quick version: There are patients and physicians who say that Lyme disease symptoms persist following the 28 days of antibiotic treatment that is the standard recommendation of the CDC and the Infectious Diseases Society of America, and also say that patients benefit from additional antibiotic regimens — sometimes IV, sometimes oral — that can last months more. The CDC, IDSA and some other medical authorities say there is no evidence to support these regimens. The ongoing bitterness has extended to antitrust charges by the Connecticut Attorney General that forced a re-evaluation of the IDSA guidelines, which physicians follow and insurance companies refer to when authorizing payment. The disagreements have continued into this year.

I've been curious about the long-term Lyme regimens from the antibiotic-resistance POV: whether giving Lyme patients such long courses of antibiotics would encourage the development or spread of resistant organisms. (NB, I don't know of any research that would answer that question, but if anyone does, cites would be welcome.)

Today, though, I spotted a new paper that describes an unintended consequence I hadn't thought of: the death of a Lyme patient from Clostridium difficile or C.diff, an infection that becomes more likely after long courses of antibiotics.

Quick lesson: C. diff (here's the CDC info page) is a toxin-producing bacteria that causes a life-threatening infection of the gut. It's normally resident in the intestines, but can roar out of control when prolonged courses of antibiotics wipe out the gut's complex and very abundant population of bacteria. (Ed Yong's post from a few days ago has excellent detail on the gut microbiome.) C. diff is rising in incidence, becoming drug-resistant, and also is extraordinarily difficult to eradicate from hospital environments — because it is spore-forming and thus protected against the alcohol in the hand gels that hospitals have encouraged in order to balance the need for hand hygiene with the time consumed by hand washing.

The paper, a letter to Clinical Infectious Diseases by representatives of the Minnesota Department of Health (Holzbauer et al., DOI: 10.1086/654808), describes the experience of a 52-year-old woman who had Lyme-like symptoms for about 5 years. She consulted a doctor in June 2009, was tested for Lyme, and was put on 5 weeks of doxycycline. She got better, but then her symptoms returned, and she sought care from a different physician who prescribed an additional 2- to 4-month course of two other antibiotics.

Five weeks after initiating this therapy, the patient developed diarrhea for 3 days and received a diagnosis of C. difficile colitis. ... The patient was started on oral metronidazole therapy but was hospitalized 2 days later with severe abdominal pain secondary to diffuse colitis and abdominal ascites. The next morning, she experienced cardiac arrest twice and succumbed to cardiac arrest during an emergency [removal of her colon].

I've been talking to Lyme patients recently, including some who decided to take long-term antibiotic regimens. Some of them describe themselves as sick enough to take any risk in an attempt to get better. I wonder whether it's made clear to them how substantial the risks might be.

Must-read: Scientopia, a new science-blog collective

2010-08-02T13:07:00.000-05:00

Constant readers will remember that Superbug exited this space in early June to go hang out at Scienceblogs, and returned in late July after an ethical dilemma there wasn't solved to my comfort level. Nothing special about me; a number of bloggers there left, about 20 or one-quarter of the roster if the numbers I've heard are correct.

Scienceblogs was a great blog community, and its implosion is a pity. But the unintended consequences turn out to be good news, which is the seeding of that concentrated array of talent back throughout the blogosphere. All kinds of exciting new arrangements are being rumored and chatted up.

And today, one makes its debut: Scientopia!

It's a very cool-looking new network — employee-owned, as it were — that turns out to be hosting a number of my former Sciblings, including Book of Trogool, Christina's LIS Rant, The Questionable Authority, Good Math/Bad Math, and excellent physician-blogger PAL MD of White Coat Underground.

There's a Twitter addy and an RSS feed and all kinds of shiny newness. Check them out, please.

Update: The French case — not MRSA but so interesting

2010-08-02T12:46:00.001-05:00

I'm flattered to have as a regular reader Dr. Peter Davies, a professor of swine health and production in the University of Minnesota's Department of Veterinary Population Medicine. (Disclosure: I worked part-time at U Minn from mid-2006 to mid-2010, but in a different school.) In a comment on my previous post, he points out — perils of reading on a smartphone — an important point where I erred: The staph strain involved in the death of the French 14-year-old was not MRSA, but MSSA, drug-sensitive staph, that had picked up a resistance factor.

Unpacking that a bit: At a minimum, MRSA is resistant to all beta-lactam antibiotics — penicillin, the semi-synthetic penicillins (including methicillin, what the M in MRSA stands for), several generations of cephalosporins, monobactams, and carbapenems. It is also separately, but variably, resistant to macrolides (such as erythromycin), lincosamides (clindamycin), aminoglycosides (gentamicin), fluoroquinolones (ciprofloxacin) and tetracycline.

Livestock-associated MRSA, known as ST398 for its performance on a particular test (multi-locus sequence typing) was first identified as having a tie to pig-farming because it was also resistant to tetracycline, which was being given to the pigs on the farms where the first human carriers worked. (Hence its jocular name, "pig MRSA," though it's since been found in other animals.)

The ST398 strain involved in the French girl's death does not have that broad array of resistance. Chiefly, it was not resistant to beta-lactams, and so can't be considered MRSA. On analysis, it was resistant to the macrolides, of which the best-known are erythromycin and azithromycin (Zithromax or Z-Pak). Here's something else intriguing: On another test (spa typing), the ST398 strain in the French girl was one known as t571; the ST398 that has spread from pigs to humans in the European Union, and subsequently to Canada and the United States, is usually t034.

Here's why this is all so interesting: MSSA ST398 t571 was reported just a few years ago in New York City, in a Bronx community that has close ties to the Dominican Republic, and also in the towns in the Dominican Republic where those Bronx residents come from and visit. (Here's my initial post on that finding from a medical meeting, and subsequent post when the paper was published.) In that case, the ST398 was fully drug-sensitive — and there was no visible link to pigs, though the authors speculated that livestock, perhaps poultry, might be playing a role on either side of the "air bridge" connecting the two communities.

In the paper (Bhat, Dumortier, Taylor et al., EID 2009, DOI: 10.3201/eid1502.080609), the authors expressed concern that, given staph's promiscuous ability to acquire resistance — and the fact that ST398 is not regularly surveilled for — the ST398 in New York could become an undetected resistant strain:

Given ST398’s history of rapid dissemination in the Netherlands, its potential for the acquisition of methicillin resistance, and its ability to cause infections in both community and hospital settings, monitoring the prevalence of this strain in northern Manhattan and the Dominican Republic will be important to understand more about its virulence and its ability to spread in these communities.

And now it appears it has become resistant — but in France, not New York City or the Dominican Republic, and to macrolides, not beta-lactams. It's one more reminder of staph's genius at acquiring genetic defenses, and of how our lack of attention to its mutability and spread continues to allow it to take us by surprise.

News break: "Pig MRSA" ST398 involved in the death of a child?

2010-07-31T15:04:00.002-05:00

The latest postings to the website of the CDC journal Emerging Infectious Diseases include a sad and very troubling letter from physicians in Lyon and Paris, reporting the death from necrotizing pneumonia of a previously healthy 14-year-old girl. That would be sad under any conditions, but here's what makes the death so troubling: It appears to have been caused by MRSA — but not by the community strain, USA300, that has been implicated in a number of deaths from necrotizing pneumonia. (Several such stories are told in SUPERBUG the book.)

Instead, her death appears to have been caused by infection with MRSA ST398 — the livestock-associated strain that was first noted in pigs raised with antibiotics, and the pig-farm workers caring for them, in the Netherlands 6 years ago, and that has since spread across the European Union, Canada and into the United States. (My 3-year archive of ST398 posts is here.)

This may be the first death associated with ST398, though I can't say that for sure as I am away from my big computer and working without my database. I'll update later today and confirm or knock that down.

The physicians say that the girl came in with flu-like symptoms and abdominal pain, was put on IV antibiotics (cefotaxime and amikacin), underwent an exploratory laparotomy that showed nothing, and shortly afterward developed acute respiratory distress and was put on a vent. A chest X-ray was shadowy on both sides. She went rapidly downhill and died 6 days later.

On analysis, the staph strain infecting her was ST398; there was no indication where she had picked it up. The strain had an unusual characteristic: It possessed the ability to make the cell-destroying toxin Panton-Valentine leukocidin, PVL for short, a genetic trick that until now has been a property only of community MRSA strains such as USA300. Though its role is disputed, PVL has been linked to community MRSA's ability to start infections on intact skin, and to the cellular damage that destroys children's lungs in cases of pneumonia caused by USA300. Until now, ST398 has been PVL-negative.

The physicians' letter is short and there's much more to find out about this case. But if the report and analysis are correct, this is bad news. One of the repeated themes in the 50-year evolution of MRSA has been its ability — all staph's ability — to promiscuously swap and share the bits of DNA that confer resistance and enhance virulence. Another, since the emergence of ST398, has been the potential peril of a staph strain adapting and mutating in the millions of farm animals around the world that are routinely given antibiotics — and that for the most part are not checked to see whether they harbor resistant organisms. If this report (and my interpretation) are correct, then those two trends are converging in a way that cannot bode well.

Advice for science writers, from science writers

2010-07-29T23:27:00.000-05:00

Ed Yong, an incisive and prolific science blogger-writer-communications officer, opened up his blog to the science-writing community earlier today, with this invitation:

Every now and then, I get an email from someone who’s keen to get into science writing and wants to know how I started. Whenever I reply, and I always try to, I’m always left with the nagging feeling that my experience is but one of a multitude of routes that people have taken. Science writing (whether you want to call it journalism, blogging, communication and so on) is a diverse field, as are the people working in it. It would be far more illuminating for a newbie to see a variety of stories rather than just one.
...I will be asking science writers around the world to do what they do best – tell a story – about the thing they know best – themselves. This will be a perpetual thread that I hope will act as a lasting resource for the writers of tomorrow to take inspiration from.

That was about 18 hours ago. So far there are 59 comment/stories posted, from some of the brightest and sharpest writers working today, with more to come tomorrow, I am sure. (Also, umm, me. I didn't get in til #51, because I was trying to catch a plane.) Collectively, the comment string is both a peek behind the curtain of how science writers and authors work and think — and think about their work — as well as a trove of advice for anyone else who wants to try this odd and taxing profession.

A selection:

Mark Henderson (#2), science editor of the Times of London: "If you can’t find great stories from everything that’s pouring out of the world’s laboratories, you’re not much of a journalist."

Jonah Lehrer (#4), author of How We Decide and Proust Was a Neuroscientist: "Writing is a craft. There are no born writers. One has to practice and practice and practice."

Maggie Koerth-Baker (#5), BoingBoing.com: "Think of yourself as a business, ask to be paid what you’re worth and stick to your guns, always turn things in on time, learn that editing is not your enemy, and work really, really hard at writing nuanced, factual stories that are still fun to read. Luck helps those who help themselves."

Raima Larter (#16), writer and former chemistry professor: " I don’t think you can go wrong when you make your choices based on what most excites you. Passion can go a long way in carrying you forward in any career."

John Pavlus (#21), writer/filmmaker: "BE curious and ACT curious. Everything else will work itself out from there."

TR Gregory (#29), an evolutionary biologist who has started a companion thread on his own blog: " There is a lot of frustration among scientists and educators with the way new studies are portrayed in the media, but when someone is recognized as an honest and skilled communicator, he or she will be among the ones that scientists hope will discuss their research."

Brendan Maher (#34), features editor, Nature: "Humility and self-assured enthusiasm can coexist."

Eric Michael Johnson (#41), blogger at The Primate Diaries: " Take risks. Make mistakes. Fall flat on your face. The difference between wanting to be a writer and actually being one is in how often you pick yourself back up."

(Stripped of the biographical material, here's my contribution: "Work nights and weekends. Seek mentors. Stay alert to serendipity. When someone wants to tell you a story, listen. Develop expertise. Distrust everyone’s motives, including your own. Always ask another question. Talk to people face to face. Rejoice in complexity, in systems and in persons, and accept that it takes its time revealing its intricacies. Try to tell the truth.")

Whooping cough: Back, with a vengeance

2010-07-27T08:00:00.004-05:00

A few years ago, I went to India on a reporting trip. When I came back, I had a troublesome cough. I figured I'd picked up a bronchitis aggravated by New Delhi's smog-laden air, or by the dung smoke from the fires in the villages where I'd spent most of my time. The cough got worse instead of better. It was especially bad at night: I'd lie down to sleep and that would trigger a paroxysm. Sometimes I'd cough until I couldn't breathe. A few times, I vomited. Eventually my side began to hurt. (Months later, I discovered I'd cracked a rib.)

As a medical reporter, I spent most of my time around doctors and nurses, but I had a rule about never bothering them — first because I was pretty healthy, and second because no one wants to be the guy at the cocktail party who finds out someone's a doc and backs them into the corner of the buffet table. But one day, worn out by the spasms, I mentioned my symptoms to a friend. His eyes got big. He went and got a textbook.

I didn't have bronchitis. I had pertussis — whooping cough.

This made no sense, of course. Between a day job as Scary Disease Girl and a childhood spent moving between continents, I am pretty much the most vaccinated person on the planet. I'd had my full series of pertussis vaccinations as a child. Surely I was protected?

Actually, no — and unless you've had a booster, neither are you. The immunity created by the 5-dose childhood series wanes over time; by the age of 12, even fully vaccinated people are vulnerable to pertussis again. Since 2006, the Advisory Committee on Immunization Practices has been recommending a single additional pertussis (Tdap) booster for anyone between the ages of 11 and 64. That may seem like overkill — adult cases of pertussis in previously vaccinated people are often milder than the child version; after all, I survived my bout. But as with so many vaccines, the beneficiary here isn't just the adult taking the booster. Even more, it's the more vulnerable person to whom that adult might pass the disease: an elderly person with age-related immune decay; someone with a chronic disease; an infant too young to be vaccinated. In those people, the disease can and does kill — as it did an 18-day-old infant, Nelyn Baker, whom I wrote about in 2004.

Because vaccine immunity fades, pertussis is always with us: in good years, about 1,000 cases across the United States. Lately, though, we're in bad years. Pertussis cases are rising dramatically, in Alabama, Georgia, Arkansas, Texas, South Carolina, Michigan, Oregon and Ohio. The worst by far is California, where so far this year almost 1,500 cases of pertussis have been reported and another 700 are suspected — compared to 258 for the same time period in 2009.

"We are facing what could be the worst year for pertussis that this state has seen in more than 50 years,” Dr. Gilberto Chávez of the California Department of Public Health said last week in a statement put out by the agency's Center for Infectious Disease.

The worst news in this upsetting trend is this: We're doing it to ourselves. As far as anyone can tell, the rise in pertussis is not due to any change in the organism, or to any mysterious error among the manufacturers who make pertussis vaccines. It's due to vaccine refusal, to parents turning away from vaccines because they think the vaccines are more harmful than the diseases they prevent — or, more selfishly, because they think the wall of immunity created by other vaccinated children will protect their unimmunized ones.

That's an incorrect assumption, by the way. Work published last year by several scientists at Kaiser Permanente of Colorado found that unvaccinated children were 23 times more likely to contract pertussis than vaccinated ones. (Glanz, McClure, Magid et al., Pediatrics 2009, doi:10.1542/peds.2008-2150.) And yet, as numerous stories (LA Times, MedPage Today) have pointed out, California's epidemic has blossomed in a state that gives some of the most generous "personal belief exemptions" from vaccination — and the epidemic's worst hot spots neatly correlate with the most concentrated areas of vaccine refusal.

Pertussis is an awful disease. A child in the throes of a paroxysm sounds like nothing else on earth. Children turn blue, give themselves black eyes, die. We kept it down to manageable levels with the help of a vaccine. That we would willingly bring it back it is beyond belief.

(For a physician's take on pertussis, see this post by my fellow former Scibling Pal MD. The CDC's information page on pertussis is here and the National Network on Immunization Information explains the vaccination schedule here. H/t to the infectious-disease mailing list ProMED for starting me thinking.)

Hospitals want patients to eat antibiotic-free meat

2010-07-21T12:18:00.001-05:00

Huge news, and hat tip to excellent food-policy writer Monica Eng at the Chicago Tribune: In a piece published Tuesday, she details that 300 hospitals in the Chicago area and nationwide have begun preferentially buying and serving meat that is raised without the use of antibiotics.

Using the ingredients is primarily a response to patient demand, said (Carolyn Lammersfeld, national director of nutrition at Cancer Treatment Centers of America) but the centers are also "watching the controversy over the nontherapeutic use of antibiotics and their potential to cause resistant strains of bacteria."

The issue is of particular concern for cancer patients, who have compromised immune systems, she noted. "Many also might already being taking antibiotics, so they don't want additional ones in food if they can avoid it," Lammersfeld said.

The drug-free meat is more expensive, but the cost balances out within the budget:

(Diane Imrie, director of nutrition services at Fletcher Allen Health Care in Vermont) estimated that her food costs rose about $67,000 last year when she switched to antibiotic-free chicken from conventional. "But that's also about the same cost as treating a single MRSA infection," she said.

It's interesting to see this story land just as a new paper in Foodborne Pathogens and Disease is making the rounds. The paper (Jiayi Zhang, Samantha K. Wall, Li Xu, Paul D. Ebner. "Contamination Rates and Antimicrobial Resistance in Bacteria Isolated from “Grass-Fed” Labeled Beef Products," doi:10.1089/fpd.2010.0562) compares the bacterial burden in grass-fed and conventionally raised beef and finds no significant differences: equivalent amounts of both drug-sensitive and drug-resistant bacteria in both types of beef.

It concludes, "There are no clear food safety advantages to grass-fed beef products over conventional beef products" — an assertion that's likely to be seized on by those who see no need to change current antibiotic use in agriculture. (For an example of that POV, here's the testimony from last week's House of Representatives hearing by Richard Carnevale, DVM of the Animal Health Institute.)

I suspect though that the paper's analysis doesn't look far enough. Here's one example: the authors found that Enterococcus species in both conventional and grass-fed meat were resistant to chloramphenicol, erythromycin, flavomycin, penicillin, and tetracyline — drugs that are used in agriculture (and that could have been given to the grass-fed animals, which were not guaranteed to have been raised drug-free). But Enterococcus spp. isolates from conventional beef were more frequently resistant to daptomycin and linezolid — which are new-to-market drugs of last resort in human medicine that are not given to animals.

That finding, right there — the migration of resistance to a human-only drug into an organism carried by an animal — signals one of the insoluble problems of overuse of antibiotics. Once created, resistance factors move horizontally among bacteria, from the farm to humans, and apparently in this case, from humans to the farm as well. We have almost no control over their movement, and on the agricultural side, almost no surveillance to detect it, either. That argues for reducing the overuse of antibiotics in human medicine and on the farm.

If this health care coalition's refusal to purchase meat raised using antibiotics helps to enlarge the market for drug-free meat, then it may reduce ag antibiotic use, and therefore the selective pressure that encourages resistant organisms to emerge. That can only be a good thing.

(The paper in Foodborne Pathogens has also been covered by my former colleagues at CIDRAP; here's their link.)

Hi, I'm back.

2010-07-20T09:15:00.000-05:00

Hello again, constant readers. If you've been following the ongoing implosion at my briefly-new-and-now-former home at Scienceblogs, you'll know why we're back here blowing the dust off things. If not, never mind: There's way too much news to talk about, anyway.

To maintain some continuity, I've changed the URL for this site to Superbugtheblog.com, though the former address, drugresistantstaph.blogspot.com, will also now redirect here. RSS feed buttons are in the sidebar.

I'll be cleaning things up in the next day or so and updating the archives. But in the meantime, I'm back and I hope you are too.

Antibiotic use in animals: The feds move, a little

2010-07-07T12:19:00.001-05:00

This is an addition for archival purposes of a post that originally appeared at Scienceblogs.

(You leave the country for a few days -- I spoke at a conference in Brussels, which was was lovely, thanks for asking -- and all kinds of news breaks out. So, sorry to be late on this, but it's an important issue.)

Last week, the Food and Drug Adminstration took the first (baby, mincing, tentative) steps to address the problem of antibiotics being used in animal agriculture, not to treat disease, but to make animals grow up to market weight faster. This practice -- variously called subtherapeutic dosing, growth promotion, and "for production purposes" in the FDA's exceedingly careful language -- has been fully banned in the European Union for 4 years, and some aspects of the practice have been banned longer.

The simple reason for the ban: There's decades of good science and real-world experience showing that it contributes to the development of drug-resistant organisms in farm animals and the farm environment, organisms that leave farms in the animals and in their manure, and also contaminate the environment beyond farm borders via leakage into groundwater and dust blowing off manure lagoons.That movement off the farm is critical because many of the drugs used in agriculture are the same, or close analogs, of drugs used in human medicine; so resistance that develops on the farm endangers human health as well. (MRSA ST398, livestock-associated MRSA, is the latest example of this. Find a long archive of posts on ST398 here.)

Just to be clear, growth-promoters don't treat disease; they're given to healthy animals solely for the purpose of getting them up to sale weight and to market faster. The ways in which antibiotics are given to livestock to treat or prevent disease have their own issues, but those are not part of the FDA effort. (Historical note: The growth-promoting effect of trace amounts of antibiotics was first recognized in 1947, when scientists at Lederle were looking for something to do with the leftover fermentation mash from the manufacture of chlortetracycline, fed it to chickens, and discovered they thrived on it. Stuart Levy's The Antibiotic Paradox tells this story in detail.)

In human medicine, when we give antibiotics to people who are not sick with a bacterial illness, we call it inappropriate use -- and aim massive education campaigns at the practice in an attempt to dial it down. In contract, the animal side has had a free pass for a long time, to the extent that it remains unclear how many antibiotics are used in farming in the US (best estimate: about 70% of all antibiotic use in the US per year), and there is no organized surveillance that would look at what organisms are emerging in animals from that use.

The FDA has been trying to put curbs on growth promoters since the 1970s, always without success; the lobbying against it, by agriculture and also by pharmaceutical interests, is reliably intense. There's been a parallel effort in Congress to limit the use in animals of drugs that have close analogs in human medicine, via the Preservation of Antibiotics for Medical Treatment Act, or PAMTA, authored by Rep. Louise Slaughter (D-NY), Congress's only microbiologist. PAMTA has been introduced in several Congresses but this year finally gained some traction. Last year, the Obama administration signaled, in testimony by then-new assistant FDA commissioner Joshua Sharfstein, that it might be friendly to the idea of dialing back on growth-promoter antibiotic use, and it looked as though the long logjam might finally be broken.

Well, OK: Not broken, exactly. Just shifted a little, and maybe showing a tiny bit of light.

On Tuesday, the FDA released a "draft guidance" that proposes animal ag do two things: stop using growth-promoting subtherapeutic dosing, and administer antibiotics to animals under the supervision of a veterinarian. That's the good news.

The bad news: It's only a guidance, not a regulation. In other words, it has no force in law. It's more like a request -- though in a press conference last week, Sharfstein suggested it might also be a shot across agriculture's collective bow:

We have the regulatory mechanisms and the industry knows that. But we are also interested in what things can be done just voluntarily that they would do them. And I think it'll be interesting to see how the industry responds to this and how - what direction their comments take. ...We're not handcuffed to the steering wheel of a particular strategy at this point. We really want to understand what people think. And but we're also - I'm not ruling out anything that we could do to accomplish these important public health goals. (Transcript)

Reactions to the FDA announcement were predictable -- effectively "No science, more research needed": Here's the National Cattlemen's Beef Association, the National Pork Producers Council, and a standing statement by the Animal Health Institute. (Supporting the FDA move: the Pew Charitable Trusts, the New York Times.)

The draft guidance stays open for public comment for 60 days, until Aug. 30. The required Federal Register posting is here, with the mailing address. Electronic comments can be left at Regulations.gov; the docket number for the guidance is FDA-2010-D-0094; 33 comments have been posted already.

Past time to pay attention to polio

2010-06-28T12:17:00.000-05:00

This is an addition for archival purposes of a post that originally appeared at Scienceblogs.

In the winter of 1999, I stood in an outpatient clinic in a pediatric hospital in New Delhi and listened to a father sobbing over the paralysis of his only son. He was a farmer and lived in Uttar Pradesh; counting walks, minibuses and trains, it had taken him 24 hours to get to the hospital. He had carried the toddler the entire way.

His son had gotten the drops, he insisted: Every time the teams came to his neighborhood -- which they did three, four times each year -- he or his wife had lined up all their children, the boy and his older sisters. His son had had 11, 12 doses, the man said. How could he have gotten polio? And it was polio, the doctor treating him confirmed, not one of the transient febrile paralyses that exist alongside the disease and make detection and diagnosis so complex in resource-poor settings. She saw this all the time, she confided. The massive polio-eradication campaigns that continually blanketed India had trouble reaching some resistant populations, and those children contracted polio because they were not vaccinated -- but children whose parents were compliant, who believed in the drops and made sure their children received them, became paralyzed as well.

I was in India that winter because the long-hoped-for goal of the worldwide eradication of polio was supposed to be achieved the following year, in 2000. The global eradication initiative -- led by the WHO, the CDC and a massive volunteer effort by Rotary International -- didn't make that goal that year. Or in 2002, or in 2005. For a variety of reasons, from the biology of the disease in the tropics to political manipulation in service of unrelated ends, several countries have remained stubborn hot spots. And as long as the disease persists within their borders, it can leak outside them and become re-established in any area where vaccination has slowed down because the goal of stopping local transmission appears to have been achieved.

Most recently, it has leaked to Tajikistan, a country that has been polio-free since 2002 but shares borders with three of the four countries -- India, Pakistan and Afghanistan (Nigeria is the fourth) -- where polio remains endemic. As of the last count, 183 children were confirmed to have polio; authorities generally estimate that for every child detected with polio, 200 others may be infected silently and can pass on the disease.

There is so much to say about polio eradication; it is an impossibly complex and expensive task, fraught with cultural complexities and burdened with an endgame of clean-up that will stretch years beyond eradication itself. It is so complex that major public health figures have periodically thrown up their hands and declared eradication unachievable. It is one of the most expensive public health campaigns every attempted, with billions spent so far (and yet chronically short of funds). And because most of the West remains fully vaccinated, polio lurks far below the radar horizon of our concern.

I say all this -- which is kind of opening the floodgates for me, because I've wanted to talk about polio for years, but it is a damn hard story to sell to editors -- because CMAJ, the Canadian Medical Association Journal, has published a great editorial calling for the West to take the threat of polio seriously again.

Although the rates of poliovirus immunization in most of Europe exceed 90%, neither the Ukraine nor Georgia has reached this target. Furthermore, regions of Canada and some European countries have very low rates of vaccine uptake. Infants and toddlers are often not vaccinated on time because of a lack of appreciation of the seriousness of poliomyelitis. Community immunization rates may also be adversely influenced by concerns about vaccine safety, religious beliefs barring vaccination and antivaccine or antigovernment sentiments... There are no cures for poliomyelitis -- prevention through vaccination is our best and only defence. We are only one asymptomatic infected traveller away from an outbreak because of low vaccination rates. (MacDonald and Hebert)

Since the year 2000, there have been two recurrences of polio in the US: one in Minnesota, sparked by the vaccine virus, and one in Arizona contracted by a college student traveling abroad. The college student, and the children in the Minnesota community, had never been vaccinated because of religious or cultural exemptions. So our protections are not as impermeable as we think.

News break: CDC alert on imported novel resistance

2010-06-24T12:16:00.001-05:00

This is an addition for archival purposes of a post that originally appeared at Scienceblogs.

There's a troubling item in this afternoon's issue of the CDC's Morbidity and Mortality Weekly Report or MMWR: The first report in the United States of a novel resistance mechanism that renders gram-negative bacteria extremely drug-resistant and that has been linked to medical care carried out in India or Pakistan.

The short item describes three isolates (E. coli, Klebsiella pneumoniae and Enterobacter cloacae) found in three patients in three states between January and June of this year. All three isolates produced New Delhi metallo-beta-lactamase (NDM-1), which has never been recorded in the US before. Because of that novel mechanism, the three isolates were resistant to the carbapenems usually used on the most serious gram-negative infections, in fact to all beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, monobactams, etc.) except for one monobactam, aztreonam -- and they were also resistant to aztreonam through another mechanism that hasn't been identified yet. All three of the patients found carrying this novel resistance factor had undergone medical care in South Asia recently.

This may be the first finding of this mechanism in the US, but it's been causing alarm in Europe for at least two years.

The first identification of NDM-1 was in 2008, in a 59-year-old resident of Sweden who was of South Asian origin and had returned to India for several months. The man was not well -- he had long-standing type 2 diabetes and had experienced a number of strokes -- and while in India he was hospitalized for an abscess, underwent surgery, developed bedsores and was treated for them as well. He returned to Sweden and was hospitalized there in January 2008, where physicians found him to be suffering from a urinary tract infection caused by a Klebsiella strain carrying this never-seen resistance mechanism.

Last July, the UK's Health Protection Agency put out a national alert about NDM-1, warning that the novel mechanism had gone from never-seen in 2007, to 4 isolates in 2008, to 18 in the first half of 2009. They were not an outbreak, but represented repeated importations: The isolates were clonally diverse and had been collected at 17 different hospitals. They were, instead, a sign that long-standing two-way population movement between England and South Asia -- augmented by elective medical tourism (two patients had gone to India for cosmetic surgery) -- was bringing the high rates of antibiotic resistance in India back to a UK medical system that is already challenged by serious infection-control problems.

And now it's here. The special challenge of NDM-1 (which as today's finding suggests is on a mobile genetic element that has carried the resistance mechanism between species) is not only that it adds to an accumulating rogues' gallery of resistance factors that are rapidly making gram-negative bacteria ferociously drug-resistant, but also that there are so few drugs under development for gram-negatives that truly untreatable infections are not far off. The UK clearly is already struggling with attempting to use drugs that are old and toxic, untested against these organisms (and therefore with no agreed-upon dosing), or wrong for the organ systems affected:

Treatment presents major challenges. Most isolates with NDM-1 enzyme are resistant to all standard intravenous antibiotics for treatment of severe infections. Polymyxin is usually active in vitro ... but of uncertain clinical efficacy, especially in pneumonia, owing to poor lung penetration. Tigecycline is often active in vitro, but has low serum levels, is unsuitable for urinary infections and, more generally, is of unproven efficacy in severe infections.

The CDC's alert today asks any clinicians who come up against carbapenem-resistant gram-negatives to ask about contact with India or Pakistan as part of history-taking, and to forward isolates through state public health labs to the the CDC.

Update + fodder: I flipped over to my RSS reader and also discovered this paper posted overnight by Clinical Infectious Diseases, about extended-spectrum beta-lactamases in a particular strain of E. coli ("an important new public health threat"), and this one in Emerging Infectious Diseases, about carbapenem resistance moving between Klebsiella and E. coli.

Pan-resistant?? The rise of Acinetobacter

2010-06-17T12:15:00.002-05:00

This is an addition for archival purposes of a post that originally appeared at Scienceblogs.

A set of papers published this month in two journals provide an unsettling glimpse into the rocketing incidence and complex epidemiology of one really scary pathogen, Acinetobacter baumanii.

In the all-star annals of resistant bugs, A. baumanii is an underappreciated player. If people -- other than, you know, disease geeks -- recognize it, that is because it's become known in the past few years for its propensity to attack wounded veterans shipped to military hospitals from Iraq and Afghanistan, earning it the nickname "Iraqibacter." (Important note: Steve Silberman of Wired magazine took an early look at this phenomenon in 2007, in a great story that analyzed the epidemiology of Iraqibacter to show that military infection control, not the environment of Iraq, was to blame for the bug's rapid emergence.) A. baumanii is a nasty bug, causing not just wound infections but pneumonia, urinary tract infections, meningitis and bacteremia. Even more nasty, it collects resistance factors like baseball cards, and is commonly resistant to at least 4 antibiotic classes. The most resistant strains are susceptible only to the so-toxic-we-put-it-back-on-the-shelf-decades-ago antibiotic colistin.

This is a particular concern because A. baumanii is a Gram-negative bacterium -- and while the drug-development pipeline for Gram-positives such as MRSA has slowed practically to a trickle, the one for Gram-negatives has dripped itself dry. As the Infectious Diseases Society of America and Jerome Groopman of the New Yorker highlighted back in 2008, drugs for Gram-negatives are barely on the agenda for the few companies still conducting antibiotic development.

So, the first piece of bad news. In Infection Control and Hospital Epidemiology (ICHE), a team from Brooke Army Medical Center in San Antonio take a look at their incidence of resistant Ab and find it exploding. Between 2001 and 2008, the percentage of A. baumanii isolates that were resistant to at least 3 classes of drugs went from 4% to 55%; of all the isolates, 17% (127) were resistant to at least 4 drug classes, and one was resistant to, well, everything.

How does A. baumanii spread so fast? A second paper in ICHE suggests a reason: The bug seems to do a better job than other resistant pathogens of contaminating the gear and hands of health care workers. A study done at University of Maryland found that when health care workers took care of A. baumanii patients, they ended up with contaminated gowns and gloves 39% of the time, and with contaminated hands (after glove removal) 4.5% of the time. Those are higher rates than for MRSA (18.5% of encounters) or VRE (8.5%).

A review article in Clinical Infectious Diseases reminds us why we should care about this: It examines the drugs to which some strains of A. baumanii are still susceptible, and finds all of them significantly toxic to different organs (kidneys, liver, pancreas, red blood cells, ) at the doses necessary to wipe out the bug.

Which is all troubling by itself. But a paper and editorial also appearing in Clinical Infectious Diseases make the case for A. baumanii as a bigger threat than has been understood. The bug's recent epidemiology has shown a distinct split, between the highly resistant forms affecting veterans, most of them being treated in the military evacuation chain, and less-resistant forms affecting civilians in hospitals (including in the Brooks data in the paper above). The severe wounds, aggressive treatment and rapid multiple transfers of personnel in the military system inadvertently created an environment that not only put A. baumanii under great selective pressure, but also spread it with startling efficiency.

The paper, reporting data from 4 community hospitals near Detroit, shows that the civilian medical system -- that would be the one that most of us live in -- has duplicated that churning as well. Between 2003 and 2008, all A. baumanii in their network increased 25%. A. baumanii resistant to the first 2 front-line drugs went from 2% to 33% of isolates. And "pan-resistant" A. baumanii -- resistant to all 8 drugs available for it, an essentially untreatable strain -- went from nonexistent to 14% of all the isolates that network found.

The effect on the patients was dramatic, of course: The more resistant their strains were, the more likely they were to never go home from the hospital, but (if they did not die there) to be discharged instead to a nursing home, long-term acute care facility, or hospice. But the larger point is that they carried that multiply-resistant strain with them, distributing it throughout the region: Patients came to those 4 hospitals, carrying A. baumanii, from 17 different nursing homes; from the 4 hospitals, carrying A. baumanii, they were transferred out to 28 different nursing homes.

This is a smart analysis, and devastating in its implications. American hospitals do a debatable job right now of handling infection control -- but overwhelmingly, they are handling infection control as individual institutions, not as competitors in a local market, and certainly not as members of a geographic region. Yet this data demonstrates clearly that cooperation between hospitals and other healthcare institutions -- most of which don't have hospitals' infection-control budgets or personnel -- is going to be essential if we want to put the brakes on Acinetobacter before it soars in the civilian medical system in the same way it did in the military one.

News break: Developing-world drug resistance

2010-06-15T12:13:00.001-05:00

This is an addition for archival purposes of a post that originally appeared at Scienceblogs.

The Center for Global Development, a DC think-tank, is releasing what looks like a thoughtful report aimed at refocusing policy debates over drug resistance toward the epidemic's global impact, with particular attention to the the developing world.

From the report's preface:

Problems with drug resistance have moved from the patient's bedside to threaten global public health. Drug resistance has dramatically increased the costs of fighting tuberculosis (TB) and malaria, has slowed gains against childhood dysentery and pneumonia, and threatens to undermine the push to treat people living with HIV/AIDS effectively. Global health funders and development agencies have cause to worry about whether their investments in access to drugs, and global health programming more broadly, are being undone by the relentless advance of drug resistance.

It calls out a sustained lack of leadership:

Past efforts to energize global action to more comprehensively address drug resistance have been sidetracked by poor timing or over-stretched budgets... In an unfortunate coincidence of timing, a WHO Strategy on Antimicrobial Resistance was launched on September 11, 2001. As a result, the action plan prepared for the Strategy did not get carried out, and over time the interest in cross-cutting drug resistance at WHO withered, even while disease-specific attention grew. For many years, the U.S. Government provided support for research, technical support, surveillance, and policy development on drug resistance in developing countries through an annual budget appropriation to the U.S. Agency for International Development (USAID). That support has become narrowed to programming in only a few areas.

It recommends 4 specific steps:

Improve surveillance by collecting and sharing resistance information across networks of laboratories
Secure the drug supply chain to ensure quality products and practices
Strengthen national drug regulatory authorities in developing countries
Catalyze research and innovation to speed the development of resistance-fighting technologies

A policy brief is here and the full report is here.

Bad news: From MRSA to LRSA

2010-06-15T12:11:00.000-05:00

This is an addition for archival purposes of a post that originally appeared at Scienceblogs

Via the Journal of the American Medical Association, a report from Spain: the first recorded outbreak, in a Madrid hospital, of Staphylococcus aureus resistant to linezolid (Zyvox), one of only a few drugs still available to treat very serious infections of drug-resistant staph, MRSA. This is bad news.

Background: The M in MRSA stands for methicillin, the first of the semi-synthetic penicillins, created by Beecham Laboratories in 1960 in response to a worldwide 1950s outbreak of penicillin-resistant staph. The central feature of the chemical structure of both penicillin and methicillin is an arrangement of four atoms, known as the beta-lactam ring, that governs both drugs' ability to interfere with bacterial cell-wall synthesis. That structure was copied into the formulas of a number of other drug families -- the cephalosporins, carbapenems and monobactams -- and so MRSA is resistant to them as well. And in addition, the bug has picked up resistance to yet other drug families through horizontal transfer; so increasing the census of new drugs that can treat resistant staph infections is a high priority for drug development. It's especially critical for severe infections such as ventilator-associated pneumonia, osteomyelitis, endocarditis and bacteremia, since all the remaining last-resort drugs have challenges from toxicities to ineffectiveness in certain organs.

Linezolid is a relatively new drug, out since 2000 (and, as a downside, still under patent and, according to patients who have been prescribed it, very expensive). It was the first of a new drug class, the oxazolidinones; since there were no "me too" similarities to older drugs, clinicians hoped that resistance to linezolid would be slow in coming.

No such luck.

The first recognized case of linezolid resistance in staph was recorded in 2001. Still, there have been relatively few cases of LRSA, or staph that possesses both linezolid and beta-lactam resistance: 8 cases in the US to date, 2 in Germany and 1 each in Brazil, Colombia and the UK.They have all been caused by a particular point mutation, G2576T.

This Spanish outbreak, though, had a different cause, the importation of the cfr gene, which also mediates resistance to the older drugs clindamycin and chloramphenicol, apparently on a plasmid, possibly from a staph strain common in cows. The outbreak caused by this new mechanism was as large as the entire known burden of LRSA to date: 12 patients, over 10 weeks in 2008, in 3 linked ICUs, pls 3 patients who were not in intensive care, but had had previous ICU stays. Six of the patients had ventilator-associated pneumonia and 3 were bacteremic. Six died -- though the authors are careful to say that all of these patients were critically ill, with brain tumor and esophageal cancer among other problems, and that LRSA was not directly responsible for all of the deaths.

More bad news: There were actually 4 clones of LRSA within this outbreak, with slightly different resistance patterns. Troublingly, one of the 4 had reduced sensitivity to glycopeptides; the chief glycopeptide is vancomycin, which has been the go-to drug for MRSA for 50 years.

The hospital checked its staff and the ICU environments, and found nothing of significance; there was no reservoir in the hospital that was passing this newly resistant strain to patients. With no obvious solution there, they dialed back sharply on their linezolid use, going from more than 200 doses per day in April 2008 to 25 doses per day in June. That aggressive antibiotic stewardship appears to have put the brakes on the outbreak, and after June, no additional cases were recorded.

An accompanying editorial underlines how critical antibiotic stewardship was in controlling this outbreak, while also pointing out how very liberal the hospital was in prescribing linezolid before the outbreak began -- suggesting that if the institution had used its antibiotics more conservatively from the start, this outbreak might not have arisen, or at least not have been as large.

No one doubts the importance of infection-control practices in limiting outbreaks with antibiotic-resistant organisms, but optimizing antibiotic use remains essential for successful control of such outbreaks...No longer can clinicians' unrestricted use of antibiotics and ignoring suggestions from those who attempt to improve or alter antibiotic use be tolerated. Clinicians must understand the sense of urgency about the appropriate use of antibiotics.

Indeed.

(NB, this outbreak was also written up a few months ago in Clinical Infectious Diseases, and was a late-breaker paper at the 2008 ICAAC meeting.)

Update: Access to dental care

2010-06-10T12:09:00.000-05:00

This is an addition for archival purposes of a post that originally appeared at Scienceblogs

A couple of days ago, I talked about the link between a potentially massive hepatitis B outbreak in West Virginia and the lack of access to primary dental care. I was ~~mushy~~ qualitatively descriptive, ahem, about the number of people who lack access to dental insurance.

Comes now the CDC to save the day. In a statistical brief posted today, the National Center for Health Statistics gives a concise but thorough overview of the state of dental insurance in the US. Short version: Ain't pretty.

Crude preliminary population math:

There are currently 309 million Americans.
Based on census tables from last summer, 39 million are 65 or older (i.e., eligible for Medicare).
Based on other census tables from last summer, 52 million are 17 or younger (of which some percentage, based on family income, would be eligible for Medicaid).
That leaves, with wiggle room, about 218 million working adults.

According to the NCHS:

172 million non-elderly Americans have private health insurance. (NB, leaving 46 million non-elderly with no health insurance, which matches the usually accepted figures.)
Of them, 45 million have no dental coverage -- which, added to the 46 million with no insurance at all, means that more than 90 million Americans have no dental coverage at all. (I believe the technical term for a number that large is a crapton. Maybe a metric crapton.)

In addition:

If you have employer-provided health insurance, your chances of having dental coverage are pretty good: 80%.
If you have privately purchased insurance of any kind, not so much: 30%.

So, reinforcing Monday's point: There are multiple millions of Americans who get no assistance paying for dental care, which is a largely cash-only business. (And judging from my own experience -- thanks to my childhood in the UK, I have teeth like chalk and consume more than my share of dental care -- dental insurance negotiates discounts. So self-pay dental care is relatively more costly.) And therefore, it is not surprising that thousands of people attended that free dental clinic in northeastern West Virginia, and were potentially exposed to hepatitis B as a result.

News break: House hearing Wednesday on the antibiotic pipeline

2010-06-08T12:08:00.001-05:00

This is an addition for archival purposes of a post that originally appeared at Scienceblogs.

The Subcommittee on Health of the Energy and Commerce Committee of the House of Representatives has announced a hearing for Wednesday: "Promoting the Development of Antibiotics and Ensuring Judicious Use in Humans."

The witness line-up is:

Janet Woodcock, M.D., Director, Center for Drug Evaluation and Research, Food and Drug Administration
Robin Robinson, Ph.D., Director, Biomedical Advanced Research and Development Authority, Department of Health and Human Services
Brad Spellberg, M.D., F.I.D.S.A., Associate Professor of Medicine, David Geffen School of Medicine at UCLA and Member, Infectious Diseases Society of America Antimicrobial Availability Task Force
Sandra Fryhofer, M.D., Council on Science and Public Health, American Medical Association
John S. Bradley, M.D., American Academy of Pediatrics, Chief, Division of Infectious Diseases, Department of Pediatrics, University of California, San Diego, School of Medicine, Clinical Director, Division of Infectious Diseases, Rady Children's Hospital
Barry Eisenstein, M.D., F.A.C.P., F.I.D.S.A., Senior Vice President, Scientific Affairs, Cubist Pharmaceuticals
Jeffrey Levi, Ph.D., Executive Director, Trust for America's Health

This is the second hearing the Health Subcommittee has had this spring, apparently at the prompting of the chairman of Energy and Commerce, Rep. Henry Waxman, who made the opening statement at the first such hearing in April:

We need to debate the health care bill and review its implementation. But we ought to be able to chew gum and walk at the same time. Because it is not going to make much difference if you have health insurance or not if you are going to die from something that could have been prevented from an antibiotic. And we are seeing more and more antibiotic resistance. (Transcript)

Reading between the lines, I'm going to guess this hearing will lean heavily on the IDSA's campaign to improve market conditions for pharma companies in order to revive antibiotic development (an issue I discussed recently at the old Superbug -- we're working on getting the archives moved over).

News: SUPERBUG is moving

2010-06-07T16:48:00.000-05:00

Constant readers, I have an exciting announcement. After 3 years here on Blogger, SUPERBUG has been invited to join the thoughtful, knowledgeable, chatty and sometimes raucous community over at Scienceblogs. From today, I'll be posting instead at a new page:
http://scienceblogs.com/superbug.

I will keep this site up as a resource, at least until we can work out the mechanics of transferring this blog's archives over to the new page.

You've been such great readers, so thoughtful and thorough. I really hope you'll follow me over to the new location. I would love to engage with you there too.

Sincere thanks to all of you for all your attention, and warmest wishes.

Dept. of Unintended Consequences: Hepatitis B in West Virginia

2010-06-07T12:05:00.011-05:00

This is an addition for archival purposes of a post that originally appeared at Scienceblogs.

Via ProMED Mail comes a news report that about 2,000 people in 5 states are being sought by health departments so they can be checked for hepatitis B infection. The potential source: the Mission of Mercy Dental Clinic, a free dental-care fair held just about a year ago in Berkeley County in the far north-east corner of West Virginia. The potentially infected include 1,137 people who were treated at the two-day clinic and 826 of the volunteers who worked there, from West Virginia, Washington, D.C., Virginia, Maryland, Pennsylvania and North Carolina. Three patients and two volunteers have already been diagnosed. The virus in four of the five matched on molecular fingerprinting, suggesting a common source; the fifth patient refused further testing.

Hepatitis B is blood-borne, so on the surface, this is a story of the tragic consequences of some failure somewhere in the clinic's infection-control procedures. (One reason why it caught my eye, since I'm interested in healthcare-associated infections.) Except that it's not -- or not only. It's important to unpick why such an extraordinarily large number of people may have been exposed at one time. Looked at through that lens, it becomes a story about what can happen when we don't fund basic health care in a timely way.

Some background: West Virginia is one of the poorest states in the country and has some of the highest rates of the usually recognized diseases of poverty: tobacco use, chronic kidney disease, asthma, cardiovascular disease. (Look for West Virginia on these CDC maps of incidence of heart disease and stroke.) But it also has extraordinarily high rates of another health problem that ought to be linked in the public mind to low socioeconomic status, but usually isn't: untreated dental disease. Eric Eyre of the Charleston Gazette (disclosure: a friend and fellow Kaiser Foundation Fellow) took a year-long close look at dental disease in the state in 2006-07 (slideshow, stories). If you're squeamish, I advise skipping the one about the woman yanking her own teeth with pliers after a few shots of moonshine.

Dental disease -- that's not just cavities, but tooth loss, bone loss, abscess, Ludwig's angina, septicemia in the most serious cases -- isn't only a problem for West Virginia, though it happens to be worst there. It's a problem all over the US because, without ever intending to, we've allowed dental care to become a primarily cash-based form of medicine.

If you have a job, you may have dental insurance, though it's a less-common employment benefit than health insurance, and covers comparatively less of the cost of any procedure. If you don't have a job, dental care is entirely out of pocket. If you're poor enough to be on Medicaid, whether or not you have dental coverage depends on which state you live in, because Medicaid dental coverage for adults falls under the portion of Medicaid funded by the states, not the federal government. In the past 12 months, California, Hawaii, Massachusetts, Michigan, Minnesota, North Carolina, and Washington state all cut or tried to cut their contributions to dental Medicaid from their state budgets. If you're the child of a poor family, you are hypothetically entitled to Medicaid-funded dental care, though that depends on being able to find a local dentist willing to accept Medicaid reimbursement; last year, the Government Accountability Office said that children have trouble finding Medicaid-accepting dentists in 43 out of 50 states.

Net result: Untreated dental disease is now the most common disease of childhood, five times more common than asthma according to a 2000 Surgeon General's report, and emergency room visits for dental crises are rising steadily. ERs are not the right place to treat dental problems -- they don't fill cavities or do extractions, though they can drain abscesses and give antibiotics and pain meds -- but as with so much else in US medicine, ERs offer a mandated clinic of last resort when there's nowhere else to go. (For more about the interplay between dental care and ER overcrowding, here's a story I wrote for the June Annals of Emergency Medicine.)

All of that explains why thousands of people from a wide swath of the East Coast were so desperate for free dental care that they were willing to stand in line overnight in a high school parking lot. (The first free dental clinic in West Virginia had to close its doors early after it got 1,100 patients in the first 2 hours.) And also why hundreds of dental-care professionals and students and community volunteers were so eager to help. And why they're all now waiting by the mailbox, wondering whether they're in line for a letter that will tell them where to get tested for infection with a life-long chronic disease.

The trend in hospital infections - good, bad, or too little data to know?

2010-06-04T08:00:00.001-05:00

Some of you may have spotted an announcement last week from the Centers for Disease Control and Prevention about a release of data from the National Healthcare Safety Network (NHSN), a repository of hospital infection data. You can guess the big news in the report from its title, "First State-Specific Healthcare-Associated Infections Summary Data Report": For the first time, database users are able to calculate healthcare-associated infections (let's call them HAIs for short) by state, as well as nationally.

Good news, you would think. And it is. According to the CDC's announcement (press release, press conference transcript), the national rate of one particular type of HAIs, central line associated bloodstream infections or CLABSIs (like it looks — pronounced "klab-sees") is down 18% from the previous 3 years. Taken together, all HAIs kill at least 100,000 Americans each year (an old number that is probably an underestimate) and cost at least $30 billion per year. CLABSIs are an important component of the spectrum of HAIs and may account for a third of all HAI deaths — so any reduction is a positive development.

And yet: The bigger news about this report, unfortunately, is that it lays bare how little we really know about HAIs, and how little progress has been made in preventing or even documenting them.

Consider:

The report includes data from only 17 states
The data does not match state to state, so state rates cannot be compared
Participation in the NHSN by hospitals is voluntary (except in states that recently have passed mandatory reporting laws) and data is self-reported
Hospitals that report to the NHSN are not identified (in fact, unless state laws say otherwise, they are guaranteed anonymity)
The NHSN does not collect data on the most problematic HAI organisms, MRSA and C. difficile.

If you think for a moment about how incomplete this data is, and how much the data collection allows hospitals to avoid saying, then Dr. Peter Pronovost's remarks to the Association of Health Care Journalists in April begin to make sense. Pronovost is a MacArthur Fellow for his championship of evidence-based infection prevention, and said (sorry, no verbatim record that I know of, but I live-tweeted his speech) that if hospital infection reporting were truly transparent and truly accountable — right now, it's neither — the problem of HAIs would end tomorrow, because consumers would be so shocked that they would rise up and demand change.

The CDC says there will be additional data and a new comparison with this first snapshot within about 6 months. Again, that's all good news. But it's worth taking a deep look at this report to really understand how little we know — which will also help to explain why this problem so persistently fails to get better.

(NB: The CDC announcement and the relevant background were covered thoughtfully by my friends Dan DeNoon of WebMD and Barbara Feder Ostrov of Reportingonhealth.org, whose post, FWIW, quotes me.)

And, constant readers, an addendum: On Monday, I'll have big news to share about this blog. It's good news and I hope you'll support it. Stay tuned.

Incentives for making new antibiotics: What would it take?

2010-05-21T19:04:00.000-05:00

Let's play a thought experiment. Imagine that you're a major pharmaceutical company, a public company, with shareholders that you answer to, and market analysts looking over your shoulder to see whether this quarter's earnings are up to projections. Imagine that you want to make a new drug. Let's make it an antibiotic, because — as we talk about here all the time (and SUPERBUG explores in detail) — new antibiotics that can leapfrog over existing drug resistance are very needed. Thus, you imagine, a new antibiotic ought to sell well, even though any individual course of that antibiotic will only be a few weeks by mouth, or maybe a few months by IV if the patient is very sick. You know there's a big market out there.

But: Imagine — as is generally accepted to be true — that it will take about 10 years, and about $1 billion dollars, to get that novel antibiotic through the development pipeline and into the marketplace. And then imagine that — as has been shown for a number of drugs, most recently the new antibiotic daptomycin — bacteria begin developing resistance to your drug within a year of its deployment in patients. And after that, imagine — as has been cited in a number of papers — that once local resistance to your antibiotic appears in approximately 20% of isolates, physicians will cease prescribing your antibiotic, for fear their patient will be one of that 20%.

So, to recap: 10 years, $1 billion; short course; short market life; rapid obsolescence.

Would you make that investment? Or would you, if you were a pharma company, opt instead to make insulin, which Type 1 diabetics will take every day for the rest of their lives? Or statins, which at this point we're practically ready to put in the water supply? Or a cancer drug that costs $10,000 per dose? Or Viagra, or Cialis?

If you're a company that is responsible to its shareholders, or listening to its analysts — or even capable of doing basic math — the answer's obvious: Antibiotics lose. Which goes a long way to explaining why so many companies have backed off from making antibiotics, and why many of the few antibiotics in the pipeline are "me too" formulations, rather than new compounds with truly new mechanisms of action.

How to respond to this impasse has been an active debate for a while, largely focused on proposals to give market incentives, changes in tax credits, or patent extensions to pharma companies to persuade them to stay in or re-enter the marketplace. The Infectious Diseases Society of America, the specialty society for infectious-disease physicians (many of whom are also academic researchers), has been addressing this through its campaign "10x 20", which has a goal of getting 10 new compounds into if not through the pipeline by the year 2020.

But, as a new article in the British Medical Journal points out, good incentivizing demands complexity — not just in developing both "push" and "pull" mechanisms (say, tax incentives to fund research v. prizes and wildcard patent extensions), but also in making sure that the incentives can be taken advantage of by companies of all sizes, not just the international mega-pharmas:

The characteristics of an ideal incentive mechanism and the desire for an equitable approach that engages developers of all sizes would suggest that neither push, pull, nor lego-regulatory mechanisms would be optimal to spur the desired investment in antibiotics .... Rather, elements of each should be combined. The exact shape of the ideal package is, however, as yet unclear. (Morel et al.)

And an accompanying editorial emphasizes that new antibiotics are not the only things needed; new diagnostic tests, for instance, need funding as well:

Catchy as 10×20 sounds, the public sector strategy for funding such research and development must prioritise among different health technologies, such as diagnostics and vaccines, to combat antibiotic resistance. For example, three million children die each year from acute respiratory bacterial infections in developing countries, but penicillin sensitive pneumococcal strains have declined to a half, even a quarter, in some countries. A diagnostic test for bacterial pneumonia would save an estimated 405 000 lives a year, by targeting treatment and avoiding overprescription of antibiotics. New vaccines may also reduce reliance on drugs as the use of pneumococcal vaccine has suggested. (So et al.)

This is a hard discussion. I confess, as a longtime reporter, I flinch reflexively at the thought of handing more money to the pharmacos. At the same time, the state of the market demonstrates that the current model is not working. And though I would much prefer we focus on the ecological model of preserving antibiotics as a resource — dialing back on overuse and encouraging rigorous stewardship — it's clear that we'll always need new drugs for the most serious, most resistant infections.

So some sort of incentivizing seems necessary. And the multi-layered approach recommended in the BMJ, with appropriate attention paid to incentivizing the development of tests and vaccines as well, seems worth heeding.

Brand-new research: Vast increase MRSA, CA-MRSA diagnoses among kids

2010-05-17T10:02:00.002-05:00

I'm on the road today and have what feels like seconds between commitments, but there's a brand new piece of research this morning that I think you folks should know about. It's an early-online release from Pediatrics by researchers from 3 states. It uses a database called the Pediatric Health Information Systems analyze diagnosis codes and antibiotic treatment of kids treated for staph at 25 US children's hospitals from 1999 to 2008, and it finds:

The incidence of methicillin-resistant S aureus (MRSA) infections during this period increased 10-fold, from 2 to 21 cases per 1000 admissions, whereas the methicillin-susceptible S aureus infection rate remained stable. Among patients with S aureus infections, antibiotics that treat MRSA increased from 52% to 79% of cases, whereas those that treat only methicillin-susceptible S aureus declined from 66% to <30% of cases. Clindamycin showed the greatest increase, from 21% in 1999 to 63% in 2008.

To translate, for those not used to reading scientific literature:

a 10-fold increase in MRSA diagnoses over 10 years
a 3-fold increase in what was not the most commonly prescribed drug, one useful for the different resistance profile of community infections
clindamycin (used in mild and also invasive infections) eclipsing vancomycin (last-resort drug for invasive cases) as the most-used drug — which could be a sign of changes in prescribing patterns, changes in seriousness of the cases seen, or a warning that with so much use, clindamycin resistance could emerge more quickly, as happened when vancomycin came off the shelf in the 1990s and began to be used more.

It will take me a while to download and read the paper (hard to do in the car), but that's the topline news. Update to come.

A great blog leaves the 'sphere

2010-05-16T15:34:00.000-05:00

Constant readers: Well, the bug finally got me, or one of its close cousins did. I've been on the road almost nonstop, and after a book event at University of Wisconsin last week, was felled by a violent bout of foodborne illness that was almost certainly staph — not MRSA, but the related strain of staph that causes very rapid food poisoning. (And, umm, thorough. Ick.) So I've been out of commission both physically and mentally. And on a plane again tonight. Back soon in both ways, promise.

But there's important sad news today that I want you all to know about. Revere, the peerless author of the marvelous public health blog Effect Measure, is bowing out of the blogosphere. For more than 5 years now, Revere (a collective voice of an unknown number of public health experts —for simplicity, let's say "he") has been a reliable, thoughtful, expert, humorous and deeply knowledgeable guide to the intricacies of public health and public health politics. He has taken a particular interest in the possibility of pandemic flu and has been the unofficial leader of the loosely knit but fiercely loyal group of bloggers and crowdsourcers who call themselves Flublogia. And though few would admit it, Revere's posts have been consistent agenda-setters in newsrooms all across the planet; insiders knew that, if Revere said something, it would start showing up in newspapers and on wires about 12 hours later.

If you are a Revere reader and missed this news, get over there and leave a note in the quickly lengthening comment string. If you never made the blog's acquaintance, now would not be too soon.

A good start?

2010-04-30T16:11:00.000-05:00

I happened to notice today that the WHO has posted an update to its campaign Save Lives: Clean Your Hands, which aims to get 10,000 hospitals around the world to sign on — by May 5, 2010, which is next week — to a global commitment to improved hand hygiene in hospitals.

As of last week, 8,173 hospitals had signed up (1899 in the United States, FYI).

If I sound skeptical, it's because we all know that merely supporting hand-washing (or the gel equivalent) is an easy thing to do. If you asked any hospital in the US, you would hear 100% support for hand-washing — including in the hospitals where healthcare workers miss 50% of opportunities to wash their hands. It's in the granular details of implementation — and the relentless laser-like focus on execution practiced, for instance, by Novant Health Care in North Carolina, whose story is told in SUPERBUG — that change really happens.

Whether this WHO campaign can bring that focus and create that change... we'll just have to see.

The WHO campaign's page includes videos, guidelines, and plans for a global survey to be executed on May 5.

SUPERBUG on BoingBoing!

2010-04-29T10:09:00.000-05:00

I was thrilled to see a review of SUPERBUG on the incredibly important blog BoingBoing.net, written by (my friend and fellow Minneapolis author) Maggie Koerth-Baker.

It's so exciting to see people completely get the book, and twice that when it is people you know.

Sample quote:

Superbug is not about an entomological caped crusader.

It's more like a grown-up version of Scary Stories to Tell in the Dark.

The bug in question is MRSA, an antibiotic-resistant bacteria that kills more Americans every year than AIDS. Superbug is the story of how we created our own monster-under-the-bed, how it spreads through hospitals and communities, and why it's damn near impossible to control. If you have a cut or a pimple while reading this book, you are pretty much guaranteed to freak yourself out. And I mean that in the best possible way.

Antibiotic resistance in food — some governments pay attention

2010-04-29T09:56:00.000-05:00

Folks, I told you Tuesday about a Congressional hearing on antibiotic resistance, featuring NIAID Director Dr. Anthony Fauci and CDC Director Dr. Thomas Frieden. Not much new was said, but it's encouraging that the hearing was held at all. (Fauci testimony here, Frieden here.)

Coincidentally, constant reader Pat Gardiner of the UK alerted me to a gathering being held on the same day in Ireland, by the quasi-government agency SafeFood—which reports to the North-South Ministerial Council of Ireland, which deals with whole-island issues under the Good Friday agreement, which is more about the Irish political structure than you probably ever wanted to know.

The conference was titled Antimicrobial resistance and food safety and featured government officials and academic researchers from across Ireland. Here's the agenda, and here's the press release with the names of key speakers. Even more important, here are links to a report on antibiotic resistance in food that Safefood released in advance of this conference: executive summary and whole thing. I especially recommend from p.25 in the big report for an accessible discussion of the connections between ag antibiotic use and human health. Key quote among many:

The majority of the evidence acquired through outbreak and epidemiological investigations of sporadic infections, field studies, case reports, ecological and temporal associations and molecular sub-typing studies support the causal link between the use of antimicrobial agents in food animals and human illness. A few papers have questioned this but these have not survived detailed scrutiny.

It's refreshing to see a government body engage seriously with this emerging issue, which we've been talking about for, well, years now, on this blog (sometime this month we passed our 3-year anniversary). I wish, wistfully, that the government doing the discussing was ours.

A blog reaction so perfect I want to print the whole thing...

2010-04-28T10:10:00.000-05:00

(...but I won't, because it's not fair use or good blogger behavior. But I want to!)

Melissa Graham of Chicago had a great corporate life — and then she re-evaluated, became a chef and caterer, and began organizing in Chicago for sustainable local food, farmers' markets, and a family-friendly food system. She blogs at the food and food-policy blog The Local Beet. And she's written a reaction to SUPERBUG that not only completely gets the book, but is emotional and thoughtful and moving besides.

She says, in part:

Before reading Superbug, the question of confinement raised animals was an ethical one for me – whether the misery inflicted upon animals and, for that matter, the humans working in those facilities by the putrid conditions outweighed the need to eat cheap meat. Even the environmental degradation resulting from the inevitable careless management of CAFOs seemed a distant and intangible casualty. For me, Superbug has changed the argument from one of ethics to a moral imperative. In every hamburger of unknown origin, I see Tony Love’s face or even worse that of Carlos Don IV.

Carlos was another healthy kid who left on a school trip to the mountain and returned with a 104°F fever. The first doctor diagnosed Carlos with walking pneumonia so his mother kept him home bundled and hydrated until she realized that he was beginning to hallucinate. She rushed Carlos to the hospital and the doctor’s ultimately diagnosed his condition as MRSA. A long slow death march ensued during which Carlos’s lungs dissolved and clotting choked off the blood to his lower intestines, legs and arms. In two weeks, he was dead.

After reading Carlos’s story late in the evening, I woke a bewildered little locavore from a dead sleep to scrub his hands clean. I hugged him as tightly as I could.

...[recently] I had the pleasure to hear Ruth Reichl speak and she implored the audience to stop eating confinement raised animals. As she put it, if everyone stopped buying them and eating them, the practice would be history. Knowing what I now know, I think it’s our moral duty.

To give the post the traffic it deserves, please go here.

Quick alert: Congressional hearing Wednesday

2010-04-27T12:04:00.000-05:00

Constant readers, I'm on the road again: Georgia Center for the Book tonight in Decatur, 7:15 p.m. But if you can't make that, take a look at this: The Energy and Commerce Subcommittee of the US House of Representatives has announced a hearing for Wednesday on "Antibiotic resistance and the threat to public health."

This is not a hearing on PAMTA, but apparently a broader hearing on the whole issue, featuring two VIPs: Dr. Anthony Fauci of NIH and Dr. Tom Frieden of the CDC. To my eye, this indicates that official, policy interest in this issue is (finally, at last) ramping up.

The hearing page is here and the preliminary memo on it is here.

SUPERBUG interest from collegial fellow bloggers

2010-04-26T09:40:00.000-05:00

I haven't been posting it all here — because, you know, that's why the book has its own website — but SUPERBUG has been getting lots of positive press and reviews. (Yay us.)

But a piece over the weekend was especially meaningful to me and I wanted to call it out: Flu blogger and DailyKos diarist DemfromCT featured the book on his DailyKos page. (And, behold the power of networks: 178 comments this morning. Wow.)

Liz Borkowski at The Pump Handle kindly reproduced Dem's post.

This builds, of course, on early, consistent and indefatigable support from flu blogger Mike Coston of Avian Flu Diary.

As the book's acknowledgments say (p. 218!), I am so grateful for our blog community's support. Sincere thanks to all.

Catching up to MRSA news (not about me)

2010-04-21T08:05:00.000-05:00

Constant readers: I'm looking forward to having the breathing space to get back to in-depth blogging. Meanwhile, though, news is zipping by — so here's a quick list of recent things worth reading.

"Cows on Drugs" — a superb history of the 30-year-old fight to get unnecessary antibiotics out of food animals. Note, written by a former commissioner of the Food and Drug Administration, not exactly a wild-eyed radical:

More than 30 years ago, when I was commissioner of the United States Food and Drug Administration, we proposed eliminating the use of penicillin and two other antibiotics to promote growth in animals raised for food. When agribusiness interests persuaded Congress not to approve that regulation, we saw firsthand how strong politics can trump wise policy and good science.Even back then, this nontherapeutic use of antibiotics was being linked to the evolution of antibiotic resistance in bacteria that infect humans. To the leading microbiologists on the F.D.A.’s advisory committee, it was clearly a very bad idea to fatten animals with the same antibiotics used to treat people. But the American Meat Institute and its lobbyists in Washington blocked the F.D.A. proposal.

Antibiotic resistance in your kitchen, playroom, car... — After years of begging from health advocates, the FDA and EPA are taking a second look at the chemical compound triclosan, an antibacterial that is put into, well, almost anything you can name: soaps, hand sanitizers, cutting boards, toys. Triclosan is suspected of interfering with hormone regulation in the body, and also increases resistance in organisms in our environment. (When I ask you to use hand sanitizers that contain only alcohol or salts, not antibacterials, triclosan is one of the things I'm thinking of.) The FDA will report its findings in a year. I'd rather see it happen sooner, but it's a great move.

No progress on hospital-acquired infections — The Agency for Healthcare Research and Quality, part of the Department of Health and Human Services, has published its 2009 National Healthcare Quality Report. The news is not good. To quote the agency's own language: "Very little progress has been made on eliminating health care-associated infections." This is all hospital-acquired infections, not just MRSA, but MRSA is a leading organism. The ugly details:

Post-operative bloodstream infections up 8%
Post-operative catheter-associated urinary-tract infections up 3.6%
"Selected infections due to medical care" up by 1.6%
Bloodstream infections as a result of central lines unchanged.

(NB, three professional organizations — the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, and the Association for Professionals in Infection Control — put out a statement in response to this report saying it "presents an outdated and incomplete picture on healthcare-associated infections (HAIs) in our healthcare system." The gist of the statement seems to be that they've got better numbers coming... soon. When there's actual data, I'll let you know.)

SUPERBUG on Capitol Hill

2010-04-16T19:31:00.001-05:00

Constant readers, I've been shamefully absent from the blog, but with reason, since I've been traveling promoting the book. There was a pretty interesting opportunity this week that I wanted to tell you about: I was asked to be part of two Congressional briefings in Washington, DC Wednesday, addressing the overuse of antibiotics in agriculture and the contribution that makes to the emergence of resistant organisms such as MRSA. I went specifically to tell the story of the emergence of MRSA ST398, which we've been talking about for years here.

The briefings (FYI, "hearings" are for Congresspersons, "briefings" are for their staff) were cosponsored by the Pew Charitable Trusts, Union of Concerned Scientists, American Public Health Association, Infectious Diseases Society of America, and the nonprofit Keep Antibiotics Working.

Here's Pew's announcement, here's the UCS version, here's a write-up from the Washington Examiner, and here's a longer one from the site Spectrum Science.

SUPERBUG is on NPR's Science Friday!

2010-04-16T17:02:00.002-05:00

With a cast of other people much more distinguished than me.

See the program page, and access the audio when it's posted, here.

My name in lights, sort of

2010-04-09T10:19:00.000-05:00

Huge appreciation to the friendly folks at Eagle Eye Book Shop in Decatur, GA, who had me in to speak last night, and who also very kindly supplied books for the panel discussion at Danya International yesterday afternoon. Many thanks to all for your support!

Surfacing. (Whew.) And some great reaction.

2010-04-06T21:43:00.000-05:00

Well, constant readers, it's been an amazing two weeks. SUPERBUG was published, and ate my life. I've been on NPR's Fresh Air, and on 21 (22?) other radio stations so far, with more radio, and TV, to come.

I'm starting to plan the next phase of the book campaign. If you work at a hospital or medical school, or are a student, contact me: Wherever you are, I'll come talk.

This week I'm headed out for some tour appearances in Atlanta: at Georgia Gwinnett College on Wednesday, and on Thursday, at the offices of Danya International in the afternoon, and then at Eagle Eye Book Shop in Decatur Thursday night. If you need more details, email or tweet me!

The book has gotten some wonderful reviews and, what matters more to me at this point, blog reactions, because the blogs signal to me that real people are really engaging with the story. I've put excerpts and links up on the book's site on this page.

Here's one that just came in over the transom that just floored me. It's from Rep. Louise Slaughter, Congress's only microbiologist, author of PAMTA, the legislation intended to bring some direction and control to agricultural use of antibiotics:

Maryn McKenna’s Superbug provides a heart-rending and enlightening portrait of the spread of Methicillin-Resistant Staphylococcus Aureus (MRSA). Commonly imagined to be a disease that only affects elderly hospital patients, McKenna’s book shows that no area of the United States is untouched. Thirty percent of high school athletic programs in one survey reported MRSA. In another study, 80 percent of farms and 40 percent of pigs had MRSA. The consequences are horrific. In 2005, 94,360 invasive MRSA infections occurred in the United States, with almost 19,000 deaths.

In the United States, the response to MRSA has been largely uncoordinated, and left to individual institutions, schools, and health care centers. American hospitals have tried a range of responses. Some hospitals have tied executive pay to staff hand-washing rates; others isolate patients with MRSA. Nationwide educational campaigns reduced antibiotic prescription rates temporarily, only to see them rise again. The pipeline for new antibiotics dried up due to economic disincentives for drug companies to invest in short-course medications like antibiotics. The medical system has not yet been able to contain antibiotic resistant pathogens like MRSA.

The problem is just as dire on American farms. Limited action has been taken to reduce misuse of antibiotics in agriculture. While the FDA did ban agricultural usage of the powerful antibiotic fluoroquinalone, farms still regularly use powerful antibiotics as ‘growth promoters’ in daily feed for animals. This year, I introduced legislation, HR 1549, the Preservation of Antibiotics for Medical Treatment Act, which would take additional steps to protect seven medically-critical classes of antibiotics for human usage against MRSA and other antibiotic resistant pathogens. Maryn McKenna’s book is a powerful call to action.

- Louise M. Slaughter, MEMBER OF CONGRESS

More from Fresh Air: handwashing and a playlist

2010-03-23T18:50:00.001-05:00

In advance of the Fresh Air interview today, their tweeter(s) asked for suggestions for a MRSA playlist! Here's some of the suggestions:
Fever, Peggy Lee
Countin' On A Miracle, Bruce Springsteen
Ready or Not, the Delfonics (or as sampled by the Fugees)
Time to Get Ill, Beastie Boys
Hurts So Good, John Mellencamp (was he John Cougar Mellencamp then?)
Infected, Bad Religion
and of course:
I've Got You Under My Skin.

They also dug up this awesome music video from University of Pennsylvania, "Heroes Wash Hands." Enjoy.

PUBLICATION DAY and so many people to thank. The short list:

2010-03-23T12:21:00.001-05:00

Sara Austin, Susan Raihofer, Emily Loose, Maura O’Brien, Ali Pisano, Dominick Anfuso, Martha Levin, Elizabeth Stein.
Andrew Dodds, David Ratner, Shirley Sandler, Chuck Monroe, Elise Bogdan.
Penny Duckham, Deirdre Graham, Matt James, Drew Altman; Bruce Shapiro, Frank Ochberg, MD, Dorie Griggs.
Barth Anderson, Frances Katz, Quinton and Jean Gregor, Anne Edwards, MD, Joanne Kenen, Howard Gleckman.
Michael Coston, Crawford Kilian, Scott McPherson, “Revere.”
Michael T. Osterholm, PhD; Kristine Moore, MD; Jim Wappes, Robert Roos, Lisa Schnirring; Kathleen Kimball-Baker; Nicholas Kelley, Paul Mamula, PhD.
Coilin Nunan; Ramanan Laxminarayan; Donald Berwick, MD, Donald Goldmann, MD Frances Griffin, Joseph McCannon, Madge Kaplan; Lisa McGiffert.
James Sliwa, Steven Baragona.
Robert S. Daum, MD, Susan Boyle-Vavra, PhD, Everly Macario, SciD, Michael Z. David, MD, PhD, Susan Crawford, MD, Christopher Montgomery, MD, Ben Yoon, Lakesha Lloyd; Robert Bielski, MD, Stephen Weber, MD, John Easton.
Henry “Chip” Chambers, MD, Francoise Perdreau-Remington, PhD, Adam Hersh, MD, Binh An Diep, PhD, Kristen Bole; Rick Loftus, MD, Steve Gray. Elizabeth Bancroft, MD, Nolan Lee, MD, Gregory J. Moran, MD, John Edwards, Jr., MD, Loren G. Miller MD.
John Bradley, MD, Bradley Peterson, MD. Don Janssen, DVM, Nadine Lamberski, DVM, Jeff Andrews.
Nicole Coffin, David Daigle, Rachel Gorwitz, MD, Jeffrey Hageman, Fred Tenover, PhD, Timothy Naimi, MD, Denise Cardo, MD, Joan Brunkard, PhD, David Sugerman, MD, Roberta Carey PhD, Brandi Limbago PhD, Lonnie King DVM, Jennifer Wright DVM; Susan Sanchez, PhD; Arthur Kellermann, MD, Katherine Heilpern, MD, Henry Blumberg, MD, Leon Haley, MD, Michael Huey, MD, Andre Nahmias, MD; Tom Keating, PhD.
David Edell, Cathy Supak, Mike Carroll, Marilyn Felkner, MD. Heinz Eichenwald, MD, Mari Nicholson-Preuss.
Gregory Belzley, Martha Sperling, Anita Alberts, Nate Wenstrup, Natalie Leonard, Carrie Takahata, Eric Balaban; John Clarke, MD, Luis Rivera, MD, Timothy Faloon, Rhonda Moore; Charles Alexander, Jr., Gary Benson, David White, Chris Pearson; Pierre Tattevin, MD, Jason Farley, PhD; Elizabeth Cumming, Katie Schwartzmann, Samuel Gore, MD.
Tara Smith, PhD, Michael Male, DVM, Abby Harper; J. Scott Weese, DVM; Andreas Voss, Md, PhD, Jan Kluytmans, Md, PhD; Pat Gardiner.
Barry Farr, MD, William Jarvis, MD, William Schaffner, MD. Jeff Bender, DVM, BJ Anderson, MD, John Odom, MD, Marjorie Hogan, MD, Kirk Smith, DVM, Patrick Schlievert, PhD.
Paul M. Wiles, Thomas N. Zweng, MD, Stephen L. Wallenhaupt, MD, James W. Lederer, Jr., MD, Suzie Rakyta, RN, Sandy Cox, RN, Patti Deltry, RN, Kati Everett. Keith M. Ramsey, MD, Kathy Cochran, RN, Delores Nobles.
Barry Eisenstein, MD, Richard Baltz, PhD, Grace Thorne, PhD Jared Silverman, PhD, Kevin Tally, MD. Joann Lindenmayer, DVM, Robert Moellering, MD, Jeffrey Linder, MD. John Powers, MD, Ron Najafi, PhD, Mary Beth Minyard, Henry Shinefield, MD, Lisa Bayne.
Allison Agwu, MD; Steven J. Barenkamp, MD; Gonzalo Bearman, MD; Benjamin Estrada, MD; Eugene L. Green; Brenda Hollier; Christoph U. Lehmann, MD; Nkuchia Mikinatha, DrPH; Michael Nagy, MD; Louis Rice, MD; Lisa Saiman, MD; Torrance Williams.
Rose Aliberti; Kepa Askenasy; James Bell; Michael Bennett; Laura Chen Davies, Robin Cook; Stephanie Crowell; Amber Don; Eva Ferguson and Beverly and Ernie Dieringer; Nick and Janet Johnson; Kevin Keller; Mollie and Brian Logan; Diane Lore and Richard Ross; Clarissa and Tony Love; Christina Marzullo; Jane McGuinn, Molly Donohue, Charlotte McGuinn Freeman; Steve, Sue and Pat McNees; Karen Moser; Carole and Ty Moss; Victoria Nahum; Melissa Quintana; Debbie Russ; Danielle Sheffler; Scott and Katie Smith; Andrea and Jay Sorensen; Jeanine Thomas; Suzanne Turpin Upton; Tom Wolff, Christine Fusco, Lourraine Stamets.
Samara Cummins, Krista Reese, Rich Eldredge. Lt. Col. Robert J. McKenna, Cerise McKenna Vablais, PhD, Zach McKenna. Rev. Robert E. Lauder, John J. McKenna. Matthew McKenna, Darla Albrigh, Davd Tuller, Randy Dotinga, Elizabeth McKenna.
Loren D. Bolstridge III.

From my heart, thank you all.

PUBLICATION DAY! And SUPERBUG will be on Fresh Air

2010-03-23T10:40:00.002-05:00

Constant readers, huge news: SUPERBUG will be featured in a segment today on the NPR program Fresh Air with Terry Gross. Please tune in if you can! Fresh Air's broadcast times vary across the country, but you can listen online or via podcast. The schedule is here.

UPDATE:
Listen to the podcast here.
Read the story here.

Early book reaction! Positive so far.

2010-03-21T14:26:00.001-05:00

Folks, it's Sunday, and SUPERBUG will be officially released on Tuesday. Press copies have been landing at last. Readers who responded to my plea for pre-orders (because pre-orders are very important to how the publisher and the market behave subsequently about the book) have been telling me they're getting emails saying the book is on its way.

And a few reviews are starting to pop up!

Kirkus said: "A gripping account of one of the most devastating infectious agents on the planet… A meticulously researched, frightening report on a deadly pathogen.”

Booklist said: "Lays bare, often all too graphically, the ravages of a disease with the potential to do grievous international harm.”

But of most value to me today, my blog-friend and supporter Michael Coston of Avian Flu Diary said this morning:

I can think of a great many superlatives to describe this book; engaging, harrowing, fascinating, powerful... even terrifying at times.
But the descriptive term that keeps coming back to me is: Important. ...
Superbug, quite frankly, should be required reading for every doctor, nurse, and health care professional, if for no other reason than to alert them to the changes they must make in order to help curb the spread of these deadly pathogens.
But it should also be on the reading list of parents, students, and teachers who need to be able to recognize the early warning signs of infection.
And just as importantly, read by those who make policy at the local, state, and Federal level. We either make institutional changes or risk serious peril from these resistant bacteria.

The cheering of Mike and other bloggers including Revere of Effect Measure and Crof of H5N1 has meant so much to me as I've worked on this book (and also written about flu and other diseases at CIDRAP.) I'm grateful.

One week to publication! And the book video is up

2010-03-16T12:21:00.008-05:00

OK, folks, mystery unveiled: Here's what I look and sound like. Simon and Schuster has put up a video for the book — not a trailer, per se, but an interview with me (backed by spooky music!).

I'm having trouble with the embed code - I can't seem to resize their monster window! — but meanwhile the link is here.

UPDATE: How's this?

MRSA research round-up: hospitals, vitamins, pets

2010-03-15T23:30:00.000-05:00

Because I've been so behind, there's so much to cover! So let's dive in:

In today's Archives of Surgery, researchers from Seattle's Harborview Medical Center report that one simple addition to the routine of caring for trauma patients made a significant difference to the patients' likelihood of acquiring a hospital-associated infection: bathing them once a day with the antiseptic chlorhexidine (in an impregnated wipe). Patients who were bathed with the antiseptic wipe, compared with patients wiped down with an inert solution, had one-fourth the likelihood of developing a catheter-related bloodstream infection and one-third the likelihood of ventilator-associated MRSA pneumonia. Cite: Evans HL et al. Effect of Chlorhexidine Whole-Body Bathing on Hospital-Acquired Infections Among Trauma Patients. Arch Surg. 2010;145(3):240-246.

How important are hospital-acquired infections? Here's a piece of research from a few weeks ago that I sadly failed to blog at the time: Just two categories of HAIs, sepsis and pneumonia, account for 48,000 deaths and $8.1 billion in health care costs in a single year. Writing in the Archives of Internal Medicine, researchers from the nonprofit project Extending the Cure analyzed 69 million hospital-discharge records issued in 40 states between 1998 and 2006. Hospital charges and number of days that patients had to stay in the hospital were 40% higher because of those infections, many of which are caused by MRSA — and all of which are completely preventable. Cite: Eber, MR et al. Clinical and Economic Outcomes Attributable to Health care-Associated Sepsis and Pneumonia. Arch Intern Med. 2010; 170(4): 347-53.

What else could reduce the rate of MRSA infections? How about Vitamin D? South Carolina scientists analyze data from the NHANES (National Health and Nutrition Examination Survey 2001-2004), a massive database overseen by the CDC, and find an association between low blood levels of Vit. D and the likelihood of MRSA colonization. More than 28% of the population is Vitamin D deficient. MRSA colonization is increasing in the US. Can giving Vit. D decrease MRSA carriage? More research needed. Cite: Matheson EM et al. Vitamin D and methicillin-resistant Staphylococcus aureus nasal carriage. Scand J Infect Dis. 2010 Mar 8. [Epub ahead of print]

And finally: Who else carries MRSA? Some unlucky pet owners have found that animals can harbor human strains, long enough at least to pass the strain back to a human whose colonization has been cleared. So it makes sense to ask whether humans who spend time with pets are carrying the bug. Last month's Veterinary Surgery reports that the answer is Yes. Veterinarians are carrying MRSA in very significant numbers: 17% of vets and 18% of vet technicians at an international veterinary symposium held in San Diego in 2008. Cite: Burstiner, LC et al. Methicillin-Resistant Staphylococcus aureus Colonization in Personnel Attending a Veterinary Surgery Conference. Vet Surg. 2010 Feb;39(2):150-7.

SUPERBUG the book: First excerpt, first interview, and news!

2010-03-11T08:00:00.002-06:00

Constant readers: It's two weeks to publication, and I'm starting to lose my grip on everything there is to do. (As you might be able to tell by my radio silence...) I'm very backed up on great research to tell you about.

First, though, let me share some book news:

EXCERPT: The first excerpt of SUPERBUG has been published on Simon and Schuster's website! It looks like the entire Chapter One.

INTERVIEW: I was invited to Chicago the past few days to do a speech for International Women's Day, and ended up doing some sneak-preview media appearances. Here's the sound file of an interview with the fabulous Alison Cuddy of WBEZ-FM.

MORE INTERVIEWS: I'll be listing forthcoming interviews and appearances on my page at BookTour.com. You'll notice there isn't much up there yet: We're still working on publicity. So help me fill this page, OK? Here's how:

TOUR, A PLEA: My publisher, Free Press, doesn't really believe in sending authors around. They have some justification: As I can testify from my last tour, sometimes a book tour mean spending two hours making painful chit-chat in an empty bookstore whose entire population is the staff, the friend who drove you, and a street person who wandered in and is conversing quietly with her demons. (Twenty-Third Street Books, Portland, OR, thanks for asking. I hear they closed.) But that bad experience notwithstanding, I believe there's value in getting out and talking to readers, victims, disease geeks and anyone else interested in this bug, and I'm willing to do it, if you'll help.

So: If you're a clinician, a professor, or a teacher, and you're willing to host SUPERBUG and me at a class, a department brown-bag or a Grand Rounds, please get in touch. Ditto if you run a Cafe Scientifique, have a book club that wants to talk about science or medicine, have a church group, a kid's group, a med-student society... you get the idea. If I can get there, I'll come. I know already that I'll be in and out of Minneapolis and Atlanta, my two home bases, and also in North Carolina, Iowa, Chicago, and I hope San Francisco, Portland and Boston as well. Help me add to the list!

Right, back to research tomorrow.

"Pig MRSA" causing human infections

2010-03-04T08:00:00.001-06:00

Hi, everyone. Apologies for dropping out of sight! As SUPERBUG's publication draws closer (and it's very close now), I keep finding new tasks that I have do to. Last week's was to go to New York to shoot a video for the Simon & Schuster website — and while there, I got caught in Snowpocalypse, got delayed coming home, and picked up a nasty cold. So I'm a bit behind.

But there's exciting news tonight to start us up again: "pig MRSA," ST398, causing human infections in Canada and Denmark.

"Infections" is important, because up til now, most evidence for the spread of MRSA ST398 in humans has been through detection of colonization, the symptomless carriage of MRSA on the skin and in the nostrils. The first finding of ST398 in the Netherlands was via colonization; so was its first identification in humans in Canada, and also in the United States just about a year ago.

But comes now a team of public and university scientists from Canada to say that ST398 is also causing infections in Canada. They analyzed 3,687 MRSA isolates that had been collected from patients seen for infections in Manitoba and Saskatchewan. Five were ST398. That is an exceedingly low percentage, of course. But it is striking, and odd, that the infections were present at all:

The earliest identified LA-MRSA isolate (08 BA 2176) associated with an infection was obtained from a postoperative surgical site. ... This patient is unlikely to have had any recent direct contact with livestock because she had been confined to her home with limited mobility for several years before her hospitalization. Additional nasal swabs from this patient remained positive for this strain for at least 7 months. ...
The isolate submitted to the NML by Sunnybrook Health Sciences Centre... was from a 59-year-old man from Ontario. He had been hospitalized in December 2007 for treatment of metastatic squamous cell carcinoma of the larynx. In the previous year, he had undergone a total laryngectomy, neck node dissection, and tracheostomy. .... He was unaware of any animal contact and had no history of exposure to pigs or pig farms. A review of the medical records and standard epidemiologic investigations determined that this was not a nosocomial or healthcare-associated isolate.

Just to underline, we have here a MRSA strain that is strongly associated with close contact with pigs, or with pig meat, and that has spread far enough from farms to be present in people who had no connection with pigs. You can argue that its very low prevalence means that it is not so much a threat as a curiosity. But I'd counter-argue that this is significant: because it establishes that this strain is spreading; because it demonstrates that the strain is causing infections, not just colonization; and because it inserts, into the swarm of isolates that make up MRSA, additional resistance factors that can be traded and exchanged unpredictably among the bacteria — and are likely not to be detected because our surveillance in animals is so sparse.

The authors say:

...additional surveillance efforts are required to monitor the emergence and clinical relevance of this MRSA strain in Canada, including communities, the environment, livestock, farmers, and production facility workers. Whether these strains pose a major threat to human health in light of the low livestock density and continued spread of epidemic hospital and community strains of MRSA in Canada remains unknown.

There's also a new and tantalizing report from Denmark that appears to describe not only human infections, but human to human transmission, resulting in a very serious pneumonia in a baby. I can't access the full-text even through my university account, but the abstract says:

Carriage of pig-associated methicillin-resistant Staphylococcus aureus (MRSA) is known to occur in pig farmers. Zoonotic lineages of MRSA have been considered of low virulence and with limited capacity for inter-human spread. We present a case of family transmission of pig-associated MRSA ST398, which resulted in a severe infection in a newborn.

Not good.

The cites for these are:
Golding GR, Bryden L, Levett PN, McDonald RR, Wong A, Wylie J, et al. Livestock-associated methicillin-resistant Staphylococcus aureus sequence type 398 in humans, Canada. Emerg Infect Dis; [Epub ahead of print] DOI: 10.3201/eid1604.091435
Hartmeyer GN, Gahrn-Hansen B, Skov RL, Kolmos HJ. Pig-associated methicillin-resistant Staphylococcus aureus: Family transmission and severe pneumonia in a newborn. Scand J Inf Dis. Epub Feb. 3, 2010 ahead of print.

Antibiotics and farming — how superbugs happen

2010-02-19T18:46:00.002-06:00

Constant readers: There's an important new paper that's been out for a week that I haven't gotten to you. I apologize; it's been busy. (Let's not even talk about the important paper that's been out for two weeks. Maybe over the weekend...)

We've talked for ages now about the potential dangers of unrestricted antibiotic use in agriculture, and how it's analogous to the inappropriate antibiotic use that human health authorities disapprove of in humans. The main culprits, in farming, are subtherapeutic dosing, also known as growth promotion — that's giving routine smaller-than-treatment doses to animals to increase their weight — and prophylactic dosing, which is giving a treatment dose to an entire herd or flock either routinely, if there is thought to be a disease threat, or when there is known to be disease in some members of the herd/flock. In either case, animals are getting antibiotics when they do not need them — when they are not sick. And just as in humans who take antibiotics when they are not sick, or take too-low doses when they are sick (such as not finishing a prescription), these practices in animals encourage the development of resistant bacteria.

(Necessary comment here: No one, to my knowledge, objects to giving the appropriate doses of antibiotics to animals that are sick. Why would you?)

The interesting research question is how, exactly, resistance develops. (My real scientist readers may want to take a break, or cut me a break, for the next few sentences. Please.) The classical assumption has been that, through a variety of stimuli and the random copying errors of reproduction, bacteria are constantly acquiring small mutations. Some of those may give the bugs an advantage when they are exposed to a drug, some slight difference that allows the bacteria to disarm or turn aside that drug's particular method of assault — so that the weak die, the strong survive, and the strong then reproduce more abundantly into that extra living space freed up by the death of the weak. The survivors and their descendants retain that mutation, because it gave them an advantage against the drug. And because bacteria can share resistance factors not only vertically mother-to-daughter, but horizontally in the same generation, once the resistance has emerged, it is likely to spread.

But no matter how quickly it spreads, that process I've just described involves acquiring resistance to just one drug or drug family at a time. Provocative new research from Boston University's medical school and deoartment of biomedical engineering now suggests, though, that multi-drug resistance can be acquired in one pass, through a different mutational process triggered by sublethal doses of antibiotics — the same sort of doses that are given to animals on farms.

In earlier work, the authors found that antibiotics attack bacteria not only in the ways they are designed to (the beta-lactams such as methicillin, for instance, interfere with staph's ability to make new cell walls as the bug reproduces, causing the daughter cells to burst and die), but also in an unexpected way. They stimulate the production of free radicals, oxygen molecules with an extra electron, that bind to and damage the bacteria's DNA.

That research used lethal doses of antibiotics, and ascertained that the free-radical production killed the bacteria. In the new research, the team uses sublethal doses, and here's what they find: The same free-radical production doesn't kill the bacteria, but it acts as a dramatic stimulus to mutation, triggering production of a wide variety of mutations — what the researchers, in a press release, called "a zoo of mutants." The plentiful, scattershot mutations included ones that created resistance to a number of different drugs — in some cases, even though no mutation was present that created resistance to the drug being administered.

You can easily see how this is applicable to factory farming: The sublethal dosing applied experimentally is analogous to the subtherapeutic dosing used in agriculture. Is it applicable to MRSA? Yes, absolutely. The two organisms the researchers used to test their hypothesis were S. aureus and E. coli.

making the implication clear, senior author James J. Collins said on the paper's release:

"These findings drive home the need for tighter regulations on the use of antibiotics, especially in agriculture; for doctors to be more disciplined in their prescription of antibiotics; and for patients to be more disciplined in following their prescriptions."

The cite is: Kohanski MA, DePristo MA and Collins, JJ. Sublethal Antibiotic Treatment Leads to Multidrug Resistance via Radical-Induced Mutagenesis. Molecular Cell, Volume 37, Issue 3, 311-320, 12 February 2010.

UPDATE: There's a great discussion of the paper at the blog Mental Indigestion.

Postscript: I suppose I've been working too long without a break, because while I was reading about this process of creating multiple resistance factors at once, what I heard in my head was Mickey Mouse chirping: "Seven at one blow!"

Antibiotics and farming — CBS follow-up video

2010-02-16T15:38:00.000-06:00

Constant readers, CBS News has posted some follow-up video to its two-part series last week on antibiotics in agriculture. It features Dr. David Kessler, former Commissioner of the Food and Drug Administration (which under its current leadership has vowed to re-examine farm-antibiotic use), and Eric Schlosser, author of Fast Food Nation.

They talk about the protests CBS has received for airing the package, the concerns public health authorities have over the lack of data on the amounts and types of antibiotics used, and much more. I especially love Schlosser's comment: "I'm a meat-eater." It's important, I think, to say that being critical of antibiotic use does not mean being opposed to animal agriculture, or wanting to see farms shut down. It means being concerned for the health of farm animals, farm families, and everyone affected by growing antibiotic resistance — which is, you know, everyone.

(H/t @EdibleSF for flagging the video's release.)

Watch CBS News Videos Online

(Hey, that's my first embedded video!)

New film on organic farming (for European readers and others)

2010-02-12T11:50:00.000-06:00

This is a little outside our usual subject matter, but it follows nicely on the past two days' discussion of the CBS packages on antibiotics in farming, so:

What looks like a marvelous new documentary exploring environmental damage and human illness from pesticides and other farming chemicals is coming out in France, but needs assistance to get onto the international festival circuit. It's called Nos enfants nous accuseront (Our Children Will Hold Us Responsible), and among other things, looks at the efforts of a French village to make all the food served in its schools organic — which, even in food-centric France, is much harder than it sounds.

You can view the trailer here. The more clicks, the more the film will be taken to have support, and the higher its rankings will go for festival consideration.

It comes well-recommended by friends of mine in Paris, so I hope you'll take a look.

CBS antibiotics and farming, day 2 - and more on the Danish experience

2010-02-11T12:23:00.001-06:00

Constant readers, I hope you watched the second day of CBS News' series on antibiotic use in farming, and how it promotes the emergence of antibiotic-resistant infections in animal and humans. I found it surprisingly hard-hitting. Here's the video and the text version.

Most of the report explored the farm experience in Denmark, which in 1998 banned its farmers from using small doses of antibiotics to make animals gain weight faster — the practice that's various called subtherapeutic dosing or growth promotion. Important distinction: The country still permits sick animals to be treated with antibiotics; the ban extends only to giving drugs to animals who are not sick.

That ban has often been represented as a failure for Danish farming [NB: See the update below], but research on the results shows that it was actually a success. Here's an article by Laura Rogers of the Pew Charitable Trusts explaining what happened in Denmark from her own on-the-ground reporting:

Antibiotic use on industrial farms has dropped by half while productivity has increased by 47 percent since 1992. Danish swine production has increased from 18.4 million in 1992 to 27.1 million in 2008. A decrease in antibiotic-resistant bacteria in food animals and meat has followed the reduced use of these vital drugs. ...

The average number of pigs produced per sow per year has increased from 21 to 25 (this is an important indicator of swine health and welfare, according to veterinarians). Most important, total antibiotic use has declined by 51 percent since an all-time high in 1992. Plus, the Danish industry group told us that the ban did not increase the cost of meat for the consumer.

There are multiple scientific papers done by Danish authors backing up her observations. Here are just a few from just last year:

Antibiotic-resistant organisms in chickens raised in Denmark declined since the ban — but they remain high in chicken meat imported from other countries that do not have such bans, and passed to Danish consumers who ate that imported meat. (Skjot-Rasmussen et al., May 2009)
Antibiotic resistance in E. coli in pigs increases when pigs are given antibiotics, and those antibiotic-resistant organisms pass to humans (Hammerum et al., April 2009)
Antibiotic-resistant organisms found in pigs when they are slaughtered increase when pigs receive more antibiotics (Abatih et al., March 2009)

The industry that supports industrial-sized farms has strongly objected to the CBS series. You can see one detailed response here, from Pork Magazine. The Minneapolis-based Institute for Agriculture and Trade Policy predicts that this is likely just the first wave, and that opposition to any change in agricultural practices will grow stronger as a bill to curb unnecessary antibiotic use gains traction in Congress.

And — you knew I had to do this — here comes the obligatory self-promotion: There is a primer on antibiotic use in farming, and an account of the emergence of MRSA ST398 as a result of antibiotic use in pigs, in SUPERBUG. Which is now 41 days away from publication. And is available for pre-order at a discount! But you knew that.)

UPDATE: FairFoodFight has a great post and a long comments conversation about the CBS series, ag antibiotic use, and particularly the World Health Organizaton research that originally made people doubt the "Danish experiment," The WHO report is here and a Pew analysis of it is here.

CBS antibiotics and farming package, day one

2010-02-09T19:29:00.000-06:00

Constant readers, I hope you saw the CBS News package on antibiotics in farming Tuesday night. (It continues Wednesday.) MRSA played a prominent role, in an account of infections among workers at a chicken plant (the same outbreak, I think, as was described by Prevention magazine last August) and in questions about MRSA in pig farms in the Midwest (with a prominent mention of Tara Smith's research into "pig MRSA" ST398).

Here's the 7-minute video and the text version.

Earlier Tuesday, CBS's Early Show ran an additional package on the death of a Chicago toddler from MRSA. That toddler's name is Simon Sparrow, and you'll be able to read his sad story — told by his mother, Everly Macario — in SUPERBUG.

Farming and antibiotics - and voices from the ag side

2010-02-09T08:00:00.004-06:00

There's a tremendous amount of buzz in the blogosphere about a series of pieces that are supposed to run on CBS News over the next several days, looking at the use of antibiotics in agriculture. For one of many posts on the topic, look at this piece from Food Safety News, an online newsletter founded by the food-safety attorney Bill Marler.

[UPDATE: CBS has put up the first video teaser for the package.]
[SECOND UPDATE: An excerpt from the Early Show, likening growth promoters to a "ticking time bomb" and to "putting (antibiotics) in your kid's cereal so they won't get sick"]

The whole issue of how antibiotics get used in agriculture — as growth promoters, as prophylatic treatment to prevent spread of infection within a farm, or as true treatment — is intensely controversial. For a sense of how farmers feel embattled, read the comments to this entry at FairFoodFight on whether there is a distinction between "Big Ag" and "small ag." and consider that the PAMTA legislation I posted about in December, which would require veterinarian oversight of farm use of antibiotics, has been strongly opposed by agricultural interests every time it has been introduced. (Large-farm use of antibiotics, let me remind you, has been concluded to be the driver behind the emergence of "pig MRSA" ST398.)

But I recently ran across two pieces online that I want to draw your attention to, because they demonstrate that thinking in agriculture about antibiotic use is not monolithic, and may be changing. Both were posted on the same site, the Illinois-based Agri-News Online.

First, from James Pettigrew, a professor of animal sciences at University of Illinois, a pessimistic but realistic assessment of how changing public attitudes about antibiotic use will affect what farmers can do, "Broad restrictions on antibiotic use would reduce animal welfare and productivity":

Many of us hope there will not be a broad ban on antibiotic use, but it is difficult to predict what will happen. Restrictions on antibiotic use may come from Congress, from regulatory agencies or from customers. The nature and extent of future restrictions are now unknown, but the direction is clear. There will be tighter restrictions on antibiotic use in the future. ...
...Planning for restrictions on antibiotic use can be valuable even if those restrictions are never imposed. The things you might do in the absence of antibiotics are also likely to be quite valuable if you continue to use antibiotics as you do now....

Second, from a writer named Darryl Ray, who isn't otherwise identified, a plea for refraining from demonizing critics of antibiotic use, "Animal producers should take antibiotics criticism seriously":

...Many — and we would suggest it is the vast majority — of those who question the present practices of antibiotic use in animal agriculture eat meat on a regular basis.
Rather than malign the critics, a better course of action for meat animal producers might be to take the issue seriously.
...To categorically claim that it is a reasonable practice to routinely administer antibiotics to animals that are not diseased will strike many as being outside what they have come to believe to be an appropriate use of antibiotics.
...It is important to consider the possibility that indisputable evidence will emerge that the continued and persistent “overuse” of antibiotics in livestock production causes or accelerates the development of super-germs for which there are virtually no effective medications.That would be a public relations and economic nightmare for production agriculture. Thought of in that light, taking the issue seriously and making meaningful adjustments in antibiotic use may have the most appeal of all.

I don't know that I agree entirely with either writer. But I'm tremendously encouraged that a publication that speaks entirely about farming, to farmers, can run thoughtful pieces looking at ag antibiotic use from several angles, as something to be evaluated, debated and potentially adjusted, and not as a practice that cannot be examined but must be maintained unchanged.

Bad news in the President's budget request

2010-02-05T08:00:00.001-06:00

It's been a few days since the rollout of the White House's proposed 2011 budget request, time enough for people to dig deep into the minutiae and figure out what that massive document really says. The Infectious Diseases Society of America has done the drilling for the health and infectious disease line items, and I'm sorry to say the news is not good.

Worst first: The proposed budget would cut funding for the CDC's antimicrobial resistance programs by 50%, $8.6 million. That means that only 20 state or local health departments, or health care institutions, will get money from CDC for surveillance and control of resistant bugs. That's only 40% of what was funded this year, when 48 health departments and health systems were funded. Which is very disturbing: If there's one thing almost everyone agrees on with regard to MRSA, it's that we need more surveillance, not less.

In addition, all state grants in the Get Smart About Antibiotics program, which runs campaigns to reduce inappropriate use, get zeroed out.

There are other cuts as well to infectious-disease program at CDC and elsewhere in HHS, including to to a major childhood immunization program and to pandemic defenses. And funding for HIV/AIDS, TB and other NIH research programs barely tiptoe upward.But these frank cuts in programs to combat antimicrobial resistance, at a time when MRSA is burgeoning, Gram negative organisms such as Acinetobacter are gaining ground, and drug development is stalling, surely cannot be smart.

The IDSA analyis is here.

SUPERBUG named a Top 50 public health blog

2010-02-03T10:33:00.000-06:00

Constant readers, the website The Science of Health has named SUPERBUG one of its Top 50 public health blogs. I'm flattered to say we're in excellent company — the other blogs listed there are very good. Please go take a look.

Back again to MRSA in animals, and spreading to humans

2010-02-03T09:00:00.001-06:00

There are two new reports out regarding new findings of "pig MRSA" ST398 (about which we have talked a lot; archive of posts here.)

First, researchers from the Complejo Hospitalario Universitario de Vigo and Complejo Hospitalario de Pontevedra, both in Pontevedra in northwest Spain, report that they have identified that country's first human cases of infection with ST398. (It was only last fall that Spain reported the first identification of the strain in animals.)

The age of the three patients was 59, 82, and 83 years, respectively. Two patients owned pigs and the other a calf. Two patients were diabetic and were hospitalized because they developed skin and soft-tissue infections by MRSA ST398. The third patient had bronchitis and the strain was isolated from a respiratory secretion submitted to the laboratory from an outpatient clinic. The three patients had had multiple hospital admissions in the last 12 months.

Tellingly, the researchers spotted these particular isolates (out of 44 analyzed at the two hospitals in 2006) because they were resistant to tetracycline. Tetracycline resistance is not common among community strains of MRSA, because the drug isn't the first-line choice for skin and soft-tissue infections; and when it is given, it's usually for a short course, so the drug does not exert much selection pressure on the bug. But tetracycline is a very common animal antibiotic, and tetracycline resistance is a hallmark of ST398; it is one of the factors that led the Dutch researchers who first identified the strain to take a second look at the bug.

Second, researchers from several institutions in Italy report a very troubling case of ST398 infection that produced necrotizing fasciitis — better known as flesh-eating disease.

In early April 2008, a 52-year-old man was admitted to an intensive care unit in Manerbio, Italy, because of severe sepsis and a large ulcerative and suppurative lesion on the right side of his neck. His medical history was unremarkable. He was a worker at a dairy farm, was obese, and did not report any previous contact with the healthcare system.

Necrotizing fasciitis is a terrible disease: If doctors don't respond very quickly, it can kill, whle the emergency surgery that forestalls death often carves away large areas of flesh or sacrifices entire limbs. This patient was fortunate: He was in the hospital for 31 days, but recovered and went home.

The Italian researchers are alert to, and troubled by, the larger meaning of this case:

... cattle-to-human transmission cannot be proven. However, because our patient did not have any other potential risk factor, dairy cows were probably the source of the human infection. ... It is difficult to prevent persons with constant exposure to MRSA in their work or home setting from becoming MRSA carriers. Revisiting policies for the use of antimicrobial drugs on livestock farms, as well as improving hygiene measures, may therefore be necessary in infection control programs.

Cites for these papers:

Potel C et al. First human isolates of methicillin-resistant Staphylococcus aureus sequence type 398 in Spain. Eur J Clin Microbiol Infect Dis. 2010 Jan 23. [Epub ahead of print] DOI 10.1007/s10096-009-0860-z

Soavi L, Stellini R, Signorini L, Antonini B, Pedroni P, Zanetti L, et al. Methicillin-resistant Staphylococcus aureus ST398, Italy [letter]. Emerg Infect Dis 2010 Feb

Recommending: Consumer Reports on hospital infections

2010-02-02T18:58:00.000-06:00

Constant readers, the magazine Consumer Reports has done an extended, state-by-state analysis of which hospitals do well, or very badly, in preventing one important category of infections: central line-associated bloodstream infections, or CLABSIs (pronounced klab-sees). It's a comprehensive package in easily understandable language. It's based on the state reporting data that some activists have managed to persuade states to disclose, along with another set of data that some hospitals voluntarily tender to the nonprofit firm The Leapfrog Group.

From the Consumer Reports story:

Poorly performing hospitals included some major teaching institutions. For instance, New York University Langone Medical Center in New York City reported 39 infections in 10,119 central-line days in 2008, roughly twice the national average for its mix of ICUs. The University of Virginia Medical Center in Charlottesville didn't do much better, reporting 77 infections in 18,572 days for the 15 months ending in September 2009, also about two times the national average.

More encouragingly, nationwide, we counted 105 hospitals whose most recent public reports tallied zero central-line infections. They ranged from modest rural institutions to urban giants such as the University of Pittsburgh Medical Center Presbyterian hospital, which reported no infections among patients who were on central lines a total of 13,596 days in 2008.

It's well worth reading, and checking to see whether a hospital you may have used, or may be considering using, is on the good list or the bad list. Take a look.

Once again, flu and bacterial co-infection

2010-02-02T09:00:00.001-06:00

With the H1N1 pandemic trending down, it may seem that the question of how much bacterial co-infection affects the outcome of flu is less important than it was. But though the pandemic is subsiding — for ever, for this season, or just until a third wave, who can say — researchers are just now getting enough good data to be able to make solid observations about what happened during the past 10 months.

Case in point: Writing in the journal Public Library of Science (PLoS) ONE, a team of researchers from Australia has pinpointed the incidence of MRSA co-infection during flu in two hospitals in Perth last summer, which was the Australian winter and the height of their flu season. Of 252 patients admitted for H1N1 infection, 3 were identified during treatment as having MRSA pneumonia. They survived, but two other patients who died were found to have MRSA pneumonia during post-mortem exams.

There were 3 female and 2 males, aged between 34 and 79 years... Two patients lived at the same long-term care facility, whilst the other patients lived independently in the community. Four of the 5 patients had conditions that may have increased their risk of pneumonia, including quadriplegia (two patients) asthma (one patient), cirrhosis (one patient) and diabetes mellitus (one patient). Two of the 5 cases (patients 3 and 4) had known MRSA infection/colonization prior to the onset of their illness (with the same cMRSA clone that subsequently caused their co-infection).

There are some interesting points embedded here. First, incidence: In the Australian patients, MRSA pneumonia was much more common. The Perth researchers found 5 MRSA cases out of 252 flu patients. When the CDC analyzed the occurrence of MRSA pneumonia in flu last summer, it found only 1 case out of 272. Second, treatment: None of the 5 patients got antibiotics that would have affected MRSA — even though two of them were already known to be MRSA carriers. The possibility of MRSA pneumonia subsequent to flu seems not to have occurred to the health professionals taking care of them.

And third, the pathogen: The 5 Australian cases were caused by 3 community MRSA strains that are common in Australia — but only one of the 3 made PVL, the toxin that has so frequently been associated with MRSA pneumonia. That is interesting, and troubling at the same time. At this point, the association of PVL and necrotizing pneumonia has become practically taken for granted; and yet here are two strains that did not make PVL and yet caused severe and fatal pneumonia. It may be an indication that the inflammation that flu causes in the lung can open the door to more severe damage even when PVL is not present; it's certainly an indication that the absence of PVL does not signal a mild or not-dangerous strain.

The cite is: Murray RJ, Robinson JO, White JN, et al. 2010 Community-Acquired Pneumonia Due to Pandemic A(H1N1)2009 Influenzavirus and Methicillin Resistant Staphylococcus aureus Co-Infection. PLoS ONE 5(1): e8705. doi:10.1371/journal.pone.0008705.

Simultaneously, a new paper in the American Journal of Pathology seeks to clarify how often and in what circumstances bacterial superinfection becomes a risk during flu. Using a range of mice — both healthy ones, and "knockout" mice bred to be without particular immune-system components — researchers from San Diego confirmed that infections with flu and with Haemophilus influenzae can be lethal when the flu infection precedes the bacterial one. That was true even for infections that, if experienced separately, would not have been lethal; it was the synergy of the two infections, flu first followed by the bacterial infection, that caused the high mortality rate. The results may not be directly applicable to human medicine (Do you all know the old flu-research saying, "Mice lie and ferrets mislead?"), but they are an important indicator both of the seriousness of bacterial infection after flu, and also of the potential vulnerability of even healthy beings to that one-two punch.

The cite is: Lee LN, Dias P, Han D, et al.: A mouse model of lethal synergism between influenza virus and Haemophilus influenzae. Am J Pathol 176: 800-811.

SUPERBUG's first web page!

2010-01-26T21:55:00.000-06:00

Folks, as with my first book, I'm having a website professionally built for SUPERBUG (by the awesome Book Report Network). But while we work on that, I've put up a proto-page on my own. Please come check it out!

You'll see the gorgeous, scary cover, the hair-raising jacket copy, and links to pages about me and about the book. You'll also see links for buying the book: at a deeply discounted pre-publication price at Amazon, and also at IndieBound.com, the site for independent book-sellers.

There's also a link through which you can check out BookTour.com, where I'll be listing appearances and speeches, and where you can request I come speak. And finally — important for academics and teachers! — there's a link through which you can order a free copy for academic evaluation.

Until we get the full site built, the page will be on my website. The URL is http://www.MarynMcKenna.com/SUPERBUG.html. Please come look.

MRSA in the journal Science - spread, outbreaks and an argument for active surveillance

2010-01-21T23:40:00.000-06:00

I have a story tonight at CIDRAP about a paper published this evening in the journal Science. To respect fair use and make sure my colleagues get clicks, I just quote the story here — but then I want to talk about why I think it's such an important study.

   A multi-national team of researchers has applied a new genomic tool to a 50-year-old bacterial foe, using minute mutations to track the spread of drug-resistant staph both across continents and within a single hospital.
   On a global scale, their sleuthing tracked the movement of one clone of methicillin-resistant Staphylococcus aureus (MRSA) back and forth across the planet, pinpointing when individual cases transported infections across national borders to spark new outbreaks. Separately, their method demonstrated that what appeared to be a hospital epidemic of MRSA was not a single outbreak, but rather a mixed event of patient-to-patient transmission of one strain that was accompanied by multiple importations from outside the hospital of similar but unrelated strains. ...
   In a briefing yesterday for the press, the authors emphasized the latter finding, pointing out that the traditional infection control measures usually applied to hospital outbreaks would not curb the spread of infections that were carried in undetected from outside. Their method, they said, provides a proof of concept for using cutting-edge genomics to uncover the precise pathways by which MRSA spreads within hospitals—not only tracing its path from patient to patient, but also identifying the bug in patients whose undetected bacterial carriage could spark outbreaks but have not yet.

If you'd like more, here's a very good story at Scientific American, one at BBC Health and one by the Associated Press; and Science Daily's version.

Now, the details. This team (which has 15 members from almost as many institutions) secured two collections of MRSA isolates: 43 collected from all over the globe between 1982 and 2003, and 20 from a single hospital in Thailand, collected between October 2006 and November 2007. All of the isolates were ST239, which is a hospital-acquired strain that is particularly prevalent in Asia. They analyzed them using high-throughput sequencing, with a particular analyzer (Illumina) that could produce whole genomes of up to 96 isolates very quickly (an extraordinary advance from the weeks and months it used to take to achieve a single whole genome). Then they compared the genomes, looking for single-letter changes in the genetic code (single-nucleotide polymorphisms, SNPs or "snips," and also insertions and deletions of nucleotides). They used those findings to construct a "family tree" of 239 that tracks very nicely with the known history of MRSA's emergence and initial spread, and that pinpoints rare but intriguing importations of clones from certain areas into other parts of the world.

But it's what they found in the Thai hospital isolates that is especially interesting. (Most of this is not explicit in the paper, but was related in the press briefing that Science conducted on Wednesday). The differences that can be seen in the whole-genome analysis can't be discerned by earlier identification methods, so the isolates collected at the hospital appeared to be the same. However, they weren't the same. Some of them were very closely related, and formed what seems to have been a chain of person-to-person transmission — a true hospital-acquired outbreak. But others of them were not so closely related, either to the outbreak or to each other. What they were, instead, were individual importations into the hospital of a hospital strain that had been acquired outside the hospital, and were carried in by staff, patients, visitors.

You can see where this is going, right? If all the cases in the hospital had represented patient to patient transmission within a known outbreak, excellent infection control might have corralled them. But some of them were not part of that outbreak, so infection control measures aimed at that outbreak would not have kept those other cases from spreading. What would have stopped them from spreading, as the authors pointed out, is detecting them at some other point in their entry into the hospital:

..."That implies you have to have a different perspective on where you are going to apply your infection-control procedures and strategies," co-author Dr. Sharon Peacock of the University of Cambridge said during the briefing.

What that sounds like — and the authors acknowledged as much — is an argument for active detection and isolation/active surveillance and testing/search and destroy, the process of screening some percentage of patients coming into a hospital for MRSA carriage so that the bug can be detected and dealt with long before its presence triggers an outbreak. It is probably not a coincidence that the majority of the authors (including Peacock) are British, and search and destroy has recently become widely accepted in the UK; in fact, the National Health Service recently made it mandatory.

But search and destroy remains remarkably controversial here in the US, despite strong proof of concept demonstrations in healthcare institutions such as Evanston-Northwestern Healthcare, and adoption throughout the VA system. I'll be interested to see whether this paper makes a dent in the overall resistance to search and destroy, and if not, to hear why not.

The cite is: Harris SR, Feil EJ, Holden MTG, et al. Evolution of MRSA during hospital transmission and intercontinental spread. Science 2010 Jan 22;327(5964):469-74

News round-up!

2010-01-19T21:35:00.002-06:00

As promised, lots to catch up on — so here's a quick round-up of some great reading that I have been stashing and that you may have missed in the past few weeks.

BBC News: Disinfectants may train bacteria to resist antibiotics
The BBC Health page (bookmark it!) translates a paper from the journal Microbiology on Pseudomonas aeruginosa's newly recognized ability to pump the active ingredient in disinfectants out of its cells — and then to apply that same ability to the antibiotic Ciprofloxacin, even when it has never been exposed to Cipro before. Money quote: "... Residue from incorrectly diluted disinfectants left on hospital surfaces could promote the growth of antibiotic-resistant bacteria."

Associated Press: Solution to killer superbug found in Norway
In the latest installment in a 6-month series, AP writers Martha Mendoza and Margie Mason examine Norway's success in forcing down rates of hospital MRSA. chiefly by extremely strict control of antibiotics dispensed in hospitals. I have some disagreements with this story; I don't think they account for how much easier it is to do antibiotic stewardship, as it's called, in a single-payer health system such as Norway or their second example, England, compared to the extremely complex US system. But I'm very glad to see the AP (and the Nieman Foundation at Harvard, where Mason was a fellow) support public exploration of antibiotic resistance, which I obviously feel gets insufficient attention. (Stay tuned for SUPERBUG's discussion of one US stewardship program that has worked and may be replicable.)

Time: Should weight factor into antibiotic dosage?
Time.com looks at a provocative new paper in the Lancet that questions whether standard prescribed dosing of antibiotics isn't really a form of inappropriate use. Money quote: "Dosage according to body mass is standard in anesthetics, pediatrics, oncology and other fields, [but] when it comes to antibiotics and antimicrobials the dosing guidelines are too broad... and may undermine a medications efficacy. ...In the face of both widespread obesity and the increasing prevalence of antibiotic-resistance, tailoring dosage for optimal results is increasingly important."

And finally, new today:
Science Daily: Bacteria Are More Capable of Complex Decision-Making Than Thought
University of Tennessee researchers explore the ability of a bacterium (the soil bacterium Azospirillum brasilense) to sense changes in its environment, process that information and make surprisingly complex decisions in response.

SUPERBUG's cover - a sneak peek!

2010-01-18T18:07:00.000-06:00

Constant readers, apologies for disappearing unexpectedly. It's been a challenging few weeks at Casa Superbug, with a death in the family and a sudden trip to a part of the country with, hmm, low connectivity.

But I'm back. And there's so much to talk about. Here's the first in a long list: The cover art for SUPERBUG!

(Let us pause for a moment while I jump up and down and hug myself with glee.)

My editor says it will be even more gorgeous in real life: There are glossy areas, and embossed areas, and color that will fly off the bookstore shelf, smack you in the eye and insist on being carried to the cashier.

(Or, alternatively, wing off the page. Such as this Amazon page, where SUPERBUG is available at a pre-release price that is 34% off.)

More to come soon, on the many stories that occurred last week, and an exciting paper in a medical journal later this week.

Warning on ST398: Monitor this now

2010-01-04T17:53:00.000-06:00

Drawing your attention: I have a story up tonight at CIDRAP on a new paper by Dr. Jan Kluytmans, a Dutch physician and microbiologist and one of the lead researchers tracking "pig MRSA," ST398. (All past stories on ST398 here.) It's a review paper, which is to say that it summarizes key existing findings rather than presenting original research.

Still, it's important reading because Kluytmans is one of the few scientists who have some history with this bug and understand how quickly and unpredictably it has spread across borders and oceans, from pigs to other livestock, to pig farmers and veterinarians, into health care workers and hospital patients who have no known livestock contact, and now into retail meat in Europe, Canada and the United States.

Take-away: A plea and warning for better surveillance, so that we can track not only the bug's vast range, but also its evolution as it moves into new ecological niches — including humans who are buying that retail meat and possibly becoming colonized with it as they prep it for cooking in their home kitchens.

To honor fair use (and in hopes you'll kindly click over to CIDRAP), I won't quote much, but here's the walk-off:

Because the novel strain has spread so widely and has already been identified as a cause of hospital outbreaks, it should not be allowed to spread further without surveillance, Kluytmans argues."It is unlikely that this reservoir will be eradicated easily," he writes. "Considering the potential implications of the reservoir in food production animals and the widespread presence in meat, the epidemiology of [MRSA] ST398 in humans needs to be monitored carefully."

The cite is: Kluytmans JAJW. Methicillin-resistant Staphylococcus aureus in food products: cause for concern or case for complacency? Clin Microbiol Infect 2010 Jan;16(1):11-5. The abstract is here.

SUPERBUG website coming - what would you like to see?

2010-01-04T13:35:00.000-06:00

Constant readers, with publication of SUPERBUG the book coming closer, I'm starting to put together the pieces for a website. It will have stuff about the book, of course: details, excerpts, behind-the-scenes goodies, news on the key characters, and more. But my hope would be for the site to go beyond that, and to be a resource for people who want information about MRSA, or who want to network with other patient and family members, or find like-minded activists to talk with about the dangers of antibiotic resistance in agriculture.

But any site is not just going to be about me: We've become a community here over the past few years. So please tell me in the comments or by email: What would be most useful to you? Let me know what your wish-list is for SUPERBUG, and I'll take it to the designers when we plan the new site.

I'd really like to know.

Questioning meat-raising and meat-eating — in eat-everything France

2010-01-02T18:22:00.000-06:00

Happy New Year, constant readers. I'm honored and flattered to have had the chance to spend the past few years with you here. 2010 is going to be a big year — not just because SUPERBUG will be published, but because the issue of antibiotic resistance really, really is gathering force in the public mind. I not only believe that, I see it in the news that flows through my computer everyday. The wind is shifting.

Here's one excellent example. In France of all places, a culture that embraces meat-eating and finds the idea of animal rights quixotic. a book has been published that questions the environmental and moral effects of modern factory farming. It's called Bidoche, L'industrie de la viande menace le monde ("Bidoche" is a slangy, dismissive term for meat), and it has made enough of a splash that the newspaper Le Monde ran both an article on the book and a readers' Q&A with the author, journalist Fabrice Nicolino. (The article ran two days before Christmas but was called out on Twitter today by Paula Crossfield of CivilEats.com, who spotted it while on holiday, and to whom hat/tip.)

Sadly, the article is behind a paywall; you can see the first 100 words or so here. The Q&A is open though. It's titled, "To save the planet, should we eat less meat?"and makes fascinating reading (GoogleTranslate into English here), as do the comments, some of which raise the issue of the use of antibiotics in agriculture. But what's most striking to me is that the conversation is taking place at all, actively and in a public forum, in a place where only a few years ago the local culture would not have been open to the debate. Things are changing indeed.

MRSA in pets - a closer look

2009-12-31T09:00:00.002-06:00

From the research team at the University of Guelph Ontario Veterinary College — who have probably done more than any other group to elucidate MRSA in companion animals — comes a look at MRSA infections in dogs.

In order to get better data, the team used a study model that is much-employed in human epidemiology — and has often been used for MRSA — but under-employed in veterinary medicine: a case-control study matching MRSA infections against MSSA, or drug-sensitive staph. Studies matching MRSA against MSSA have been able, for instance, to show that certain (human) MRSA infections have higher death rates, keep patients in the hospital longer, and cause more healthcare expense.

The Guelph team used the same method to compare the presentation and outcome for 40 MRSA-infected dogs and 80 dogs with MSSA who were seen between 2001 and 2007 in three veterinary hospitals, in Guelph, Philadelphia and Boston. Their verdict:
MRSA is an emerging problem in dogs, and the risk factors for MRSA infections are similar to those in humans, particularly the use of IV catheters and both beta-lactam and fluoroquinolone antibiotics.

The researchers were not able to say whether MRSA in dogs causes more deaths than MSSA, because the infections that were recorded by the hospitals were mostly superficial ones in skin and ears:

Infection types for which death would be a more realistic possible outcome were limited... Comparison of mortality rates between patients with MRSA or MSSA infections would be best performed among on ly those with invasive infections and should be considered for future studies. Here, mortality rate information was obtained retrospectively and only recorded up to the time of discharge. Therefore, whether dogs died from their infections after discharge from the referral hospital, causing an underestimate of deaths, is unknown.

Dr. Scott Weese, senior author of this paper and chief of the Guelph group, has an excellent blog on infections in companion animals, called Worms and Germs. (It's in the blogroll.) And if you are looking for further information on MRSA in pets, the best resource I know of is the UK-based, but international, Bella Moss Foundation, named for a dog that died of a MRSA infection.

Antibiotics in chickens and links to human infections

2009-12-30T09:00:00.005-06:00

From the January issue of Emerging Infectious Diseases, published by the CDC (and therefore free. Must I keep urging you to read it? Go, already), here's a roundup of bad news about bad bugs.

In Canada, researchers from that country's Public Health Agency have found a "strong correlation" between the use of ceftiofur, a third-generation cephalosporin, in chickens; the rates of a resistant strain of Salmonella in chickens; and the appearance of that same strain in humans. The strain is Salmonella enterica serovar Heidelberg, one of the most common salmonella strains in North America, and one which can be nasty: It may cause mild illness, but also causes septicemia and myocarditis and can kill. Quebec created an unplanned natural experiment: Hatcheries there were broadly using ceftiofur until 2004, backed off from its use in 2005 and 2006, and then began using it again in 2007 in response to a growing problem with a particular infection. When the drug was withdrawn, resistant infections in birds and humans plunged; when it was reintroduced, they rose again. (Look at the black and red lines in the graph above left.)

Meanwhile, broiler chickens in Iceland are passing fluoroquinolone-resistant E. coli to humans there. Researchers at the University of Iceland were puzzled by an earlier finding that bacteria resistant to fluoroquinolones (a family that includes the human drug Cipro) were increasing among chickens raised in Iceland, despite strict controls on antibiotic use in food animals and stringent disinfection in chicken batteries after cohorts of birds were sold for slaughter and removed. They have two findings: The source of the resistant bacteria in the birds appears to be feed contaminated with resistant E. coli; and resistant bacteria in Iceland residents are microbiologically indistinguishable from those in the birds. Because E. coli is a very diverse organism, the very close resemblance between the isolates from chickens and the isolates from humans pins chickens as the likely source.

And just to make clear we're not blaming every microbiological evil on farming: Seagulls in Portugal have been found carrying multi-drug resistant E. coli in their feces. The public health concern here is obvious: Just think back to the last time you were at a beach, or anywhere else seagulls frequent, and envision a seagull perch — and the masses of seagull droppings streaking it. Now imagine those droppings transmitting antibiotic-resistant E. coli into the surrounding environment: the boardwalk, the beach, the towels... Additional problem: Seagulls are migratory birds, so the resistant bacteria easily cross borders and oceans.

Another resistant bug rising: Acinetobacter

2009-12-29T09:00:00.003-06:00

From the excellent and forward-thinking research team at Extending the Cure comes a dismaying report: over 7 years, a more than 3-fold increase in resistance in the Gram-negative bacterium Acinetobacter baumanii to its drug of last resort, imipenem.

Because MRSA is a Gram-positive, we don't talk much here about the Gram-negatives — the two categories of bacteria have different cell-wall structures and thus are treated using different categories of drugs. (That structural difference causes them to react in different ways to a stain invented by a scientist named Gram in the 19th century.) But the resistance situation with Gram-negatives is at least as dire as with MRSA, possible more so, because there are fewer new drugs for Gram-negatives in the pharmacology pipeline (as discussed in a New Yorker article by Dr. Jerome Groopman last year.)

And Acinetobacter is one nasty bug, as science journalist Steve Silberman ably documented in Wired in 2007 when he traced the spread of the organism through the military medical-evacuation chain from Iraq, demonstrating that the vast increase in resistant Acinetobacter among US forces was due to our own poor infection control.

The Extending the Cure paper (which will be published in February in Infection Control and Hospital Epidemiology) puts hard numbers to the Acinetobacter problem. Drawing on data from the private Surveillance Network, which gathers real-time electronic results from 300 US hospitals, they find:

full resistance to imipenem rose from 4.5% of isolates in 1999 to 18.2% in 2006 — a 300% increase
intermediate resistance rose from 1.3% of isolates to 9.4 — a 623% increase
susceptible isolates declined from 94.1% to 72.4% — a 23% decrease.

The authors write:
Our results demonstrate substantial national and regional increases in carbapenem resistance among clinical isolates of Acinetobacter species over the period 1999–2006. Increasing carbapenem resistance among Acinetobacter species is particularly troubling, because it is very often associated with multidrug resistance and because it is occurring in the context of increases in the incidence of Acinetobacter infection.

There's a further point to be made that is not explicit in the paper that I can see (though it is often made by Extending the Cure researchers). Acinetobacter needs attention, just as MRSA does — but if we focus just on the individual organisms, we are not going far enough. Antibiotic resistance is a system problem: It is an issue of infection control, of drug development, of agricultural organization, of federal priorities. It needs sustained attention and comprehensive, thoughtful, wide-ranging response. Now would not be too soon.

One surgical infection with MRSA: $61,000

2009-12-28T09:00:00.004-06:00

From a multi-state, public-private research team — Duke University, Wayne State University, and the Durham, NC VA — comes a precise and alarming calculation of MRSA's costs in hospitals: For one post-surgery infection, $61,681.

The group compared the course, costs and final outcome of three matched groups of patients from one tertiary-care center and six community hospitals in one infection-control network run by Duke. The three groups were: patients with a MRSA surgical-site infection; patients with a surgical-site infection (SSI) due to MSSA, drug-sensitive staph; and surgery patients who did not experience infections, matched to the other two groups by hospital, type of procedure, and year when the procedure took place. (This same cohort has been described in an earlier prospective study that looked at risks for MRSA SSIs.) Altogether, there were 150 patients with MRSA SSIs, 128 with MSSA SSIs, and 231 uninfected surgery patients to serve as controls.

Here's what they found. Patients with post-surgical MRSA infections:

stayed in the hospital 23 days longer
incurred an average extra cost of $61,681
were more likely to be readmitted to the hospital within 90 days
were more likely to die before 90 days had passed.

The authors write:

Our study represents the largest study to date of outcomes due to SSI due to MRSA. Our findings confirm that SSIs due to MRSA lead to significant patient suffering and provide quantitative estimates of the staggering costs of these infections. SSI due to MRSA led to a 7-fold increased risk of death, a 35-fold increased risk of hospital readmission, more than 3 weeks of additional hospitalization, and more than $60,000 of additional charges compared to uninfected controls.

For just the patients in this study, the excess costs (across 7 hospitals) totalled $19 million.

This is a highly useful study on several axes. First, remarkably, there has not been agreement over whether and how much of a problem MRSA poses in post-surgical settings, particularly when compared to drug-sensitive staph. This study provides careful, thoughtful, well-documented proof that combating MRSA infection is worthwhile. (NB, MRSA infections did not increase the risk of death relative to MSSA infections, which should remind us both of the often-forgotten virulence of MSSA, and also that MRSA's perils can lie in extended illness and disability as much or more as in early death.) Second, by putting a very specific number on the cost of a post-surgical MRSA infection, it gives healthcare administrators a benchmark against which they can judge the cost of a prevention program. We've all heard complaints that prevention programs can be costly and their benefit is hard to measure in a bottom-line way. With this very specific number, that complaint should no longer be valid.

There's a final point that is implied in the paper but not called out, so let me call it out on the authors' behalf. These results are very likely an under-estimate of MRSA's costs. That's because, first, the specific procedures the patients underwent were cardiothoracic and orthopedic; those are not the surgical procedures most likely to be followed by a MRSA infection. And second, data collection for this study ceased in 2003, about a year after the first emergence of USA300 and several years before that very successful community strain began its current move into hospitals. However much MRSA was extant in 2003, there is more now.

The cite is: Anderson DJ, Kaye KS, Chen LF, Schmader KE, Choi Y, et al. 2009 Clinical and Financial Outcomes Due to Methicillin Resistant Staphylococcus aureus Surgical Site Infection: A Multi-Center Matched Outcomes Study. PLoS ONE 4(12): e8305. doi:10.1371/journal.pone.0008305

SUPERBUG now on Kindle!

2009-12-26T15:45:00.003-06:00

Constant readers — any of you who are Kindle users can now find SUPERBUG the blog in the Kindle store. I placed it there today; it may take 48 hours for it to propagate through the system.

SUPERBUG the book will of course be on Kindle as well, in March. Stay tuned!

Holiday gratitude, and a brief blogging break

2009-12-24T16:27:00.002-06:00

Constant readers, my warmest greetings for Christmas or whatever winter holiday you celebrate! You are high on the list of the many gifts in my life. Thank you for gathering here and contributing to this truly international community of concern about antibiotic resistance.

I'll be back early next week with news of two fascinating new studies. Snow-dusted (12" and rising here) holiday wishes 'til then.

A plea, and not for me: Support ProMED

2009-12-16T10:39:00.004-06:00

Constant readers, I don't often ask you for anything — OK, I did ask you to consider an advance buy of SUPERBUG, but that's a win-win for all of us, right?

But today I'm going to ask you for something, and I hope you'll trust me that it, too, is a win-win all 'round.

ProMED Mail, the disease early-warning website and listserv of the International Society of Infectious Diseases, is having its annual fundathon. If you have any cash to spare, I would like you to consider making a small donation. Here's why. Here on the net:

We value crowdsourcing. In the disease world, ProMED has been doing that longer and better than anyone. Their network of volunteer spotters — physicians, epidemiologists, animal-health experts, journalists and engaged citizens — has been running since 1994.

We value passion. ProMED has more than 30 expert editors, all significant researchers in their respective specialties, who comb through those crowdsourced reports to find them gems. They all have lives and more than full-time jobs already. And they don't do this for glory: They don't even attach their names to their pieces, just their initials. (Among ProMED aficionados, it's a moment of insider glee to spot the initials and translate them to an important name.)

We value reach. ProMED has more than 57,000 subscribers, each of them a potential contributor, in 187 countries. It runs sub-lists of news with articles relevant to particular parts of the world, volunteer-translated into Portuguese, Spanish, Russian, and French (for West Africa), and also runs sublists in English of articles relevant to the Mekong Basin and to English-speaking East Africa.

More than anything, we value effectiveness — and as a subscriber since sometime in the 1990s, I can testify that ProMED delivers. The listserv is the primary reason that the government of China fessed up to the existence of the international epidemic of SARS in spring 2003, after attempting to conceal its burgeoning outbreak for almost six months. ProMED pried loose that admission simply by posting a note from within its network: a question from a pseudonymous man in southern China that was relayed to an acquaintance in northern California and then to an epidemiologist in Annapolis who sent it to ProMED. (That story is told in my book Beating Back the Devil, and you can read it in this excerpt here.)

That is the power of a network, and that's why ProMED deserves our support.

Antibiotics in animals - a warning from the poultry world

2009-12-15T09:00:00.001-06:00

Constant reader Pat Gardiner guided me to an enlightening post at the website of the agricultural magazine World Poultry that questions the routine use of antibiotics in food animals. It's written by Wiebe van der Sluis, a Netherlands journalist from a farming background, founder of World Poultry and also the magazines Pig Progress and Poultry Processing.

The Netherlands, let's recall, is the place where MRSA ST398 first emerged, and also the place where that livestock-MRSA strain has caused the most serious human cases and triggered the largest changes in hospital infection-control practices. In the Netherlands, swine farmers and veterinarians are considered serious infection risks because of their exposure to animals, and are pre-emptively isolated when they check into hospitals until they can be checked for MRSA colonization.

Van der Sluis takes seriously the tie between the use of antibiotics in animals and the emergence of MRSA:

Although most of the time MRSA is linked to pig production, it is also related to the veal and poultry industry. The industry, therefore, cannot shrug its shoulders and move on if nothing was wrong. In this case it would be wise to redefine the term prudent use of antibiotics. Time is up for those who use antibiotics to cover up bad management, poor housing conditions or insufficient health care. The standard rule should be: Do not use antibiotics unless there is a serious health issue and no other remedy applies. Veterinary practitioners, who usually authorise producers to use antibiotics, should also take responsibility and prevent unnecessary antibiotic use and the development of antibiotic resistance in animals and humans.

It's unusual in the US context so hear someone so immersed in agriculture speak so candidly about antibiotic use. It's refreshing.

Guest Q&A: Dr. Brad Spellberg and RISING PLAGUE

2009-12-14T10:41:00.004-06:00

I'm thrilled today to present another guest blogger: Dr. Brad Spellberg, associate professor of medicine at the David Geffen School of Medicine at UCLA and author of the new book Rising Plague: The Global Threat from Deadly Bacteria and Our Dwindling Arsenal to Fight Them (Prometheus Books). This new book is important reading for anyone concerned, as all of us are here, about the narrowing pipeline for new antibiotics against MRSA and other resistant pathogens. That pipeline problem is something Dr. Spellberg knows well: He is not only a practicing infectious-disease physician, but also a member of the Antimicrobial Availability Task Force of the Infectious Diseases Society of America, the specialty society that produced the "Bad Bugs" reports that I've posted on before.

Below, Dr. Spellberg thoughtfully answers some questions about the difficulties of treating resistant infections and of developing drugs to control them.

From your point of view as a practicing ID physician, why is it so difficult to prevent resistant infections?

It's difficult to prevent all infections period. Not more difficult to prevent infections caused by resistant organisms than any other organisms. However, also difficult to prevent the spread of resistance among bacteria that are causing infections.

So, why is it difficult? People have this crazy belief that hospital acquired infections are the result of sloppy medicine. Not so. They are the result of very sick people with tremendously sophisticated levels of intensive medical care being delivered in a concentrated environment (i.e., a hospital). Crowd a bunch of sick people together with plastic catheters, mechanical ventilators, and nasty bacteria, and such infections are inevitable. What we are learning is that we have to go above and beyond normal to stop these infections from happening. Research is needed on how best to do this. It's not as simple as people think.

You can't stop the spread of the resistance itself. It is inevitable.

You say in Rising Plague that physician misuse and overuse of antibiotics is not the cause of antibiotic resistance. What do you consider the primary driver?

This is by far the biggest misperception among the public. Let's start from first principles. Who invented antibiotics? Who invented antibiotic resistance? When were both invented?

Humans did NOT invent antibiotics. Bacteria did...about 2 billion years ago. And they invented antibiotic resistance at the same time. So, bacteria have been creating and defeating antibiotics for 20 million times longer than humans have even known that antibiotics exist (about 78 years, as the original sulfa compound was developed in late 1931 by Gerhard Domagk). Over the past 2 billion years, bacteria warring among themselves have learned to target virtually every targetable biochemical pathway with antibiotics, and have learned to create defense mechanisms to defeat virtually all such antibiotics. They are already resistant to drugs we haven't even developed yet. It is bacteria that cause antibiotic resistance, not humans.

What humans do, is we apply natural selection when we use antibiotics. We kill off susceptible bacteria, leaving behind already resistant bacteria to replicate and spread their resistance genes.

This may seem like a subtle distinction: We don't create antibiotic resistance, we just increase its rate of spread. But, from the perspective of effective response planning, this is a critical distinction. If inappropriate antibiotic use caused antibiotic resistance, all we would have to do to defeat resistance is never prescribe drugs inappropriately. Unfortunately, that won't work. All antibiotic prescription, even appropriate antibiotic prescription, increases selective pressure, which increases the rate of spread of resistance.

Eliminating inappropriate antibiotic use, and always using antibiotics appropriately is indeed critical, because it will slow the spread of resistance, buying us time to develop new antibiotics. But if 100% of our efforts are focused on antibiotic conservation, all we will achieve is a slowing of the inevitable exhaustion of the antibiotic resource. What is needed is to marry antibiotic conservation with antibiotic restoration. That is, we need new drugs to be developed. Just conserving what we have is not enough.

Why are "antibiotic stewardship" policies not a sufficient remedy for controlling resistance?

See above. Stewardship leads to conservation. That is half the battle, but by itself it will only lead to a slowing of the inevitable exhaustion of the resource.

Furthermore, the initial calls for stewardship were made by people like Max Finland in the late 1940s and early 1950s. This is not a new call. It's more than a half century old. It just doesn't work very well. An analogy is the temptation to say that we don't need condoms to stop the spread of STDs, we just need abstinence. It is true that abstinence will stop the spread of STDs. But, an abstinence-only policy just doesn't work. You've got to have the condoms too. Well, stewardship, by itself, just hasn't worked after more than 60 years of calls for it. It is too hard to change behavior, and the pressures on physicians not to be wrong about their patients' illnesses is too great.

What do you consider the chief impediments to developing newer/better antibiotics?

The two major impediments are: 1) economic, and 2) regulatory.

The primary economic impediment is that antibiotics have a lower rate of return on investment than other classes of drugs. You make a lot more money back on your R&D investment if the drug is taken every day for the rest of the patient's life (e.g. cholesterol, hypertension, dementia, arthritis) than if it is taken for 7 days and then the patient stops because he/she is cured.

The regulatory problem is a startling degree of confusion at the FDA regarding what types of clinical trials should be conducted ot lead to approval of new antibiotics. There has been a total rethinking of antibiotic clinical trials at the FDA over the past 5 years. Right now, companies don't know what trials they are supposed to do to get drugs done, and increasingly the standards are calling for infeasible study designs that simply can't be conducted. This revisionist thinking is being driven by statisticians who know nothing about clinical medicine or patient care. They are asking for things to be done that can't be done to human beings. The balance of clinical and statistical concerns is totally out of whack, and must be restored if this problem is to be solved.

What types of policies are needed to kick-start development of new antibiotics?

Simple. Solutions follow the problems above.

For the economic problem, we need Congress to pass legislation that creates special economic incentives for companies to re-enter the antibiotic R&D market. The return on investment calculation must be changed. Antibiotics are a unique, critical public health need. Congress should recognize this. Examples of programs that would work include increase in funding to scientists (e.g. via NIH) who study bacterial resistance and antibiotic development. Increased small business grants to help translate basic science discoveries to lead compound antibiotics. Tax credits, guaranteed markets, patent extensions, and prizes to serve as pull strategies to help companies improve the return on investment for antibiotics.

For the regulatory problem, Congress needs to stop hammering the FDA into a state of paralysis, where fear permeates every decision to approve a drug. We should be encouraging a balance between statistical concerns and clinical concerns, and we need to restore a sense that the agency is regulating drugs used by physicians for patients, and that trials showing those drugs are safe and effective must be feasible to conduct and relevant to how the drugs will be used in clinical medicine after they are approved.

Book news: SUPERBUG available for pre-order!

2009-12-12T12:29:00.003-06:00

Constant readers: To my complete surprise, SUPERBUG is up on Amazon!

Mind you, the page is almost blank. The cover image has not been added; the flap copy hasn't even been finalized; and my bio is out of date. (For an up-to-date bio, visit my Amazon author page, where posts from here will soon be mirrored.)

Nevertheless, there it is — and at a lovely pre-release deep discount (34%!) too.

I had plans to roll out news about the book over the next two months, but this has scooped me, a bit. So here's the first bit of news, which you'll see confirmed on the Amazon page: We finally decided on a subtitle. So the full title of the book now is:

SUPERBUG: The Fatal Menace of MRSA

Has a nice ring to it, no?

Here's something else this scoops me on: the release date. SUPERBUG will be published on March 23, 2010.

And here's an important detail: My own experience with Amazon orders has been that pre-orders are not only discounted — they also move out from Amazon very quickly as release date approaches. So if you'd like to get a copy of SUPERBUG into your hand as soon as can be, a pre-order is one sure way to do it. (Plus, it makes my publisher happy.)

$17.16, folks. 34% off! How can you go wrong?

Bad news from California: MRSA quadrupled

2009-12-10T09:00:00.000-06:00

Via the Fresno Business Journal and the Torrance Daily Breeze come reports of a new study by California's Office of Statewide Health Planning and Development: Known MRSA cases in the state's hospitals increased four-fold between 1999 and 2007, from 13,000 to 52,000 cases per year.

From the Torrance paper:

The good news is that the percentage of people who die of MRSA has decreased, from about 35 percent in 1999 to 24 percent in 2007. The raw number of deaths, however, more than doubled to about 12,500. (Byline: Melissa Evans)

From the Fresno paper (no byline):

Fresno, Kings, Madera and Tulare counties were among 38 counties in California that had 61 to 80% of patients with staph infections.
Only one county, Sierra, fared worse. Eight-one to 100% of patients ended up with staph infections in that county’s hospitals.
In 1999, Kings and Madera counties were in the 0 to 20% range and Fresno and Tulare counties were in the 21 to 40% range.

100%??

My guest-post elsewhere: Bad news on hospital error rates

2009-12-09T21:59:00.001-06:00

It's been 10 years since the publication of the pathbreaking Institute of Medicine report, "To Err is Human," which for the first time focused policy attention on medical errors. The Interdisciplinary Nursing Quality Research Initiative has been running a two-week special series of posts to mark the occasion, and they very kindly asked me to contribute.

Here's a link to my guest-post, "Hospital Error Rates — Still a Long Way To Go," looking at a recent paper and editorial in the Journal of the American Medical Association that reported very discouraging results in rates of infections in ICUs worldwide. (And, umm, yes, that is what I look like.)

While you're there, please take a look also at another guest post by my good friend Nancy Shute, former staff writer and now blogger for US News & World Report, who discusses the difficulty of speaking up as a patient, based on her own experience in the hospital last summer. It's very worth a read.

NEJM: Antibiotics for pneumonia in H1N1

2009-12-03T14:56:00.003-06:00

The New England Journal of Medicine has been running an open-access blog on H1N1 flu, and they've put up a post on when to give antibiotics to prevent secondary bacterial pneumonia, including MRSA pneumonia, in flu patients.

There's a table of key clinical points to consider, and these important points are made:

For the child or adult admitted to a hospital intensive care unit in respiratory distress, we believe that empirical initial therapy with broad-spectrum antibiotics to include coverage for MRSA, as well as Streptococcus pneumoniae and other common respiratory pathogens, is appropriate.
For the previously healthy child or adult with influenza who requires admission to a community hospital and has features that suggest a secondary pneumonia (Table 1), we would recommend empirical treatment with a drug such as intravenous second- or third-generation cephalosporin, after an effort has been made to prove the association with influenza and to get adequate lower respiratory tract specimens for Gram’s stain and bacterial culture.
If the Gram’s stain suggests the presence of staphylococci or if there is a rapidly progressive or necrotizing pneumonia, an additional antimicrobial agent to cover MRSA is appropriate. ...
We do not believe that initial coverage for MRSA is indicated in all patients who are thought to have secondary bacterial pneumonia.

So, to recap:

Development of apparent pneumonia in the presence of flu should be met with antibiotics that will treat drug-sensitive bacteria, along with a test to show which bacteria are causing the illness.
If staph is present (or the pneumonia appears very serious), then the antibiotics should be upped to one that can control MRSA.
But if the pneumonia is serious enough to send a patient straight to the ICU, then drugs that can quell MRSA should be started right away.

For anyone concerned about pneumonia in the aftermath of H1N1, this is worth bookmarking.

Wednesday a.m.: Congressional briefing on antibiotics in livestock - live-tweeted!

2009-12-01T16:42:00.004-06:00

Folks: On Wednesday 2 December, at 9:30 a.m. EST, Rep. Louise Slaughter (D-NY) will host a Congressional briefing about antibiotic use in food animals. As a reminder, Rep. Slaughter is an MPH and Congress's only microbiologist, and the chief sponsor of PAMTA, the Preservation of Antibiotics for Medical Treatment Act that proposes restricting antibiotic use in animals to therapeutic uses under the guidance of a veterinarian and phases out "growth promotion" with sub-therapeutic doses, which consumes millions of pounds of antibiotics every year, many of them close analogs to human drugs.

Appearing at the briefing along with Rep. Slaughter are leaders of efforts that have produced an important string of reports on antibiotic overuse — the Pew Commission on Industrial Farm Animal Production and the Extending the Cure project of Resources for the Future:

Michael Blackwell, DVM, MPH–former Vice Chair, Pew Commission on Industrial Farm Animal Production; Assistant Surgeon General, USPHS (ret.); Former Dean, College of Veterinary Medicine, University of Tennessee, Knoxville, TN.
Robert Lawrence, MD–Director, The Johns Hopkins Center for a Livable Future, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Ramanan Laxminarayan, PhD, MPH–Senior Fellow, Center for Disease Dynamics, Economics, and Policy, Resources for the Future, Washington, DC
Robert Martin–Senior officer, Pew Environmental Group; former Executive Director, Pew Commission on Industrial Farm Animal Production, Washington, DC
Lance Price, PhD– Director, Center for Metagenomics and Human Health, Translational Genomics Research Institute, Flagstaff, AZ

Here's a post explaining the importance of this issue from the blog of the Center for a Livable Future, a Johns Hopkins University research group that has produced some of the most mportant papers on leakage of antibiotic-resistant bacteria and antibiotic residues from CAFOs ("confined" or "concentrated" "animal-feeding operations" — very, very large-scale farms). And here's some video on the issue from last summer from Lou Dobbs Tonight.

Because the event Wednesday is an informational briefing, not a hearing, I can't find any link for a live webcast. (I'll update if I find one.) But the hearing will be live-tweeted by the staff of the Center for a Livable Future (@LivableFuture) at the hashtag #CLF09. BLOGGERS: They will take tweeted questions toward the end of the hearing, ~10:45 a.m. — use the hashtag.

Antibiotics - the EU pipeline is empty too

2009-11-27T09:00:00.002-06:00

We've talked before about the shrinking number of drugs available to treat MRSA and about the challenges of getting new drugs to market. Well, it's not just a problem in the United States.

A new report from the European Centre for Disease Prevention and Control (ECDC) and the European Medicines Agency (EMEA) — that's the CDC and the FDA of the European Union — analyzes the bench-to-market "pipeline" of new drug development in the EU and finds... not good news. Out of 167 antibacterial agents that are somewhere in the pipeline of development, only 15 look likely to improve treatment of resistant organisms over drugs that already exist — and 10 of those 15 are in early-stage trials and will not come to market anytime soon.

That leaves 5 potential new drugs, for an epidemic of antibiotic resistance that, just in the EU, causes 25,000 deaths and $1.5 billion Euros ($2.27 billion) in extra healthcare spending each year.

(Within that epidemic of resistance, by the way, the single most common organism is MRSA.)

It's worth understanding how the agencies conducted their analysis. When we look for new drugs to treat resistant organisms, we ideally need several things:

a formula or molecule that is new (and not just an improved version of an existing one, because if bacteria have developed resistance against the existing one, they have a head start in developing resistance against the new one)
a new mechanism or target on the bacterial cell, and not an improved version of an existing one (ditto)
evidence that it works in living organisms, and not just in lab dishes (in vivo, not just in vitro)
evidence that it can be given internally, not just topically (necessary for addressing the most serious infections)
and some indication that it is making its way through the regulatory approval process in time to achieve some practical good.

Here's what the EU pipeline looks like:

167 agents in process
90 that have shown effectiveness in vivo
66 that are new substances
27 that have a new target or mechanism
15 that can be administered systemically

If you're wondering whether you should be depressed, the answer is Yes.

... it is unclear if any of these identified agents will ever reach the market, and if they do, they may be indicated for use in a very limited range of infections.

The agencies call for a concerted government effort to turn this around, and ask for quick action because it takes years to get drugs through the pipeline:

...a European and global strategy to address this serious problem is urgently needed, and measures that spur new antibacterial drug development need to be put in place.

This echoes a call that has already been made in this country by the Infectious Diseases Society of America, which has asked for changes in incentives to drug-makers, and has backed what's known as the STAAR Act (STrategies to Address Antimicrobial Resistance). With this latest EU report — which comes on the heels of a US-ER agreement to work cooperatively on resistance — the IDSA is asking for an international commitment to bringing forth 10 new drugs in 10 years, what they are calling 10 x '20.

New pig strain in China

2009-11-26T09:00:00.004-06:00

Via Emerging Infectious Diseases comes the full version of a piece of research I posted on in September that was presented at the London conference Methicillin-resistant Staphylococci in Animals: Veterinary and Public Health Implications. A new MRSA variant — not ST398 — has been spotted in pigs in China.

Luca Guardabassi and Arshnee Moodley of the University of Copenhagen and Margie O'Donoghue, Jeff Ho, and Maureen Boost of the Hong Kong Polytechnic University report that they found a pig-adapted MRSA strain in 16 of 100 pig carcasses collected at 2 wet markets in Hong Kong. By multi-locus sequence typing, the strain is ST9, previously found in pigs in France; by PFGE, they fall into categories that tend to carry the community-strain cassettes SCCmec IV and V.

Here's the bad news: This strain possesses resistance factors that resemble human hospital-associated MRSA more than they do ST398.

Twelve isolates displayed a typical multiple resistance pattern, including resistance to chloramphenicol, ciprofloxacin, clindamycin, cotrimoxazole, erythromycin, gentamicin, and tetracyline. The remaining 4 isolates were additionally resistant to fusidic acid. ... All isolates were negative for Panton-Valentine leukocidin and susceptible to vancomycin and linezolid.

The further bad news, of course, is that this is being found in Hong Kong, adjacent to China, which is the world's single largest producer of pork, raising tens of millions of tons of pig meat per year. Most of the pigs sold in Hong Kong come from the Chinese mainland, not from the SAR. Pig surveillance for MRSA in China is practically non-existent (which is not much of a criticism since it does not exist in the United States, either). A human infection with ST9 has already been recorded in Guangzhou, the province adjacent to Hong Kong.

The question, for this strain as for all MRSA strains in pigs, is what is its zoonotic potential? Here again, the news is not good. According to Maureen Boost, who presented this research at the London conference, the isolates were obtained by the researchers from intact heads from butchered pigs; the researchers took the snouts to the lab and and swabbed them there. Pig snout happens to be a desirable meat in China; it is bought in markets, taken home and made into soup. Boiling in broth would probably kill MRSA bacteria — but home butchering of a pig snout could pass the bug on to the human cutting it up, or to that human's kitchen environment, long before the snout ever got into the pot.

The cite is: Guardabassi L, O'Donoghue M, Moodley A, Ho J, Boost M. Novel lineage methicillin-resistant Staphylococcus aureus, Hong Kong. Emerg Infect Dis. 2009 Dec. DOI: 10.3201/eid1512.090378

"Pig MRSA" in the EU - long-awaited survey

2009-11-26T08:30:00.004-06:00

It's not very likely that people will be eating much pork today — OK, maybe some pancetta in the Brussels sprouts — and that's good, because there's lots of news today about MRSA in pigs.

(In fact, there's a ton of news just this week. Make it stop.)

The European Food Safety Authority has published a long-awaited, European Union-wide survey looking for the presence of MRSA in pigs. Here's the key points: Investigators found MRSA on 1 out of 4 farms where pigs were being raised and in 17 of the 24 EU states. (Two non-member states were included in the analysis.)

Strictly speaking, this is not a survey of MRSA in pigs; the study samples not the pigs themselves, but the dust in pig-raising sheds. The sites were 1,421 breeding farms and 3,176 farms where pig are raised to slaughter age. By far the most common strain was MRSA ST398, though other strains were detected, including some known human strains. The prevalence in various countries went from a low of 0 to as high as 46% of farms. (Highest, in descending order: Spain, Germany, Belgium, Italy, Portugal. The Netherlands, where St398 was first identified, had a prevalence of 12.8%. Countries reporting no MRSA: Bulgaria, Cyprus, Denmark, Estonia, Finland, Hungary, Ireland, Latvia. Lithuania, Luxembourg, Sweden, the United Kingdom, Norway and Switzerland.)

The report closes by recommending comprehensive monitoring of pigs for MRSA, as well as monitoring of poultry and cattle.

About the potential of ST398 crossing to humans, it has this to say:

In humans, colonisation with MRSA ST398 originating from pigs has been identified as an occupational health risk for farmers and veterinarians and their families. Although MRSA ST398 represents only a small proportion of the total number of reports of human MRSA infections in the EU... in some countries with a low prevalence of human MRSA infection, CC398 is a major contributor to the overall MRSA burden.
In most cases, colonisation with MRSA ST398 in humans is not associated with disease, although clinical cases associated with MRSA ST398 have been reported. MRSA ST398 can be introduced into hospitals via colonised farmers and other persons in a region with intensive pig farming. Therefore, MRSA ST398 may add substantially to the MRSA introduced in health care settings. However, it seems that the capacity for dissemination in humans (patient-to-patient transmission) of livestock-origin MRSA, in particular ST398, is lower as compared to hospital-associated MRSA).
... Food may be contaminated by MRSA (including ST398), however there is currently no evidence for increased risk of human colonisation or infection following contact or consumption of food contaminated by ST398 both in the community and in hospital.

Britain's Soil Association, which pressed for the study to be done, has released a statement quoting the food safety agency warning that the testing method may have underestimated MRSA's presence on farms, and warning that if ST398 is not yet in England, it is certainly soon to arrive. Germany's Federal Institute for Risk Assessment also released a statement, admitting that ST398 in German pig stocks is "widespread."

The report is here, executive summary here, and press release here. All well worth reading.

CDC warns of deaths from H1N1 flu + bacterial infections

2009-11-25T18:01:00.002-06:00

Over at CIDRAP, my colleague Lisa Schnirring writes tonight about the CDC's concern over increasing numbers of deaths from bacterial pneumonia in people who have come down with H1N1 flu.

We've talked about this before here. Our concern of course has been MRSA, and there is good evidence that there have been fatal MRSA infections in flu victims. But the primary culprit now is not MRSA but pneumococcus (S. pneumoniae):

Anne Schuchat, MD, director of the CDC's National Center for Immunization and Respiratory Diseases, told reporters at a press briefing that the CDC is seeing an increasing number of invasive pneumococcal disease cases around the country, but the numbers were particularly high in Denver at a time when pandemic H1N1 activity was peaking in the area.
Over the past 5 years the Denver area averaged 20 pneumococcal disease cases in October, but this year the area recorded 58, and most were in adults between the ages of 20 and 59, many of whom had underlying medical conditions.
Health officials expect to see more pneumococcal disease when seasonal flu circulates, but the infections typically strike people who are older than 65. In past pandemics secondary bacterial pneumonia infections, particularly those involving Streptococcus pneumoniae, frequently contributed to illnesses and deaths.

This is particularly troubling and sad because we have good vaccines for pneumococcus, one for adults and a different one for children. Only, people are not taking them: Uptake is only about 25% in high-risk groups and much lower in the general population, despite urgings from CDC and other health advisory boards.

Perhaps it's not surprising that people have not heeded advice to get the pneumococcus vaccine as a protection against flu's worst effects, given that uptake of the flu vaccine itself has been so low. But if you or someone you love is in a high-risk group, it would be a really good idea to rethink that.

Two good reports published elsewhere

2009-11-25T17:37:00.004-06:00

Some holiday reading:

Mike the Mad Biologist, who often blogs about MRSA, has an analysis up about the varying degrees of attention that the Senate and House healthcare reform bills give antibiotic resistance and healthcare infections
And Jacob Goldstein at the Wall Street Journal's WSJHealth blog describes and links to a program at UCLA Medical Center that uses volunteer undergraduate observers to make sure healthcare staff wash their hands. (h/t @ePatientDave)

Community MRSA rates rising, and epidemics converging

2009-11-25T17:35:00.003-06:00

A study published Tuesday in Emerging Infectious Diseases makes me happy, despite its grim import, because it confirms something that I will say in SUPERBUG: Community MRSA strains are moving into hospitals, blurring the lines between the two epidemics.

The study is by researchers at the excellent Extending the Cure project of Resources for the Future, a group that focuses on applying rational economic analysis (think Freakonomics) to the problem of reducing inappropriate antibiotic use. (Here's a post from last year about their work.)

Briefly, the researchers used a nationally representative, commercial (that is, not federal) database of isolates submitted to clinical microbiology labs, separated out MRSA isolates, divided them into whether they originated from hospitals or outpatient settings (doctors' offices, ambulatory surgery centers, ERs), and analysed them by resistance profile, which has been a good (thogh not perfect) indicator of whether strains are hospital or community types (HA-MRSA or CA-MRSA). They cut the data several different ways and found:

Between 1999 and 2006, the percentage of staph isolates from outpatient settings that were MRSA almost doubled, increasing 10% every year and ending up at 52.9%. Among inpatients, the increase was 25%, from 46.7% to 58.5%.
Among outpatients, the proportion of MRSA isolates that were CA-MRSA increased 7-fold, going from 3.6% of all MRSA to 28.2%. Among inpatients, CA-MRSA also increased 7-fold, going from 3.3% of MRSA isolates to 19.8%.
Over those 7 years, HA-MRSA did not significantly decrease, indicating that CA-MRSA infections are not replacing HA-MRSA, but adding to the overall epidemic.

So what does this mean? There are a number of significant aspects — let's say, bad news, good news, bad news.

Bad: CA-MRSA strains are entering hospitals in an undetected manner. That could simply be because patients entering the hospital are colonized by the bug and carry it with them. But it could also be because healthcare staff who move back and forth between outpatient and in-patient settings — say, an ambulatory surgical center and a med-surg ward — could be carrying the bug with them as well.

Good: If they are detected (analyzed genotypically or for drug sensitivity), CA-MRSA strains are less expensive to treat because they are resistant to fewer drugs, and some of the drugs to which they are susceptible are older generics, meaning that they are cheaper.

Very Bad: The entrance of CA-MRSA strains into hospitals risks the trading of resistance factors and genetic determinants of transmissibility and colonization aptitude in a setting where bacteria are under great selective pressure. Several research teams have already seen this: In several parts of the country, CA-MRSA strains have become resistant to multiple drug families.

Is there a response? The work of Extending the Cure focuses on developing incentives that will drive changes in behavior around antibiotic use. These results, lead author Eili Klein told me, call for developing incentives for creating rapid diagnostic tests that will identify not just that a bug is MRSA, but what strain it is, so that it can be treated appropriately and not overtreated.

The results also underline the need for something that is particularly important to me: enhanced, appropriately funded surveillance that will define the true size of the MRSA epidemic and delineate the behavior of the various strains within it. Right now, surveillance is patchy and incomplete, done partially by various CDC initiatives and partially by the major MRSA research teams at academic medical centers. As we've discussed, there is no national requirement for surveillance of patients, and very few state requirements; there is no incentive for insurance companies to pay for surveillance, since it benefits public health, not the patient whose treatment the insurance is paying for; and there is a strong disincentive for hospitals to disclose surveillance results, because they will be tarred as dirty or problematic. Yet to know what to do about the MRSA epidemic, we first have to know the size and character of what we are dealing with, and we do not now.

The cite is: Klein E, Smith DL, Laxminarayan R. Community-associated methicillin-resistant Staphylococcus aureus in outpatients, United States, 1999–2006. Emerg Infect Dis. DOI: 10.3201/eid1512.081341

Antibiotic misuse in animals - one example

2009-11-23T08:22:00.001-06:00

Via the Minneapolis Star Tribune and the excellent blog Fair Food Fight comes the story of two cows, from two Minnesota farms, that have been reprimanded by the US Food and Drug Administration for bringing cows to slaughter that turned out to have been massively overdosed with antibiotics.

From the Strib:

In a rare move, federal officials sent stern warning letters to two central Minnesota dairy farms, which were among only 30 farms nationwide reprimanded so far this year for violating the rules governing how animal drugs can be used.
J&L Dairy, in Clarissa, Minn., sent a dairy cow to slaughter in March, even though it was drugged with 129 times the amount of penicillin allowed under federal regulations.
Another farm, Evergreen Acres Dairy, LLC, in Paynesville, Minn., was warned by the FDA last month, after one of its cows was found to have more than four times the allowed amount for a certain type of antibiotic. Further inspection found that the farm had misused 10 other drugs. (Byline Lora Pabst)

From one of the FDA's reprimand letters, to J&L Dairy of Clarissa, Minn.:

Our investigation ... found that you hold animals under conditions that are so inadequate that medicated animals bearing potentially harmful drug residues are likely to enter the food supply. ... Our investigation found that you routinely administered penicillin G procaine to dairy cows without following the daily dosage amount or dosage amount per injection site as stated in the approved labeling. Your extralabel use of penicillin G procaine was not under the supervision of a licensed veterinarian, in violation of 21 CFR 530.11 (a), and your extralabel use of penicillin G procaine resulted in illegal drug residue, in violation of 21 CFR 530.11(d).

From the other reprimand letter, to Evergreen Acres Dairy of Paynesville, Minn.:

Our investigation ... found that you hold animals under conditions that are so inadequate that medicated animals bearing potentially harmful drug residues are likely to enter the food supply.
...The investigation ... found that you adulterated the new animal drugs neomycin sulfate, sulfadimethoxine oral solution, oxytetracycline injection, oxytetracycline hydrochloride injection, ceftiofur hydrochloride, ceftiofur crystalline free acid, ceftiofur sodium, penicillin G procaine aqueous suspension, florfenicol, tetracycline hydrochloride soluble powder, and tylosin. Specifically, the investigation revealed that you did not use these drugs as directed by their approved labeling. Use of these drugs contrary to their approved labeling is an extralabel use.

There are some important points to make here.

As we've talked about before, many of the antibiotics used in food animals are effectively over-the-counter drugs; farmers can buy them in feed stores and administer them without a veterinarian's supervision. (Putting an end to OTC animal antibiotics is the goal of Rep. Louise Slaughter's legislation, the Preservation of Antibiotics for Medical Treatment Act (PAMTA), supported by the Obama Administration supports; post here.) Without such supervision, it is easier for a farmer to make a mistake in dosing, or to give the drugs too close to animal's slaughter time, so that the drug's don't wash out of the animal's system but remain in its meat after death.

A second important point is that we talk a lot here about the dangers of industrial-scale farming, in which antibiotics are given to animals that are not sick, either in small doses as growth promoters or in treatment-size doses to prevent illness spreading through a flock or herd. Antibiotic misuse has become linked in the public mind with the enormous animal-raising operations known as CAFOs. But both these reprimanded farms were family farms, not CAFOs. These reprimands underline that inappropriate antibiotic use is not a function of farm size — it's a by-product of market pressure.

It's (European) Antibiotic Awareness Day

2009-11-18T08:00:00.000-06:00

UK and EU readers can hug themselves with self-congratulation this morning (OK, admittedly, for you it's afternoon already): It's Antibiotic Awareness Day across the European Union, featuring a slate of public-awareness activities, public-service announcements, educational efforts, and random appearances by the charming little hedgehog above (kicking antibiotics, don't you see). It's all meant to convince people that antibiotics are a precious resource and that misusing them encourages antibiotic resistance.

The campaign is organized by the European Centre for Disease Prevention and Control (the EU equivalent of the US CDC) and is being carried out by an enviably long list of national agencies within the EU. It's accompanied by the publication in the journal Eurosurveillance of an article setting out the challenges of controlling antibiotic resistance across such diverse nationalities and geographies.

There are materials on the site that would be useful for anyone attempting to get the message of antibiotic stewardship across to physicians, family members or friends: There's a fact sheet for the general public, one for physicians and other experts, and one that specifically addresses the temptation to take antibiotics in cases of H1N1 flu.

There's also a short film explaining the genesis of Antibiotic Awareness Day and the basics of antibiotic resistance, and a marvelous set of pull-no-punches short video spots. This one — comparing antibiotics to a lightbulb slowly burning out — is my favorite.

Antibiotic resistance: international news

2009-11-16T22:37:00.003-06:00

Constant readers, we've often talked about MRSA and other resistant pathogens as a global problem (cf. these posts for resistance issues in Europe and these for resistance around the world).

But now there has been formal recognition that resistant bacteria respect no borders. On Nov. 3, the US government and the European Union signed an agreement to form a joint task force to investigate and combat antibiotic resistance. From the Joint Declaration, posted on WhiteHouse.gov:

[We therefore agree}... To establish a transatlantic task force on urgent antimicrobial resistance issues focused on appropriate therapeutic use of antimicrobial drugs in the medical and veterinary communities, prevention of both healthcare- and community-associated drug-resistant infections, and strategies for improving the pipeline of new antimicrobial drugs, which could be better addressed by intensified cooperation between us.

You may not have heard much about it here, but in Europe, this declaration was big news. Here's a story from the Swedish newspaper Arbetarbladet (Sweden currently holds the EU Presidency) and another from the Irish Times. But while it merited barely a blink in the US mainstream media, US nonprofits were deeply involved in the declaration, notably the Infectious Diseases Society of America and the Pew Charitable Trusts:

"Antimicrobial resistance and the lack of new antimicrobial agents to effectively treat resistant infections are problems that no country can deal with alone -- they threaten the very foundation of medical care," said Richard Whitley, MD, FIDSA, president of the Infectious Diseases Society of America (IDSA). "Without effective antimicrobial drugs, modern medical treatments such as operations, transplants, intensive care, cancer treatment and care of premature babies will become very risky if not impossible." Dr. Whitley joined with Javier Garau, MD, president of European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Shelley A. Hearne, managing director of the Pew Health Group in welcoming the multi-country initiative.
..."Antibiotic resistant bacteria respect no political borders, so we must work together to combat them," Dr. Hearne said. "Resistance takes a terrible toll on health worldwide and is measured in lives lost, greater suffering and higher health care costs. One way that U.S. leaders can demonstrate their commitment to solving this issue is by immediately joining the EU in banning non-judicious antibiotic uses in food animal production." (Pew press release)

This fresh focus on the problem of resistance will be sharpened in Europe this week with the celebration of European Antibiotic Awareness Day. (We should be so lucky.) More on that on Wednesday.

Antibiotic-resistant infections: millions in cost to hospitals, families, all of us

2009-11-03T09:25:00.005-06:00

Folks, I mentioned that I'm way behind in working down a stack of great articles. Here's a very good one that I missed when it came out two weeks ago and is well worth your time.

A team from John H. Stroger Hospital (the new location of the iconic Cook County Hospital, public hospital for downtown Chicago) and from the Alliance for the Prudent Use of Antibiotics at Tufts University (headed by Dr. Stuart Levy, dean of antibiotic resistance scholarship in the US) has analyzed the direct and distributed costs of resistant infections, and their results are stunning. They took a random sample of patients seen at the hospital, sorted out a subgroup that suffered from resistant infections, and computed the costs that those infections imposed: in medical costs, increased length of stay, and excess deaths. Those sort of calculations have been done before at other institutions (cf. for instance the excellent work of Susan Cosgrove of Johns Hopkins), but what makes this Chicago study striking is an additional layer of analysis that computes the "social cost" to the families of those infected.

In the study's words:

In a sample of 1391 patients, 188 (13.5%) had [antibiotic-resistant infections]. The medical costs attributable to ARI ranged from $18,588 to $29,069 per patient in the sensitivity analysis. Excess duration of hospital stay was 6.4–12.7 days, and attributable mortality was 6.5%. The societal costs were $10.7–$15.0 million.

(Just to underline: These are almost certainly underestimates of the current problem and its current costs — because to get very solid data, the Stroger team went back in their database to patients who were treated in 2000. That's before the emergence and dominance of CA-MRSA USA300 nationwide, and its subsequent movement into hospitals. Since 2000, the MRSA epidemic has gotten worse.)

An accompanying editorial takes the next step in logic, stressing that if we're not going to work to reduce ARIs because it is good medicine to do so, we should do it because it is critically cost-saving:

...[T]he findings of Roberts et al [11] are significant, making a strong case for both the medical and financial benefits of reducing antimicrobial resistance. This is an important and timely question, considering the national focus on the prevention of health care–acquired infections, a significant proportion of which are caused by antimicrobial-resistant organisms, and the call for institutions to develop antimicrobial stewardship programs. These data should help inform decisions regarding the structure and implementation of health care initiatives designed to improve patient care while controlling unnecessary costs.

The cite for the study is: Rebecca R. Roberts, Bala Hota, Ibrar Ahmad et al. Hospital and Societal Costs of Antimicrobial‐Resistant Infections in a Chicago Teaching Hospital: Implications for Antibiotic Stewardship. Clinical Infectious Diseases 2009 49:8, 1175-1184.

It's World Pneumonia Day

2009-11-02T09:07:00.002-06:00

Readers, we talk all the time here about the unexpected and deadly attack of MRSA pneumonia, both on its own and as a sequela of influenza infection. But we should acknowledge that MRSA pneumonia is part of an epidemic of pneumonia, an under-appreciated disease of severe lung inflammation that takes the lives of 2 million children each year around the world.

Today, Nov. 2, has been declared World Pneumonia Day by an enormous coalition of global health organizations that includes UNICEF and Save the Children. (Mis amigos Latinos sabrán que está hoy también Dia de los Muertos. Fitting, no?) From their press release: "Pneumonia takes the lives of more children under 5 than measles, malaria and AIDS combined. The disease takes the life of one child every 15 seconds, and accounts for 20% of all deaths of children under 5 worldwide."

World Pneumonia Day is being marked by events around the globe (here's a clickable map) and by the release of a World Health Organization report, the Global Action Plan for Prevention and Control of Pneumonia. The plan has three main goals, aimed at the recourse-poor countries where most pneumonia deaths occur:

promote breastfeeding to ensure children's nutrition and good immune status
protect immunity by guaranteeing the distribution in the developing world of the pneumonia vaccines we take for granted in the industrialized world, against Haemophilus influenzae and Strep pneumoniae (pneumococcus)
treat children when they need it by making sure that there is adequate, local primary care and — important for our purposes especially — also making sure that antibiotics are used appropriately, but not overused.

The international organization GAVI (formerly known as the Global Alliance for Vaccines and Immunization, now going just by its acronym) has announced plans to immunize 130 million children worldwide against pneumonia and other diseases by 2015.

I want to underline that pneumonia is of interest to us for several reasons: not just because we are concerned for MRSA pneumonia, but also because we are in the midst of the H1N1 pandemic, and as we have talked about before, bacterial infections appear to be playing a role in a significant percentage of the deaths. There is no MRSA vaccine, but there are Hib and pneumo vaccines, which might have prevented some of those deaths. So increasing the administration of pneumonia vaccines could affect the course of this pandemic right now, as well as the fates of children all over the world who have not contracted this flu but will be in danger of bacterial pneumonia in the future.