14 September 2010

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

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.

08 September 2010

Antibiotic resistance: Scandinavia gets it

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.

02 September 2010

Every once in a while: Some stuff about me

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.)

31 August 2010

On the road this week, and a reading rec

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.

26 August 2010

New CDC flu numbers: This may not go well

(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)

20 August 2010

Friday comic relief

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

NDM-1: The World Health Organization warns governments

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).

18 August 2010

NDM-1: The early warnings

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.

13 August 2010

More on NDM-1

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.

11 August 2010

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

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

10 August 2010

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

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

04 August 2010

Unintended consequences: C. diff death after extended Lyme treatment

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.

02 August 2010

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

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

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.

31 July 2010

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

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.

29 July 2010

Advice for science writers, from science writers

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.")

27 July 2010

Whooping cough: Back, with a vengeance

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 Ch├ívez 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.)

21 July 2010

Hospitals want patients to eat antibiotic-free meat

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.)

20 July 2010

Hi, I'm back.

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.

07 July 2010

Antibiotic use in animals: The feds move, a little

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.

28 June 2010

Past time to pay attention to polio

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.

24 June 2010

News break: CDC alert on imported novel resistance

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.

17 June 2010

Pan-resistant?? The rise of Acinetobacter

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.