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).

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

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

Warning on ST398: Monitor this now

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.

Community MRSA rates rising, and epidemics converging

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

H1N1 flu and swine surveillance - more relevance for MRSA

Constant readers, you probably know that yesterday the World Health Organization declared the first flu pandemic in 41 years. I want to point out for you a side issue in the H1N1 story that has great relevance for MRSA, especially ST398.

As described in this article I wrote last night for CIDRAP, three medical journal articles have now pointed out that the virus, or its major components, could have been recognized in swine months to years ago. We missed it, though, because there is so little regular surveillance in pigs for diseases of potential importance to humans. As the authors of the most recent article, in Nature, said yesterday: "Despite widespread influenza surveillance in humans, the lack of systematic swine surveillance allowed for the undetected persistence and evolution of this potentially pandemic strain for many years."

This is important for our purposes because we know that we are in the same situation with MRSA ST398: The strain was first spotted in France, and has been a particular research project in the Netherlands, but has been found pretty much wherever researchers have looked for it, throughout the European Union, in Canada, and most recently in the United States. All told, though, the scientists concerned with it are still a small community; there is no broad surveillance looking for this bug.

And that's a problem, for MRSA, for influenza, and for any number of other potentially zonotic diseases: We cannot anticipate the movement of pathogens from animals to humans if we don't know what's in the animals to start with. That's the argument behind the "One Health" movement, which has been arguing for several years now for including veterinary concerns in human health planning. (The human health side would probably say that the animal health side just wants more money. This is also true, which does not make it unimportant.)

To understand the need to look at animal health in order to forecast threats to human health, you can't do better than the map I've inserted above (because Blogger, annoyingly, won't let me put it below). It has appeared in various forms in various publications for about 10 years but originates I think from the IOM's Emerging and Reemerging Diseases report in the early 90s. (This iteration comes from the One Health Initiative website.) It depicts the movement of new diseases from animals to humans over about 30 years. It's up-to-date through SARS and through the 2003-05 movement of H5N1 avian flu around the world. I'm sure H1N1 will be added soon. How many of those outbreaks could we have shortcircuited if we had been warned of their threat in good time?

Infections rise, but hospital budgets - and infection control - shrink

Bad news from the Association of Professionals in Infection Control and Epidemiology (APIC): In a survey of almost 2,000 of their 12,000 members, 41% say that their hospitals' infection-prevention budgets have been cut due to the down economy.

According to the survey, conducted March 2009 and released Tuesday morning:

Three-quarters of those whose budgets were cut experienced decreases for the necessary education that trains healthcare personnel in preventing the transmission of healthcare-associated infections (HAIs) such as MRSA and C. difficile.
Half saw reductions in overall budgets for infection prevention, including money for technology, staff, education, products, equipment and updated resources.
Nearly 40 percent had layoffs or reduced hours, and a third experienced hiring freezes.

As we know here, there are (by CDC estimate) 1.7 million hospital-acquired infections and 99,000 deaths as a result of them, each year. These are numbers we are supposed to be trying to reduce. That is going to be less likely if less money flows toward what may already be an underfunded goal:

A third of survey respondents say that cuts in staffing and resources have reduced their capacity to focus on infection prevention activities.
A quarter of respondents have had to reduce surveillance activities to detect, track and monitor HAIs.

Disturbingly, at a time when electronic health records are such an important part of the health-reform debate, "Only one in five respondents have data-mining programs – electronic surveillance systems that allow infection preventionists to identify and investigate potential infections in real time." (APIC press release)

The full report is here.

MRSA reductions in ICUs - good news, but qualified

Constant readers, you will no doubt have seen the overnight news about a paper by CDC authors in the Journal of the American Medical Association, reporting a significant decline in catheter-associated bloodstream infections (known by the uncatchy acronym CLABSIs, and yes, people pronounce it "klab-seez") in intensive care units.

Our results show that the 6 most common adult ICU types reporting central line–associated BSIs to the CDC, which together account for 96% of all reported MRSA central line–associated BSIs among studied ICU types, have experienced declines of 50% or more in the incidence of MRSA central line–associated BSI since 2001. This means that the risk of primary MRSA bloodstream infections among patients with central lines in these ICUs has substantially decreased in recent years.

First, let's stipulate that any reduction in healthcare-associated infections is good, good news.

Having said that, let's drill down into the paper a bit. Because in some of the coverage last night and this morning, this paper is being represented as "Hooray, the MRSA problem is over," and that's an over-reaction. Here are some reasons why.

The data come from several overlapping CDC databases: the National Nosocomial Infections Surveillance system (NNIS) and the National Healthcare Safety Network (NHSN). The NNIS existed from 1970 to 2004; there was a data gap in 2005, and the NHSN sprang up in 2006. There were 300 hospitals in 37 states reporting to the NNIS when it shut down, and in 2007 there were 518 reporting to the NHSN, many of which joined that year as a result of new mandatory HAI reporting in New York, Colorado and South Carolina. Participation in either database was/is voluntary.

The CDC analysis abstracts data from the reports to those systems for the years 1997-2007. But, as you can guess from those numbers above, the data does not cover all 7,500 US hospitals; and because it is more weighted to certain states, it does not represent a nationally representative sample. In addition, hospitals came into the system(s) during the study, and also dropped out; an accompanying editorial estimates that only 6% of the 599 hospitals in the study reported data for all 11 years.

Second, it's important to note that all CLABSIs went down: MRSA infections, drug-sensitive staph (MSSA) and other organisms. So something is going on — but it is not MRSA-specific. Optimistic interpretation: Enhanced infection control in hospitals is suppressing all HAIs. Pessimistic interpretation: Enhanced scrutiny, in the states that account for the most additional hospitals, is negatively affecting HAI reporting. Can we distinguish which? Probably not. On the one hand, CLABSIs started trending down in 2001, before the earliest mandatory reporting legislation became effective. On the other hand, the study doesn't/can't associate declines in CLABSIs with any specific interventions — so it is not possible to know from this study whether one particular strategy was responsible for this decline.

Third, to put the study focus in context, MRSA accounts for only about 7% of CLABSIs; according to the paper, it is not those infections' most common causative organism. And CLABSIs do not account for the largest proportion of MRSA HAIs; according to a 2007 paper, they fall third on the list behind nosocomial pneumonia and septicemia.

Fourth, since it is abstracted from a hospitals data base, this study doesn't address community MRSA infections — and there are some scientists in the family of MRSA researchers who would insist that it is the increasing prevalence of community infection that is the true driver of the MRSA epidemic.

So: Decreased MRSA HAIs, good news. Reasons, unfortunately unclear. Significance, possibly less than the headlines this morning maintain. But whatever it is that those hospitals were doing, let us hope they keep doing it.

The cite is: Burton, DC, Edwards, JR, Horan, TC et al. Methicillin-resistant Staphylococcus aureus Central Line-Associated Bloodstream Infections in US Intensive Care Units, 1997-2007. JAMA. 2009. 301(7): 727-36.
The accompanying editorial is: Climo, MW. Decreasing MRSA Infections: An End Met by Unclear Means. JAMA. 2009. 301(7)772-3.

Hospital MRSA - taking local action

If you follow hospital-acquired infections, you know there's enormous debate nationally over the best strategies to use: "search and destroy" versus targeted surveillance; guidelines from SHEA, APIC, CDC, or elsewhere. The competing assertions and the lack of clarity can be dizzying.

Here's news though of one local area that has decided to cut through the fog. A private healthcare organization, state universities and a state hospital association have teamed together to create the South Carolina Healthcare Quality Trust, a partnership that says it will test evidence-based best practices and use IT tools to rapidly distribute them to the 60+ smaller hospitals in the state.

There's not a lot of detail up yet about what the trust plans, so let's applaud the effort while reserving judgment until we see what strategies they choose to test and why. Meanwhile, though, here is the announcement from Health Sciences South Carolina, which is a collaborative of several universities, and a FAQ; a story from the national publication Modern Healthcare; and one from the state newspaper, the Columbia State.

New newspaper series on HA-MRSA

The Seattle Times this morning launched an three-day investigative project on incidence of HA-MRSA in Washington State that is worth reading.

As readers here already know, MRSA is not a reportable disease, and there are no diagnosis codes that directly correspond to MSRA that make infection or death easily trackable through hospital records or death certificates. The Times' team came up with some innovative data-drilling techniques and apparently did a massive amount of number-crunching to come up with the incidence estimates that underpin their reporting. They use those to challenge hospitals' reluctance to undertake surveillance and treatment that would wipe out MRSA on colonized patients and thus reduce the likelihood of MRSA infecting those patients or spreading to others via healthcare workers who neglect infection control. (NB, Michael Berens, the series' co-author, did a huge project on nosocomial infections when he was at the Chicago Tribune a number of years ago.)

I am puzzled by one thing I am seeing on the story's web page — one of the items in the break-out box that sums the story up very quickly to attract eyeballs to it. It says: "About 85 percent of people infected with MRSA get the germ at a hospital or other health-care facility. " That figure doesn't make sense to me; it sounds as though it is a mis-translation of the CDC finding a year ago (in the Klevens JAMA paper) that approximately 85% of invasive cases of MRSA have hospital-associated risk factors. Constant readers will remember that estimate has been challenged by researchers on community MRSA, who believe that CA-MRSA accounts for a much larger proportion of the current epidemic than has been acknowledged, and think that the wide spread of the community strain is the actual driver of the overall epidemic. I can't see where in the text the Times team has done the math to support that assertion, so if anyone else spots it, or knows the reference it comes from, please let me know.

Much new news on hospital-acquired infections

There's a ton of new, and conflicting, findings on prevention and detection of hospital-acquired MRSA and other infections.

First: Today, in the journal Infection Control and Hospital Epidemiology, three researchers from Virginia Commonwealth University add to the ferocious debate on "search and destroy," the colloquial name for active surveillance and testing: that is, checking admitted patients for MRSA, isolating them until you have a result, and and if they are positive, treating them while continuing to isolate them until they are clear. "Search and destroy" has kept in-hospital MRSA rates very low in Europe, and has proven successful in some hospitals in the United States; in addition, four states (Pennsylvania, Illinois, California and New Jersey) have mandated it for some admitted patients at least. Nevertheless, it remains a controversial tactic, with a variety of arguments levelled against it, many of them based on cost-benefit.

Comes now Richard P. Wenzel, M.D., Gonzalo Bearman, M.D., and Michael B. Edmond, M.D., of the VCU School of Medicine, to say that the moment for MRSA search and destroy has already passed, because hospitals are now dealing with so many highly resistant bugs (Acinetobacter, vancomycin-resistant enterococci (VRE), and so on). They contend that hospitals would do better to pour resources into aggressive infection-control programs that broadly target a spectrum of HAIs.

The abstract is here and the cite is: Richard P. Wenzel, MD, MSc; Gonzalo Bearman, MD, MPH; Michael B. Edmond, MD, MPH, MPA. Screening for MRSA: A Flawed Hospital Infection Control Intervention. Infection Control and Hospital Epidemiology 2008 29:11, 1012-1018.

Meanwhile, the US Government Accountability Office recently released a substantive examination of HAI surveillance and response programs, in states and in hospitals, that looks at:

• the design and implementation of state HAI public reporting systems,
• the initiatives hospitals have undertaken to reduce MRSA infections, and
• the experience of certain early-adopting hospitals in overcoming challenges to implement such initiatives. (from the cover letter)
  

The report is too thick to summarize here, but here are some key points:

• No two places are doing this the same way — which means that data still does not match state to state
• Experts are still divided about how much MRSA control is necessary
• Hospitals that have undertaken MRSA-reduction programs have taken different paths
• But MRSA control does work: It does reduce in-hospital infections, but at a cost.

This report is an important bookend to an earlier GAO report from last April that explored the poor state of MRSA surveillance nationwide. Read it if you wonder why we don't really know how much MRSA - in hospitals or in the community - we have.

I am stillworking my way through the new Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals, released a week ago by a slew of health agencies (Joint Commission, CDC, et al.) and health organizations (American Hospital Association, ACIP, SHEA, IDSA et al.), to see how much the MRSA strategies have actually changed. If anyone has any comments, please weigh in!

Five-fold increase in flu+MRSA deaths in kids

I have a story up this evening at CIDRAP News about a new paper in the journal Pediatrics that analyzes the incidence of child deaths from pneumonia caused by the combination of MRSA and flu, a sad and scary development that we've talked about here, here and here.

(NB: CIDRAP News is the original-reporting and news-aggregation arm of the Center for Infectious Disease Research and Policy at the University of Minnesota, an infectious disease research center headed by noted epidemiologist Michael Osterholm, PhD. I have a part-time appointment there. CIDRAP News is the best-read infectious-disease website you have never heard of, with about 10 million visitors a year, and is a notable resource for news on seasonal and pandemic flu, select agents and bioterrorism, and foodborne disease.)

It is bad netiquette and not fair use to reproduce another publication's entire story here, even if I wrote it. Here though are the highlights:

• 166 children died of influenza in the past three seasons (2004-05, 2005-06, 2006-07) according to 39 states and 2 local health departments (86 this year in preliminary reporting)
• The proportion of deaths from bacterial co-infection rose each year, from 6% to 15% to 34%, a five-fold increase
• Almost all of the bacterial co-infections were staph; 64% of them MRSA
• The rapid rise in MRSA colonization (from 0.8% of the population in 2001 to 1.5% in 2004 — that's more than 4 million people) may be playing a role
• And, some of these deaths could have been avoided if children had had flu shots — but overall, only 21% of under-2s and 16% of 2- to 5-year-olds get the two shots they need to be fully protected against flu.
  

Please click through to CIDRAP for more.

The cite is: Finelli L, Fiore A, Dhara R, et al. Influenza-associated pediatric mortality in the United States: increase of Staphylococcus aureus coinfection. Pediatrics 2008;122:805-11.

Not-reimbursing hospitals for MRSA: The reaction

You'll remember that early in the summer we talked about the proposal by the Center for Medicare and Medicaid Services to cease reimbursing hospitals for the additional care of a patient that is required when a hospital gives a patient a nosocomial infection. CMS has been debating whether to include several types of hospital-acquired infection in the 2009 iteration of its "never event" no-reimbursement list. (CMS has not announced its final choices.)

Healthcare's reaction has been, hmmm, not positive. At The New Health Dialogue, Joanne Kenen captures the reactions, many of which run along the lines of "infections are inevitable because patients are so sick." But she's also found a marvelous (and appalling?) argument that goes, more or less, "Preventing infections will be more costly, not less, because hospitals will introduce additional procedures to protect themselves."

This recalls the intriguing and dismaying suggestion in JAMA a few weeks ago that "search and destroy" active surveillance is driven less by wanting to halt in-hospital transmission and more by hospitals wanting to build a case that patients brought the infection with them.

Antibiotic resistance in food animals all across Europe

Via a journal that's new to me — the Acta Veterinaria Scandinavica, the open-access journal of the Veterinary Associations of the Nordic Countries — comes an amazing review of the prevalence of antibiotic resistance in cattle in 13 European countries. Based on 25,241 isolates collected over three years, Denmark, Britain, the Netherlands, Norway, Sweden and Switzerland do well, but "many isolates from Belgium, France, Italy, Latvia and Spain were resistant to most antimicrobials tested."

Most resistant pathogen: E. coli. MRSA is present as well:

Of major concern is the level of resistance to oxacillin and 3rd generation cephalosporins (i.e. ceftiofur) in S. aureus. The prevalence of oxacillin resistance in Spain (3.7%) and France (8.3%) and the resistance towards cephalosporins in Spain (0.9% in 2004) and France (4.2% in 2002; 1% in 2003) indicate the presence of methicillin resistant S. aureus (MRSA) in these two countries.

The authors ascribe the differences among countries to different patterns of antimicrobial use by veterinarians and stress that it is time for veterinarians to begin using measurements of local resistance patterns (in human medicine, an "antibiogram") before prescribing. Cite coming when the Acta site is updated. UPDATE: The paper is here; cite is: Hendriksen, RS et al. Prevalence of antimicrobial resistance among bacterial pathogens isolated from cattle in different European countries: 2002-2004. Acta Veterinaria Scandinavica 2008, 50:28doi:10.1186/1751-0147-50-28.

I wasn't aware that this same set of authors (Hendriksen, RS et al.) just a few weeks ago published a similar review of antimicrobial resistance in pigs in Europe. It looks at several bacterial species in pigs, but unfortunately for our purposes, no S. aureus.

Child deaths from flu + MRSA

Steve Smith of the Boston Globe (who is really good, and I say that as someone who used to compete against him) has a story up regarding state and national concern over children's deaths from MRSA pneumonia. There have been two such deaths in Massachusetts this year. These are the sort of deaths that make headlines, as they did last October with the death of 17-year-old Ashton Bonds in Virginia: The pneumonia is very fast-moving and very destructive of lung tissue, and young children have died from it in less than 24 hours.

The CDC is concerned about this: Twice in two years (last May, blogged here, and last January), the agency pushed out an advisory to state health departments, asking them to report any children's deaths in which flu played a role. Surveillance for pediatric flu deaths is a relatively new thing for the CDC — the agency set up a system after the bad early flu season of 2003-04, in which more than 150 children died — so there is relatively little history to draw on. But MRSA has played a role in child deaths in each of the past three years, according to that January bulletin:

From October 1, 2006 through September 30, 2007, 73 deaths from influenza in children were reported to CDC from 39 state health departments and two city health departments. Data on the presence (or absence) of bacterial co-infections were recorded for 69 of these cases; 30 (44%) had a bacterial co-infection, and 22 (73%) of these 30 were infected with Staphylococcus aureus.

The number of pediatric influenza-associated deaths reported during 2006-07 was moderately higher than the number reported during the two previous surveillance years; the number of these deaths in which pneumonia or bacteremia due to S. aureus was noted represents a five-fold increase. Only one S. aureus co-infection among 47 influenza deaths was identified in 2004-2005, and 3 co-infections among 46 deaths were identified in 2005-2006. Of the 22 influenza deaths reported with S. aureus in 2006-2007, 15 children had infections with methicillin-resistant S. aureus (MRSA).

Among MRSA researchers, concern over these necrotizing pneumonia cases has been growing for a few years. Some surveillance suggests that such cases may be increasing, though that could be an issue of, "once you start looking for something, you find it." And the cases are undeniably severe: 56% of children with MRSA pneumonia die, according to a 2007 paper.

But at leaast some of those deaths may be avoisable — or would be if doctors in the community were more attuned to the possibility of MRSA. In a poster at last autumn's ICAAC meeting (first author AJ Kallen) CDC researchers reported thay reviewed charts of all the children admitted with a stah infection at Atlanta's three children's hospitals during the 2006-07 flu season. There were 53 cases of Staph aureus pneumonia; 22 of the children saw a physician an average of 3.5 days before being admitted to the hospital, and THREE of them got drugs that would work against staph.

And yes, you read that right: Active case-finding in Atlanta in 2006-07 found 53 cases of flu-related staph pneumonia; 22 of them, according to the paper, were MRSA. But from the entire country during 2006-07, according to the advisory quoted above, the CDC received reports of 22 flu/staph pneumonias, 15 of them MRSA. Which suggests that flu/MRSA pneumonias in children are more common than current surveillance reveals.

"Leaky" hospitals redux: When HA is CA

The CDC work below and several other papers published recently attribute a good proportion of CA-MRSA to hospital strains that have left the institution in a colonized patient and sickened that patient at some point post-discharge. But several papers presented at the annual meeting of the Society for Healthcare Epidemiology of America underline that MRSA traffic is two-way: Community strains can enter the hospital and cause outbreaks there as well.

Cases in point:

• Between 2004 and 2007, the Medical University of South Carolina in Charleston identified 272 hospital-acquired infections that were caused by USA300, the dominant CA-MRSA clone. That's 21.3% of all HAIs in that hospital in those years. (Lead author K Hardman)
• At Johns Hopkins University in Baltimore, nine out of 757 patients admitted to the pediatric intensive care unit became colonized or infected with MRSA 48 hours or longer after they were admitted. Six of the nine were found to have USA300, and one developed invasive MRSA disease. (Lead author AM Milstone, MD)
• And at New York-Presbyterian Hospital, a 5-day-old baby who had not yet left the hospital became infected with USA300, the first casualty in a complex outbreak involving several MRSA strains that eventually comprised 21 infants (12 colonized and nine with infection; 14 of the 21 with USA300) and 10 mothers (five infected Caesarean incisions, two with breast abscesses, two with mastitis and one with a skin infection; six out of 10 with USA300). (Lead author Jean-Marie Cannon, RN)
  

New news on invasive MRSA rates: headed down?

I am at the annual conference of the Society for Healthcare Epidemiology of America, where authentic news was released Sunday, in a very quiet way.

Last fall, a team of authors from the Centers for Disease Control and Prevention published a paper in the Journal of the American Medical Association that for the first time estimated the burden of invasive MRSA disease in the United States. Using data from the Active Bacterial Core Surveillance System — which comprises nine sites around the country and takes in about 14 million people — the team estimated that the annual incidence of invasive MRSA in the US is 94,360 cases, including 18,650 deaths. In an important (and to some researchers controversial) contribution to defining MRSA disease, the team also estimated that 13.7% of the invasive infections were community-associated, 26.6% were hospital-acquired (which they called "hospital-onset"), and by far the largest proportion, 58.4%, were a new category they called "hospital-acquired, community-onset" — the patients acquired the bug while in the hospital, but did not develop disease until after they were discharged. (Cite: Klevens RM et al., Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA, 2007 Oct 17;298(15):1763-71. Full text here.)

The important event Sunday was the first release of an update to that data, adding a second year of analysis. The news: Hospital-acquired infections declined in a small but significant way, by 8.1% — though community-associated and community-onset cases did not change.

The original paper analyzed data from July 20o4, when the ABC system expanded from a pilot program to the full nine sites, through December 2005. The update both reslices that data and adds fresh numbers: It compares calendar year 2005 to calendar year 2006. It finds small downward trends as well in community-onset and community-associated cases, but judges those trends not statistically significant. But Dr. Scott Fridkin, who presented these numbers and was an author on last fall's paper, said the dip in nosocomial cases is statistically robust and a true decline, though adding a third year of data will make the analysis yet more solid.

The decline is intriguing and raises the question: If infection-control interventions in hospitals are pushing down rates of hospital-acquired cases, then why are "hospital-acquired/community-onset" cases not down as well?

As usual with conference papers, the abstract is not online; the CDC says it will be posted today and I'll update when they do. (NB: The data presented at the conference is actually an update of the data in the abstract, and so when the abstract goes up the numbers will not match; the decline presented today is a few percentage points smaller, due to a re-cut of the data after the abstract was written.)

UPDATE 8 April 08: The abstract is now online here.

(Financial disclosure: I am at SHEA for book research and to participate in a session on interactions between researchers and media. In exchange for that session, the organization paid my airfare.)

CA-MRSA increasing in Denmark

Again from the annual meeting of the Society for General Microbiology, a report that CA-MRSA cases are rising in Denmark, a country with a very low incidence rate of HA-MRSA — about 1% of isolates — thanks to aggressive screening of any patient who has been treated abroad as well as any health care worker who has worked outside the country.

But a team from the Statens Serum Institut in Copenhagen says that is now changing as CA-MRSA moves into the country. From an SGM press release:

"We have managed to hold the frequency of MRSA cases down to under one per cent in Denmark for over 30 years. But in 1997 we recognised the first cases of community acquired MRSA, a new strain independent of hospital and nursing home contacts, in a young adult and two families in a rural town", says Professor [Robert] Skov [of Statens]. "From the families we traced the superbug being transmitted through a kindergarten, a school, a factory and a farm. Between 1999 and 2006 the number of community acquired MRSA infections increased from 11 to 175 a year, making up more than 22% of all MRSA infections, as a rising proportion."

As is commonly the case, the paper presented at the SGM is not online. The press release was carried by the site Medical News Today. It contains no details on whether the cases were identified as CA-MRSA by risk factor or by microbiology, and therefore doesn't answer the obvious question of whether they are truly CA-MRSA, or hospital-acquired/community-onset HAIs.

However: A 2005 paper on which Skov was an author did include typing results, and suggests that Denmark now is seeing cases of a new MRSA type, similar (allowing for the vast difference in scale) to what has happened in the US since the 1990s. From the abstract:

Comparison of the 45 community-onset MRSA (CO-MRSA) infections with the 36 hospital-acquired MRSA (HA-MRSA) infections showed several striking contrasts. Most CO-MRSA were recovered from skin and soft tissue infections caused by isolates carrying the Panton-Valentine leucocidin toxin genes, and the majority (84%) of isolates belonged to a single clonal type, ST80-IV, which has been found in the community in other European countries. Clone ST80-IV could be traced in Denmark back to 1993. ST80-IV was rarely found in HA-MRSA infections.

The paper is Faria, NA et al. Epidemiology of Emerging Methicillin-Resistant Staphylococcus aureus (MRSA) in Denmark: A Nationwide Study in a Country with Low Prevalence of MRSA Infection. J Clin Micro April 2005, 43 (4) 1836-1842. The abstract is here.

CA-MRSA — not just a US problem

One of the mysteries of MRSA research has been the apparent difference in MRSA prevalence in different countries. Hospital-associated MRSA is a well-understood foe in Europe, but identification of CA-MRSA is infrequent. So is CA-MRSA actually less common in other countries, or is that an artifact produced by less surveillance there or more awareness here?

A new journal sheds some light on the question, and also sounds a warning. A team from University College-London's Centre for Infectious Disease Epidemiology analyzed data that are easily available in the UK because the country has a national healthcare system: "hospital episode statistics" (hospital admissions by primary diagnostic code) from 1989 to 2004. The team chose the codes that would indicate admissions for a variety of community-onset staph-related diseases: septicemia, pneumonia, bone and joint infections, and an array of skin and soft-tissue infections.

What they found: Over those 15 years, admits for staph septicemia, pneumonia and scalded-skin syndrome rose 5-fold; abscesses and cellulitis, 3-fold, and bone and joint infections, 1.5-fold. These were much larger increases than in the only national surveillance system which collects voluntary reports just of Staph bacteremia and showed a 2.5-fold increase from 1990 to 2004.

Because the study is based on ICD-9/ICD-10 codes, it contains no microbiological information. However, the authors point out that the invasive diseases captured by the codes are associated with PVL toxin, which in turn is associated with CA-MRSA more than HA-MRSA or MSSA. They say:

We identified a previously undescribed but major increase in pathogenic community-onset staphylococcal disease over the past 15 years. These trends are of concern given the international emergence of invasive community-onset staphylococcal infections.

The paper has been published ahead of print by Emerging Infectious Diseases. The cite is: Hayward A. et al. Increasing hospitalizations and general practice prescriptions for community-onset staphylococcal disease, England. Emerg Infect Dis. 2008 May; [Epub ahead of print]

Typing and fingerprinting: Who pays?

More on the issue of doing more microbiology to track the epidemiology of CA-MRSA (raised in an exchange below between me and Medifix, to whom many thanks for being my first commenter!). In my slog through the endless and growing MRSA literature, I came across a paper that poses the problem much better than I did.

In Use of Routine Wound Cultures to Evaluate Cutaneous Abscesses for Community-Associated MRSA (Annals of Emergency Medicine, July 2007; cite here, no abstract), Fredrick Abrahamian and Sunil Shroff of UCLA School of Medicine say that cultures and susceptibility testing are not always necessary. The tests might not be needed, for instance, if a skin/soft-tissue infection suspected of being MRSA is going to be incised and drained without antibiotics being prescribed; or if antibiotics are going to be prescribed, but physicians already know local susceptibility patterns and plan to order a drug that will provide coverage. In both cases, having additional information about the strain infecting the patient is not going to make any difference to the patient's treatment.

That information will make a difference to understanding the local, regional, national epidemic. But as Abrahamian and Shroff say: "One must determine if it is ethical to make an individual pay the cost of a test for a perceived public health benefit."

The obvious answer is to say the CDC should do it — they are after all the arbiters of population-level public health. Only, you know, their budgets have been being cut...

Yes, it is everywhere

Via the journal Emerging Infectious Diseases, a report from a multi-country European team that surveyed CA-MRSA isolates from around the world to determine their ability to produce Panton-Valentine leukocidin, the potent toxin blamed for CA-MRSA's unique ability to cause eruptions on healthy-appearing skin.

Deep-seated infections due to PVL-positive S. aureus can be extremely severe. For example, necrotizing pneumonia carries a mortality rate close to 75%.

Research published in 2003 found that some clones of CA-MRSA were "continent-specific," confined to some extent to particular locations or countries. That appears no longer to be the case.

The ST1 clone USA400 is now detected in Europe and Asia. Some PVL-positive clones, such as ST1 and ST30, can now be considered pandemic, as they are detected in America, Europe, and Asia. Second, on a given continent, PVL-positive CA-MRSA have spread from country to country. For instance, in Europe, PVL-positive CA-MRSA were recently detected in Slovenia, Romania, and Croatia. Third, new PVL-positive CA-MRSA clones are emerging in strains with different genetic backgrounds. While most of the clones described in 2003 by Vandenesch et al. (4) had an agr3 background, the newly described clones are agr1 or agr2. Fourth, PVL-positive CA-MRSA, which were initially susceptible to most antistaphylococcal antimicrobial agents, have acquired new antimicrobial resistance determinants, to gentamicin and ofloxacin, for instance.

The isolates were gathered between 1999 and 2005 and sent to the French National Reference Center for Staphylococci, where the work for this paper was conducted. Yes, 2005. That gap between the obtaining of the isolates adn this analysis underlines one more time the critical need for comprehensive national and global suveillance to track MRSA's movement and evolution. If we don't know where it is, or how it is changing, how can we begin to talk about control?

Link to the full-text paper here.