Maryn McKenna

Journalist and Author

NDM-1: The World Health Organization warns governments

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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).

News break: Developing-world drug resistance

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

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

From the report’s preface:

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

It calls out a sustained lack of leadership:

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

It recommends 4 specific steps:

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

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

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

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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.

[Read more…]

Warning on ST398: Monitor this now

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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

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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

Decolonization: disappointing news

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I know that many of you who are MRSA patients, especially with recurrent infections, are especially interested in the issue of decolonization, the grueling regimen of antibiotic nasal gel (containing mupirocin; usually sold as Bactroban) combined with body washes with chlorhexidine (Hibiclens) that is believed to eradicate MRSA carriage in the nose and on the skin. Decolonization is an essential part of the “search and destroy” measures practiced by zero-tolerance hospitals who want to detect any MRSA transport in their institution, and it is a last-ditch hope in recurrent community-strain infections. (I told the story of several women’s struggles with recurrent infections in SELF and Health magazines.)

It’s disheartening, then, to realize that decolonization is not a universally agreed-upon measure, and there is relatively little research that can say in which setting (household, hospital, ICU) it works best, and why. There have been a few studies, and a few review papers summing up studies, on the role that decolonization can play in reducing the risk of infection in already hospitalized, colonized patients — ones about to undergo surgery, for instance. A meta-analysis by the Cochrane group, of 8 trials, found that decolonization in the hospital did reduce the likelihood of infections in surgical patients.

The role that decolonization can play in short-circuiting community infections is much less clear, though there are many, many people who have suffered recurrent infections and testify that it worked for them. (Please speak up in the comments if you are!) One problem is that outside hospitals, there is no one recommended regimen: One physician might tell her patient to use mupirocin and chlorhexdine only, whereas another might tell his patient to also take bleach baths, or bleach all the laundry or household surfaces. The CDC has so far declined to put its muscle behind decolonization in community-strain infections, recommending only that frustrated patients with recurrences seek the advice of an infectious-disease specialist. (See this flowchart of treatment options (.pdf) that the CDC published in 2007.)

Comes now the infectious-diseases division of Evanston Northwestern Healthcare, whom some of you will recognize as being among the most successful and evangelical practitioners of “search and destroy” in the United States. (ENW has recently been renamed NorthShore University HealthSystem and is affiliated with Northwestern University. Disclosure, in case you care: I went to grad school at Northwestern, though not in medicine.) In a paper published in Infection Control and Hospital Epidemiology, the group evaluates the use and success rate of decolonization in ENW/NorthShore’s 3 hospitals and finds, well, not such good news: a temporary reduction in patients’ being colonized with MRSA, but no success in preventing infection.

This is an important and troubling finding, because decolonization comes with costs. There is the obvious cost to hospitals (and the follow-on cost to insurance companies and consumers) of paying for mupirocin and chlorhexidine themselves. But there is also a hidden cost that we here should be particularly sensitive to: Because mupirocin is being used so lavishly, mupirocin resistance is rising.

In the same issue of ICHE (which, yes, is pronounced Itchy), a related editorial by Dutch researchers reviews the difficulty of conducting decolonization trials, but summarizes the ENW/NorthShore study as not an endorsement of decolonization regimens:

It is clear that staphylococcal carriage is an important risk factor for infection and that eradication of carriage has proven successful for patients who are undergoing elective surgery. For other groups of patients, it is still unclear what the benefits are. It is obvious that indiscriminate use of mupirocin is associated with development of resistance. Therefore, additional studies are warranted to define the optimal MRSA decolonization strategy, including what should be given, to whom, and at what moment and who should guide and supervise the regimen.

The cites are:
Robicsek A, Beaumont JL, Thomson RB Jr et al. Topical therapy for methicillin-resistant Staphylococcus aureus colonization:impact on infection risk. Infect Control Hosp Epidemiol. 2009 Jul;30(7):623-32.
Kluytmans J, Harbarth S. Methicillin-resistant Staphylococcus aureus decolonization: “Yes, we can,” butwill it help? Infect Control Hosp Epidemiol. 2009 Jul;30(7):633-5.

H1N1 flu and swine surveillance – more relevance for MRSA

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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

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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.