Maryn McKenna

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

January 22, 2010 By Maryn Leave a Comment

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

Filed Under: hospitals, infection control, international, nosocomial, surveillance

A plea, and not for me: Support ProMED

December 16, 2009 By Maryn Leave a Comment

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

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

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

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

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

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

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

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

Filed Under: international, personal

Antibiotic resistance: international news

November 17, 2009 By Maryn Leave a Comment

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

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

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

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

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

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

Filed Under: Europe, international, legislation, MRSA

Seriously, a global problem

January 13, 2009 By Maryn Leave a Comment

Serendipitously, as I was preparing the previous post (an intro to GlobalPost.com, which will be featuring posts from SUPERBUG), an auto-push email from the National Library of Medicine‘s PubMed service landed in my inbox.

For those of you whose bedtime reading is not obscure medical journals (I know: This is what you have me for), PubMed is a search interface that allows you to pull articles for medical journals wordwide. It also offers a push option: Set a search term, fill in your email, and links to the latest articles on your term of choice are delivered. I have my search set to “MRSA” and have the results pushed once a week; there are never fewer than 25 new papers, which is a great gauge of how active an area of research — and how important a topic — MRSA is.

The latest push — 26 articles — vividly reminded me that, as NIAID Diretor Dr. Anthony Fauci said a few months ago, we are in the midst of “a global pandemic.”

Here is a sampling of those latest papers, from, again, a single week:

  • Russia: Clinical isolates of Staphylococcus aureus from the Arkhangelsk region
  • Pakistan: Antimicrobial resistance among neonatal pathogens in developing countries
  • The Netherlands: Genetic diversity of MRSA in a tertiary hospital
  • Spain: Familial transmission of community acquired MRSA infection (in Spanish)
  • Korea: Emergence of CA-MRSA Strains as a Cause of Healthcare-Associated Bloodstream Infections
  • UK: A simple prophylaxis regimen for MRSA: its impact on the incidence of infection in patients undergoing liver resection
  • Republic of Georgia: Important aspects of nosocomial bacterial resistance and its management
  • Italy: Decrease of MRSA prevalence after introduction of a surgical antibiotic prophylaxis protocol

No question, constant readers: What we are talking about here is an international problem, a truly global bug.

Filed Under: Asia, community, Europe, hospitals, international, MRSA, UK

British infection control: Epic fail

November 24, 2008 By Maryn Leave a Comment

Via the Guardian comes news that British hospitals are failing miserably at hygiene and infection-control targets set by the Healthcare Commission, a government-funded but independent watchdog agency somewhat analogous to the United States’ Joint Commission (formerly called JCAHO).

While community-associated MRSA is still a somewhat new story in the the UK, hospital or nosocomial MRSA is a major epidemic, with resistant Clostridium difficile (“C.diff”) coming close behind. So there has been significant attention paid in the UK to improving infection control programs in hospitals, through the vehicle of benchmarks set for the National Health Service trusts (essentially, regional organizational groupings of hospitals).

And the results, according to unannounced spot-checks made by the UK commission, are appalling. Only 5 of 51 trusts ( 51 = 30% of all acute-care hospitals in the UK) that were checked hit the mark. For those slow at math, that means 3% of UK hospitals are doing what they should to protect patients from infections they cause. (UPDATE: To be fair, if we assume the “5 out of 51” holds true across the NHS, then 10% are doing what they should. That’s still appalling.)

“At nearly all trusts we have found gaps that need closing,” said Anna Walker, the commission’s chief executive. “It is important to be clear that at these trusts we are not talking about the most serious kind of breaches. But these are important warning signs to trust boards that there may be a weakness in their systems.” (Byline: Sarah Boseley)

How weak? This weak, according to the commission’s own report:

  • 27 of the 51 trusts inspected were failing to keep all areas of their premises clean and well maintained. These lapses covered issues ranging from basic cleanliness, to clutter which makes cleaning difficult, to poorly maintained hospital interiors.
  • One in five trusts in this sample did not comply with all requirements for the decontamination of instruments and other equipment used in the care of patients. Trusts that breached this duty tended to have no clear strategy for decontamination or to lack an effective process to assure compliance.
  • In one in eight trusts, the provision of isolation facilities was not adequate. The containment of infections is extremely important to managing outbreaks. Hospitals without adequate facilities must ensure they have contingency plans so that the risk of infections spreading between patients is minimised.
  • For over one in five trusts there were issues related to staff training, information and supervision. While training on preventing and controlling infection was often in place, boards could not always ensure that training days were well attended or that staff used their knowledge in practice.

UK hospitals have until next April to learn to hit these benchmarks or be held accountable under a new Care Quality Commission.

For infection-control geeks, the full text of the “hygiene code” which the hospitals must abide by is here. Details of inspections at individual trusts are here.

Filed Under: Europe, hospitals, infection control, international, medical errors, MRSA, UK

Contributing to resistance: fake drugs?

November 18, 2008 By Maryn Leave a Comment

There’s news this morning that Interpol has seized $6.65 million of counterfeit medicines in the culmination of a 5-month undercover investigation that stretched across Cambodia, China, Laos, Myanmar, Singapore, Thailand and Vietnam. The fakes included purported antiretrovirals for HIV, anti-TB drugs, antimalarials (especially artemisinin) — and, chillingly for our purposes here, fake antibiotics for pneumonia and other bacterial illnesses.

Bloomberg News says:

Under Operation Storm, which ran from April 15 to Sept. 15, police seized more than 16 million pills…
Asia is the world’s biggest producer of all counterfeit products, the Organization for Economic Cooperation and Development said in a report last year. About 40 percent of 1,047 arrests related to fake drugs worldwide last year were made in Asia, according to the Washington-based Pharmaceutical Security Institute.
Counterfeits account for as much as 30 percent of all drugs in developing nations and less than 1 percent of all medicines in developed nations such as the U.S. (Byline Simeon Bennett.)

Counterfeiting medicines is both a huge business — the World Health Organization estimates that “counterfeit drug sales will reach US$ 75 billion globally in 2010, an increase of more than 90% from 2005” — and an appalling crime that attacks the most vulnerable people at their most vulnerable moments. In a recent issue brief, the WHO recounts a number of instances of counterfeiting that led to deaths in a number of countries.

Why should we care here? Because some counterfeits are not complete fakes; they contain a small amount of the active ingredient of the drug they purport to be. That means that, if someone takes a faked version of an antibiotic, they may not be going untreated. Instead, they may be undertreated, the exact situation that can lead to the emergence of resistance. Just last year, according to the Pharmaceutical Security Institute, known counterfeiting episodes involving anti-infective drugs rose 26%.

Now, NB: Activism against counterfeit drugs is politically complicated; it is supported by the pharma industry (PSI is a coalition of 26 manufacturers) and is tangled up with opposition to online pharmaceutical sales and to decisions by developing-world countries to abrogate Western drug patents. But that turf-defending by the pharma industry does not alter the reality that counterfeit drugs are an enormous international problem that imperil not only people unfortunate enough to take them, but anyone who contracts a resistant strain that those drugs helped foster.

And anyone concerned about MRSA will already know that resistant strains do not stay where they are generated. They have already demonstrated their ability to move rapidly around the world.

Filed Under: antibiotics, counterfeit, drug development, international

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