Maryn McKenna

Journalist and Author

Antibiotic resistance: Scandinavia gets it

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

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

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

The release also mentions some promising events coming next year:

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

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

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

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

Antibiotic resistance in food — some governments pay attention

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Antibiotics in chickens and links to human infections

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

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

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

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

Antibiotics – the EU pipeline is empty too

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

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

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

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

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

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

Here’s what the EU pipeline looks like:

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

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

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

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

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

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

“Pig MRSA” in the EU – long-awaited survey

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

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

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

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

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

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

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

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

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

It’s (European) Antibiotic Awareness Day

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

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

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

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

Antibiotic resistance: international news

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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.

New reports on animals, food, MRSA ST398

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Well, constant readers, didn’t expect to be gone *that* long. Many apologies. There was a good reason — actually, several: I attended a journalism meeting, and spoke at a second meeting. But most important, I received, marked up, and returned the galleys of SUPERBUG. Yes, it’s really starting to look like a book now. There will be things to share, soon.

Meanwhile, I’ll try to roll out some of the many, many pieces of news and research related to staph that have emerged in the past few weeks. Today: News on animals, and our old opponent, MRSA ST398.

First: A team from the Universidad de La Rioja reports in the Journal of Antimicrobial Chemistry the first finding of MRSA ST398 (“pig MRSA,” archive here) in food in Spain. They tested 318 raw meat and wild-game samples (chicken, pork, veal, lamb, turkey, rabbit, game bird, wild boar, deer, hare) and found ST398 and other MRSA strains in 5 of them, an incidence of 1.6%. The authors write: “Although MRSA prevalence in raw food is low, the risk of its transmission through the food chain cannot be disregarded.”

Importantly, one of the other strains found in the meat of these animals is an uncommon variant, ST125-t067, that has already been implicated in large numbers of hospital infections in Spain and is resistant to ciprofloxacin (Cipro), erythromycin and a third antibiotic, tobramycin, in addition to the usual suspects. The other non-ST398 strain is ST217, which is a variant of a long-known hospital strain, and is also resistant to Cipro, a very valuable drug for skin and soft-tissue infections. So it appears the contamination may cross both ways, from animals, and to animals as well.

No link, but the cite is: Lozano, Carmen, et al. Detection of methicillin-resistant Staphylococcus aureus ST398 n food samples of animal origin in Spain. Journal of Antimicrobial Chemistry. e-pub Oct. 21 2009 AOP doi:10.1093/jac/dkp378

Next: If the prevalence of ST398 is so low in food, why do we care? We care because of where those organisms go next — into hospitals, among other places. A Dutch/German team that includes the original identifier of ST398 in humans are reporting that they have found an association between the density of pig-farming in parts of Germany and the probability that patients admitted to hospitals will be carrying ST398 with them, creating a possible source for nosocomial infections. R. Kock and colleagues screened 1,600 pigs on 40 German farms, and also reviewed screening results for every MRSA-positive patient admitted to the University Hospital-Munster from 2005 through 2008. They found ST398 on 70% of the farms, and also found that ST398 represented 15% of the MRSA isolates at the hospital in 2005, rising to 22.4% in 2008. The key association: The patients carrying St398 were more likely to have contact with pigs in their daily lives, and also with cattle, than patients who had other forms of MRSA or no MRSA at all.

The cite for that paper: Kock, R. et al. Prevalence and molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) among pigs on German farms and import of livestock-related MRSA into hospitals. European Journal of Clinical Microbiology and Infectious Diseases, e-pub Aug 25, 2009. DOI 10.1007/s10096-009-0795-4

And finally: How do you stop the evolution and spread of antibiotic-resistant organisms in livestock? One good way is to stop giving teh livestock antibiotics in the first place. In a column at the Huffington Post, Laura Rogers, project director of the Pew Campaign on Human Health and Industrial Farming, takes on the oft-repeated assertion that you can’t farm without them without risking the lives and market place of your livestock, and offers the example of Denmark, which did ban antibiotics in animals, and which has healthier, more profitable livestock as a result:

American agribusiness often has criticized Denmark’s 1998 ban on antibiotics, calling it an outright failure. But compelling new research presented by a Danish scientist earlier this year showed the opposite, revealing that antibiotic use on industrial farms has dropped by half while productivity has increased by 47 percent since 1992. Danish swine production has increased from 18.4 million in 1992 to 27.1 million in 2008. A decrease in antibiotic-resistant bacteria in food animals and meat has followed the reduced use of these vital drugs.

MRSA in pig-farm workers – very high rates

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Let’s go back for a moment to what I think of as the “third epidemic” of MRSA: ST398 and the other strains that reside in animals and cross to humans. (In my personal taxonomy, the first and second epidemics are hospital-acquired and community-associated.)

Via Emerging Infectious Diseases, the open-access journal published by the CDC (Do I have to keep telling you to read it? It’s free. It’s good. Your tax dollars pay for it.), comes a report of surveillance for MRSA colonization of pig-farm workers, conducted in Belgium by researchers from Erasmus Hospital of the Free University of Brussels, and the Veterinary and Agrochemical Research Centre of Brussels. The group persuaded 127 farm workers on 49 farms to be tested for colonization, or asymptomatic carriage, of MRSA; at the same time, they tested 30 randomly selected pigs on each farm.

They found very high rates of colonization, higher than have been found in patients in hospitals or residents of nursing homes: 38% of the farm workers carried MRSA ST398, the pig strain (plus, an additional 17% carried various strains of MSSA, drug-susceptible staph). There was a clear association between colonized farmers and colonized pigs: Out of 1500 pigs sampled, 44% carried ST398 — and half of the workers on farms with colonized pigs were colonized also, compared to only 3% of workers on farms where pigs did not carry the bug.

In a bit of good news, the researchers found only one farm worker who had suffered any MRSA disease from ST398, a man with a lesion on his hand. There was no invasive disease, though ST398 has been associated in the past with pneumonia and endocarditis.

Workers were more likely to acquire the bug if they had regular contact with pigs, dogs or horses, which makes intuitive sense. But in an odd finding, their odds of acquiring ST398 did not go down if they wore protective clothing — which is to say, aprons, gloves and masks did not protect them from picking up the bug, leading the researchers to wonder whether airborne spread or contaminated surfaces are playing a role in transmission.

So what does this mean? The lack of invasive disease in this population must be good news; and it’s consistent with a number of papers that have reported low rates of disease from ST398 even when colonization is present. But to me, the high rate of colonization must be bad news. The more of this bug there is (and every researcher who looks for it seems to find it), the more chance there is of the bug adapting in an unpredictable — potentialy more resistant, potentially more virulent — way. If that did happen, it could well go undetected for a while — because as swine flu has been teaching us, disease surveillance in animals is patchy at best, and new pathogens can and do arise and ciruclate for years before being detected.

For more on the paucity of surveillance in animals, see my CIDRAP colleague Lisa Schnirring’s story here. For a complete archive of posts on “pig MRSA” ST398, go here.

The cite is: Denis O, Suetens C, Hallin M, Catry B, Ramboer I, Dispas M, et al. Methicillin-resistant Staphylococcus aureus ST398 in swine farm personnel, Belgium. Emerg Infect Dis. 2009 Jul; [Epub ahead of print] DOI: 10.3201/eid1507.080652.

MRSA in the House of Lords — the silly, the serious

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Thanks to constant reader Pat Gardiner, we have the transcript of the UK House of Lords discussion on community MRSA, called there PVL-MRSA after the toxin. (Go to the linked page, and click down to the time-mark 3.16 pm.) It’s encouraging to see some members of a government taking MRSA seriously. The members are asking for

  • better surveillance
  • better infection control
  • consideration of MRSA as a notifiable disease
  • and promotion of both vaccine research and point-of-care diagnostics.

Hear, hear to Baroness Masham of Ilton for bringing it up.

To get to that discussion, though, you’ll have to click down through some silliness (the ghost of Monty Python is never far from the British government, is it?): a discussion at time-stamp 3.07 p.m. of whether a House of Lords restaurant can afford to serve British bacon, rather than Dutch bacon, given that British bacon is almost twice as expensive and Dutch pigs are associated with MRSA ST398:

Lord Hoyle: My Lords, I thank the noble Lord for that reply, although there is more than a whiff of hypocrisy about it. After all, I and many others on all sides of the House have argued that it should not be a matter of price. We have urged the British consumer to buy British bacon because of the higher welfare standards that are applied in this country. Will the noble Lord also take into account the presence in Dutch bacon of a deadly form of MRSA, ST398, which can cause skin infection, heart trouble and pneumonia? Is he not putting people in this country at risk, particularly as the strain has passed from animals to humans? Indeed, when Dutch farmers go into hospital, they go into isolation. Why is he putting the British consumer and those who buy bacon in this House at risk in this way?

The discussion quickly devolves into foolishness about British Tomato Week — but if you read carefully, you’ll see that behind the silliness, there are serious issues at stake: animal welfare, farming standards, truth in labeling (the Lord Bishop of Exeter advances the very newsworthy claim that pork imported from other countries is subsequently labeled “British” only because it is packaged in the UK) and movement of zoonotic pathogens across national borders thanks to globalized trade.

Sadly, the leader of the discussion — the Chairman of Committees, AKA Lord Brabazon of Tara (no, really) — appears not to have been keeping up with the news, since he notes of ST398:

As far as MRSA is concerned, I read the article in, I think, the Daily Express a couple of weeks ago. I do not think that it has been followed up by anybody else.

Apparently the Lord’s staff have not been keeping up, since MRSA in pigs in the EU has been covered by the Daily Mail, the Independent, comprehensively by the Soil Association, and by, ahem, us.

MRSA strains crossing borders: US CA-MRSA to Italy

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Swine flu continues to dominate the headlines, but other pathogens don’t read the papers. Case in point: New news about a US community strain being found and treated in a woman in Italy — better treated, as it turns out, than she was in California, where she was infected.

In a new letter in Emerging Infectious Diseases (a free journal published online and in print by the CDC — it’s your tax dollars at work, just read it, already), Carla Vignaroli, Pietro E. Varaldo, and Alessandro Camporese of the Polytechnic University of Marche in Ancona amd the Santa Maria degli Angeli Regional Hospital, Pordenone report the case of

a 36-year-old Italian woman (who) was seen at Pordenone Hospital (northeastern Italy) for spider-bite–like skin lesions on the face, characterized by rapid evolution to furuncles and small abscesses. The infection had started ≈1 month earlier in California, where she had spent several months on business (wine import-export), and where she had been treated empirically with amoxicillin/clavulanate for 10 days (1 g, 3×/day), with no clinical improvement.

(At this point, I know every clinician reader and everyone who has had a MRSA skin infection is shaking his or her head. Surely by now the knowledge that “spider bite” is practically diagnostic for CA-MRSA has penetrated? But apparently not, since she was given amoxicillin/clavanulate, AKA Augmentin, which is partially penicillin-based.)

When the woman’s lesions were cultured, they turned out to be caused by USA400, the original community strain, which back in the 1990s was known as MW2. That’s interesting, especially in California, since USA300 has become such a dominant strain. Nevertheless, the key point is that USA400, as with USA300, has barely been recorded in Italy:

All 3 previously reported cases of CA-MRSA infection in Italy were caused by type IV SCCmec, PVL-positive strains, none of which, however, belonged to the ST80 clonal lineage that predominates in Europe (7). The first case (in 2005) was a necrotizing pneumonia caused by an ST30 isolate; the 2 other cases (2006) were severe invasive sepsis and a neck abscess, both caused by ST8 (USA300) isolates.

The concern, of course, is that once imported, they will not remain rare:

The case we note here documents the importation of a US pathogen into a country in Europe, from an area where the pathogen is widespread and has been highly virulent since the late 1990s, to an area where its penetration in the past has been poor.

The cite is: Vignaroli C, Varaldo PE, Camporese A. Methicillin-resistant Staphylococcus aureus USA400 clone, Italy [letter]. Emerg Infect Dis. 2009 Jun; [Epub ahead of print]. DOI: 10.3201/eid1506.081632

ST398 found again — in Italy

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There’s a letter in the upcoming issue of Emerging Infectious Diseases (hat tip Pat Gardiner) alerting the medical community that “pig MRSA” ST398 has been found in Italy, adding t the steadily enlarging list of countries where this strain has been identified.

(NB: Because most of these surveys are one-offs, we don’t yet know whether ST398 is truly expanding its range, or has always been there, but no one looked until now.)

Angelo Pan and colleagues of the Cremona Hospital and other institutions report that a pig-farm worker was discovered to have a severe pyomyositis (abscess buried in muscle):

The case-patient was a 58-year-old man admitted to a surgical department in Cremona, Italy, on July 30, 2007, because of a 1-week history of fever and intense pain in his right buttock. He worked on a pig farm, was obese, consumed high volumes of wine (1.5 L/day), was taking medication for hypertension, and had not had recent (<5 years) contact with the healthcare system. At the time of hospital admission, he was moderately ill, oriented, and cooperative. His right buttock was extremely painful. He reported neither recent trauma nor anything that would explain infection. ...
Based on clinical and magnetic resonance imaging data, the diagnosis was cellulitis, pyomyositis, and pelvic multiloculated abscess of the buttock. A needle aspiration of the abscess, guided by computed tomography, was performed. Because of persistent fever (38.5°C), oral ciprofloxacin was added to the patient’s treatment regimen on day 3. Blood and abscess cultures yielded MRSA that was sensitive to glycopeptides, rifampin, linezolid, gentamicin, and mupirocin and resistant to co-trimoxazole, macrolides, clindamycin, and fluoroquinolones. After treatment was switched to vancomycin plus rifampin, the patient’s general condition improved; he was discharged from the hospital after 24 days.

An investigation was launched, and the results were intriguing:

Two fellow workers were colonized with S. aureus, 1 with methicillin-sensitive S. aureus (MSSA) and the other with MRSA. The pig farm, a farrow-to-finish production farm with 3,500 pigs, was screened for MRSA … Dust swabs were taken from 5 areas of the farm; 7 MRSA isolates were detected.
The isolate from the patient belonged to spa type t899, was ST398, carried an SCCmec type IVa cassette, and was PVL negative. The isolate from the MRSA-colonized worker was a t108 strain carrying SCCmec type V. The isolate from the MSSA-colonized worker was identified as t899. The dust swabs yielded 7 isolates: 2 belonged to t899 and carried SCCmec IVa; 5 belonged to t108 and carryied SCCmec V. The isolates obtained from the patient, farrowing area 7, and gestation area 1 were indistinguishable (i.e., same spa type, SCCmec type, and ST profile; Table), thus confirming the animal origin of transmission.

So, we have:

  • A high rate of carriage on the farm (3 of 4 workers with ST398, either MR or MS)
  • A strain-type that is both MRSA and MSSA, suggesting that in its drug-sensitive state it can acquire resistance factors rather easily
  • A PVL-negative strain that nevertheless causes invasive disease requiring more than 3 weeks hospitalization

None of these are good news.

The authors very sensibly call for more public-health attention to this strain, which — we have contended before — is long overdue:

…attention should be given to the emergence of MRSA strains among animals, and continuous surveillance in humans should monitor the extent of disease from MRSA ST398, especially in areas of intensive animal farming. Collaboration between infectious disease specialists, microbiologists, and epidemiologists, on both the human and the veterinary sides, should be strengthened and readied for appropriate action whenever complex, zoonotic, public health issues occur.

The cite is: Pan A, Battisti A, Zoncada A, Bernieri F, Boldini M, Franco A, et al. Community-acquired methicillin-resistant Staphylococcus aureus ST398 infection, Italy [letter]. Emerg Infect Dis [serial on the Internet]. 2009 May. DOI: 10.3201/eid1505.081417

Does ethanol production produce resistant bacteria too?

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One of the challenges of disappearing down the rabbit hole of a gnarly chapter — gee, it’s dark down here — is that I get behind on my RSS feeds, and suddenly every entry in my Google Reader is at 1000+ and it’s all just too daunting.

So, trying to catch up a bit, I found two related, interesting and troubling stories from the Associated Press (4 April) and the online magazine Grist (7 April — yes, I said I was behind…).

Synopsis/synthesis: Corn-based ethanol, former darling of the energy and large-scale agriculture industries, suddenly doesn’t look like such a good idea – and not just because the market for it is crashing. Turns out that ethanol is made by adding yeast and sugar to corn mash; the yeast convert the carbohydrates to the alcohol that is the basis of the fuel. (Yes, just like making beer.) However, the mash is particularly attractive to Lactobacillus and other bacteria that produce lactic acid as a waste product rather than alcohol, and a tank full of lactic acid doesn’t make very good fuel. So, to keep the bacteria under control, ethanol producers add antibiotics. Specifically, penicillin and erythromycin — you’ll recognize those — and tylosin and virginiamycin, two macrolides, related to erythromycin, that are approved in the US for veterinary use.

Now, the problem with this practice, as you might predict, is that if the mash is not appropriately dosed, the presence of antibiotics within it can prompt some of the bacteria to develop resistance. (Here’s an article from the trade magazine Ethanol Producer discussing just that possibility.)

And the further complication of this is that the leftover mash, now called “distillers’ grains,” is sold as animal feed. Ask yourself: Where in animal production are animals most likely to eat grains? Answer: At finishing, in feedlots. In other words, fermented grains that may contain antibiotic residue, and may contain resistant bacteria, are being sold as feed to animals that are already being raised in conditions that have been shown to foster the development of resistant bacteria through subtherapeutic and prophylactic antibiotic use. In fact, some research has drawn an explicit link: Kansas State University scientists have found higher levels of E. coli O157 in the guts of cattle that were fed distillers’ grains.

All of this was new to me, but there’s an additional facet to the story that the AP and Grist pieces don’t highlight, and that just makes my head hurt: the use of virginiamycin. For those new to the story, virginiamycin is an allowed, widely used veterinary antibiotic in the US. However, it is not used in the European Union: It was banned there in 1998 because the EU’s ag authorities believed that it promoted resistance to the drug Synercid (quinupristin+dalfopristin), which is a drug of last resort against vancomycin-resistant bacteria such as VRE. (Here’s a Lancet paper that talks about that resistance mechanism.) Synercid was approved by the FDA in 1999 — two years after Synercid resistance had already been found in the US. (For a long but cogent explanation of the complex story of virginiamycin, see the book The Killers Within.)

So, just to recap: We have an industry whose long-term earnings are shaky, whose economic survival is partially secured by the sale of its waste product, and which via that waste product is putting antibiotic residues and antibiotic-resistant bacteria into the environment, and is conveying them into food animals, and is making particular use of an antibiotic that other countries have banned because they believe that, via its use in animals, it exerts an adverse impact on human health.

Something to remember the next time ethanol subsidies come up.

More MRSA in pigs, in Portugal

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A brand-new report, in a letter to the International Journal of Antimicrobial Agents, indicates that ST398 “pig MRSA” has been found in Portugal for the first time.

Constanca Pomba and colleagues from the Technical University of Lisbon swabbed and cultured the noses of pigs and veterinarians on two pig farms in different regions of Portugal, and also checked the air at both farms.

What they found:

  • On Farm A: All pigs and the veterinarian positive for ST398, the pig-origin strain that has been found so far in Iowa, Ontario, the Netherlands, France, Denmark, Germany and Austria and has, depending on the country, caused human disease and/been found on retail meat. The veterinarian was transiently colonized, which is to say that he was not carrying the bug long-term.
  • On Farm B: All pigs — but neither of two veterinarians — positive for a different MRSA strain, CC (or ST) 30. This is very interesting, because CC30 is usually a drug-sensitive strain (MSSA, methicillin-sensitive S. aureus), and has been found in pigs primarily in Denmark and France. In Portugal, it is a human MSSA hospital-infection strain.

Strains from both farms were resistant to tetracycline; this is turning out to be a great marker for these strains having emerged due to antibiotic pressure in animals, because tetracycline is very commonly used in pigs. but not much used for MRSA in humans. The strains have the genes tetK and tetM, so they are resistant not just to tetracycline itself, but to the whole class of tetracyclines including doxycycline and minocycline. The Farm B strains also carried the gene ermC, which encodes resistance to erythromycin.

So what does this tell us?

  • First, that (once again), every time people look for ST398, they find it; it is now a very widely distributed colonizing bug in pigs, and is repeatedly spreading to humans. What we don’t know, because all these studies are so new, is whether ST398 is actively expanding its range, or has been present in all these countries for a while. We have been anticipating its presence or spread (take your pick at this point) through the European Union because of open cross-border movement of food animals, meat, and agriculture and health care workers.
  • And second, it should tell us that it is really past time to start looking for this more systematically. Every finding of ST398 that we have (long archive of posts here) is due to an academic research team who decided to look for the bug. None of the findings, to date, have come from any national surveillance system. (NB: Except for the first human colonizations in the Netherlands, which were found as a result of the national “search and destroy” rules in hospitals.)

Of note, the European Union is running a study now that is supposed to report ST398 prevalence at any moment (as they have been saying since 2007). It is not expected to be comprehensive, since it was piggy-backed onto another study, but it is something. The US government has not been so enterprising.

The cite is: Pomba, C. et al. First description of meticillin-resistant Staphylococcus aureus (MRSA) CC30 and CC398 from swine in Portugal. Intl J Antimicrob Agents (2009), doi: 10.1016/j.ijantimicag.2009.02.019

More news on ST398, “pig MRSA,” in Europe

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Two new papers have been posted ahead-of-print to the website of Emerging Infectious Diseases, the free journal published monthly by the CDC. (It’s a great journal. Just go.)

One, from the Austrian National Reference Center for Nosocomial Infections, reports that out of 1,098 isolates from infected or colonized hospital patients collected between 2006 and 2008, 21 were ST398, the “pig strain” that we have talked so much about here. Of the 21, 15 were colonized and 5 had actual infections (one person lost to followup, apparently); of the 5 infections, 4 were minor, and one was a very serious infection in a knee replacement in a 64-year-old farmer.

In a separate piece of math that is not fully explained, the researchers note that the prevalence of ST398 in Austria has risen to 2.5% of MRSA isolations, from 1.3% at the end of 2006 — close to double, and especially rapid given that Austria’s very first ST398 sample was found during 2006.

The second paper is much more complex; it deals with the prevalence of multiple MRSA strains in the cross-border region where Germany, Belgium and the Netherlands bump up. (Apparently EU bureaucracy calls an area like this a “Euregio.” Ah, jargon. This is the EMR, the Euregio Meuse-Rhin.) The concern here is that MRSA prevalence is very different in different EU countries; in the Netherlands, which has an active surveillance “search and destroy” policy in its hospitals, MRSA represents only 0.6% of all staph — but the rates are 13.8% in Germany and 23.6% in Belgium, which either do not do active surveillance or began to much more recently. So as people move freely across borders, from a high-prevalence area to a low-prevalence one, they could bring a resistant bug with them that then could find a foothold because there is an open ecological niche.

This study analyzed 257 MRSA isolates from hospitals in the border region that were collected between July 2005 and April 2006: 44 from Belgium, 92 from Germany, and 121 from the Netherlands. Of the Dutch isolates, according to typing, 12 (10%) were ST398. These were all from patients who were identified as colonized when they checked into hospitals practicing “search and destroy”; none represented actual infections.

So, what does this tell us? A couple of things, I think. First, it documents the continued presence of ST398 in Europe; in other words, it wasn’t a blip and doesn’t appear to be going away. Second, it underlines both that you find it when you look for it, and also that it remains a small portion of the overall MRSA picture. But, we immediately have to add, it’s a small portion that wasn’t present at all just a few years ago.

And it should underline that what we need, and are not getting in this country or in Europe, is much more comprehensive surveillance and research to understand ST398’s place in MRSA’s natural history, so that we can understand where it is only an emerging disease, or truly an emerging threat.

The cites are:
Krziwanek K, Metz-Gercek S, Mittermayer H. Methicillin-resistant Staphylococcus aureus ST398 from human patients, Upper Austria. Emerg Infect Dis. 2009 May; [Epub ahead of print]
Deurenberg RH, Nulens E, Valvatne H, et al. Cross-border dissemination of methicillin-resistant Staphylococcus aureus, Euregio Meuse-Rhin region. Emerg Infect Dis. 2009 May; [Epub ahead of print]

More MRSA, more meat – poultry, this time

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Constant readers: Fresh from the journal Emerging Infectious Diseases — posted AOP (electronic publication/ahead of print) this afternoon — comes more news of MRSA ST 398, the “pig strain,” in food animals. This time, it’s chickens, in Belgium.

The authors (from Ghent University and the Veterinary and Agrochemical Research Center in Brussels) took swabs from living chickens — laying hens and broilers — from 24 farms, 50 layers and 75 broilers total; one broiler-raising farm was sampled twice. They found no MRSA in the layers, which is important for reasons I’ll get to in a moment, and ST 398 in 8 broilers. From each chicken, they took two samples, nasal and cloacal, and in the 8 positive chickens, they got 15 MRSA isolations; one cloacal swab was negative. Of the positive chickens, several (I deduce three, but the math is a bit cloudy) were spread across the two visits to the farm that was sampled twice. Since chicken farms are depopulated between batches — yes, just what it sounds like, farms sell/kill all the birds and clean the place — that finding suggests that MRSA is persisting in the environment on that farm.

Important point: This strain was ST 398, which we here have been calling the pig strain from many previous findings, most of them in pigs. However, ST 398 is an identification using a particular technique called MLST (multi-locus sequence typing), which is used for this strain because the standard typing method, PFGE (pulsed-field gel electrophoresis), did not return a readable result when the strain was first identfied back in 2004. (Trivia: That’s why the initial reports of this strain called it NT, for “nontypeable.”) It’s becoming increasingly clear, though, that ST 398 is actually a category, not a single strain. And within that category, today’s research is a new find: a strain with the unusual spa type t1456, which has only been found 10 times in the past three years, in Germany and the Netherlands, not in Belgium. The author suggest that this particular strain may be adapting to poultry in the same manner that the ST 398 we have been talking about (different spa type — sorry, I will have to look it up) has adapted to pigs.

So, as before: Why do we care? We care for two reasons: First, because since this strain is in a food animal, the possibility exists that it could contaminate the chickens’ meat during slaughter and pass to humans. As has happened with some ST 398, the humans could be only colonized, and not become ill. But, second, any increase in colonization is a bad thing: The more strains out there, the greater the chance that they will exchange virulence and resistance factors and become something unpredictable.

Now, about those layers, here’s an interesting factor that the authors call out in their paper: Layers, unlike broilers, do not receive antibiotics. The layers did not carry MRSA. The broilers did. It’s a pretty potent argument, in case anyone needed convincing, of the effect of the selective pressure that antibiotic use in food animals exerts on these strains.

The site is: Persoons D, Van Hoorebeke S, Hermans K, Butaye P, de Kruif A, Haesebrouck F, et al. Methicillin-resistant Staphylococcus aureus in poultry. Emerg Infect Dis. 2009 Mar; [Epub ahead of print] DOI: 10.3201/eid1503.080696

Appearing tonight at SciAm.com

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Folks, last summer I told you about the very exciting though disturbing development of ST 398 MRSA — the “untypable” Dutch strain that originated in pigs and spread to humans — being found in pigs in the US for the first time.

But here’s the brand-new second half of that story: It was found in pig handlers as well, on a set of linked farms — a closed production system that takes pigs from birth to just before slaughter — in Iowa and Illinois.

The full study has just been published, in the online Public Library of Science journal PLoS One.

And I have a story describing the research and the background — and the alarming spread of ST 398 in Europe — up tonight at ScientificAmerican.com.

The cite is: Smith, TC, Male, MJ, Harper, AL et al. Methicillin-Resistant Staphylococcus aureus (MRSA) Strain ST398 Is Present in Midwestern U.S. Swine and Swine Workers. PLoS ONE 4(1): e4258 doi:10.1371/journal.pone.0004258

UPDATE: Lead author Tara Smith talks about the paper at her own blog, Aetiology. And for good measure, her Science Blogs sibling (AKA “scibling”) Ed Yong discusses the paper at Not Exactly Rocket Science.

Seriously, a global problem

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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:

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