Maryn McKenna

Journalist and Author

Update: The French case — not MRSA but so interesting

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I’m flattered to have as a regular reader Dr. Peter Davies, a professor of swine health and production in the University of Minnesota’s Department of Veterinary Population Medicine. (Disclosure: I worked part-time at U Minn from mid-2006 to mid-2010, but in a different school.) In a comment on my previous post, he points out — perils of reading on a smartphone — an important point where I erred: The staph strain involved in the death of the French 14-year-old was not MRSA, but MSSA, drug-sensitive staph, that had picked up a resistance factor.

Unpacking that a bit: At a minimum, MRSA is resistant to all beta-lactam antibiotics — penicillin, the semi-synthetic penicillins (including methicillin, what the M in MRSA stands for), several generations of cephalosporins, monobactams, and carbapenems. It is also separately, but variably, resistant to macrolides (such as erythromycin), lincosamides (clindamycin), aminoglycosides (gentamicin), fluoroquinolones (ciprofloxacin) and tetracycline.

Livestock-associated MRSA, known as ST398 for its performance on a particular test (multi-locus sequence typing) was first identified as having a tie to pig-farming because it was also resistant to tetracycline, which was being given to the pigs on the farms where the first human carriers worked. (Hence its jocular name, “pig MRSA,” though it’s since been found in other animals.)

The ST398 strain involved in the French girl’s death does not have that broad array of resistance. Chiefly, it was not resistant to beta-lactams, and so can’t be considered MRSA. On analysis, it was resistant to the macrolides, of which the best-known are erythromycin and azithromycin (Zithromax or Z-Pak). Here’s something else intriguing: On another test (spa typing), the ST398 strain in the French girl was one known as t571; the ST398 that has spread from pigs to humans in the European Union, and subsequently to Canada and the United States, is usually t034.

Here’s why this is all so interesting: MSSA ST398 t571 was reported just a few years ago in New York City, in a Bronx community that has close ties to the Dominican Republic, and also in the towns in the Dominican Republic where those Bronx residents come from and visit. (Here’s my initial post on that finding from a medical meeting, and subsequent post when the paper was published.) In that case, the ST398 was fully drug-sensitive — and there was no visible link to pigs, though the authors speculated that livestock, perhaps poultry, might be playing a role on either side of the “air bridge” connecting the two communities.

In the paper (Bhat, Dumortier, Taylor et al., EID 2009, DOI: 10.3201/eid1502.080609), the authors expressed concern that, given staph’s promiscuous ability to acquire resistance — and the fact that ST398 is not regularly surveilled for —  the ST398 in New York could become an undetected resistant strain:

Given ST398’s history of rapid dissemination in the Netherlands, its potential for the acquisition of methicillin resistance, and its ability to cause infections in both community and hospital settings, monitoring the prevalence of this strain in northern Manhattan and the Dominican Republic will be important to understand more about its virulence and its ability to spread in these communities.

 And now it appears it has become resistant — but in France, not New York City or the Dominican Republic, and to macrolides, not  beta-lactams. It’s one more reminder of staph’s genius at acquiring genetic defenses, and of how our lack of attention to its mutability and spread continues to allow it to take us by surprise.

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

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The latest postings to the website of the CDC journal Emerging Infectious Diseases include a sad and very troubling letter from physicians in Lyon and Paris, reporting the death from necrotizing pneumonia of a previously healthy 14-year-old girl. That would be sad under any conditions, but here’s what makes the death so troubling: It appears to have been caused by MRSA — but not by the community strain, USA300, that has been implicated in a number of deaths from necrotizing pneumonia. (Several such stories are told in SUPERBUG the book.)

Instead, her death appears to have been caused by infection with MRSA ST398 — the livestock-associated strain that was first noted in pigs raised with antibiotics, and the pig-farm workers caring for them, in the Netherlands 6 years ago, and that has since spread across the European Union, Canada and into the United States. (My 3-year archive of ST398 posts is here.)

This may be the first death associated with ST398, though I can’t say that for sure as I am away from my big computer and working without my database. I’ll update later today and confirm or knock that down.

The physicians say that the girl came in with flu-like symptoms and abdominal pain, was put on IV antibiotics (cefotaxime and amikacin), underwent an exploratory laparotomy that showed nothing, and shortly afterward developed acute respiratory distress and was put on a vent. A chest X-ray was shadowy on both sides. She went rapidly downhill and died 6 days later.

On analysis, the staph strain infecting her was ST398; there was no indication where she had picked it up. The strain had an unusual characteristic: It possessed the ability to make the cell-destroying toxin Panton-Valentine leukocidin, PVL for short, a genetic trick that until now has been a property only of community MRSA strains such as USA300. Though its role is disputed, PVL has been linked to community MRSA’s ability to start infections on intact skin, and to the cellular damage that destroys children’s lungs in cases of pneumonia caused by USA300. Until now, ST398 has been PVL-negative.

The physicians’ letter is short and there’s much more to find out about this case. But if the report and analysis are correct, this is bad news. One of the repeated themes in the 50-year evolution of MRSA has been its ability — all staph’s ability — to promiscuously swap and share the bits of DNA that confer resistance and enhance virulence. Another, since the emergence of ST398, has been the potential peril of a staph strain adapting and mutating in the millions of farm animals around the world that are routinely given antibiotics — and that for the most part are not checked to see whether they harbor resistant organisms. If this report (and my interpretation) are correct, then those two trends are converging in a way that cannot bode well.

Antibiotic use in animals: The feds move, a little

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

(You leave the country for a few days — I spoke at a conference in Brussels, which was was lovely, thanks for asking — and all kinds of news breaks out. So, sorry to be late on this, but it’s an important issue.)

Last week, the Food and Drug Adminstration took the first (baby, mincing, tentative) steps to address the problem of antibiotics being used in animal agriculture, not to treat disease, but to make animals grow up to market weight faster. This practice — variously called subtherapeutic dosing, growth promotion, and “for production purposes” in the FDA’s exceedingly careful language — has been fully banned in the European Union for 4 years, and some aspects of the practice have been banned longer.

The simple reason for the ban: There’s decades of good science and real-world experience showing that it contributes to the development of drug-resistant organisms in farm animals and the farm environment, organisms that leave farms in the animals and in their manure, and also contaminate the environment beyond farm borders via leakage into groundwater and dust blowing off manure lagoons.That movement off the farm is critical because many of the drugs used in agriculture are the same, or close analogs, of drugs used in human medicine; so resistance that develops on the farm endangers human health as well. (MRSA ST398, livestock-associated MRSA, is the latest example of this. Find a long archive of posts on ST398 here.)

Just to be clear, growth-promoters don’t treat disease; they’re given to healthy animals solely for the purpose of getting them up to sale weight and to market faster. The ways in which antibiotics are given to livestock to treat or prevent disease have their own issues, but those are not part of the FDA effort. (Historical note: The growth-promoting effect of trace amounts of antibiotics was first recognized in 1947, when scientists at Lederle were looking for something to do with the leftover fermentation mash from the manufacture of chlortetracycline, fed it to chickens, and discovered they thrived on it. Stuart Levy’s The Antibiotic Paradox tells this story in detail.)

In human medicine, when we give antibiotics to people who are not sick with a bacterial illness, we call it inappropriate use — and aim massive education campaigns at the practice in an attempt to dial it down. In contract, the animal side has had a free pass for a long time, to the extent that it remains unclear how many antibiotics are used in farming in the US (best estimate: about 70% of all antibiotic use in the US per year), and there is no organized surveillance that would look at what organisms are emerging in animals from that use.

The FDA has been trying to put curbs on growth promoters since the 1970s, always without success; the lobbying against it, by agriculture and also by pharmaceutical interests, is reliably intense. There’s been a parallel effort in Congress to limit the use in animals of drugs that have close analogs in human medicine, via the Preservation of Antibiotics for Medical Treatment Act, or PAMTA, authored by Rep. Louise Slaughter (D-NY), Congress’s only microbiologist. PAMTA has been introduced in several Congresses but this year finally gained some traction. Last year, the Obama administration signaled, in testimony by then-new assistant FDA commissioner Joshua Sharfstein, that it might be friendly to the idea of dialing back on growth-promoter antibiotic use, and it looked as though the long logjam might finally be broken.

Well, OK: Not broken, exactly. Just shifted a little, and maybe showing a tiny bit of light.

On Tuesday, the FDA released a “draft guidance” that proposes animal ag do two things: stop using growth-promoting subtherapeutic dosing, and administer antibiotics to animals under the supervision of a veterinarian. That’s the good news.

The bad news: It’s only a guidance, not a regulation. In other words, it has no force in law. It’s more like a request — though in a press conference last week, Sharfstein suggested it might also be a shot across agriculture’s collective bow:

We have the regulatory mechanisms and the industry knows that. But we are also interested in what things can be done just voluntarily that they would do them. And I think it’ll be interesting to see how the industry responds to this and how – what direction their comments take. …We’re not handcuffed to the steering wheel of a particular strategy at this point. We really want to understand what people think. And but we’re also – I’m not ruling out anything that we could do to accomplish these important public health goals. (Transcript)

Reactions to the FDA announcement were predictable — effectively “No science, more research needed”: Here’s the National Cattlemen’s Beef Association, the National Pork Producers Council, and a standing statement by the Animal Health Institute. (Supporting the FDA move: the Pew Charitable Trusts, the New York Times.)

The draft guidance stays open for public comment for 60 days, until Aug. 30. The required Federal Register posting is here, with the mailing address. Electronic comments can be left at Regulations.gov; the docket number for the guidance is FDA-2010-D-0094; 33 comments have been posted already.

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.

A blog reaction so perfect I want to print the whole thing…

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(…but I won’t, because it’s not fair use or good blogger behavior. But I want to!)

Melissa Graham of Chicago had a great corporate life — and then she re-evaluated, became a chef and caterer, and began organizing in Chicago for sustainable local food, farmers’ markets, and a family-friendly food system. She blogs at the food and food-policy blog The Local Beet. And she’s written a reaction to SUPERBUG that not only completely gets the book, but is emotional and thoughtful and moving besides.

She says, in part:

Before reading Superbug, the question of confinement raised animals was an ethical one for me – whether the misery inflicted upon animals and, for that matter, the humans working in those facilities by the putrid conditions outweighed the need to eat cheap meat. Even the environmental degradation resulting from the inevitable careless management of CAFOs seemed a distant and intangible casualty. For me, Superbug has changed the argument from one of ethics to a moral imperative. In every hamburger of unknown origin, I see Tony Love’s face or even worse that of Carlos Don IV.

Carlos was another healthy kid who left on a school trip to the mountain and returned with a 104°F fever. The first doctor diagnosed Carlos with walking pneumonia so his mother kept him home bundled and hydrated until she realized that he was beginning to hallucinate. She rushed Carlos to the hospital and the doctor’s ultimately diagnosed his condition as MRSA. A long slow death march ensued during which Carlos’s lungs dissolved and clotting choked off the blood to his lower intestines, legs and arms. In two weeks, he was dead.

After reading Carlos’s story late in the evening, I woke a bewildered little locavore from a dead sleep to scrub his hands clean. I hugged him as tightly as I could.

…[recently] I had the pleasure to hear Ruth Reichl speak and she implored the audience to stop eating confinement raised animals. As she put it, if everyone stopped buying them and eating them, the practice would be history. Knowing what I now know, I think it’s our moral duty.

To give the post the traffic it deserves, please go here.

Catching up to MRSA news (not about me)

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Constant readers: I’m looking forward to having the breathing space to get back to in-depth blogging. Meanwhile, though, news is zipping by — so here’s a quick list of recent things worth reading.

“Cows on Drugs” — a superb history of the 30-year-old fight to get unnecessary antibiotics out of food animals. Note, written by a former commissioner of the Food and Drug Administration, not exactly a wild-eyed radical:

More than 30 years ago, when I was commissioner of the United States Food and Drug Administration, we proposed eliminating the use of penicillin and two other antibiotics to promote growth in animals raised for food. When agribusiness interests persuaded Congress not to approve that regulation, we saw firsthand how strong politics can trump wise policy and good science.Even back then, this nontherapeutic use of antibiotics was being linked to the evolution of antibiotic resistance in bacteria that infect humans. To the leading microbiologists on the F.D.A.’s advisory committee, it was clearly a very bad idea to fatten animals with the same antibiotics used to treat people. But the American Meat Institute and its lobbyists in Washington blocked the F.D.A. proposal.

 Antibiotic resistance in your kitchen, playroom, car... — After years of begging from health advocates, the FDA and EPA are taking a second look at the chemical compound triclosan, an antibacterial that is put into, well, almost anything you can name: soaps, hand sanitizers, cutting boards, toys. Triclosan is suspected of interfering with hormone regulation in the body, and also increases resistance in organisms in our environment. (When I ask you to use hand sanitizers that contain only alcohol or salts, not antibacterials, triclosan is one of the things I’m thinking of.) The FDA will report its findings in a year. I’d rather see it happen sooner, but it’s a great move.

No progress on hospital-acquired infections — The Agency for Healthcare Research and Quality, part of the Department of Health and Human Services, has published its 2009 National Healthcare Quality Report. The news is not good. To quote the agency’s own language: “Very little progress has been made on eliminating health care-associated infections.” This is all hospital-acquired infections, not just MRSA, but MRSA is a leading organism. The ugly details:

  • Post-operative bloodstream infections up 8%
  • Post-operative catheter-associated urinary-tract infections up 3.6%
  • “Selected infections due to medical care” up by 1.6%
  • Bloodstream infections as a result of central lines unchanged.

(NB, three professional organizations — the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, and the Association for Professionals in Infection Control — put out a statement in response to this report saying it “presents an outdated and incomplete picture on healthcare-associated infections (HAIs) in our healthcare system.” The gist of the statement seems to be that they’ve got better numbers coming… soon. When there’s actual data, I’ll let you know.)

SUPERBUG on Capitol Hill

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Constant readers, I’ve been shamefully absent from the blog, but with reason, since I’ve been traveling promoting the book. There was a pretty interesting opportunity this week that I wanted to tell you about: I was asked to be part of two Congressional briefings in Washington, DC Wednesday, addressing the overuse of antibiotics in agriculture and the contribution that makes to the emergence of resistant organisms such as MRSA. I went specifically to tell the story of the emergence of MRSA ST398, which we’ve been talking about for years here.

The briefings (FYI, “hearings” are for Congresspersons, “briefings” are for their staff) were cosponsored by the Pew Charitable Trusts, Union of Concerned Scientists, American Public Health Association, Infectious Diseases Society of America, and the nonprofit Keep Antibiotics Working.

Here’s Pew’s announcement, here’s the UCS version, here’s a write-up from the Washington Examiner, and here’s a longer one from the site Spectrum Science.

“Pig MRSA” causing human infections

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Hi, everyone. Apologies for dropping out of sight! As SUPERBUG’s publication draws closer (and it’s very close now), I keep finding new tasks that I have do to. Last week’s was to go to New York to shoot a video for the Simon & Schuster website — and while there, I got caught in Snowpocalypse, got delayed coming home, and picked up a nasty cold. So I’m a bit behind.

But there’s exciting news tonight to start us up again: “pig MRSA,” ST398, causing human infections in Canada and Denmark.

“Infections” is important, because up til now, most evidence for  the spread of MRSA ST398 in humans has been through detection of colonization, the symptomless carriage of MRSA on the skin and in the nostrils. The first finding of ST398 in the Netherlands was via colonization; so was its first identification in humans in Canada, and also in the United States just about a year ago.

But comes now a team of public and university scientists from Canada to say that ST398 is also causing infections in Canada. They analyzed 3,687 MRSA isolates that had been collected from patients seen for infections in Manitoba and Saskatchewan. Five were ST398. That is an exceedingly low percentage, of course. But it is striking, and odd, that the infections were present at all:

The earliest identified LA-MRSA isolate (08 BA 2176) associated with an infection was obtained from a postoperative surgical site. … This patient is unlikely to have had any recent direct contact with livestock because she had been confined to her home with limited mobility for several years before her hospitalization. Additional nasal swabs from this patient remained positive for this strain for at least 7 months. …
The isolate submitted to the NML by Sunnybrook Health Sciences Centre… was from a 59-year-old man from Ontario. He had been hospitalized in December 2007 for treatment of metastatic squamous cell carcinoma of the larynx. In the previous year, he had undergone a total laryngectomy, neck node dissection, and tracheostomy. …. He was unaware of any animal contact and had no history of exposure to pigs or pig farms. A review of the medical records and standard epidemiologic investigations determined that this was not a nosocomial or healthcare-associated isolate.

Just to underline, we have here a MRSA strain that is strongly associated with close contact with pigs, or with pig meat, and that has spread far enough from farms to be present in people who had no connection with pigs. You can argue that its very low prevalence means that it is not so much a threat as a curiosity. But I’d counter-argue that this is significant: because it establishes that this strain is spreading; because it demonstrates that the strain is causing infections, not just colonization; and because it inserts, into the swarm of isolates that make up MRSA, additional resistance factors that can be traded and exchanged unpredictably among the bacteria — and are likely not to be detected because our surveillance in animals is so sparse.

The authors say:

…additional surveillance efforts are required to monitor the emergence and clinical relevance of this MRSA strain in Canada, including communities, the environment, livestock, farmers, and production facility workers. Whether these strains pose a major threat to human health in light of the low livestock density and continued spread of epidemic hospital and community strains of MRSA in Canada remains unknown.

There’s also a new and tantalizing report from Denmark that appears to describe not only human infections, but human to human transmission, resulting in a very serious pneumonia in a baby. I can’t access the full-text even through my university account, but the abstract says:

Carriage of pig-associated methicillin-resistant Staphylococcus aureus (MRSA) is known to occur in pig farmers. Zoonotic lineages of MRSA have been considered of low virulence and with limited capacity for inter-human spread. We present a case of family transmission of pig-associated MRSA ST398, which resulted in a severe infection in a newborn.

Not good.

The cites for these are:
Golding GR, Bryden L, Levett PN, McDonald RR, Wong A, Wylie J, et al. Livestock-associated methicillin-resistant Staphylococcus aureus sequence type 398 in humans, Canada. Emerg Infect Dis; [Epub ahead of print] DOI: 10.3201/eid1604.091435
Hartmeyer GN, Gahrn-Hansen B, Skov RL, Kolmos HJ. Pig-associated methicillin-resistant Staphylococcus aureus: Family transmission and severe pneumonia in a newborn. Scand J Inf Dis. Epub Feb. 3, 2010 ahead of print.

Antibiotics and farming — CBS follow-up video

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Constant readers, CBS News has posted some follow-up video to its two-part series last week on antibiotics in agriculture. It features Dr. David Kessler, former Commissioner of the Food and Drug Administration (which under its current leadership has vowed to re-examine farm-antibiotic use), and Eric Schlosser, author of Fast Food Nation.

They talk about the protests CBS has received for airing the package, the concerns public health authorities have over the lack of  data on the amounts and types of antibiotics used, and much more. I especially love Schlosser’s comment: “I’m a meat-eater.” It’s important, I think, to say that being critical of antibiotic use does not mean being opposed to animal agriculture, or wanting to see farms shut down. It means being concerned for the health of farm animals, farm families, and everyone affected by growing antibiotic resistance — which is, you know, everyone.

(H/t @EdibleSF for flagging the video’s release.)


Watch CBS News Videos Online

(Hey, that’s my first embedded video!)

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.