Maryn McKenna

Journalist and Author

Non-medical use of antibiotics: A whole new problem with ethanol

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Constant readers, we’ve talked frequently about the emerging recognition that the enormous use of antibiotics in agriculture is fueling the development of resistance, both directly in the case of specific organisms such as MRSA ST-398, and indirectly in that it pushes the evolution of resistance factors that bacteria then trade amongst themselves. (For a superb overview of the antibiotics/agriculture problem, see this article in the June issue of the Johns Hopkins (University) Magazine. Hopkins is the home of the Center for a Livable Future, which is doing excellent research on this issue.)

And we’ve also talked about the related issue of antibiotic residues elsewhere in the environment, in sewage and wastewater supplies.

But here’s a whole new peril: Antibiotic resistance generated by ethanol production, that vast corn-based industry that has been pitched as a homegrown biofuel alternative to foreign oil.

Food-policy blogger (and farmer and chef) Tom Philpott has been doggedly following this story for more than a year at Grist. And in a study published last month the Institute for Agriculture and Trade Policy brings some important numbers-based analysis. The gist of the problem is this:

  • Ethanol production uses yeast to convert corn starches into alcohol
  • Bacterial contamination, usually by lactobacilli, can hijack the process and covert the starches to unusable lactic acid instead
  • To prevent that from happening, ethanol producers dose their corn mash with antibiotics
  • Because contamination is frequent and persistent, producers use increasing amounts of antibiotics to overcome bacteria that have become resistant
  • After ethanol is extracted, the mash residue remains tainted with those resistant bacteria and with antibiotics — including penicillin, erythromycin and streptogramin (an analog of the human antibiotic Synercid)
  • The dried mash residue is sold to farmers as livestock feed, exposing livestock to resistant bacteria and dosing them with unsuspected additional antibiotics as well.

If there is any good news in this, it is that (according to the IATP), some of the faltering ethanol industry is aware of the problem and working on it, with about 45% of plants now working on non-antibiotic alternatives. The bad news is that 55% — more than 90 of the 170 ethanol facilities in the United States — are not.

Media round-up: recommending MRSA stories

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By chance — or is it because interest is really picking up? — a couple of worthwhile stories on MRSA have been published almost simultaneously:

  • For when the science gets wonky: Environmental Health Perspectives has an excellent lay-language explanation of how drug resistance emerges and spreads — with gorgeous graphics!
  • For when yet another drug doesn’t work: Scientific American covers development of new antibiotics, and even more important, development of new ways of creating antibiotics.
  • For yet more depressing news about MRSA in meat: Prevention adds to the discussion of MRSA in the food supply with a “special report” review. Constant readers who have been following along as we’ve drilled into this topic over the past two years won’t find a lot new, except for an intriguing account of an outbreak of MRSA in an Arkansas chicken plant (in which the bug went disappointingly untyped, so we don’t know whether it was a human strain or ST398). The story hits on issues we have talked about here: Surveillance for MRSA in animals is non-existent, practically speaking, and when the bug is found, investigation falls between human and animal health agencies. It’s a longer than usual story for Prevention, and should bring the knotty food-policy questions around MRSA in meat to a new audience.

Antibiotic overuse in animals: Obama administration comes out against

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For anyone who cares about the overuse of antibiotics in food animals, and the resistant bacteria that overuse has been shown to produce, this is important news.

In testimony today, new FDA Commissioner Dr. Joshua Sharfstein announced the administration’s opposition to the use of growth promoters: sub-therapeutic doses of antibiotics used not as disease treatment, but to encourage animals to put weight on rapidly. Further, he also came out against the administration of antibiotics in food animals without the involvement of a veterinarian — a common situation out here in farm country, where veterinary antibiotics are freely available over the counter. (We discussed Scott Weese’s proposal to end that practice here.)

Both of these practices have been repeatedly linked to antibiotic resistance, and for the administration to come out against them is highly significant — not just for the struggle against resistant bacteria, but also for the movement to reduce industrial-scale agriculture, which relies on antibiotics to keep food animals healthy while they are in the close confinement of CAFOs.

Sharfstein made the announcement while giving testimony on behalf of Rep. Louise Slaughter (D-NY)’s Preservation of Antibiotics for Medical Treatment Act of 2009, which has been introduced (and opposed into nonexistence) multiple times over the past decade. (Earlier post on the legislation, including its text, here.) He said:

To avoid the unnecessary development of resistance under conditions of constant exposure (growth promotion/feed efficiency) to antibiotics, the use of antimicrobials should be limited to those situations where human and animal health are protected. Purposes other than for the advancement of animal or human health should not be considered judicious use. …
Important factors in determining whether a prevention use is appropriate include evidence of effectiveness, evidence that such a preventive use is consistent with accepted veterinary practice, evidence that the use is linked to a specific etiologic agent, evidence that the use is appropriately targeted, and evidence that no reasonable alternatives for intervention exist. FDA also believes that the use of medications for preventino and control should be under the supervision of a veterinarian. …
FDA supports the treatment of ill animals according to appropriate veterinary practice within a valid veterinary-client-patient relationship.

Also on the docket at Slaughter’s hearing:

  • Margaret Mellon, PhD, of the Union of Concerned Scientists (who specifically discussed MRSA ST398): “As long as the massive use of antibiotics continues, animals … will remain a fountain of resistant pathogens, dangerous to both animals and humans. The straightforward solution to the problem is to reduce the use of antibiotics in animal production and thereby diminish the pool of resistant organisms and traits.”
  • Robert Martin of the Pew Environment Group (Pew Charitable Trusts): “The present system of producing food animals in the United States is not sustainable and presents an unacceptable level of risk to public health, damage to the environment, as well as unnecessary harm to the animals we raise for food.”
  • And statements of support from the Chipotle restaurant chain and the Bon Appetit Management Company (which operates catering services in corporations and universities).

Of note, the Pew Commission on Human Health and Industrial Farming, which supports Slaughter’s bill, said after the hearing that Sharfstein’s proposals are only necessary but not sufficient: ““The proposed FDA position does not go far enough in this regard and would allow the continuation of conditions that necessitate the improper use of antibiotics in the first place.”

Food and ag policy sites: New in the blogroll

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Folks, when I was writing the last post (regarding Scott Weese’s blog), I had to stop and look up several sites. In mid-click, I realized how silly that was, because they are sites I visit all the time — and you should too, if you’re concerned about the veterinary, zoonotic, agricultural and food-policy issues that we discuss here so frequently.

So I’ve created a new category in the blogroll to the right, showcasing food and ag-policy sites that I think are worth reading. Among them you’ll find:

If you have other recommendations, please send them!

Restricting antibiotics in animals: Start by restricting access

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Constant readers, those of you who follow the pressing issue of MRSA in animals will know the work of J. Scott Weese, DVS, associate professor of pathobiology at the University of Guelph in Ontario and supervising author of many crucial papers on MRSA in food and companion animals, including the first finding of MRSA in pigs and pig farmers in North America.

You may not know that Weese and his postdoc Maureen Anderson publish an excellent blog on veterinary and zoonotic diseases called Worms and Germs (in the blogroll at right). This weekend they have an important post that deserves wider attention: Antibiotics: A Dose of Common Sense. In it, they propose that one way to reduce the overuse of drugs in food animals is to make animal antibiotics prescription-only. It’s worth taking the time to read it.

Those of you in the cities may not know this, but out here in the Great Flyover, antibiotics for veterinary use are surprisingly easy to buy (as I discovered when I stumbled into a farm-related store in search of a Carhartt jacket against the Minnesota winter). They’re not even over-the-counter — they’re on the shelf, or stacked on the floor with the implements and feed, or blended into the feed itself. And as Weese points out in this post, they are also available without prescription over the Internet (as human antibiotics are too).

It’s a potentially controversial proposal: I don’t think I have any farming readers, but I would imagine their response would start with an objection to the extra cost of hiring a veterinarian to assess whatever situation might require the drugs. And since most farmers (NB: not the overarching ag-biz companies, but the farmers themselves) exist on razor-thin economic margins, they would have a point. But as we know from the excellent work of Extending the Cure and the Center for a Livable Future, unnecessary antibiotic use comes with a cost as well — one that is borne by all of us when antimicrobial resistance prevents antibiotics from working.

MRSA and pets

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It’s been a while since we’ve focused on the presence of MRSA strains in pets, and the complications that can cause for the pets’ human owners/custodians/companions (or, in the view of my own two cats, abject servants. No, I will not post their pictures. I have some shreds of pride).

The problem with MRSA and pets is not the same as the problem of MRSA ST398 in food animals. Rather, pets tend to carry human strains, passed to them by their owners. The carriage is usually asymptomatic, but not always; there are cases in the medical literature of cats and dogs suffering serious skin and soft-tissue infections from community-strain MRSA, usually USA300. But the emerging consensus seems to be that pets carry the bug transiently — not long, but long enough to reinfect the person who passed the bacterium to the pet in the first place. (This can be, but is not always, the source of recurrent infections in humans: The human takes antibiotics and recovers, but the animal holds onto the bug long enough to pass it back to the now-clear human.)

For anyone who needs to go deeper on this, the current issue of Lancet Infectious Diseases has a good overview of the problem that community MRSA strains pose to pets and their humans. There’s a thorough review of the major papers:

  • Cefai, 1994: hospital outbreaks traced to two nurses and through them to their dog
  • Simoons-Smit, 2000: household epidemic of three humans, one cat, one dog
  • Manian, 2003; dog is source for owner’s recurrences
  • Vitale, 2006: owner is (apparently) source of cat’s MRSA.

(This is a good place to say that this entire history, including personal stories of human and animal infection, is covered in a chapter of SUPERBUG. Publication date coming soon!)

The Lancet paper incorporates reminders of some powerful and troubling trends. As with MRSA ST398, one thing can distinguish MRSA that has been in an animal is a resistance pattern that is slightly different from what we expect but that has arisen because the animals receive different drugs. In the case of pigs and ST398, the intriguing marker is tetracycline resistance; humans don’t usually get tetracycline for MRSA, but pigs do. In the case of companion animals, it tends to be fluoroquinolone resistance; pets are more likely to get that class of drugs for a skin/soft-tissue infection. But, the authors caution, that may mean that pets serve as a breeding ground for multi-drug resistant MRSA, with their fluoroquinolone treatment adding another resistance factor into the bug’s already potent arsenal.

The authors also remind us that MRSA can come from animals much more directly than through silent carriage: that is, in a bite. Both dog and cat bites have been found infected with MRSA, due to bacterial contamination of the wound either from the pet or from colonization on the human’s skin.

The cite is: Oehler RL et al. Bite-related and septic syndromes caused by cats and dogs. The Lancet Infectious Diseases, 9(7):439 – 447, July 2009. doi:10.1016/S1473-3099(09)70110-0.

H1N1 flu and swine surveillance – more relevance for MRSA

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

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

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

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

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

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.

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