Antibiotics and farming — how superbugs happen

Constant readers: There's an important new paper that's been out for a week that I haven't gotten to you. I apologize; it's been busy. (Let's not even talk about the important paper that's been out for two weeks. Maybe over the weekend...)

We've talked for ages now about the potential dangers of unrestricted antibiotic use in agriculture, and how it's analogous to the inappropriate antibiotic use that human health authorities disapprove of in humans. The main culprits, in farming, are subtherapeutic dosing, also known as growth promotion — that's giving routine smaller-than-treatment doses to animals to increase their weight — and prophylactic dosing, which is giving a treatment dose to an entire herd or flock either routinely, if there is thought to be a disease threat, or when there is known to be disease in some members of the herd/flock. In either case, animals are getting antibiotics when they do not need them — when they are not sick. And just as in humans who take antibiotics when they are not sick, or take too-low doses when they are sick (such as not finishing a prescription), these practices in animals encourage the development of resistant bacteria.

(Necessary comment here: No one, to my knowledge, objects to giving the appropriate doses of antibiotics to animals that are sick. Why would you?)

The interesting research question is how, exactly, resistance develops. (My real scientist readers may want to take a break, or cut me a break, for the next few sentences. Please.) The classical assumption has been that, through a variety of stimuli and the random copying errors of reproduction, bacteria are constantly acquiring small mutations. Some of those may give the bugs an advantage when they are exposed to a drug, some slight difference that allows the bacteria to disarm or turn aside that drug's particular method of assault — so that the weak die, the strong survive, and the strong then reproduce more abundantly into that extra living space freed up by the death of the weak. The survivors and their descendants retain that mutation, because it gave them an advantage against the drug. And because bacteria can share resistance factors not only vertically mother-to-daughter, but horizontally in the same generation, once the resistance has emerged, it is likely to spread.

But no matter how quickly it spreads, that process I've just described involves acquiring resistance to just one drug or drug family at a time. Provocative new research from Boston University's medical school and deoartment of biomedical engineering now suggests, though, that multi-drug resistance can be acquired in one pass, through a different mutational process triggered by sublethal doses of antibiotics — the same sort of doses that are given to animals on farms.

In earlier work, the authors found that antibiotics attack bacteria not only in the ways they are designed to (the beta-lactams such as methicillin, for instance, interfere with staph's ability to make new cell walls as the bug reproduces, causing the daughter cells to burst and die), but also in an unexpected way. They stimulate the production of free radicals, oxygen molecules with an extra electron, that bind to and damage the bacteria's DNA.

That research used lethal doses of antibiotics, and ascertained that the free-radical production killed the bacteria. In the new research, the team uses sublethal doses, and here's what they find: The same free-radical production doesn't kill the bacteria, but it acts as a dramatic stimulus to mutation, triggering production of a wide variety of mutations — what the researchers, in a press release, called "a zoo of mutants." The plentiful, scattershot mutations included ones that created resistance to a number of different drugs — in some cases, even though no mutation was present that created resistance to the drug being administered.

You can easily see how this is applicable to factory farming: The sublethal dosing applied experimentally is analogous to the subtherapeutic dosing used in agriculture. Is it applicable to MRSA? Yes, absolutely. The two organisms the researchers used to test their hypothesis were S. aureus and E. coli.

making the implication clear, senior author James J. Collins said on the paper's release:

"These findings drive home the need for tighter regulations on the use of antibiotics, especially in agriculture; for doctors to be more disciplined in their prescription of antibiotics; and for patients to be more disciplined in following their prescriptions."

The cite is: Kohanski MA, DePristo MA and Collins, JJ. Sublethal Antibiotic Treatment Leads to Multidrug Resistance via Radical-Induced Mutagenesis. Molecular Cell, Volume 37, Issue 3, 311-320, 12 February 2010.

UPDATE: There's a great discussion of the paper at the blog Mental Indigestion.

Postscript: I suppose I've been working too long without a break, because while I was reading about this process of creating multiple resistance factors at once, what I heard in my head was Mickey Mouse chirping: "Seven at one blow!"

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

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.

CBS antibiotics and farming package, day one

Constant readers, I hope you saw the CBS News package on antibiotics in farming Tuesday night. (It continues Wednesday.) MRSA played a prominent role, in an account of infections among workers at a chicken plant (the same outbreak, I think, as was described by Prevention magazine last August) and in questions about MRSA in pig farms in the Midwest (with a prominent mention of Tara Smith's research into "pig MRSA" ST398).

Here's the 7-minute video and the text version.

Earlier Tuesday, CBS's Early Show ran an additional package on the death of a Chicago toddler from MRSA. That toddler's name is Simon Sparrow, and you'll be able to read his sad story — told by his mother, Everly Macario — in SUPERBUG.

Warning on ST398: Monitor this now

Drawing your attention: I have a story up tonight at CIDRAP on a new paper by Dr. Jan Kluytmans, a Dutch physician and microbiologist and one of the lead researchers tracking "pig MRSA," ST398. (All past stories on ST398 here.) It's a review paper, which is to say that it summarizes key existing findings rather than presenting original research.

Still, it's important reading because Kluytmans is one of the few scientists who have some history with this bug and understand how quickly and unpredictably it has spread across borders and oceans, from pigs to other livestock, to pig farmers and veterinarians, into health care workers and hospital patients who have no known livestock contact, and now into retail meat in Europe, Canada and the United States.

Take-away: A plea and warning for better surveillance, so that we can track not only the bug's vast range, but also its evolution as it moves into new ecological niches — including humans who are buying that retail meat and possibly becoming colonized with it as they prep it for cooking in their home kitchens.

To honor fair use (and in hopes you'll kindly click over to CIDRAP), I won't quote much, but here's the walk-off:

Because the novel strain has spread so widely and has already been identified as a cause of hospital outbreaks, it should not be allowed to spread further without surveillance, Kluytmans argues."It is unlikely that this reservoir will be eradicated easily," he writes. "Considering the potential implications of the reservoir in food production animals and the widespread presence in meat, the epidemiology of [MRSA] ST398 in humans needs to be monitored carefully."

The cite is: Kluytmans JAJW. Methicillin-resistant Staphylococcus aureus in food products: cause for concern or case for complacency? Clin Microbiol Infect 2010 Jan;16(1):11-5. The abstract is here.

H1N1 flu and swine surveillance - more relevance for MRSA

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?

Does ethanol production produce resistant bacteria too?

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.

Great op-ed in the LA Times on antibiotics in animals

By Paul Roberts, author of the new book The End of Food. Find it here.

(H/t to indefatigable animal activist Karen Dawn, author of Thanking the Monkey, for the link!)

Antibiotic resistance in food animals all across Europe

Via a journal that's new to me — the Acta Veterinaria Scandinavica, the open-access journal of the Veterinary Associations of the Nordic Countries — comes an amazing review of the prevalence of antibiotic resistance in cattle in 13 European countries. Based on 25,241 isolates collected over three years, Denmark, Britain, the Netherlands, Norway, Sweden and Switzerland do well, but "many isolates from Belgium, France, Italy, Latvia and Spain were resistant to most antimicrobials tested."

Most resistant pathogen: E. coli. MRSA is present as well:

Of major concern is the level of resistance to oxacillin and 3rd generation cephalosporins (i.e. ceftiofur) in S. aureus. The prevalence of oxacillin resistance in Spain (3.7%) and France (8.3%) and the resistance towards cephalosporins in Spain (0.9% in 2004) and France (4.2% in 2002; 1% in 2003) indicate the presence of methicillin resistant S. aureus (MRSA) in these two countries.

The authors ascribe the differences among countries to different patterns of antimicrobial use by veterinarians and stress that it is time for veterinarians to begin using measurements of local resistance patterns (in human medicine, an "antibiogram") before prescribing. Cite coming when the Acta site is updated. UPDATE: The paper is here; cite is: Hendriksen, RS et al. Prevalence of antimicrobial resistance among bacterial pathogens isolated from cattle in different European countries: 2002-2004. Acta Veterinaria Scandinavica 2008, 50:28doi:10.1186/1751-0147-50-28.

I wasn't aware that this same set of authors (Hendriksen, RS et al.) just a few weeks ago published a similar review of antimicrobial resistance in pigs in Europe. It looks at several bacterial species in pigs, but unfortunately for our purposes, no S. aureus.

Great post elsewhere on antibiotic use in animals

There will be a bit of a blog break, as I'm traveling for a week. But here as a walk-off is an excellent post from the marvelous public-health blog Effect Measure about the complexities (to be kind) of food companies declaring antibiotic use in food animals.

Very short version of the story: Massive chicken producer Tyson advertised its chickens as being "raised without antibiotics"; the chicken eggs were actually being treated with gentamicin before hatch (therefore technically not being "raised"; the US Department of Agriculture objected, then backed down, then objected again after Tyson's competitors acted on their own.

Tyson announced it is "voluntarily" withdrawing the label. Which is more than the USDA did, apparently, its hand having been forced by Tyson's competitors organized into the Orwellian-named Truthful Labeling Coalition (including Perdue Farms Inc., Sanderson Farms Inc. and Livingston, California-based Foster Farms). Perdue and Sanderson had sued over a label they considered "clearly false and misleading," and a federal judge agreed, ordering Tyson to stop them from running any advertisements with the claim last month. Now, belatedly, the USDA is acting.

The entire post is worth reading, as is Effect Measure (which is running on a "summer schedule" and therefore posting only once a day, thus making us all look bad. Hmm, perhaps a Public Health Blog Truthful Labeling Coalition is in order...)

Closing the loop: meat, meat-eaters, health-care workers

A posting on the international disease-alert mailing list ProMED led me to a scientific abstract presented at a European meeting this spring on the ST 398 MRSA strain. It adds another, quite unnerving piece to the emerging interplay of MRSA in pigs, humans who have close contact with pigs, humans who have contact only with pig meat, and health-care workers who treat those humans.

Brief precis: About a year ago, Dutch health authorities discovered that a patient who had come in for surgical debridement of a diabetic foot ulcer had an unrecognized MRSA strain in that ulcer. Subsequently, they discovered that four other patients and five health-care workers in the same institution were carrying the same strain. None of the patients reported any contacts with pigs (or calves, which have also been found to carry the strain). One of the health-care workers lived on a farm that raised pigs, but said that she had no contact with the animals in her daily life; nor did her partner.

The authors conclude:

While the source is not fully established it could be the HCW living on a pig farm. This outbreak makes clear that transmission on a larger scale can occur, even with NT-MRSA.

(Hat-tip to Helen Branswell of the Canadian Press for telling me about the ProMED report. And a note to loyal readers: The "MRSA in meat" story is being picked up by some US newspapers. Doesn't it feel good to know you've been reading about the issue here for months? And if you're a reader of Helen's work, months more? Of course it does.)

New blog on animal health including MRSA

Dr. J. Scott Weese of the Ontario Veterinary College (author of many important papers, discussed in many posts here, on MRSA in food and companion animals) has started a blog on animal-health issues. Here is a recent post on tracking down the source of a MRSA infection when there is a pet in the house.

The blog is called Worms and Germs and I've added it to the blogroll at right.

One more on MRSA in meat

It turns out that European governments — in contrast to the United States — are taking very seriously the emergence of MRSA in food animals and its potential for transfer to humans. (For background, posts here, here, here and here.)

How seriously? They're doing a sampling survey of pigs on farms across the European Union, at a cost of about $3 million in EC funds, with matching funds expected from each government.

The MRSA survey piggybacks (sorry) on a year-long survey of Salmonella incidence that the EC called for in September 2007. But in December, following publication of several significant papers about the ST 398 MRSA strain in pigs and pig farmers, the EC Directorate-General for Health and Consumer Protection pushed for an addition to the Salmonella study: a same-time sampling for the presence of MRSA strains in pig operations across 29 countries.

The sampling is taking place from January to December of this year, with results mandated by mid-2009, though individual country authorities may release data earlier if they choose. (In the wake of the finding of three ST 398 cases apparently caused by retail meat in the UK, the Soil Association has called on the British government to release whatever data it has ASAP. Before the EC decision, the UK government had refused to test its pigs; cf. these House of Lords minutes.)

Of note: The Soil Association is pressing the argument that ST 398 has developed in the setting of widespread use of antibiotics in food animals, and contends the strain's arising in the Netherlands is especially alarming because they have some of the lowest animal-antibiotic use rates in the EC it illustrates the difficulties that even a society conscientious about antibiotic overuse can have keeping track of veterinary applications. The Netherlands has been successful limiting overuse in humans, but has found controlling veterinary use much more of a struggle. (Thanks to the Soil Association for correcting my misunderstanding!)

MRSA in the food chain?

Behind the growing number of findings of MRSA in food animals and the humans who work with them — in the Netherlands, Canada and now in the US — there lurks a persistent concern that the meat of those animals could be a vector for MRSA transmission. Dr. J Scott Weese of the Ontario Veterinary College raised the possibility in a presentation I reported on at the International Conference on Emerging Infectious Diseases, and Dutch researchers raised it in a paper last year as well.

Until now, though, it has been a hypothetical concern, since the humans found with pig-associated MRSA (both the already-recognized community and hospital strains and the emerging ST 398 strain) have all been animal workers.

So much for hypothesis. The London newspaper The Independent is reporting that the ST 398 strain has sickened three patients in Scotland who have no connection to animal raising or slaughtering, suggesting their infections came from contact with raw meat.

All three patients, who were being treated in at least two different Scottish hospitals, recovered. Confirming the cases, Dr Giles Edwards, director of the Scottish MRSA Reference Laboratory, said: "A lot of the patients who got this infection in Holland and Canada have been people who work with animals, such as farmers and vets. But none of the three individuals in Scotland have been in contact with animals, not that we could find." (Byline: Martin Hickman)

The bug has not currently been found in pigs raised in England, but about two-thirds of pork sold in the UK is actually imported from the Netherlands. So the Soil Association (the British farming lobby) has asked the government to begin testing imported pork for MRSA strains. The British Food Standards Agency disagrees, however, telling the Independent it does not "see serious food safety issues."

Which is strikingly close to what CDC Director Dr. Julie Gerberding said in February when asked by the House Committee on Agriculture about the Dutch and Canadian reports:

... although the finding of MRSA in retail meats suggests a possible role for foodborne transmission, if such transmission occurs, it likely accounts for a very small proportion of human infections in the United States. (Letter .pdf archived here on the site of the National Pork Producers Council.)

Hmmm.

UPDATE: The Soil Association's statement, with some good additional references (including to a newspaper report by the Sunday Post two days before the Independent's) is here. More to come on this, I think.

Meat animals, antibiotics and resistance

Just published: Two big, thought-provoking reports that should do a great deal to illuminate the murky debate over the use of antibiotics in animal feed and the question of how much that promotes antibiotic resistance.

Extremely brief back-story:

• For roughly the past 50 years, animal production in the US has morphed from a horizontal industry of small family farms to a vertical one populated mostly by very large breeding-feeding operations that are closely tied to slaughter-processing-distribution businesses.
• These industrial farms — commonly called CAFOs for "concentrated animal feeding operations" — start at about 1,000 cattle or 10,000 chickens and often are orders of magnitude larger. That many animals crowded together exceeds the carrying capacity of any pasture, and CAFO animals are commonly fed industrial feed.
• Those conditions obviously do not match the ones for which the animals evolved, and as a result the animals do not grow well in them. So to keep them healthy and speed their growth — they are an industrial product after all, and production speed affects profit — industrially raised animals are routinely fed small doses of antibiotics; by one estimate, 70% of all antibiotics used in the United States are given to food animals not humans.
• And as human medicine has demonstrated, the more that antibiotics are used, and therefore the more that organisms are exposed to them, the more likely it is that antibiotic resistance will develop.

The reports just published attempt some next steps in addressing those concerns.

• CAFOs Uncovered, by Doug Gurian-Sherman and the Union of Concerned Scientists, estimates that the cost to taxpayers of CAFOs' promotion of resistance equals $1 billion to $3 billion per year.
• Putting Meat on the Table, a joint project of the Pew Charitable Trusts and the Johns Hopkins Bloomberg School of Public Health, calls on Congress to phase out and then ban all non-therapeutic use of antimicrobials in animals (that is, in any animals that are not sick or have not been exposed to disease).

And in a lovely bit of either synergy or serendipity, the nonprofit Trust for America's Health released today a report that illuminates the near-complete breakdown of the US food safety system and the increasing vulnerability of Americans to food contamination and foodborne disease — proof, in case anyone needed it, that all those antibiotics fed to animals are doing us no good at all.

(For earlier posts on MRSA in food animals, go here.)

MRSA and animals and hospitals

I am at the annual meeting of the Association of Health Care Journalists, where last night we heard actor Dennis Quaid discuss the severe medical error that led to his infant twins being given 1000x the appropriate dose of heparin - twice. (Interesting tidbit: The twins were in the hospital because of a staph infection.) Quaid and his wife have set up a foundation that will work to reduce medical errors and is soliciting stories from victims and families.

Later today I'll be moderating a panel on mandatory reporting of hospital infections that we hope will provoke an, ahem, free and frank exchange of views. More on that to come.

Meanwhile, though, a wrinkle in the possibility that companion animals might spread MRSA: What if they are therapy animals?

An international collaborative group has contemplated that question and come out with a thoughtful set of guidelines that are published in this month's issue of the American Journal of Infection Control. The guidelines address both official therapy animals and also pets who live in long-term care facilities or are brought to visit patients.

Key considerations: Animals could not only spread disease to patients because they are colonized; they may also become colonized because they are handled by patients. Because transmission and colonization may be so dynamic, the most important preventive measure will be hand hygiene rather than attempting to evaluate the animal's bacterial carriage at any single point. And key points: To minimize opportunities for transmission, exclude animals that have come directly from a shelter or pound; animals that eat a raw-food diet; animals that haven't been or can't be housebroken or litter-trained.

The guidelines are here, and there's a good MSM summary by Helen Branswell of the Canadian Press here.

MRSA and animals - not pets, meat

The International Conference on Emerging Infectious Diseases ended today with more news about a range of infections including MRSA. Most eyebrow-raising: Dr. J. Scott Weese of the Ontario Veterinary College in Guelph, an author of the original MRSA-in-cats paper I described a few posts ago.

Weese's news, tucked in at the end of a comprehensive presentation on MRSA and animals: Analysis of 212 raw pork products sold in four Canadian provinces reveals an average rate of MRSA contamination of more than 9%.

This shouldn't be surprising: Research by Weese and others has been revealing a complex and not well-understood interplay of infection between pigs and nearby humans.

• A 2005 French paper reported a rate of resistant-staph nasal colonization in pig farmers that was twice as high as among human controls; 57% of the isolates from the farmers were identical to nasal isolates in pigs.
• Last June, a Dutch study found 39% of pigs in nine major slaughterhouses in the Netherlands carried an identical novel MRSA strain.
• In December, two studies filled out the picture. A Dutch study reported the prevalence of that novel MRSA strain (dubbed ST 398 and first found in a human in 2003) has risen to more than 21% of all MRSA isolates in the country. A Canadian study (with Weese as senior author), published online ahead-of-print, found MRSA colonization rates of 25% among Ontario pigs and 20% among pig farmers, with most of them sharing the ST 398 strain but some possessing the CA-MRSA strain USA100.
• A Dutch study in January (first author Engeline van Duijkeren, who did the S. intermedius study from a few posts ago) found that pigs were colonized with MRSA on a variety of types of farms, such as ones that birth pigs and ones that raise them to slaughtering weight.
• And just to erase any doubts, several Dutch studies have established that the ST 398 strain causes human disease: endocarditis, mastitis, severe hospital-acquired pneumonia and bloodstream infection.

Weese stressed today that his team's finding of MRSA in raw retail meat is very preliminary (though it is backed by a Dutch study from last November that found 34 MSSA strains and two MRSA strains — ST 398 and USA300 — in 79 pork samples). He added, though:

"People don’t tend to handle pork like it is biohazardous, unlike chicken. So there may be a theoretical concern that pork could be a vehicle of methicillin resistance colonization — but it is way too early to say anything about that."

But if you're not already handling raw meat in a careful manner (sterilizing cutting boards, avoiding cross-contamination), it might not be too early to start.

More on pets and human infections

Another snippet from the International Conference on Emerging Infectious Diseases in Atlanta — again, not about staph, but about the unique role that pets may play in disease transmission:

In the exhibit hall that houses the "posters" (which are just what they sound like: broad swaths of shiny paper printed with graphical presentations of research), there is an intriguing report from West Virgina and the CDC about a novel infection in a cat. The infection is very serious: Corynebacterium diphtheriae, the bacillus that causes diphtheria (the "D" in the childhood DPT vaccine). Diphtheria seldom occurs in the United States — five or fewer cases per year — which is a good thing since it is a horrible disease that causes a membrane to grow across the throat and cut off breathing. It occurs so seldom because humans are the sole host for the disease, and when vaccination renders humans inaccessible territory, diphtheria fades away.

Well, make that: Humans were thought to be the sole host. The report at ICEID describes a pet cat (by the picture, a charming tortoiseshell) who came into a West Virginia veterinary hospital with a very severe ear infection. The infection turned out to be caused by C. diphtheriae that was present not only in that cat, but in a second household cat as well — but not in the cats' two human household members, nor in the eight vet personnel who had been exposed to the cats. Four isolates from the two cats had identical genetic fingerprints, but did not match any C. diphtheria isolates ever analyzed by the CDC.

And this means... what, exactly? It's not not clear how significant a development it is — "More research needed," the CDC says — but it's not good. A disease that was thought to exist only in humans, and thus could be chased out of humans if the percentage of vaccination is high enough, might instead be sustained in humans' environment by another species. And that species just happens to be a very common animal that shares our space very intimately. (Reports that my cats sleep on my pillow are merely vicious rumors. Anyway, it's only during the day.)

If vaccination coverage of the population were perfect, this would not matter: We would be protected anyway. But it's not.

More on pets and staph

I am at the International Conference on Emerging Infectious Diseases, a biannual meeting sponsored by the CDC that is a disease geek's dream of heaven. The days are extremely packed — about 2,000 attendees and presentations every 15 minutes for most of three days — so blogging may be a little light. Lots of MRSA news here though, so there will be a lot to catch up on.

Here's one example: Engeline Van Duijkeren of Utrecht University reported this afternoon on an outbreak of Staphylococcus intermedius, a staph species that colonizes and causes disease in dogs and cats but is rarely found in humans. Between late 2006 and early 2007, the lab at Utrecht received samples for analysis from six animals, all of which had surgery at the same veterinary hospital: five dogs with orthopedic surgery, one cat with abdominal surgery. The samples yielded identical strains of S. intermedius that were all methicillin-resistant — and resistant to a host of other drugs as well, from 3d and 4th generation cephalosporins to clindamycin to tetracycline to Bactrim.

The lab group found the case cluster and the resistance pattern so striking that they looked around for a common source, including among the clinic's veterinary personnel. They swabbed the surgeon, six technicians, two healthy dogs who lived in the clinic, and the local environment. They found the identical strain in the noses of the surgeon, three of the technicians, and one of the house dogs. Conclusion, van Duijkeren said: The humans (who were colonized, not sick) picked up the strain and redistributed it to the animals under their care. It's the first recorded transmission of MRSI between humans and animals.

(Worth noting: A questioner from the University of Pennsylvania, which has done a lot of work on staph in animals, rose during the Q/A to suggest that the hospital was experiencing a clonal cluster of cases that arose independently, rather than a chain of transmission. Oooh, more fodder.)

MRSA and cats - an earlier paper

In journalism, there sometimes arises a situation in which a reporter for a major outlet writes a story that is very similar to one that has already been published by a minor outlet, without crediting the minor outlet. We call it "bigfooting." It's not a compliment.

The flurry of attention to the new letter in the New England Journal of Medicine about a pet cat harboring MRSA and reinfecting the cat's owner has a whiff of bigfooting about it. The letter describes a German family with MRSA that particularly persisted in the wife/mother despite treatment until one of their three pet cats was swabbed and decolonized.

The three authors from the Bavarian Food and Health Safety Authority write, "There is evidence that companion animals, mainly dogs, harbor MRSA, and interspecies transmission has been shown in the members of a family and their dog. This case illustrates that MRSA transmission also occurs between humans and cats." There are five cites appended to the letter, on MRSA epidemiology and sequencing and MRSA in dogs. The inference that this is the first recorded case of cat-human MRSA exchange was picked up by several media outlets: — Associated Press, Reuters — and explicitly stated by HealthDay. com, whose story was carried by the Washington Post.

So, the bigfooting: This isn't the first report of cat-human transmission at all. A very nice paper published in December 2006 in Emerging Infectious Diseases (not NEJM, but not exactly obscure as it is published by the CDC) reports the first isolation of the CA-MRSA strain USA300 from a California cat along with an identical strain in the cat's human. And it shows up close to the top of a Medline search, so it wasn't exactly hard to find.

(There is also a 2005 Veterinary Microbiology paper that reports a PVL+ strain in a cat along with several from dogs, but the researchers didn't type the strains and were unable to say whether they were CA or HA; and two letters in the Veterinary Record in 2004 and 2006 citing multiple MRSAs in cats. Neither draw a direct link to human illness.)

OK, enough truth-squadding. Back to HAI and search-and-destroy soon.

Got (wallaby) milk?

Researchers in Melbourne, Australia report finding a broad-spectrum antimicrobial compound in the milk of the Tammar wallaby, which lives on islands off Australia's south and west coasts. Like other young, wallabies are born with an undeveloped immune system yet seem notably resistant to infection; the compound, AGG01, may be why.

Using advanced computer systems, researchers at the state of Victoria's Department of Primary Industries in Melbourne, Australia, found more than 30 potential bug-fighting compounds in the milk of the Tammar Wallaby (Macropus eugenii). One compound, known as AGG01, was particularly potent said lead researcher and animal geneticist, Ben Cocks.

Some experiments showed small amounts of a synthetic form of the drug were able to kill all bacteria in 30 minutes. "We found in lab tests that AGG01 is very effective against multidrug-resistant gram negative bacteria, including those that are most difficult to treat," he said.

Next research step: Designing a wallaby-milking machine.

Full text: Anti-superbug weapon developed from wallaby milk

(Hat tip to Boing Boing.)