Maryn McKenna

Journalist and Author

News break: FDA estimates US livestock get 29 million pounds of antibiotics per year

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This afternoon, the Food and Drug Administration posted without fanfare a report that many people have been waiting a long time for: Its first-ever estimate of the amount of antibiotics sold for use in food animals in the United States.

And the number is: almost 29 million pounds in 2009.

That’s a lot.

Is it more or less than was expected? It’s almost impossible to say. Estimates of the amount of antibiotics given to food animals in the United States are ferociously contested and plagued by squishy definitions and category creep. In 2000, the Animal Health Institute, which represents veterinary drug manufacturers, put total use at 17.8 million pounds. In 2001, the Union of Concerned Scientists, which campaigns (among other issues) to dial back use of agricultural antibiotics, estimated that 24.6 million pounds per year are used only for “non-therapeutic purposes” — that is, to make animals grow to market weight faster and to prevent them catching diseases in the close quarters of confinement agriculture.

The reason why antibiotic use on farms is a concern, of course, is because such use stimulates the emergence of drug-resistant organisms that move off the farm in animals, in groundwater, in dust, on the wind and in the systems and on the clothes of those who work there, and makes new resistance factors available to be swapped among bacteria. (For much more about that, see these three posts and this long archive at my former blog.)

The FDA’s estimate comes as the agency has been moving to curb agricultural antibiotic use after years of non-action. Today’s report, which is very short — basically a table and a bunch of footnotes — is the direct result of a 2008 amendment to the Animal Drug User Fee Act of 2003, which required manufacturers to report yearly on sales of agricultural antimicrobials. (Here’s an FDA Q&A on the report background.)

More important, though, today’s report dovetails with the FDA’s new effort to curb antibiotic use in agriculture, which Commissioner Dr. Margaret Hamburg said in October would involve “very serious scrutiny.” (Video here.) The main instrument of that effort is a “draft guidance” that the FDA opened for public comment over the summer, “The Judicious Use of Medically Important Antimicrobial Drugs in Food-Producing Animals” (pdf here). The point of that guidance is to ask agriculture to voluntarily withdraw from use the ag drugs that are functionally identical to drugs that are important in human medicine — because if bacteria become resistant to those drugs when they are used in animals, that newly derived resistance will also affect humans, making common diseases difficult or impossible to treat.

In addition to the volume figure, the real value of today’s brief report may be simply to make clear just what antibiotics are used in agriculture. Take a look at the report table at right, which lists the animal drugs used by amount sold within drug classes. (Note that the amounts are given in kilograms.) It lists:

Aminoglycosides: Human versions include streptomycin and amikacin.

Cephalosporins:  Human versions include Keflex and Rocephin.

Lincosamides: Human versions include clindamycin.

Macrolides: Human versions include erythromycin.

Sulfas: Human versions include half of the very common drug combos Bactrim and Septra.

Penicillins and tetracyclines: Yup, just what they sound like.

“NIR”: That’s FDA shorthand for “not independently reported” because they have few manufacturers or make up a small portion of the market. Among them are fluoroquinolones. Human versions: Cipro and Levaquin.

There’s much more to be said about the issue of antibiotic use in agriculture, especially because the lone piece of legislation addressing it, the Preservation of Antibiotics for Medical Treatment Act, is currently in lame-duck limbo. This report is an important piece of data for the ongoing debate.

Update: I asked some experts in the field to comment on the release of this data. Dr. David Wallinga, director of the Food and Health program at the Institute for Agriculture and Trade Policy in Minneapolis (also William T. Grant Foundation Distinguished Fellow in Food Systems and Public Health at the University of Minnesota School of Public Health) replied:

Clearly, antibiotic use in animal agriculture is huge, and as the FDA and CDC and WHO all agree, much of it is unnecessary. Data collection is important. But, because resistant bugs quickly adapt, we can’t afford to wait for data to take action to reduce antibiotic use wherever possible. That includes routine uses of antibiotics for cattle developing liver abscesses because they’re force-fed grain rather than grass, as well as antibiotics used to make animals get fatter faster.

Update 2: A day after the release of this report, Rep. Louise Slaughter (D-NY), author of PAMTA and a public-health microbiologist, commented on the data — and also said she’ll be reintroducing the legislation again in the next Congress in January.

This report illustrates the overuse of antibiotics in food animal production and makes a strong case for some common-sense limits on antibiotic use. We are putting millions of pounds of antibiotics into the food supply unnecessarily every year. This cannot continue and it’s my hope that these new data from the FDA will encourage even more members of Congress to join me next year when I reintroduce this legislation.  Moreover, the FDA must move fast to issue strong regulations on antibiotic usage in agriculture.

Update 3: Tom Philpott, senior food and agriculture writer at Grist — and a farmer, so he knows the territory — covered the FDA report and this post in a very kind and typically forthright post of his own.

Update 4: Helena Botttemiller, ace food-policy reporter for Food Safety News, covers this as well, noting how little mainstream media interest there has been. Any opinions why?

Cite: 2009 Summary Report on Antimicrobials Sold or Distributed for Use in Food-Producing Animals, FDA, Dec. 9, 2010

Image via Flickr user net_efekt under CC

Alarm over "pig MRSA" — but not in the US

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There’s some new news out — along with a fair amount of public reaction — regarding “pig MRSA” or, to use the technical term, MRSA ST398, the “third epidemic” strain that emerged in pigs in the Netherlands in 2004 and has since appeared, in animals, retail meat, and humans, across the European Union, in Canada, and in the United States. (My last post on it is here, and a long archive of my posts on it starts here.)

I wish I could say the attention to ST398 was being paid in the United States, where there is almost certainly more MRSA in livestock than has been recorded, given that the only published surveillance, from 2009, covered only Iowa and Illinois. Unfortunately, there is still no indication that federal agencies have any intention to test for the presence of the organism in animals or in meat. In fact, the major surveillance mechanism for drug-resistant organisms in meat animals, retail meat and meat-eaters in the US, the National Antimicrobial Resistance Monitoring System or NARMS, doesn’t test for MRSA at all; it handles only enteric or gut-borne bacteria such as Salmonella and Campylobacter. (NARMS IS shared among three agencies: the CDC handles drug-resistant foodborne bacteria in humans, the FDA looks for the same bacteria in food, and the USDA looks for those bacteria being carried by livestock.)

Instead, as so often seems to happen with antibiotic resistance, the country paying attention is in Scandinavia — in this case, Denmark. The annual report from Denmark’s surveillance scheme, DANMAP (Danish Integrated Antimicrobial Resistance Monitoring and Research Programme) is out. Denmark does surveil for MRSA, and here’s what they found: 13% of pigs, at slaughter, were positive for MRSA ST398.
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News break: FDA head promises "very serious scrutiny" of farm antibiotics

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Since July, the Food and Drug Administration has been moving — quietly and cautiously, but moving — to raise the stakes in its long and so-far unsuccessful battle to rein in overuse of antibiotics in agriculture. For those new to the topic, this is the use of antibiotics not in treatment-sized doses, to cure disease in farm animals, but in smaller doses to prevent disease or simply to make the animals gain weight faster so they can raised more efficiently and sold off more quickly than they would have otherwise.

There are decades of research by now, demonstrating that this contributes to the development of antibiotic-resistant organisms on farms that then move off harms and threaten human health. It’s not really a scientific question any longer; it’s a question of economics and politics.

(For a long discussion of what the FDA is proposing — and how much force it will, or won’t, have — see this post — at SUPERBUG’s earlier location, because we haven’t yet moved over all the archives.)

Yesterday, FDA Commissioner Dr. Margaret Hamburg gave a speech at the National Press Club at which she raised this issue and made some intriguing remarks. The overall point of the speech (see this AP article) was to promise increased investment and modernization — but she raised both the problem of antibiotic resistance generally and, in answer to a question, the problem of antibiotic use in farming.

First, here’s what she said generally about resistance (my transcription from CSPAN’s video above, starting at about 7:00):

There is increasing alarm about the problem of antibiotic resistance, and we worry with good cause. Today, antibiotic resistance mechanisms have been reported for virtually all known antibacterial drugs currently available for clinical use, which affects everything from global infectious diseases to ear infections in school children to staph infections in locker rooms. People actually talk today about a potential return to the, quote, pre-antibiotic era, unquote, where we no longer have effective tools to treat serious infectious disease. Clearly we must encourage more judicious use of these important drugs through improved infection control,  rational prescribing and better patient compliance.

But even if we improve these practices, resistant bacteria will continue to develop no matter what. We need new and better drugs and we need them now. Yet the research and development pipeline is distressingly low. The number of newly approved antibiotics, not just new formulations of previously existing drugs, has fallen steadily since the 1980s, and the range of new antibiotics in distribution is limited in terms of the types of classes of new antibiotics available and the diseases they can treat.

And here’s what she said about farm use, in response to a question (starting at about 31:00):

There historically has been a very considerable use of antibiotics as part of animal husbandry and also agriculture. I think that for many years individuals and organizations in public health and medicine have raised those very concerns, about what is the impact of the use of antibiotics in animal populations on human health and the availability of effective antibiotics to treat disease. We are in the midst of very serious scrutiny of these issues and we have made recommendations in support of judicious use of antibiotics. Nobody wants to deny antibiotics to animals that need medical treatment. But the use in certain preventive contexts, where it is not clearly medically indicated, is of growing concern,. And it is an area that, working with our partners in government, both the CDC and the USDA and others, that we are taking a very serious look at. (Emphasis mine.)

C. diff: Blame hospitals? Or food?

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People who are interested in infections that are transmitted in hospitals (umm, ghouls like me) have a special sick relish for Clostridium difficile, or in its short form, C. diff. C. diff lives in the intestines, part of a complex population of many bacteria — you did know there are more bacteria in your body than there are cells that belong to you, right? — but it roars out of control if those other bacteria are wiped out by a course of antibiotics, especially clindamycin. Removing the other bacteria clears out space for C. diff to reproduce in much greater numbers; the toxins it produces irritate the lining of the intestine, producing colitis, and triggering fever, cramps and diarrhea, and in the worst cases, sepsis. miscarriage and death.

C. diff colitis is one of the most common and serious hospital-acquired infections because — if you’re reading this over breakfast, you might want to stop eating now — severe diarrhea in a hospital patient who is confined to a bed and using a bedpan tends to get everywhere. Really, everywhere: bed linens and bedrails, floors and walls, stethoscopes, telephones, computer keyboards, and the hands of the healthcare personnel who operate those devices and then touch another patient.

C. diff persists so spectacularly because in the outside air, it forms a hard-shelled spore that protects its genetic material from assault — including from the alcohol in the hand gel that most healthcare workers use to clean their hands in between patients, and from the stomach acid of patients who swallow it. (See, I told you to stop eating.) Because of that, and because it’s such a devastating infection, hospitals toil incredibly hard at sanitizing to get rid of it.

C. diff colitis is a stubborn and ugly infection. Earlier this summer, an Illinois man named Ed Corboy Jr. described his mother Joan’s experience with it to the Infectious Diseases Society of America:

I watched helplessly as [she] grew weaker, more dehydrated, and nearly died. She was started on intravenous fluids and standard antibiotics while in the hospital two different times that December. Her blood pressure dipped dangerously low on many occasions. She had lost almost 55 pounds in the previous five months, and she was so profoundly exhausted, tired, and wasting away that it became apparent in early January she might die from this. She could hardly get to a bedside commode without two people helping her. Prior to this she was able to walk to her bathroom with her walker on her own for years.

Starting about 10 years ago, C. diff got dramatically more problematic: more virulent, more resistant to treatment, and more commonly occurring in people who would not have been expected to have it — often, healthy young people who had not been in hospitals, who seemed to be developing the illness in the outside world. Two CDC researchers said in 2008:

In the United States, the number of hospital discharges where (C. diff associated diarrhea, CDAD) was listed as any diagnosis doubled between 2000 and 2003, with a disproportionate increase for persons aged > 64 years. By 2003, regional reports of CDAD outbreaks from hospitals throughout the US and in Quebec, Canada emerged, describing severe disease associated with greater numbers of complications, including colectomies, treatment failures, and deaths. In 2004, the attributable mortality rate of nosocomial CDAD in Quebec hospitals was 6.9%, compared to 1.5% among Canadian hospitals in 1997. In the US, death certificate data suggest mortality rates due to CDAD increased from 5.7 per million population in 1999 to 23.7 per million in 2004. (Gould, Critical Care, 2008)

The reason for the surge has been understood to be the emergence of a new, hypervirulent strain of C. diff that produces up to 20 times more toxin than earlier ones. (C. diff nomenclature will make your brain hurt, but the strain is generally known as NAP1/027/BI, toxinotype III.) But increased virulence doesn’t explain the increased incidence, and the transmission patterns of the new strain have been murky.

An emerging line of inquiry suggests that the transmission patterns become much more clear if you look in a different place for the bacterium’s origin: not in hospitals, but in food.

C. diff has been identified in live pigs, cows and chickens. The bacterium has been found in retail meat in the United States and in Canada (in three separate studies), and in salad greens in Scotland. And in a paper published this month, the main authors from those Canada studies establish that minimum recommended cooking temperatures for ground beef don’t kill C. diff spores.

(You’re really not eating now, right?)

So, OK: But are the C. diff strains found in animals the same ones that are causing human disease? The answer turns out to be Yes. Several researchers have found overlaps, in 2007, 2009 and earlier this year, in a study with the perfect title: “Innocent bystander or serious threat?”.

And in what looks certain to be a provocative presentation, a team of researchers from Houston is going to present a paper at the annual meeting of the Infectious Diseases Society of America in a few weeks, titled: “Potential Foodborne Transmission of Clostridium Difficile Infection In a Hospital Setting.” (Uh-oh.)

The case for C. diff as a foodborne illness still isn’t made. In an excellent paper published last month, L. Hannah Gould and Brandi Limbago of the CDC go over the findings so far, and detail what evidence and further research are still needed.

It is reasonable to assume that the general public is and has been often exposed to low numbers of potentially infectious C. difficile spores. There is currently limited epidemiologic evidence to support or refute the hypothesis that C. difficile is transmitted by the foodborne route; the presence of C. difficile on retail foods suggests but does not prove that some proportion of infections is acquired this way. The food supply may thus serve as a source of new strains causing human infections; alternatively, food could be another constant and normally innocuous exposure. (Gould, Emerging Infectious Diseases, 2010)

What’s really interesting, though, is that microbiologists aren’t the only ones noticing this accumulation of evidence. C. diff as a possible foodborne pathogen caught the attention of foodborne-illness attorney Bill Marler early last year.  If Marler — the most aggressive and, I suspect, successful foodborne-injury lawyer on the planet, dating back to the 1993 Jack-in-the-Box outbreak — is starting to notice the evidence tying C. diff outbreaks to food, there might be a lot more attention paid to this connection fairly soon.

Image of C. diff by Janice Carr, courtesy of Public Health Image Library, CDC.

Pigs, antibiotics, and staph where it shouldn't be

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The “third epidemic” of MRSA (drug-resistant staph) — the one that started in farm animals given antibiotics, and subsequently spread to humans — has been contentious since its emergence. This week there are several pieces of new news about it. They’re not likely to solve any of the disagreements, but they’re certainly interesting.

Very quick recap for those coming in late: MRSA, short for methicillin-resistant Staphylococcus aureus, describes strains of staph that have become resistant to most common antibiotics. It’s been gaining ground on us for about 50 years, first in hospitals, then in the everyday world and now in farm animals and farm-workers. Surveillance for it is not excellent, but in various studies, it kills 19,000 Americans, puts about 370,000 in the hospital, and sends possibly 7 million to a primary care visit or ER, and causes billions of additional dollars in health care spending — all in a year. For the most serious infections, there are only a few drugs that still work. It’s the leading organism in the under-appreciated international epidemic of antibiotic resistance. (If you’d like to know more, I wrote a book about it.)

Livestock-associated MRSA — many researchers just call it “pig MRSA,” which makes swine agriculture very unhappy, but the more technical term is MRSA ST398 — was first noted in 2004 in a Dutch toddler being prepped for surgery; then identified in her family and their social circle, all of whom were pig farmers; and then was found in their pigs. Along with the standard suite of MRSA resistance factors — all the beta-lactam antibiotics, which means anything ending in “-illin,” most cephalosporins, the monobactams and carbepenems, and also erythromycin — this new strain was resistant to tetracycline. That was odd, because the Netherlands’ rate of MRSA was so low that they were not bothering to give humans tetracycline for MRSA; but tetracycline was the most common drug given to pigs in large-scale agriculture there. It was proof the organism had been resident in pigs, become resistant as a result of ag antibiotic use, and then crossed to humans. (Yeah, this is all told in the book. OK, no more shilling.)

Since that first finding, ST398 has spread throughout the European Union, into Canada, and in one state in the US, Iowa. (Veterinarians assume it has spread more widely than that, but Iowa happens to be the only state where researchers have looked for it.) It is less common than other strains of MRSA, but it has been identified as the cause of mild skin infections among farm workers, serious hospital infections such as ventilator-associated pneumonia, and life-threatening community infections such as flesh-eating disease. It’s also been found in retail meat in several different countries. (We haven’t yet managed to move my archives over, but there’s a 2-year history of ST398 coverage at my old blog.)

Despite the low number of known cases, MRSA ST398 is important, for several reasons: First, because as those death and illness numbers demonstrate, any additional MRSA is bad news. Second, because MRSA ST398 bridges the human and animal worlds, demonstrating how easily an organism that is resident in animals can cause illness to humans, and also can move across the world with agricultural trade. And third, because its occurrence underlines the consequences of antibiotic overuse in agriculture: If they hadn’t been giving tetracycline to pigs in the Netherlands — a country that, within about a decade, went from small family farms to the largest user of ag antibiotics in the EU — “pig MRSA” might not exist.

So, this week’s update, courtesy again of the Interscience Conference on Antimicrobial Agents and Chemotherapy, or ICAAC: two findings that are somewhat contradictory.

First, a team in the Netherlands wanted to know how much of an infection risk ST398 truly poses. That’s an especially important question in the country where the strain got going. In the Netherlands, which exerts very close control over MRSA overall, certain categories of hospital patients are checked to see whether they are carrying the resistant bug, and if so, put into isolation and treated until they are clear. But some people are considered to be such high infection risks that they are put into isolation presumptively — and since 2007, those categories have included farm workers and veterinarians.

That’s a lot of tests, which means a lot of expense. So the team who presented this week tried to assess whether that isolation and testing are necessary, by measuring how often carriage of MRSA ST398 converts to an active infection. They looked at every MRSA isolate identified in 2009 at two hospitals in the southeast, where pig-raising is most dense, and identified a huge reservoir of carriage of ST398: 61% of the MRSA-positive patients, or 298 out of 486. But of those 298, only 7 developed an infection, and none of them passed the infection to a second patient. The 188 patients carrying hospital MRSA, on the other hand, caused 83 secondary cases — enough to force closure of a department in one of the hospitals. (van de Sande et al., ICAAC 2010)

So while pig MRSA’s easy to acquire, given the right exposure, it may not often cause illness. Problem is, according to a second piece of research discussed this week, when it does, it can be unexpected and devastating.

A coalition of 21 hospitals in Spain wanted to know how many of the MRSA bloodstream infections occurring in their institutions were caused by the community strain of MRSA instead of the hospital strain — something that would signal a change in the epidemiology of what can be a devastating illness. They checked every MRSA bacteremia case from June 2008 through December 2009. They found 324, overall, with 10 of them caused by community strains. But they also found something they didn’t expect: Almost as many, eight of 324, were caused by ST398. (Camoez et al., ICAAC 2010)

This isn’t the first time that MRSA ST398 — an organism linked to agriculture and to spread through farm workers and veterinarians — has been found to cause hospital infections or serious infection. It has caused ventilator-associated pneumonia in Germany and post-surgical infections in Canada.

One of the ways that epidemiology measures the seriousness of an outbreak is to compare it to the expected background occurrence of a disease. In the case of MRSA ST398, that background rate is zero. The strain’s an artifact of the overuse of antibiotics in agriculture. It’s really worth thinking about how many more such organisms we want to produce.

Image: photographer unknown.

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.

Hospitals want patients to eat antibiotic-free meat

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Huge news, and hat tip to excellent food-policy writer Monica Eng at the Chicago Tribune: In a piece published Tuesday, she details that 300 hospitals in the Chicago area and nationwide have begun preferentially buying and serving meat that is raised without the use of antibiotics.

Using the ingredients is primarily a response to patient demand, said (Carolyn Lammersfeld, national director of nutrition at Cancer Treatment Centers of America) but the centers are also “watching the controversy over the nontherapeutic use of antibiotics and their potential to cause resistant strains of bacteria.”

The issue is of particular concern for cancer patients, who have compromised immune systems, she noted. “Many also might already being taking antibiotics, so they don’t want additional ones in food if they can avoid it,” Lammersfeld said.

The drug-free meat is more expensive, but the cost balances out within the budget:

(Diane Imrie, director of nutrition services at Fletcher Allen Health Care in Vermont) estimated that her food costs rose about $67,000 last year when she switched to antibiotic-free chicken from conventional. “But that’s also about the same cost as treating a single MRSA infection,” she said.

It’s interesting to see this story land just as a new paper in Foodborne Pathogens and Disease is making the rounds. The paper (Jiayi Zhang, Samantha K. Wall, Li Xu, Paul D. Ebner. “Contamination Rates and Antimicrobial Resistance in Bacteria Isolated from “Grass-Fed” Labeled Beef Products,” doi:10.1089/fpd.2010.0562) compares the bacterial burden in grass-fed and conventionally raised beef and finds no significant  differences: equivalent amounts of both drug-sensitive and drug-resistant bacteria in both types of beef.

It concludes, “There are no clear food safety advantages to grass-fed beef products over conventional beef products” — an assertion that’s likely to be seized on by those who see no need to change current antibiotic use in agriculture. (For an example of that POV, here’s the testimony from last week’s House of Representatives hearing by Richard Carnevale, DVM of the Animal Health Institute.)

I suspect though that the paper’s analysis doesn’t look far enough. Here’s one example: the authors found that Enterococcus species in both conventional and grass-fed meat were resistant to chloramphenicol, erythromycin, flavomycin, penicillin, and tetracyline — drugs that are used in agriculture (and that could have been given to the grass-fed animals, which were not guaranteed to have been raised drug-free). But  Enterococcus spp. isolates from conventional beef were more frequently resistant to daptomycin and linezolid — which are new-to-market drugs of last resort in human medicine that are not given to animals

That finding, right there — the migration of resistance to a human-only drug into an organism carried by an animal — signals one of the insoluble problems of overuse of antibiotics. Once created, resistance factors move horizontally among bacteria, from the farm to humans, and apparently in this case, from humans to the farm as well. We have almost no control over their movement, and on the agricultural side, almost no surveillance to detect it, either. That argues for reducing the overuse of antibiotics in human medicine and on the farm.

If this health care coalition’s refusal to purchase meat raised using antibiotics helps to enlarge the market for drug-free meat, then it may reduce ag antibiotic use, and therefore the selective pressure that encourages resistant organisms to emerge. That can only be a good thing.

(The paper in Foodborne Pathogens has also been covered by my former colleagues at CIDRAP; here’s their link.)

Antibiotic use in animals: The feds move, a little

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(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.

[Read more…]

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

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This is a little outside our usual subject matter, but:

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

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

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

Farming and antibiotics – and voices from the ag side

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The whole issue of how antibiotics get used in agriculture — as growth promoters, as prophylatic treatment to prevent spread of infection within a farm, or as true treatment — is intensely controversial. For a sense of how farmers feel embattled, read the comments to this entry at FairFoodFight on whether there is a distinction between “Big Ag” and “small ag.” and consider that the PAMTA legislation I posted about in December, which would require veterinarian oversight of farm use of antibiotics,  has been strongly opposed by agricultural interests every time it has been introduced. (Large-farm use of antibiotics, let me remind you, has been concluded to be the driver behind the emergence of “pig MRSA” ST398.)

But I recently ran across two pieces online that I want to draw your attention to, because they demonstrate that thinking in agriculture about antibiotic use is not monolithic, and may be changing. Both were posted on the same site, the Illinois-based Agri-News Online.

[Read more…]

Back again to MRSA in animals, and spreading to humans

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There are two new reports out regarding new findings of “pig MRSA” ST398 (about which we have talked a lot; archive of posts here.)

First, researchers from the Complejo Hospitalario Universitario de Vigo and Complejo Hospitalario de Pontevedra, both in Pontevedra in northwest Spain, report that they have identified that country’s first human cases of infection with ST398. (It was only last fall that Spain reported the first identification of the strain in animals.)

The age of the three patients was 59, 82, and 83 years, respectively. Two patients owned pigs and the other a calf. Two patients were diabetic and were hospitalized because they developed skin and soft-tissue infections by MRSA ST398. The third patient had bronchitis and the strain was isolated from a respiratory secretion submitted to the laboratory from an outpatient clinic. The three patients had had multiple hospital admissions in the last 12 months.

Tellingly, the researchers spotted these particular isolates (out of 44 analyzed at the two hospitals in 2006) because they were resistant to tetracycline. Tetracycline resistance is not common among community strains of MRSA, because the drug isn’t the first-line choice for skin and soft-tissue infections; and when it is given, it’s usually for a short course, so the drug does not exert much selection pressure on the bug. But tetracycline is a very common animal antibiotic, and tetracycline resistance is a hallmark of ST398; it is one of the factors that led the Dutch researchers who first identified the strain to take a second look at the bug.

Second, researchers from several institutions in Italy report a very troubling case of ST398 infection that produced necrotizing fasciitis — better known as flesh-eating disease. [Read more…]

Warning on ST398: Monitor this now

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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.

Questioning meat-raising and meat-eating — in eat-everything France

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Happy New Year, constant readers. I’m honored and flattered to have had the chance to spend the past few years with you here. 2010 is going to be a big year — not just because SUPERBUG will be published, but because the issue of antibiotic resistance really, really is gathering force in the public mind. I not only believe that, I see it in the news that flows through my computer everyday. The wind is shifting.

Here’s one excellent example. In France of all places, a culture that embraces meat-eating and finds the idea of animal rights quixotic, a book has been published that questions the environmental and moral effects of modern factory farming. It’s called Bidoche, L’industrie de la viande menace le monde (“Bidoche” is a slangy, dismissive term for meat), and it has made enough of a splash that the newspaper Le Monde ran both an article on the book and a readers’ Q&A with the author, journalist Fabrice Nicolino. (The article ran two days before Christmas but was called out on Twitter today by Paula Crossfield of CivilEats.com, who spotted it while on holiday, and to whom hat/tip.)

Sadly, the article is behind a paywall; you can see the first 100 words or so here. The Q&A is open though. It’s titled, “To save the planet, should we eat less meat?”and makes fascinating reading (GoogleTranslate into English here), as do the comments, some of which raise the issue of the use of antibiotics in agriculture. But what’s most striking to me is that the conversation is taking place at all, actively and in a public forum, in a place where only a few years ago the local culture would not have been open to the debate. Things are changing indeed.

Antibiotics in chickens, and links to human infections

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

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

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

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