I am bashfully flattered to report that this blog has inspired, and been quoted in, an episode of the webcomic Lola Lollipop:
Big-eyed kids, talking animals, nutrition, sustainability, and major cute. And, umm, me. Huge thanks to Lola!
Drug-Resistant Bacteria: To Humans From Farms via Food
You have to love a scientific commentary that starts this in-your-face:
“Show us the science that use of antibiotics in animal production is causing this antibiotic resistance,” Dave Warner of the National Pork Council told the Washington Post back in June 2010, responding to a Food and Drug Administration (FDA) guidance document advising against the sub-therapeutic use of antibiotics in livestock.
Well, here’s some.
To be clear: That’s the paper’s language, not mine. The gut-punch challenge comes from an editorial that is only on the web so far but is scheduled for publication in the journal Clinical Microbiology and Infection. It accompanies a research article that makes an important claim:
Chickens, chicken meat and humans in the Netherlands are carrying identical, highly drug-resistant E. coli — resistance that is apparently moving from poultry raised with antibiotics, to humans, via food. [Read more…]
Ag antibiotic use: Risky — but also sloppy and wasteful
So, antibiotics. Given to farm animals. (Yeah, that again.) How does that work, anyway? Pills? Injections? Daily massage with specially compounded creams?
Not quite. Farm animals overwhelmingly get antibiotics in their feed. (You knew that.) And a new paper in the journal Environmental Health Perspectives explains what a bad idea that is: Animals that are given “free choice medicated feeds” (FCMF, in the jargon) can overdose or under-dose themselves, leading not only to the creation of antibiotic-resistant bacteria but to the accumulation of antibiotic residues in their flesh that can persist past slaughter.
There are two issues hidden in this. The first is the practice of giving tiny doses of antibiotics as “growth promoters,” a use that dates back to the late 1940s. Despite a fair amount of study, there are still competing explanations for how this actually works, but the results are clear: Give animals micro-doses of antibiotics, and they put on weight faster, meaning they get to market size and can be sold — and replaced by another batch to whom the same thing happens — more quickly than if the drugs were not being used. The second is using treatment-sized doses in feed to take care of any illnesses among animals, as well as to protect animals who might pick up those illnesses in the close quarters of confinement agriculture.
If you view animal raising as an industrial-style process, the equivalent of making widgets on a production line, then medicated feed appears to make economic sense, because it offers a substantial return for little forward investment of money or labor. But as this paper picks apart, medicated feeds are not the bargain they seem. [Read more…]
News break: Slaughter will reintroduce PAMTA (and cites data from this blog)
Rep. Louise Slaughter (D-NY), Congress’s only microbiologist, said late today that she plans shortly to reintroduce PAMTA, the Preservation of Antibiotics for Medical Treatment Act, a timely move given the collapsing antibiotic market (see this morning’s post) and continuing reports of resistance moving off farms (as in this post).
PAMTA would direct the FDA to re-examine its approvals of veterinary antibiotics that are close analogs of ones used in humans, because they can stimulate the development of resistant organisms. When those organisms move off the farm, as research shows they do, they then cause illnesses that cannot be treated by the functionally identical human drugs.
The Union of Concerned Scientists said in 2008 about an earlier version of the bill:
The FDA is aware of the problem of antibiotic resistance due to overuse in animal agriculture, but the agency’s process for reviewing and withdrawing drugs from the market is far too slow and cumbersome. A recent effort to withdraw an antibiotic from use by poultry producers due to concerns about human antibiotic resistance lasted for more than five years, costing millions of taxpayer dollars. And while the judicial proceedings dragged on, disease-causing bacteria continued to outwit antibiotics.
While some producers and retailers of meat products have announced policies that take steps to curb antibiotic use, private-sector initiatives to reduce antibiotic use in animal agriculture are relatively rare, limited in scope, and difficult to verify. Federal action is needed to achieve comprehensive reductions and create a level playing field for all producers and retailers.
Passage of PAMTA is critical to keep antibiotics working for human health. In addition to averting the harmful effects of antibiotic overuse on human health, curtailing animal use of antibiotics will encourage producers to raise animals in better living conditions that are less conducive to disease.
Parenthetically, it is flattering to see Slaughter reference new data on the amount of antibiotics used in animals in the United States — almost 29 million pounds — and the percentage of the total market antibiotic market that represents: 80 percent. Those pieces of news were broken over the Congressional break by myself, here at SUPERBUG, and by Ralph Loglisci at the blog of the Center for a Livable Future.
Running out of antibiotics — and other drugs too
Last night, the Journal of the American Medical Association posted ahead of print an editorial by Dr. James Hughes, former director of the National Center for Infectious Diseases at the CDC and now a professor of medicine and global health at Emory University. It’s a blunt and eloquent plea for attention to a problem that many people haven’t yet faced up to: We’re running out of antibiotics.
Antimicrobial agents have saved millions of lives and improved the outcomes for countless patients since these drugs were introduced in the early 1930s. However, the effectiveness of these lifesaving resources is at risk. Many medical advances that physicians and patients take for granted—including cancer treatment, surgery, transplantation, and neonatal care—are endangered by increasing antibiotic resistance and a distressing decline in the antibiotic research and development pipeline. (JAMA Hughes)
Drug resistance is a biologic inevitability — but in the 83-year history of the antibiotic miracle, starting from Fleming’s first recognition of natural penicillin, whenever resistance made one drug useless, another drug came along to save us. Those days are over. [Read more…]
Giant pig farms: Antibiotic resistance is not the only problem
When I talk about farming, I usually focus on antibiotic over-use and the way that it stimulates the emergence of drug-resistant organisms. That’s part of what my recent book is about, and to me, it’s the critical piece in the entire discussion of industrial-scale agriculture. If we didn’t use antibiotics in such vast quantities, confined animal-feeding operations, CAFOS, couldn’t exist: Animals couldn’t survive in those conditions without them.
But so many other negatives come from CAFOs — not just antibiotic resistance, but air and water contamination, and chronic human diseases caused by effluent and pollution. I’m grateful to be reminded of that via a webinar hosted this afternoon by the Institute for Agriculture and Trade Policy, which threw a sharp light on the impact of industrial-scale hog farming in North Carolina.
The webinar took a close look at new research by University of North Carolina associate professor Steven Wing. His paper, just published on the website of the journal Epidemiology, details the acute physical symptoms experienced by North Carolina residents who live in areas near very large hog farms: eye irritation, wheezing, chest tightness, shortness of breath, sore throat and nausea.
Emerging from the farms, Wing said, are “dust, and particles from dried feces, as well as spraying of waste that aerosolizes that material. There are several important gases such as ammonia and hydrogen sulfide… as well as bioaerosols, which include endotoxin from dead bacteria. Some of these materials… are allergenic and can cause respiratory problems.”
(See Wing’s image above of manure spraying, and dead-pig disposal, outside a North Carolina hog farm.)
To get that data, Wing and colleagues at UNC and Mount Sinai School of Medicine collaborated with residents of eastern North Carolina, especially the Concerned Citizens of Tillery, in a project dubbed Community Health Effects of Industrial Hog Operations (CHIEHO). They recruited 101 adults in 16 communities who agreed to sit outside for 10 minutes twice a day, every day for two weeks, and to log their symptoms and also measure their lung function with a flow meter. Separately, the team measured ambient air pollution with continuous monitors that were parked in each community.
Overall, between September 2003 and 2005, they received 2,900 responses about people’s symptoms in the previous 12 hours, 2,600 about symptoms that were provoked by those episodes of sitting outdoors, and 1,900 error-free measurements of lung function. And — no surprise for anyone who knows what these farms look like and smell like — the symptoms tracked with the air pollution measurements.
Wing asked: “Is it fair to tell anyone they can’t go outside their own home because it is too polluted to be there?”
Here’s why conditions outside those eastern North Carolina houses are so bad. Within two miles of each of the communities that contributed to the research, there was an average of 42,000 hogs. Within North Carolina as a whole, there are more than 10 million hogs on more than 2,400 farms. The distribution looks like this:
The spots where the dots cluster most densely are Duplin and Sampson counties. Duplin contains 45 hogs for every resident; Sampson, 32. Something else those areas have in common, mentioned during the webinar by Naeema Muhammad, from Concerned Citizens of Tillery:
Most of those operations are in eastern North Carolina, and eastern North Carolina is where you have your predominantly African-American communities, …other communities of color and also your highest rates of poverty. Looking at that map, we are able to use the phrase “environmental racism.”
Wing and colleagues add in their paper:
…in low-income communities of color… there is more potential for exposure to outdoor air pollutants due to older homes that are not air tight and have no air conditioning. Many residents also lack the financial resources to travel and choose activities that could help them avoid high pollution. Exposure to air pollution from hog operations is an environmental injustice in rural areas hosting facilities that supply pork to populations spared the burdens of its production.
IATP said today they will subsequently post a recording of the webinar along with its slides; I’ll update when it goes live.
Cite: Schinasi, L et al. Air Pollution, Lung Function, and Physical Symptoms in Communities Near Concentrated Swine Feeding Operations. Epidemiology 2011;22: 208–215. DOI: 10.1097/EDE.0b013e3182093c8b
Images: Dead pigs and manure spraying at a North Carolina farm/Institute for Agriculture and Trade Policy + S. Wing, UNC; map of North Carolina hogs farms/IATP + S. Wing, UNC (adapted from Wing et al. 2001)
Drug residues and drug resistance in water: Not good
When we talk about the emergence of antibiotic resistance, two factors usually get the blame: the overuse of antibiotics in human medicine and in agriculture. In both cases, the drugs’ presence exert selective pressure on bacteria, encouraging them to develop or acquire resistance genes that will protect them.
But there’s another way that bacteria are exposed to antibiotics. It’s through wastewater: residues from antibiotic manufacturing, retail drugs dumped because they are expired or no longer needed, and sewage — because a percentage of the drugs we take (and give to animals) pass through our bodies unused, and also pass intact through municipal wastewater treatment when it exists.
I wrote about this a bit last September, just after this blog launched, in the context of how difficult it can be to get rid of prescription drugs that you no longer need or want. (Plea: Don’t flush them.) But a new paper in PLoS One underlines that this problem is much bigger than the bottles cluttering your medicine cabinet.
For several years, faculty from several universities in Sweden have been tracking the content of wastewater flowing into a river near Hyderabad in India, a city that is a center of generic drug manufacturing. (For a sense of how saturated the local environment is with pharma firms — more than 90 — check the map at right.) Previously, they had found levels of fluoroquinolones high enough to kill fish and permeating drinking-water wells in villages. (For humans, the most familiar fluoroquinolone is Cipro.) For this paper, researchers looked specifically at bacteria living in parts of the river where that industrial pharma effluent is flowing, to see whether they were developing resistance in response to that exposure.
Answer: Oh, yeah. Using a method called “multiplexed massively parallel pyrosequencing” (which I love just saying out loud), the team analyzed the bacterial DNA and found it loaded with resistance genes that would confer protection to multiple classes of antibiotics: fluoroquinolones, aminoglycosides and sulfonilamides. At three sites downstream of the key wastewater plant that processes the effluent, known resistance genes accounted for 1.7% of all the DNA they analyzed. Along with those genes, they also found two previously unknown plasmids that contained genes conferring resistance to fluoroquinolones (qnrD) and sulfa drugs (sul2).
It’s important to say that the bacteria in the river that were harboring these resistance genes were not disease-causing bacteria. It’s also important to say that is only minimally relevant. Once resistance factors arise, they move with surprising speed between bacteria and also across bacterial species. In the downstream samples, they also found abundant integrons and transposons that would allow the genes to move, reinforcing the case that resistance was evolving at these spots because of the antibiotic-laden effluent.
This Indian river is a hot spot because of the concentration of manufacturing along it — but it’s not the only offender. Last year, Chinese scientists reported on very high levels of oxytetracycline stimulating bacterial resistance in a river in China. In January, British scientists reported similar results for a river in Cuba. And as I said last fall, the US Geological Survey has found pharmaceutical residues in 80% of the 139 US streams they sampled in 2002.
National and international health agencies, and medical societies and NGOs, have programs that seek to reduce the overuse of antibiotics in human medicine. There’s increasing pressure, as we talk about here all the time, to push back against the overuse of antibiotics in farming. But the thought that antibiotics are spreading freely in groundwater, lakes and rivers is truly disturbing. Curbing that will require a whole different level of effort.
Cite: Kristiansson E, Fick J, Janzon A et al. 2011 Pyrosequencing of Antibiotic-Contaminated River Sediments Reveals High Levels of Resistance and Gene Transfer Elements. PLoS ONE 6(2): e17038. doi:10.1371/journal.pone.0017038
Superbugs in Canadian chicken? Yes, and US too
CBC News, the Canadian national TV network, has caused a stir in the food-blog world with the results of a nationwide investigation that found antibiotic-resistant bacteria contaminating supermarket chicken. In its words:
Chicken bought at major supermarkets across Canada is frequently contaminated with superbugs — bacteria that many antibiotics cannot kill — an investigation by CBC TV’s Marketplace has found.
Marketplace researchers — along with their colleagues at Radio-Canada’s food show L’Epicerie — bought 100 samples of chicken from major grocery chains in Vancouver, Toronto and Montreal… The 100 samples were sent to a lab for analysis. Two-thirds of the chicken samples had bacteria. That in itself is not unusual — E. coli, Salmonella and Campylobacter are often present in raw chicken.
What was surprising was that all of the bacteria uncovered during the Marketplace sampling were resistant to at least one antibiotic. Some of the bacteria found were resistant to six, seven or even eight different types of antibiotics.
“This is the most worrisome study I’ve seen of its kind,” said Rick Smith, the head of Environmental Defence, a consumer advocacy group.
I haven’t had time to watch the full program, but no question I think this kind of reporting is worth doing. Nothing brings the threat of agricultural antibiotic use home to people like showing them that resistant bacteria are living on the meat they might have brought home last night.
One important point, though: Don’t think for a moment this is just a Canadian problem.
Last month, a team from the University of Ioannina in Greece analyzed in Foodborne Pathogens and Disease 428 samples of various retail meats they bought in northwest Greece over three years:
E. coli from chicken exhibited high rates of resistance to ciprofloxacin (62.5%) followed by lamb/goat (10.9%), pork (15.7%), and beef (27.9%) meat. Resistance to nitrofurantoin dominated in the lamb/goat isolates (60%). Resistance to tetracycline predominated in pork (68.2%) and chicken (62.5%), and resistance to aminoglycosides dominated in lamb/goat meat isolates. S. aureus resistance to clindamycin predominated in lamb/goat isolates (50%), whereas resistance to ciprofloxacin predominated in the pork strains, but no resistance to methicillin was observed. Of the enterococci isolates 21.1% were resistant to vancomycin. High resistance to ampicillin (96%) was observed in Y. enterocolitica and all of the C. jejuni isolates were resistant to ampicillin, cephalothin, and cefuroxime. These results indicate that meat can be a source of resistant bacteria, which could potentially be spread to the community through the food chain.
Last year, a team from the University of Iceland found fluoroquinolone-resistant E. coli passing from chickens to humans there (the drug Cipro is a fluoroquinolone, and the human isolates were Cipro-resistant), a multi-institution team from Canada found resistance to third-generation cephalosporins in Salmonella enterica spreading from chicken meat to humans, and the Irish quasi-governmental group SafeFood released a long report (and hosted a conference) on “The Problem of Antimicrobial Resistance in the Food Chain.” And of course MRSA ST398, the strain of drug-resistant staph that arose in food animals, has now been found in retails meats across the EU.
Oh, but none of those countries are the United States, you say. Then take a look at these:
Those graphics come from a little-read report put out every year by the US Food and Drug Administration as part of its participation in NARMS, the National Antimicrobial Resistance Monitoring System that’s shared by the FDA, USDA and CDC. The FDA handles the part of NARMS that looks for resistant bacteria in meat (CDC does human illnesses, USDA does live animals), and the figures above show the percentages of Salmonella and enterococci that were found in retail chicken breasts between 2002 and 2008 (the most recent report) and were resistant to various drugs. The bar along the bottom of each figure shows the major drug classes. So in 2008: 45% of Salmonella on chicken were resistant to tetracycline and 30% to penicillins; among enterococci (common gut bacteria, and therefore common contaminants of meat during slaughtering), 65% resistant to tetracycline and more than 90% to lincosamides, which include the everyday drug clindamycin.
In the narrative portion of the report, the FDA said:
38.2% of chicken breast Salmonella isolates were resistant to ≥ 3 antimicrobial classes in 2008 compared to 51% in ground turkey, an increase in both from previous years. From 2002–2007, multidrug resistance to ≥ 3 antimicrobial classes ranged from 20–34.4% among chicken breast and 20.3–42.6% for ground turkey. More than 15% of chicken breast and ground turkey isolates showed resistance to ≥ 4 classes in 2008.
So, just to underline: Multi-drug resistant superbugs aren’t only on chicken in Canada; if you buy chicken in the United States, they are more than likely on your chicken too.
And whatever country they are occurring in, the solution is the same. Drug-resistant bacteria in food won’t diminish until we reduce the amount of drugs that food animals receive while they are raised.
Update: At Grist’s Meat Wagon, Tom Philpott very kindly points out that I actually broke the news of the latest NARMS report, which I didn’t realize (it was a busy day; see my next post for why). Apparently the report was posted to the FDA web site on Dec. 17, but neither of us can find any evidence that it was publicized, such as a press release on the FDA’s press site. His larger point is important:
We find out from the report that the FDA has been monitoring the situation since 2002 — and finding plenty of antibiotic-resistant strains on meat sold directly to consumers. And they’ve been sharing the information with other leading regulatory/public health agencies — but not so much to the people they’re supposed to be protecting and informing: i.e., us. … six weeks since the FDA report and a year since Sharfstein’s testimony [in 2010, promising scrutiny by the Obama adminsitration – m.], policy hasn’t moved at all. Where are the loud public statements from the FDA trumpeting the fact that our factory farms are cooking up superbugs that make their way to our meat? Where’s the USDA on this topic, which is supposed to protect the public from tainted meat? Where’s CDC?
New antibiotics: Not many and fewer all the time
The New England Journal of Medicine last week published the results of a Phase 3 trial of a new antibiotic called fidaxomicin, made by a company called Optimer Pharmacuticals. Fidaxomicin is the first of a new class of antibiotics called macrocycles; it’s a narrow-spectrum drug aimed specifically at Clostridium difficile, the bacterial, toxin-producing, potentially fatal infection of the gut that occurs when broad-spectrum antibiotics have killed off the other populations of bacteria that normally live in the intestines.
Fidaxomicin’s existing competition is vancomycin, the 50-year-old broad-spectrum big gun used for MRSA and many other serious bacterial infections. As compared against vancomycin, fidaxomicin was “noninferior,” in industry jargon; its selling point was a lower rate of recurrence of C. diff among patients who received it compared to those getting the older drug. From the paper:
A total of 629 patients were enrolled, of whom 548 (87.1%) could be evaluated for the per-protocol analysis. The rates of clinical cure with fidaxomicin were noninferior to those with vancomycin in both the modified intention-to-treat analysis (88.2% with fidaxomicin and 85.8% with vancomycin) and the per-protocol analysis (92.1% and 89.8%, respectively). Significantly fewer patients in the fidaxomicin group than in the vancomycin group had a recurrence of the infection, in both the modified intention-to-treat analysis (15.4% vs. 25.3%, P = 0.005) and the per-protocol analysis (13.3% vs. 24.0%, P=0.004). The lower rate of recurrence was seen in patients with non–North American Pulsed Field type 1 strains. The adverse-event profile was similar for the two therapies. (NEJM Louie et al.)
Fidaxomicin has been in the works for a while — it was given Fast Track status by the Food and Drug Administration back in 2003 — and it has faced some criticism for not being different enough from vanco to justify the price that a new drug can charge. Nevertheless, on the basis of this and other trials, Optimer has completed its New Drug Application, and the FDA’s Anti-Infective Drugs Advisory Committee will review it at a meeting in April.
Opposing industrial-scale pig farming — in Europe
Well, wow. National legislators stand up to oppose the use of tax revenues to subsidize large-scale confinement pig farms out of concern for food safety and antibiotic resistance, declaring that they are “going to war in defense of pigs.”
In Europe, though.
At the European Parliament today, three national representatives — Janusz Wojciechowski of Poland, José Bové of France and Dan Jørgensen of Denmark — declared their opposition to industrial-scale swine agriculture, positioning themselves for a fight over the European Union’s Common Agriculture Policy, which is up for revision this summer.
Jørgensen represents the country that has done the most to place controls on agricultural antibiotic use; Bové is a farmer and political organizer who famously destroyed a McDonald’s by driving a tractor through it; and Wojciechowski is the son of pig farmers who wrote on his blog today:
Chcemy poruszyć sumienia posłów i doprowadzic do likwidacji tego typu “fabryk miesa” w Unii Europejskiej, no czywiscie takze w Polsce, gdzie takich fabryk jest juz ponad sto.
Chcemy doprorowadzic do tego, aby wielkie fermy nie były wspierane środkami europejskimi, aby wstrzymać lokalizacje nowych obiektów, po czym stopniowo likwidować te, które już istnieją.
Chcemy, żeby na miejsce fabryk miesa powróciła normalna hodowla świń.
We want to move the conscience of members and lead to the liquidation of this type of “meat factories” in the European Union, also in Poland, where such plants are already over a hundred.
We want to ensure that large farms are not supported by the European funds to stop the locations of new facilities, then gradually eliminate those that already exist.
We want “meat factories” returned to normal breeding of pigs. (via GoogleTranslate)
As I’ve written before (long archive here and here),the MRSA strain ST398 arose on Dutch pig farms in 2004, among pigs that had been given prophylactic doses of antibiotics, especially tetracycline. It has since spread through the EU, Canada and the United States, affecting not only farm workers and veterinarians, but also hospital patients with no connection to agriculture.
(Self-promotion alert: This may be a good time to tell you that my book SUPERBUG: The Fatal Menace of MRSA, which tells the full story of the emergence and spread of ST398, has just been released in paperback.)
In advance, this morning the trade paper Farming UK wrote this about the planned European Parliament announcements:
(Members of the European Parliament) will hear evidence that European taxpayers’ money is being used by the European Bank for Reconstruction and Development, together with Common Agriculture Policy payments, to subsidise industrial pig farming even though there is increasing concern over the impact on human health. With a vote this summer over reforms to the Common Agricultural Policy, MEPs will come together to take a stance against the crisis in agriculture with critically low prices for pork, poor labelling, and widespread disregard for animal welfare laws.
MEPs and NGOs will condemn the overuse of antibiotics in factory farms which has led to the emergence of antibiotic-resistant bacteria such as MRSA and ESBL E. coli. A recent report by the Dutch Food Standards Agency estimated that one third to one half of all antibiotic resistance in human diseases in the Netherlands derives from farm antibiotic use. American scientists recently found that flies and cockroaches from intensive pig farms carry bacteria resistant to the same antibiotics routinely used in pig farming, and warned that the insects were likely to be able to spread the disease from the farms to local people.
The event was co-organized by Tracy Worcester, who is both a British aristocrat and director of a documentary, Pig Business, that has not yet been shown in the US. Here’s its trailer:
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In both medicine and agriculture, Europe has been ahead of the US in addressing concerns about antibiotic resistance. This morning’s announcements are yet more evidence of just how far ahead they are.
Farm antibiotics, human illness and what connects them. (It has legs.)
When it comes to the impact of farm antibiotics on human health, there’s a data gap.
That the use of antibiotics on conventional/confinement farms provokes the emergence of drug-resistant bacteria really isn’t in dispute; it’s been proven, over and over again, for about 30 years now. (Here’s a long bibliography from the Pew Charitable Trusts that lists the major pieces of research.) And there’s good research as well that those bacteria move off farms via animals, farm workers, groundwater and air currents. (Another long bibliography here, from the Center for a Livable Future.)
But proving the links between resistant farm bacteria and human illness is trickier. Among the reasons: When an individual person who is sick with a foodborne illness goes to the doctor, that doctor does only enough testing to figure out how to treat them. The kind of subtyping you would need to do on a foodborne organism to prove its farm-drug link isn’t useful to a primary-care physician, and the equipment isn’t accessible either; it’s found in academic medical centers and state public health labs. But the public health system isn’t filling the data gap either. The CDC’s main foodborne outbreak-tracking program, FoodNet, monitors the prevalence of 10 illness-causing organisms, but doesn’t test for antibiotic resistance. And the joint federal program that does monitor resistance, NARMS (for National Antimicrobial Resistance Monitoring System, shared by the CDC here, USDA here and FDA here) uses randomized anonymized samples from humans, animals and retail meat, so it can’t illuminate whether resistant bacteria are causing outbreaks.
So are resistant bacteria from farms causing outbreaks of human illness? The Center for Science in the Public Interest says yes. In a white paper published this week, the group documents 35 outbreaks between 1973 and 2009 for which epidemiologic and microbiological links are clear. Quoting from the report:
- Reporting of outbreaks due to antibiotic-resistant bacteria has increased in each decade since the 1970s, with 40% (14 out of 35) occurring in the last decade … Outbreaks were most common in dairy products (34%) and ground beef (26%). Two outbreaks each were linked to poultry, pork, produce, and seafood, and one outbreak each was linked to eggs and multi-ingredient foods. The food vehicle was unknown in four of the outbreaks.
- A total of 19,897 people were sickened from these 35 outbreaks, resulting in 3,061 hospitalizations and 26 deaths.
- For the 31 outbreaks for which antibiotic-resistance patterns were determined, the responsible bacteria displayed resistance to a total of 14 different antibiotics … Of those antibiotics, seven are classified by the World Health Organization (WHO) as ‘critically important’ to human medicine and eight as ‘highly important’ to human medicine. Bacteria showed resistance to tetracycline in 30 outbreaks. Resistances to streptomycin and ampicillin, both classified as critically important antibiotics, were the next most common. Bacteria associated with 19 outbreaks were resistant to at least five antibiotics. Fifteen of those occurred between 1990 and 2009.
There’s still a data gap, of course: Exactly how are the organisms getting from the animals or their manure into the guts of humans? Via meat, or milk, is the logical assumption. But an article also published this week suggested the organisms might have help — from cockroaches and flies.
Researchers from Kansas State University and North Carolina State University scooped up house flies and German (common) cockroaches on conventional confinement farms in both states, and also scooped up poop from the pigs being grown on the farms. They tested all three for the presence of resistant forms of the common gut bacteria Enterococci. Almost all — 89 percent of the pig-manure samples, 94 percent of the cockroach guts and 98 percent of the flies’ guts — contained Enterococci. Of the Enterococci, at least 90 percent of those found in each species were resistant to tetracycline; from 50 percent to 70 percent were resistant to erythromycin; and from 10 percent to 40 percent were resistant to ciprofloxacin and streptomycin — NB, all drugs used in essentially identical forms in humans as well as livestock. PFGE analysis of the Enterococci from the pigs and the insects showed they were carrying the same bacterial clones.
The researchers write:
Organic wastes in and around animal production
facilities including swine farms provide excellent habitats for house flies and German cockroaches. Several features of house flies and cockroaches, including their dependence on live microbial communities, active dispersal ability and human-mediated transport, attraction to places where food is prepared and stored, developmental sites, and mode of feeding/digestion make these insects an important “delivery vehicle” for transport of bacteria including antibiotic resistant enterococci from reservoirs (animal manure), where they pose minimal hazard to people, to places where they pose substantial risk (food)…High frequency of resistance to tetracycline, erythromycin, streptomycin, kanamycin, and
ciprofloxacin in our study likely reflects use of tetracyclines, macrolides, aminoglycosides and
fluoroquinolones as feed additives for swine in the USA… The source of antibiotic resistant
enterococci in house flies and cockroaches in this study was the swine manure due to very high
prevalence of antibiotic resistant enterococci in all three sources.
Cite: Ahmad, A et al. Insects in confined swine operations carry a large antibiotic resistant and potentially virulent enterococcal community. BMC Microbiology, 26 January 2011, 11:23doi:10.1186/1471-2180-11-23
News break: First guidelines for treating MRSA
For my book SUPERBUG: The Fatal Menace of MRSA (came out last March; paperback will be out in February), I spent several years talking to about 100 victims of antibiotic-resistant staph, and family members of victims who did not survive their infections. There were some striking things about their stories.
One was the variability of the bug, which can cause anything from mild one-time skin infections to lethal necrotizing pneumonia, adding up to almost 19,000 deaths, 369,000 hospitalizations and possibly 7 million medical office visits a year. The other was the variability of the patients’ treatment. Some had the good luck to find physicians who knew about the bug, understood the layers of testing needed to determine the best antibiotics to use, and were sensitive to the possibilities of over- and under-treatment. Others were not so lucky: They went to doctors who didn’t recognize the infection, didn’t prescribe drugs that worked, didn’t have anything to offer when the infection recurred — a whole panoply of errors.
It was a lesson for me in how long it can take news of a new medical development to percolate through the clinical community, especially to primary-care practitioners — people who don’t have a channel for new news because they don’t work for an academic medical center or belong to a specialty society that puts out a journal or at least a substantial newsletter. But it was also a lesson on how few agreed-upon standards of practice there were for treating MRSA. For many presentations, there was no evidence refer to; clinicians were thrown back onto poring through the literature, or on making educated guesses based on their past experience.
As of this week, that should change. The Infectious Diseases Society of America has publshed the first-ever clinical practice guidelines for treating MRSA in adults and children. It’s a substantial document, 38 pages (in the advance access section of Clinical Infectious Diseases) and should be a tremendous resource for patients and their physicians. (I know of one patient who printed it out yesterday and took it to an office visit — only to find the physician had just downloaded a copy himself.) [Read more…]
Update: Farm Animals Get 80 Percent of Antibiotics Sold in U.S.
Two weeks ago, I broke the news of a new FDA report that estimated for the first time the amount of antibiotics sold in the United States every year for use in agriculture: 28.8 million pounds.
That long-awaited report didn’t answer a crucial question: What volume of antibiotics are sold in the United States each year for human use. It’s a crucial question because, in answer to concerns about antibiotic resistance arising on farms, the answer has always been that human medicine is equally culpable because it uses similar volumes of antibiotics.
The only research that has attempted to answer that question is contained in a decade-old report by the Union of Concerned Scientists that put the proportion of antibiotics going to animals at 70 percent of the U.S. total.
That UCS report and estimate are a decade old not because no one has cared about the topic, but because accurate updated figures have been so hard to get. So we owe a special holiday thank-you to the researchers at the Center for a Livable Future, who decided the release of the FDA report justified another attempt to get the numbers straight. They succeeded.
The proportion of antibiotics sold in the United States each year that go to animals turns out to be not 70 percent, but rather 80 percent. Here’s CLF’s Ralph Loglisci, who got the confirmatory numbers from the FDA:
In accordance with a 2008 amendment to the Animal Drug User Fee Act, for the first time the FDA released last week an annual amount of antimicrobial drugs sold and distributed for use in food animals. The grand total for 2009 is 13.1 million kilograms or 28.8 million pounds. I … contacted the FDA for an estimate of the volume of antibiotics sold for human use in 2009. This is what a spokesperson told me:
“Our Office of Surveillance and Epidemiology just finished an analysis based on IMS Health data. Sales data in kilograms sold for selected antibacterial drugs were obtained as a surrogate of human antibacterial drug use in the U.S. market. Approximately 3.3 million kilograms of antibacterial drugs were sold in year 2009. OSE states that all data in this analysis have been cleared for public use by IMS Health, IMS National Sales Perspectives™.”
3.3 million kilograms is a little over 7 million pounds. As far as I can determine, this is the first time the FDA has made data on estimates of human usage public.
At its blog, CLF lays out the math for each major drug class as sold for animal use and human use, with a long discussion of the significance of the different drug classes. Here’s the CLF table summing up the math, but please go over to CLF’s blog for its discussion.
Most important to note: Most of the drugs used in animal agriculture and in human medicine are functionally identical. That’s one reason why the overuse of antibiotics in animals is such a concern: When organisms become resistant on the farm to drugs used on livestock, they are becoming resistant to the exact same drugs used in humans. (One major drug category used in animals, ionophores, do not have a direct human analog. But use of them on farms is still a concern, because resistance factors can move freely between species of bacteria. That’s a discussion for another day.)
Loglisci’s conclusion is also worth underlining:
The next battle, which industry has already begun, is defining what non-therapeutic use will constitute. Producers are already claiming that the use of antibiotics for growth promotion has decreased, maintaining current low-dose usage is aimed at disease prevention. Regardless, all low-dose usage of antibiotics can lead to a significant increase in antibiotic resistance.
Image: Flickr/Epsos
News break: FDA estimates US livestock get 29 million pounds of antibiotics per year
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
ResistanceMap and Get Smart About Antibiotics Week
Among the many skills admired by journalists (always finding the free food; never going out of the office; yes, those are said in jest), skidding in just under deadline may be the most valued. I am making a flourish of that skill here, sliding in a mention of an important observance this week just as the week ends.
(Sorry. There was a lot of news this week.)
So: In case you hadn’t yet noticed, this is (was) Get Smart About Antibiotics Week, 2010.
The Get Smart week is co-sponsored by the CDC and the FDA, and its goal is to alert people to the continuing overuse of antibiotics in human medicine. (A separate but just as important issue as overuse of antibiotics on the farm, which I’ve talked about a number of times here.)
If you’re concerned about this — and who shouldn’t be — the CDC’s sites have a plethora of information about this crucial issue. There are briefings, posters, brochures, radio and TV PSAs, a blog by federal researchers and others and — possibly the most directly useful to parents in the whole campaign — a form letter that doctors can download and fill out to give to working parents, explaining why a child with a sniffle or a sore ear can be admitted to daycare without an antibiotic prescription. [Read more…]
News break: House hearing on antibiotic pipeline
The Subcommittee on Health of the Energy and Commerce Committee of the House of Representatives has announced a hearing for Wednesday: “Promoting the Development of Antibiotics and Ensuring Judicious Use in Humans.”
The witness line-up is:
- Janet Woodcock, M.D., Director, Center for Drug Evaluation and Research, Food and Drug Administration
- Robin Robinson, Ph.D., Director, Biomedical Advanced Research and Development Authority, Department of Health and Human Services
- Brad Spellberg, M.D., F.I.D.S.A., Associate Professor of Medicine, David Geffen School of Medicine at UCLA and Member, Infectious Diseases Society of America Antimicrobial Availability Task Force
- Sandra Fryhofer, M.D., Council on Science and Public Health, American Medical Association
- John S. Bradley, M.D., American Academy of Pediatrics, Chief, Division of Infectious Diseases, Department of Pediatrics, University of California, San Diego, School of Medicine, Clinical Director, Division of Infectious Diseases, Rady Children’s Hospital
- Barry Eisenstein, M.D., F.A.C.P., F.I.D.S.A., Senior Vice President, Scientific Affairs, Cubist Pharmaceuticals
- Jeffrey Levi, Ph.D., Executive Director, Trust for America’s Health
This is the second hearing the Health Subcommittee has had this spring, apparently at the prompting of the chairman of Energy and Commerce, Rep. Henry Waxman, who made the opening statement at the first such hearing in April:
We need to debate the health care bill and review its implementation. But we ought to be able to chew gum and walk at the same time. Because it is not going to make much difference if you have health insurance or not if you are going to die from something that could have been prevented from an antibiotic. And we are seeing more and more antibiotic resistance. (Transcript)
Reading between the lines, I’m going to guess this hearing will lean heavily on the IDSA’s campaign to improve market conditions for pharma companies in order to revive antibiotic development (an issue I discussed recently at the old Superbug — we’re working on getting the archives moved over).
Incentives for making new antibiotics: What would it take?
Let’s play a thought experiment. Imagine that you’re a major pharmaceutical company, a public company, with shareholders that you answer to, and market analysts looking over your shoulder to see whether this quarter’s earnings are up to projections. Imagine that you want to make a new drug. Let’s make it an antibiotic, because — as we talk about here all the time (and SUPERBUG explores in detail) — new antibiotics that can leapfrog over existing drug resistance are very needed. Thus, you imagine, a new antibiotic ought to sell well, even though any individual course of that antibiotic will only be a few weeks by mouth, or maybe a few months by IV if the patient is very sick. You know there’s a big market out there.
But: Imagine — as is generally accepted to be true — that it will take about 10 years, and about $1 billion dollars, to get that novel antibiotic through the development pipeline and into the marketplace. And then imagine that — as has been shown for a number of drugs, most recently the new antibiotic daptomycin — bacteria begin developing resistance to your drug within a year of its deployment in patients. And after that, imagine — as has been cited in a number of papers — that once local resistance to your antibiotic appears in approximately 20% of isolates, physicians will cease prescribing your antibiotic, for fear their patient will be one of that 20%.
So, to recap: 10 years, $1 billion; short course; short market life; rapid obsolescence.
Would you make that investment? Or would you, if you were a pharma company, opt instead to make insulin, which Type 1 diabetics will take every day for the rest of their lives? Or statins, which at this point we’re practically ready to put in the water supply? Or a cancer drug that costs $10,000 per dose? Or Viagra, or Cialis?
If you’re a company that is responsible to its shareholders, or listening to its analysts — or even capable of doing basic math — the answer’s obvious: Antibiotics lose. Which goes a long way to explaining why so many companies have backed off from making antibiotics, and why many of the few antibiotics in the pipeline are “me too” formulations, rather than new compounds with truly new mechanisms of action.
How to respond to this impasse has been an active debate for a while, largely focused on proposals to give market incentives, changes in tax credits, or patent extensions to pharma companies to persuade them to stay in or re-enter the marketplace. The Infectious Diseases Society of America, the specialty society for infectious-disease physicians (many of whom are also academic researchers), has been addressing this through its campaign “10x 20”, which has a goal of getting 10 new compounds into if not through the pipeline by the year 2020.
But, as a new article in the British Medical Journal points out, good incentivizing demands complexity — not just in developing both “push” and “pull” mechanisms (say, tax incentives to fund research v. prizes and wildcard patent extensions), but also in making sure that the incentives can be taken advantage of by companies of all sizes, not just the international mega-pharmas:
The characteristics of an ideal incentive mechanism and the desire for an equitable approach that engages developers of all sizes would suggest that neither push, pull, nor lego-regulatory mechanisms would be optimal to spur the desired investment in antibiotics …. Rather, elements of each should be combined. The exact shape of the ideal package is, however, as yet unclear. (Morel et al.)
And an accompanying editorial emphasizes that new antibiotics are not the only things needed; new diagnostic tests, for instance, need funding as well:
Catchy as 10×20 sounds, the public sector strategy for funding such research and development must prioritise among different health technologies, such as diagnostics and vaccines, to combat antibiotic resistance. For example, three million children die each year from acute respiratory bacterial infections in developing countries, but penicillin sensitive pneumococcal strains have declined to a half, even a quarter, in some countries. A diagnostic test for bacterial pneumonia would save an estimated 405 000 lives a year, by targeting treatment and avoiding overprescription of antibiotics. New vaccines may also reduce reliance on drugs as the use of pneumococcal vaccine has suggested. (So et al.)
This is a hard discussion. I confess, as a longtime reporter, I flinch reflexively at the thought of handing more money to the pharmacos. At the same time, the state of the market demonstrates that the current model is not working. And though I would much prefer we focus on the ecological model of preserving antibiotics as a resource — dialing back on overuse and encouraging rigorous stewardship — it’s clear that we’ll always need new drugs for the most serious, most resistant infections.
So some sort of incentivizing seems necessary. And the multi-layered approach recommended in the BMJ, with appropriate attention paid to incentivizing the development of tests and vaccines as well, seems worth heeding.
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?)
Farming and antibiotics – and voices from the ag side
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.
Questioning meat-raising and meat-eating — in eat-everything France
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.
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