Journalist and Author
There’s a new paper out in the CDC’s journal Emerging Infectious Diseases that makes a provocative claim: There is enough similarity between drug-resistance genes in E. coli carried by chickens and E. coli infecting humans that the chickens may be the source of it.
If it is correct — and it seems plausible and is backed by past research — the claim provides another piece of evidence that antibiotic use in agriculture has a direct effect on human health.
My college boyfriend and I used to have this conversation:
Me: “I’m so broke.”
Him: “Yeah, me too.”
Which was almost always followed, a few days later, by this conversation:
Him: “Let’s go get a beer.”
Me: “I thought you said you were broke?”
Him (after a puzzled pause): “Well, yeah, I was. But then I went to the bank.”
How is this relevant, you ask? Like this. When it comes to antibiotic resistance — that is, to the increasing number of infections against which many drugs are no longer effective — people seem to think like my ex: When we’re out, we go back to the bank for more. The problem is, when it comes to antibiotics, we’re not temporarily out. We’re broke for real.
File under: Really not good news.
Deep in the back of the weekly bulletin of the Centers for Disease Control and Prevention, there is a note that NDM-1, the “Indian supergene,” has been isolated from a patient in a U.S. military field hospital in Bagram, Afghanistan.
It’s been a few months since NDM-1 was in the news, so let’s recap. The acronym (for “New Delhi metallo-beta-lactamase 1”) indicates an enzyme that allows common gut bacteria to denature almost all the drugs that can be used against them, leaving two or three that are inefficient or toxic. It was first identified in a resident of Sweden, of Indian origin, who had returned to India for a visit, was hospitalized there, went back to Sweden, and was hospitalized again.
A little less than a year ago, the Food and Drug Administration took a step that, depending on your point of view, was either far too activist or nowhere-near-enough-but-good-try: It proposed, in a draft document, that the agricultural industry voluntarily restrict its use of growth-promoting micro-doses of antibiotics.
It was a significant step. The FDA has been trying to restrict subtherapeutic use of antibiotics in livestock since the 1970s because of the practice’s clear contribution to the development of antibiotic resistance, and had always been defeated. At the same time, it was far from bold: The proposal was made in a draft document that would be made final at some unspecified future date, and that when it became final would have behind it no force of regulation or law. (Here’s my long discussion from last year of the context and history of FDA’s move.)
And there things rested, while the FDA’s docket reportedly filled up with thousands of comments from both sides of the issue. The document — formally, Draft Guidance #209, Judicious Use of Antimicrobial Drugs in Food-Producing Animals — is scheduled to be finalized sometime before the end of this year. But in its draft form, it excited abundant opposition, and the administration official who seemed to be leading the charge on it, memorably suggesting, “We have the regulatory mechanisms and the industry knows that,” has left the FDA for a state-government job.
Clearly, things aren’t moving very fast. So today, a coalition of nonprofit groups attempted to get the issue jump-started: They sued.
It’s been just about seven years since an alert epidemiologist in the Dutch town of Nijmegen identified an aberrant strain of MRSA, drug-resistant staph, in a toddler who was going in for surgery to fix a hole in her heart. The strain was odd because it didn’t behave normally on the standard identifying tests, and because it had an unusual resistance factor — to tetracycline, a drug that it should not have been resistant to, because the Netherlands had such low rates of MRSA that tetracycline wasn’t being used against the bacterium there.
Pursuing the source of the strain, researchers at Radboud University found it in the toddler’s parents and sister, and in the family’s friends. Not knowing where else to look, they asked what the parents and their friends did for a living; discovered they were all pig farmers; and went to their farms, and checked the pigs, and found it being carried by them, too. Suddenly, that strange resistance pattern made sense: The Netherlands uses more antibiotics in pig agriculture than any other country in the European Union, and the drug that it uses the most is tetracycline. Clearly, the aberrant strain — known as MRSA ST398 for its performance on a particular identifying test — at some point had wandered into pigs, become resistant to the drugs being given to the pigs, and then crossed back to humans, carrying that new resistance factor as it went.
So if we wanted to reduce the danger of pathogens passing to people via food — not just drug-resistant bacteria, which are an increasingly significant problem, but all disease-causing ones — where to start?
Formulating a strategy is more difficult than it seems. In the US, policing food safety is divided among several federal agencies: the FDA, USDA and CDC. The FDA has responsibility for most of the food supply, including seafood, produce, processed food and fresh eggs. The USDA’s Food Safety and Inspection Service (FSIS) regulates fresh meat and poultry and egg products. The CDC surveys the illnesses that result from any of them, estimating most recently that one in six US residents, or about 48 million people, get sick each year, 128,000 are hospitalized and 3,000 die.
But most of those illnesses are never investigated, because a substantial portion of them occur individually or in small clusters, not in major outbreaks. Many of them have long-term consequences that are never recorded by any federal counting mechanism. And there’s currently no surveillance system that links pathogens and food — which means there’s no way to target which foods, or food-raising practices, pose the greatest risks.
The new food-safety bill, signed in January, addresses at least some of those barriers, by requiring a risk-based approach to foodborne illness — meaning, you look at what is causing the greatest problem, and aim your efforts and funding in that direction. But the bill — which certain Congressmen have threatened to starve of funding — covers primarily the FDA. And a new analysis suggests that’s not where the greatest problems lie. [Read more…]
So if we agree that the untrammeled rise in antibiotic resistance is a bad thing — and given the unexpected World Health Day news that an incredibly resistant bacterium is in New Delhi’s water supply, I think many do agree — what do we do next?
How about charging everyone who buys an antibiotic a user fee?
That’s one of the surprisingly nervy proposals that surfaced Thursday during World Health Day, a refreshing change from the somber but predictable rhetoric put forward by the WHO and CDC. It comes from a comprehensive set of policy recommendations released Thursday by the Infectious Diseases Society of America in the journal Clinical Infectious Diseases and at a press event in Washington DC.
The direct language in the recommendations’ introduction indicates their tone:
The availability of effective antibiotics is not a ‘‘lifestyle’’ issue, and the lack of availability of these agents is not theoretical. Society worldwide is facing a public health crisis due to stagnation in the antibiotic drug pipeline combined with rapidly spreading, deadly antibiotic-resistant pathogens. The lack of effective antibiotics already is resulting in deaths and maiming of patients and the problem will only continue to worsen until Congress and the Administration act. The time for debate about the problem has passed. Immediate action is critically needed now.
Last fall, not long after the bloom of news about the “Indian superbug” NDM-1 — a newly identified enzyme that renders common gut bacteria indifferent to almost all antibiotics — I spoke to one of its lead researchers, Timothy Walsh of the University of Cardiff, about next steps in their research.
His work and his collaborators’ had demonstrated that many of the people infected with or carrying bacteria that incorporated the gene had undergone medical treatment in India and Pakistan, sometimes for elective surgery such as medical tourism, sometimes because they had been injured or ill while traveling. But not all, he said — and that was making them wonder whether the spread of NDM-1 had an environmental component. It was a plausible hypothesis given the apparent concentration of NDM-1 in India, a country whose sanitation systems have not kept up with its booming population. A recent UN report estimated that almost half of India’s residents — that would be up to 650 million people — lack treated drinking water and modern toilets. If you sat down to design a system to facilitate the spread of an enzyme carried by bacteria in the gut — that is, in feces — you couldn’t do better than what India already has.
“There has been very little work done or analysis done on the effect that (poor sanitation) would have on the spread of resistance and on carriage of NDM-1 within a normal population,” Walsh told me at the time. “There’s no water sampling for fecal flora or antibiotic-resistant flora.”
Well, now there is: Walsh and his collaborators have done it. And the news, as they suspected, is bad. [Read more…]
Tomorrow, Thursday, is World Health Day, an annual observance that the World Health Organization uses to focus attention on some critical global-health issue. This year, they’ve chosen antimicrobial resistance as the issue that most needs highlighting. Noting the choice, the Lancet editorialized: “Resistance has joined the front rank of global health concerns.”
On the day, the WHO and some other agencies and organizations will be announcing plans and strategies. I’ll cover those tomorrow. For today, a scene-setter: Why you should care.
Having spent the last couple of years immersed in antibiotic resistance (because, you know, I wrote a book about it), I’m often puzzled why it doesn’t excite more alarm. I’ve concluded our situation is similar to the overused analogy of the frog in the slowly warming water: We don’t realize how bad things have gotten, even when we’re in imminent danger of death.
So here’s a round-up to remind us, drawn just from recent news.
In hospitals: Very large hospital systems are using more broad-spectrum last-resort drugs. Last weekend, representatives of the Veterans Health Administration disclosed that over 5 years, vancomycin use has gone up 79 percent, and carbapenem use, 102 percent. Vancomycin is the only affordable drug of last resort for MRSA; carbapenems are the drugs of last resort for gram-negative infections such as Klebsiella. The use of those drugs is growing because organisms are becoming multi-resistant to less-powerful drugs, but they are becoming resistant to the big guns too. Carbapenem resistance in Acinetobacter, a bacterium that afflicts ICU patients and gravely wounded military members, rose from 5 percent of isolates in US hospitals in 2000 to 40 percent in 2009. Israeli scientists reported this month that carbapenem-resistant Klebsiella pneumoniae (CRKP, subject of my Scientific American article this month) caused a nationwide outbreak in 2007 and 2008, sickening 1,275 patients in 27 hospitals before it was brought under control. [Read more…]
Remember NDM-1, the “Indian supergene” that created a media furor last fall and then fell below the news horizon? This is worse.
I have a story in the April Scientific American (“The Enemy Within,” just previewed online) about a new and very troubling form of antibiotic resistance: Carbapenem resistance, spreading through Gram-negative bacteria such as Klebsiella (above, from the CDC) and E. coli.
Carbapenems are drugs of last resort for Gram-negatives, which include many of the bacteria that cause potentially deadly infections in debilitated ICU patients and frail elderly in nursing homes. Gram-negatives have been becoming ever-more resistant to antibiotics, but the carbapenems remained reliable drugs of last resort for even the most serious cases. Then, in 1996, researchers at the Centers for Disease Control and Prevention spotted the first signal that carbapenems were under threat: A single bacterial sample, found in a patient in a North Carolina hospital, that was resistant to the carbapenems and could only be treated by a few remaining drugs that were much less effective or so toxic that medicine had put them on the shelf years ago.
By 2000, that same resistance pattern surfaced in hospitals in Manhattan: first one, then another, then a third and fourth. Then it began to spread to cities where New Yorkers vacation, and then to countries where they travel. Now, more than a decade later, it has reached at least 37 states and at least a dozen countries around the world.
It is spreading much faster than drugs to combat it could be developed — if there were such drugs. One of the difficulties, indeed tragedies, of carbapenem resistance is that there are very few such drugs left — because, for reasons I’ve explored before, drug development in the United States has ground to a halt. For resistant Gram-negatives, there are almost no drugs left, and none on the immediate horizon. If that scares you, well, it should.
Here’s a quick snip from the article:
The end of the antibiotic miracle is not a new theme. For as long as there have been antibiotics, there has been antibiotic resistance: The first penicillin-resistant bacteria surfaced before penicillin was even released to the marketplace in the 1940s. And for almost that long, doctors have raised the alarm over running out of drugs, sparked by the global spread of penicillin-resistant organisms in the 1950s and followed by methicillin resistance in the 1980s and vancomycin resistance in the 1990s.
This time, though, the prediction of post-antibiotic doom comes from a different part of the microbial world. The genes that confer carbapenem resistance have appeared over the past decade or so in a particularly challenging grouping of bacteria called gram-negatives.
Gram-negative bacteria are promiscuous: They facilely exchange bits of DNA, so that a resistance gene that arises in Klebsiella, for example, quickly migrates to E. coli, Acinetobacter and other gram-negative species. Gram-negative germs are also harder to dispatch with antibiotics because they have a double-layered membrane that even powerful drugs struggle to penetrate, and possess certain internal cellular defenses as well. In addition, fewer options exist for treating them. Pharmaceutical firms are making few new antibiotics of any type these days. For the protean, stubborn gram-negatives, they have no new compounds in the pipeline at all.
Carbapenem resistance has already brought hospital-acquired infections to the brink of untreatable. The imagined future that keeps health authorities awake at night is the undetected dissemination of carbapenem resistance genes into organisms that cause everyday maladies—such as E. coli, which is responsible for most of the millions of urinary tract infections in the U.S. every year.
Carbapenem resistance in Klebsiella — which is sometimes called KPC or CRKP for short — got a spike of attention last week just as my piece hit the web. Coincidentally, the article posted just as the Los Angeles County Department of Public Health released results of a survey showing 356 cases just between June and December 2010 just in LA County medical facilities.
This SciAm piece is the first that we know of to tell the whole tangled, troubling story. I hope you’ll take a look.
And while you’re there, please read SciAm’s brave and cogent editorial against antibiotic overuse in industrial-scale agriculture. It’s marvelous.
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.
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…]
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)
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
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?
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
Since the first identification in 2004 of MRSA ST398, also known as “pig MRSA” or livestock-associated MRSA (archives of posts here and here), that drug-resistant organism has been found being carried asymptomatically by farm workers and veterinarians, and causing illness in health care workers, hospital patients, and people with no known ties to agriculture. One of the persistent data gaps, though, has been whether farm workers themselves have been made sick by it.
It’s a difficult question to answer for a nested set of reasons: First, in most of the states, MRSA (methicillin-resistant Staphylococcus aureus, or drug-resistant staph) is not a reportable disease; that is, a doctor who diagnoses it in a patient is under no obligation to tell any public health authority about that patient’s case. And second, the testing required to distinguish livestock-associated MRSA from community-acquired or hospital-acquired is not something that primary-care medical personnel have access to; you have to go to a state laboratory or an academic medical center to do the appropriate molecular typing. Those tests are expensive to perform, and their results primarily are useful to public health, not to individual medical practitioners. So finding out where that nascent epidemic is going has been unusually challenging.
Comes now a team from the University of Iowa — the same team that first identified ST398 in pigs and pig-farm personnel in the United States — to start to fill the gap. [Read more…]
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…]
So it looks like the researchers who named NDM-1 — New Delhi metallo-beta-lactamase, the “Indian super-enzyme” that renders common gut bacteria impervious to all but one or two antibiotics — were right all along.
According to a study just published in Antimicrobial Agents and Chemotherapy, the problematic gene that produces it has been circulating in Indian hospitals since at least 2006.
Kinda undermines the claims by Indian politicians and the country’s health ministry that the resistance factor did not originate in India, but was given its name in an act of “malicious propaganda” aimed at undermining the subcontinent’s multimillion-dollar medical-tourism industry.
A brief recap: [Read more…]
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
