FDA restricts antibiotic use in livestock

This is the best news in a long time.

WASHINGTON — The Food and Drug Administration on Wednesday put in place a major new policy to phase out the indiscriminate use of antibiotics in cows, pigs and chickens raised for meat, a practice that experts say has endangered human health by fueling the growing epidemic of antibiotic resistance.

This is the agency’s first serious attempt in decades to curb what experts have long regarded as the systematic overuse of antibiotics in healthy farm animals, with the drugs typically added directly into their feed and water. The waning effectiveness of antibiotics — wonder drugs of the 20th century — has become a looming threat to public health. At least two million Americans fall sick every year and about 23,000 die from antibiotic-resistant infections.

“This is the first significant step in dealing with this important public health concern in 20 years,” said David Kessler, a former F.D.A. commissioner who has been critical of the agency’s track record on antibiotics. “No one should underestimate how big a lift this has been in changing widespread and long entrenched industry practices.”

The change, which is to take effect over the next three years, will effectively make it illegal for farmers and ranchers to use antibiotics to make animals grow bigger. The producers had found that feeding low doses of antibiotics to animals throughout their lives led them to grow plumper and larger. Scientists still debate why. Food producers will also have to get a prescription from a veterinarian to use the drugs to prevent disease in their animals.

Federal officials said the new policy would improve health in the United States by tightening the use of classes of antibiotics that save human lives, including penicillin, azithromycin and tetracycline. Food producers said they would abide by the new rules, but some public health advocates voiced concerns that loopholes could render the new policy toothless.

Health officials have warned since the 1970s that overuse of antibiotics in animals was leading to the development of infections resistant to treatment in humans. For years, modest efforts by federal officials to reduce the use of antibiotics in animals were thwarted by the powerful food industry and its substantial lobbying power in Congress. Pressure for federal action has mounted as the effectiveness of drugs important for human health has declined, and deaths from bugs resistant to antibiotics have soared.

Under the new policy, the agency is asking drug makers to change the labels that detail how a drug can be used so they would bar farmers from using the medicines to promote growth.

The changes, originally proposed in 2012, are voluntary for drug companies. But F.D.A. officials said they believed that the companies would comply, based on discussions during the public comment period. The two drug makers that represent a majority of such antibiotic products — Zoetis and Elanco — have already stated their intent to participate, F.D.A. officials said. Companies will have three months to tell the agency whether they will change the labels, and three years to carry out the new rules.

Additionally, the agency is requiring that licensed veterinarians supervise the use of antibiotics, effectively requiring farmers and ranchers to obtain prescriptions to use the drugs for their animals.

“It’s a big shift from the current situation, in which animal producers can go to a local feed store and buy these medicines over the counter and there is no oversight at all,” said Michael Taylor, the F.D.A.’s deputy commissioner for foods and veterinary medicine.

 

Recommendations for the control of Multi-drug resistant Gram-negatives> carbapenem resistant Enterobacteriacea

Australian Commission on Safety and Quality in Health Care. Recommendations for the control of Multi-drug resistant Gram-negatives: carbapenem resistant Enterobacteriaceae (October 2013). Sydney. ACSQHC, 2013.

(…snip…) Gram-negative bacteria have now emerged that are resistant to most types of antibiotics, including a key “last resort” class of antibiotic, the carbapenems. These organisms are referred to as carbapenem resistant Enterobacteriaceae (CRE). Multi-resistant Gram-Negative bacteria, such as CRE, place Australian patients at greater risk of potentially untreatable infection and increased mortality. CRE is of particular concern because Enterobacteriaceae cause infections at a high frequency and resistant infections are associated with high mortality.

Patients in residential aged care facilities are also potentially at increased risk. Multi-drug resistant Gram- negative organisms have been isolated more frequently in overseas long term care facilities than some other Gram-positive multi-resistant organisms.

Over the past 2 years there have been an increasing number of cases of CRE in Australian patients. Some patients contracted the infection overseas and unfortunately some within Australia. In November 2011, the National Healthcare Associated Infection Advisory Committee of the Australian Commission on Safety and Quality in Health Care discussed the potential implications of CRE in Australian hospitals. A taskforce was established in partnership with the Australasian Society Infectious Diseases, Australasian College of Infection Prevention and Control, Public Health Laboratory Network and Australasian Society of Antimicrobials to develop recommendations for the management and testing of patients with CRE.

This paper incorporates recommendations for patient management that are contained in the Australian Guidelines for the Prevention and Control of Infection in Healthcare and the National Safety and Quality Health Service Standards. These include the use of standard and transmission based precautions, especially for patient placement, patient movement, cleaning and disinfection and antimicrobial stewardship. There are also additional recommendations for laboratory screening methods. 

The bottom line is there is no place to hide. Not even Australasia.

Rising Plague: The Global Threat from Deadly Bacteria and Our Dwindling Arsenal to Fight Them

Maryn McKenna cited this book, so after reading hair-curling reviews I just bought the Kindle edition. Maybe no sleep tonight…

Antibiotic-resistant microbes infect more than 2 million Americans and kill over 100,000 each year. They spread rapidly, even in such seemingly harmless places as high school locker rooms, where they infect young athletes. And throughout the world, many more people are dying from these infections. Astoundingly, at the same time that antibiotic resistant infections are skyrocketing in incidence creating a critical need for new antibiotics research and development of new antibiotics has ground to a screeching halt!

In Rising Plague, Dr. Brad Spellberg an infectious diseases specialist and member of a national task force charged with attacking antibiotic resistant infections tells the story of this potentially grave public health crisis. The author shares true and very moving patient stories to emphasize the terrible frustration he and his colleagues have experienced while attempting to treat untreatable infections, not to mention the heart-break and tragedy that many of these patients' families had to endure.

Dr. Spellberg corrects the nearly universal misperception that physician misuse of antibiotics and “dirty hospitals” are responsible for causing antibiotic-resistant infections. He explains the true causes of antibiotic resistance and of the virtual collapse of antibiotic research and development. Most important, he advocates ways to reverse this dire trend and instead bolster the production of desperately needed new and effective antibiotics.

He also warns against complacency induced by the decades-old assumption that some miracle drug will always be available to ensure the continuation of our “antibiotic era”. If we do nothing, we run the risk of inviting a bleak future when infectious diseases will once again reign supreme. Then many of the medical breakthroughs that we now take for granted from routine surgery and organ transplants to intensive care and battlefield medicine might all be threatened.

 

Maryn McKenna: When We Lose Antibiotics, Here’s Everything Else We’ll Lose Too

Maryn McKenna has a terrifying “report from the field” of the fast-approaching post-antibiotic world. That we are living in New Zealand amplifies the report only slightly, because this reality is happening everywhere — and the origin of the particular KPC-Oxa 48 bacterium was Vietnam, not NZ.

This week, [health authorities in New Zealand announced][1] that the tightly quarantined island nation — the only place I’ve ever been where you get x-rayed on the way into the country as well as leaving it — has experienced its first case, and first death, from  a strain of totally drug-resistant bacteria. From the New Zealand Herald:

[1]: http://m.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=11159413

In January, while he was teaching English in Vietnam, (Brian) Pool suffered a brain hemorrhage and was operated on in a Vietnamese hospital.

He was flown to Wellington Hospital where tests found he was carrying the strain of bacterium known as KPC-Oxa 48 – an organism that rejects every kind of antibiotic.

Wellington Hospital clinical microbiologist Mark Jones (said): “Nothing would touch it. Absolutely nothing. It’s the first one that we’ve ever seen that is resistant to every single antibiotic known.”

Pool’s death is an appalling tragedy. But it is also a lesson, twice over: It illustrates that antibiotic resistance can spread anywhere, no matter the defenses we put up — and it demonstrates that we are on the verge of entering a new era in history. Jones, the doctor who treated Pool, says in the story linked above: “This man was in the post-antibiotic era.”

(…snip…)

If we really lost antibiotics to advancing drug resistance — and trust me, we’re not far off — here’s what we would lose. Not just the ability to treat infectious disease; that’s obvious.

But also: The ability to treat cancer, and to transplant organs, because doing those successfully relies on suppressing the immune system and willingly making ourselves vulnerable to infection. Any treatment that relies on a permanent port into the bloodstream — for instance, kidney dialysis. Any major open-cavity surgery, on the heart, the lungs, the abdomen. Any surgery on a part of the body that already harbors a population of bacteria: the guts, the bladder, the genitals. Implantable devices: new hips, new knees, new heart valves. Cosmetic plastic surgery. Liposuction. Tattoos.

We’d lose the ability to treat people after traumatic accidents, as major as crashing your car and as minor as your kid falling out of a tree. We’d lose the safety of modern childbirth: Before the antibiotic era, 5 women died out of every 1,000 who gave birth. One out of every nine skin infections killed. Three out of every 10 people who got pneumonia died from it.

And we’d lose, as well, a good portion of our cheap modern food supply. Most of the meat we eat in the industrialized world is raised with the routine use of antibiotics, to fatten livestock and protect them from the conditions in which the animals are raised. Without the drugs that keep livestock healthy in concentrated agriculture, we’d lose the ability to raise them that way. Either animals would sicken, or farmers would have to change their raising practices, spending more money when their margins are thin. Either way, meat — and fish and seafood, also raised with abundant antibiotics in the fish farms of Asia — would become much more expensive.

Read more..

The last paragraph I quoted bumps the priority on my todo list – to understand better the realities of agricultural antibiotics. I’m carrying around the idea that the Danes have demonstrated on the farm that pigs could be raised without antibiotics at lower cost, higher productivity and healthier pigs. Yes, the farmers did have to innovate and adopt new husbandry methods. But there must be more to the story than my simple memory.

More important, do not miss Maryn’s new in-depth report “Imagining a Post-Antibiotics Future“.

Maryn McKenna on the post-antibiotic planet

…our post-antibiotic grandchildren will be less healthy than we are: more likely to die young or spend their lives crippled by disease. In the face of such a large problem, it’s an amazement that our public-health experts have any time to spare on any other problem.

Megan McArdle:

I imagine how our descendants will look back on our world. Unless something is done about antibiotic resistance, I’m very much afraid that they’ll look upon us the way 19th-century science fiction writers viewed Atlantis: as a lost paradise of magical technology — in this case, one in which you could go to a child coughing her life out with pneumonia, stick a needle in her arm, and watch the disease melt away almost before your eyes. The first doctors who treated patients with antibiotics felt like they were witnessing miracles. Our grandchildren may feel much the same way about the ease with which we cured disease. At Wired, Maryn McKenna outlines all the medical miracles that antibiotics have made possible:

If we really lost antibiotics to advancing drug resistance — and trust me, we’re not far off — here’s what we would lose. Not just the ability to treat infectious disease; that’s obvious.But also: The ability to treat cancer, and to transplant organs, because doing those successfully relies on suppressing the immune system and willingly making ourselves vulnerable to infection. Any treatment that relies on a permanent port into the bloodstream — for instance, kidney dialysis. Any major open-cavity surgery, on the heart, the lungs, the abdomen. Any surgery on a part of the body that already harbors a population of bacteria: the guts, the bladder, the genitals.

Implantable devices: new hips, new knees, new heart valves.

Cosmetic plastic surgery. Liposuction. Tattoos.We’d lose the ability to treat people after traumatic accidents, as major as crashing your car and as minor as your kid falling out of a tree. We’d lose the safety of modern childbirth: Before the antibiotic era, 5 women died out of every 1,000 who gave birth. One out of every nine skin infections killed. Three out of every 10 people who got pneumonia died from it.And we’d lose, as well, a good portion of our cheap modern food supply. Most of the meat we eat in the industrialized world is raised with the routine use of antibiotics, to fatten livestock and protect them from the conditions in which the animals are raised. Without the drugs that keep livestock healthy in concentrated agriculture, we’d lose the ability to raise them that way. Either animals would sicken, or farmers would have to change their raising practices, spending more money when their margins are thin. Either way, meat — and fish and seafood, also raised with abundant antibiotics in the fish farms of Asia — would become much more expensive.

We are, she writes, on the brink of the “post-antibiotic era.” Already, some bacteria are resistant to everything we can throw at them. They’re mostly confined to hospitals at the moment, but they’re increasingly seen “in the community” – i.e., in all the homes and stores and workplaces where we like to spend our time.

Read more…

Antibiotic resistance: a return to the pre-antibiotic world is coming faster than you think

Photo credit: Julian Stratenschulte/EPA/Corbis

We are seeing an alarming increase in new reports on the growth rate of antibiotic resistance. We cannot forecast the future date when we will return to the pre-antibiotic world. But we can be confident that if coordinated global action is undertaken straight away then the costs and social impact will be much lower than coping with the frightening future ahead.

This is a hard problem, possibly a “wicked problem“, thought not quite like the scale of climate change solutions. The costs of effective action to save antibiotics are a small fraction of what is required to decarbonize developing economies. And the required cooperation is not nearly so diffuse.

I will cite a couple of recent links that offer a survey of what is happening and what should be done to prolong our “golden age” of effective antibiotics. First Megan McArdle’s Bloomberg piece  Life Without Antibiotics Would Be Nasty, Brutish and Short(er); second CDC Threat Report: ‘We Will Soon Be in a Post-Antibiotic Era’ by Maryn McKenna, author of Superbug; and third, the key source for the McKenna article Antibiotic Resistance Threats in the United States, 2013, Centers for Disease Control and Prevention. Sept. 16, 2013.

From the press release for the CDC Threat Report 2013:

This report, Antibiotic resistance threats in the United States, 2013 gives a first-ever snapshot of the burden and threats posed by the antibiotic-resistant germs having the most impact on human health.

Each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die each year as a direct result of these infections. Many more people die from other conditions that were complicated by an antibiotic-resistant infection.

Antibiotic-resistant infections can happen anywhere. Data show that most happen in the general community; however, most deaths related to antibiotic resistance happen in healthcare settings such as hospitals and nursing homes.

For thoughts on some policy solutions I recommend Megan McArdle’s October 2011 analysis. And lastly, become a member of the International Society for Infectious Diseases (we are). Members of the ISID can subscribe to the International Journal of Infectious Diseases at a discount – but note the journal goes open access in 2014.

Antibiotic-resistance: we need better incentives

(…) And going to the hospital has itself become alarmingly risky. Already, 1.7 million people in the U.S. acquire infections in the hospital each year, resulting in 99,000 deaths, according to the Centers for Disease Control and Prevention.

(…) “A lot can happen in the several days that it takes for the doctor and the patient to determine that the first antibiotic that was given didn’t work,” Mellon said.

We were traveling and thus missed Megan McArdle’s Ocober 2011 analysis. I highly recommend a careful read to reflect on the scale of the problem and some possible policy solutions. There are a number of problems contributing to poor investment incentives plus poor incentives to maximize the utility of new molecules.

(…) The problem is, efforts at promoting conservation may discourage innovation—and vice versa. Some hospitals now require infectious-disease doctors to sign off on the use of newer and more powerful antibiotics. But this has a cost. “When a new antibiotic comes out,” Pfizer’s Utt says, “physicians don’t necessarily use it—they tend to hold it in reserve. So by the time it’s being used, it’s already used up part of its marketable patent life.” As a result, fewer large firms may want to spend the time and money to get these drugs approved—according to the IDSA, only two major drug companies (GlaxoSmithKline and AstraZeneca) still have strong active research programs, down from nearly 20 in 1990. Antibiotics are not big moneymakers: Every time a doctor writes a prescription for Lipitor, Pfizer may gain a customer for decades. But short-course drugs like antibiotics sell perhaps a dozen doses.

(…) Those same critics suggest that perhaps we should take this out of the invisible hands of the market. Historically, we’ve solved tragedy-of-the-commons problems either through privatization, as Britain did with its land, or through nationalization, as many nations have done with their military and police. If the market doesn’t work, why not try the government?

Even many libertarian types agree that the commons problem seems to call for stronger state controls over antibiotics. But how far should that go? Government and academia perform vital basic research, but they haven’t delivered a lot of working drugs. “What would be nice,” says Daemmrich, “would be to have free-market mechanisms reward new-drug discovery even as the use of antibiotics was limited to infections that don’t go away on their own.”

One possibility is to have the government buy all the antibiotics on a sliding scale: so many billion dollars for a first-in-class antibiotic, half that amount for a second-in-class, and so forth. The government could then restrict the antibiotic’s use. I’ve posed this possibility to people at pharmaceutical companies and gotten a surprisingly warm reception. Another idea, proposed by Outterson and a colleague, Harvard’s Aaron Kesselheim, is to change the reimbursement system so that companies get paid more when fewer of their drugs are prescribed, as part of a conservation plan. “Let’s say Bayer had a diagnostic test that could quickly tell whether you had a bacterial or viral infection. Right now, the only thing that this would do is knock down their unit sales [of antibiotics]. We should reward companies like Bayer if they bring out a diagnostic like this—their unit sales might decrease by half, but if so, we should quadruple their unit price.” Or we could have special rules for antibiotics patents: instead of a 20-year term, make them renewable annually for drug companies that promote conservation.

These ideas sound elegant and simple in a magazine article. In the real world, they’d be messy and controversial. The government would be getting into the business of fixing prices. Likely, it would overshoot, handing windfall profits to firms, or undershoot, leaving us without enough drugs to treat emerging resistant infections. But the potential for such mistakes shouldn’t stop us from trying to pursue creative public-private solutions. We just need to be prepared to face a lot of yelling.

Especially since the way to reward conservation is not entirely clear. Laxminarayan notes, “Whether resistance develops is not entirely a function of what the manufacturer does—it’s a function of what other manufacturers do as well.” Not to mention doctors, and patients, not all of whom are, ahem, entirely compliant.

If you are not totally depressed, read the June 14, 2011 McArdle analysis “How Superbugs Will Affect Our Health Care Costs. That article is based on “The ‘return of our old enemies in an untreatable form’” by the Remapping Debate. Please read both articles for discussion of the following two figures — these two trends can only end very badly:

Note that the first chart does not include the resurgence of multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis.

Multi-drug resistant staph in 25% of supermarket meat samples

This should make you very angry – that farmers are still allowed to use unjustified, excessive application of antibiotics in industrial animal husbandry. Maryn McKenna writing for Ars Technica reports on a new study published in Clinical Infectious Diseases: Multidrug-Resistant Staphylococcus aureus in US Meat and Poultry [PDF].

Here are the details: A team from the Translational Genomics Research Institute in Flagstaff, Arizona, led by Lance B. Price, Ph.D., bought 136 packages of ground beef, chicken breasts and thighs, pork chops and ground pork, and ground turkey, under 80 brand names, in 26 supermarkets in Flagstaff, Chicago, Fort Lauderdale, Los Angeles and Washington, DC. They analyzed the meat for the presence of staph, because staph has been found in the past in several food-animal species. They did a second round of testing to define which strain of staph was on the meat, and then they did a third round, testing the isolates against five important classes of antibiotics, to see whether the staph they had found was resistant.

Which it was. Very. The antibiotics to which the staph was resistant included: penicillin and ampicillin; erythromycin; tetracycline; oxacillin, the more modern form of the drug methicillin; the drug combination quinupristin/dalfopristin, known as Synercid; the fluoroquinolones levofloxacin (Levaquin) and ciprofloxacin (Cipro); and the last-resort drugs for very serious staph infections vancomycin and daptomycin. One staph isolate was resistant to nine different antibiotics.

Among the types of meat tested, turkey carried the most resistance, with 77 percent of the meat samples showing at least some; that was followed by pork (42 percent), chicken (41 percent) and beef (37 percent). Interestingly, it wasn’t all the same staph. Though there was a great diversity of staph types, each animal species seemed to carry mostly one sequence type or strain of staph: ST1 in pigs, ST5 in chickens and ST398 in turkey. (More on that below.)

I spoke to Lance Price about his team’s work. “This is the first study to show that antibiotic-resistant staph is highly prevalent in the American food supply,” he told me.

He added: “There’s an important second point: We found that each of the meat and poultry types had their own distinctive staph on them. That provides strong evidence that food animals were the primary source of the resistant staph. The source wasn’t human contamination of the meat at slaughter, or when it was packaged for retail sale.”

How much resistant staph is present in food animals and on the meat they become has been an urgent question for about seven years, since a team of Dutch researchers identified an unusual staph strain—MRSA ST398—in a family who operated a pig farm. That strain has since spread to pigs across the European Union and into Canada, and has been found to cause human illness in all those areas. It’s also been found in pigs in the United States, though it has not yet been proven to cause human illness here. (I’ve been covering ST398 for several years, and a long archive of posts is available.)

Read the whole thing. You can follow Maryn at Wired Science/Superbug.

For more background on Denmark’s success in stopping the use of NTA (non-therapeutic antimicrobials), try this Seekerblog search.

Antimicrobial resistance: revisiting the "tragedy of the commons"

John Conly is a Professor of Medicine, Microbiology and Infectious Diseases and Pathology and Laboratory Medicine at the Centre for Antimicrobial Resistance at the University of Calgary, Canada. He is also the co-director for the Snyder Institute of Infection, Immunity and Inflammation at the University of Calgary, and the former Chairman of the Board for the Canadian Committee on Antibiotic Resistance.

The November Bulletin of the World Health Organization includes an interview with Prof. Conly. The second interview question is:

Q: Is this the doomsday scenario of a world without antibiotics?

A: Unfortunately yes, with these new multiresistant NDM1-containing strains and their potential for worldwide spread. Doctors will face a terrible dilemma when a pregnant woman develops a kidney infection that spills over into the bloodstream with a pan-resistant strain containing NDM1 and there are no treatment options. We are essentially back to an era with no antibiotics.

The first interview question leads to a good summary of the threat:

Q: What’s special about this new type of resistance labelled as NDM1?

A: NDM1 is an enzyme that confers resistance to one of the most potent classes of antibiotics, known as carbapenems, but what has been observed is different in many ways to what we have seen to date. This new resistance pattern has been reported in many different types of bacteria compared to previously and at least one in 10 of these NDM1-containing strains appears to be pan-resistant, which means that there is no known antibiotic that can treat it. A second concern is that there is no significant new drug development for antimicrobials. Third, this particular resistance pattern is governed by a set of genes that can move easily from one bacterium to another. Fourth, NDM1 has been found in the most commonly encountered bacterium in the human population, E. coli, which is the most common cause of bladder and kidney infections. A further concern is that of the two drugs potentially capable of treating an infection due to one of these new multiresistant strains, one of them, colistin, causes toxic effects to the kidney in about a third of people.

For more on NDM-1 and the general topic, just click this query for the tag antibiotic resitance. If you are thinking “no worries, this is just in India and Pakistan” think again:

Does the spread of NDM1-containing strains of resistant bacteria constitute a public health event of international concern? In my opinion the answer is an unequivocal “yes”. We have seen such strains spread internationally. By early September this year, the United States of America (USA) had reported cases in three states and Canada, in three provinces. Australia, Belgium, Japan, Sweden and Viet Nam have all reported cases…