Tag Archives: Antibiotic resistance

Re-Examining the FDA Antibiotics Decision: Banning Growth Promoters Won’t Be Enough

Denmark weaner pigs experience

Chart via Hagan Vigre, Danish Technical University, 2009

Further to the Denmark experience, Maryn McKenna has a new essay at Wired

The object lesson in changing antibiotic patterns is Denmark, which in 2000 made farm antibiotics prescription-only, and banned nontherapeutic uses altogether. It’s often pointed out, on the ag side, that Denmark had an increase in deaths among weaner pigs immediately after that ban was rolled out; but within 3 years, weaner pig survival improved and returned to where it had been before the ban.

What reversed the trend was Danish farmers’ understanding that it wasn’t enough just to remove antibiotics from meat production. What was necessary was to change the conditions in which meat animals were raised, so that the welfare threats which the antibiotics had addressed no longer existed.

That seems to me to be the lesson that meat production in America needs to learn, if the FDA’s intention to remove growth promoters is going to be meaningful. Simply reducing antibiotic use (if that does indeed happen) isn’t adequate; by itself, it may even be a threat to welfare. Changing the livestock practices that made antibiotic use necessary will improve animal and human health both.


How to protect effective antibiotics: a conversation with Doc Ricky

MRSA

I believe that the rapid spread of antibiotic resistance should be recognized as an urgent public health priority – possibly the #1 priority. E.g., CRE [1].

After reading Betsy McCaughey [2] “U.S. Lacks Will to Fight Superbugs” [3] I tweeted the citation for her op-ed

CRE the “nightmare bacteria”: U.S. Lacks Will to Fight Superbugs j.mp/1au0EbR

Shortly Doc Ricky replied:

@stevedarden I’m kind of perplexed by the media repetition of “fighting superbugs” – what do ppl expect anyway? Some secret weapon?

What an excellent framing question! I replied with some suggestions:

  1. Transparency of hospital performance on sanitation standards.
  2. No excuses policy on resistance cases e.g. Israel
  3. Strict limitation of agriculture use to disease, no routine NTA dosing
  4. Transparency on physician prescribing by doctor

Shortly Doc Ricky replied:

“@drricky: @stevedarden but problem is most of these are preventative, what is expected when MDR {Multi Drug Resistance} is detected?”

I replied over several tweets: By #2. what I meant is that the CDC publishes “best practice” on procedures to execute upon every identified case of MDR[4]- beginning with effective quarantine and decontamination. The “best practice” level of response is mandated to be the minimum response. It should be the top priority of the hospital to eliminate the detected microbe from the institution. I appreciate that is a statistical goal, as we have no way to validate that “we killed it”.

For examples of such best practices consider the 2011 NIH Clinical Center response to a CRE outbreak [5], and of Israel 2006 (from Betsy McCaughey):

When CRE invaded Israel’s hospitals in 2006, public health authorities launched a military-style campaign requiring reports from all hospitals, which were ordered to test patients and undergo rigorous cleaning efforts. This reduced CRE by 70 percent in one year. Israeli researchers just announced a drug that may protect patients exposed to CRE from becoming infected.

My personal bias is that regulation is a blunt and ineffective tool in complex, fast-changing domains like this one. My question: How to incentivize hospitals to succeed?

Suggestion: first try transparency. E.g., if the Johns Hopkins data, such as MDR cases, hand hygiene and infection-control scores are published on the web every month – that is a powerful incentive to improve – to be ranked among the very best institutions globally.

Meanwhile Doc Ricky tweeted a critique of my first try on agriculture:

@stevedarden The agriculture issue is more nuanced than that, after all, how does one exactly limit the use?

Exactly:

@drricky Legislating detailed Rx rules not practical. How about transparency of farm usage per animal-KG? Is public shame effective?

I am thinking of the Denmark experience beginning 1999 where they succeeded to eliminate NTA use in agriculture. See my 2010 Denmark: results of stopping NTA (non-therapeutic antimicrobials)

Doc Ricky moves the discussion to the next level, biology:

@stevedarden only skirts around the real problem, which is biology. We culture animals with similar physiology to ours

The microbes shared by humans and pigs, chickens, beef are why we are so concerned about agricultural applications of antibiotics. Agriculture uses roughly 80% of the antibiotics effective in the human population – but in vastly larger quantities. If we were all vegetarians that would eliminate the whole worry about agriculture.

Doc Ricky is truly the expert in this topic – I’m looking forward to learning from him. We agreed to shift the conversation from Twitter to a long-form-friendly fora.

@stevedarden clearly a complicated topic, and hope you’ll continue to discuss.

NOTES:


  1. The CDC on CRE Carbapenem-Resistant Enterobacteriaceae.  ↩

  2. Betsy McCaughey founder of Committee to Reduce Infection Deaths  ↩

  3.  (…snip…) CRE was first uncovered in North Carolina in 1999. By 2008, it had spread to 24 states and was “routinely” seen in certain New York and New Jersey hospitals. But hospitals kept quiet. Now it’s in at least 43 states.
    (…snip…) Two months ago at a press conference, CDC Director Thomas Frieden dubbed CRE the “nightmare bacteria,” warning that “without urgent action now,” superbugs like CRE will prevent patients from getting joint replacements, cancer therapy and other treatments. The risk of incurable infections will make these treatments too dangerous. Yet, where’s the urgent action?
    The CDC doesn’t even have accurate data on how many CRE infections are occurring and where, because according to the director of the CDC’s Office of Antimicrobial Resistance, Steven Solomon, the government agency has never reached out to state officials to make CRE a reportable disease. Only 12 states require hospitals to report cases. Astoundingly, New York State did not require reports until July 2013, despite CRE menacing some of its hospitals for a decade.  ↩

  4. I am using the shorthand MDR to represent all the emerging multi-drug resistant microbes.  ↩

  5. This is what happened at the National Institutes of Health Clinical Center in Maryland in 2011. A 43-year-old woman known to have CRE was admitted from a New York City hospital. The NIH treated her, using CDC infection-control precautions, but three weeks later, a male cancer patient who had had no contact with her came down with CRE. Week after week, more and more patients contracted the infection introduced by the New York woman. Six of those patients ultimately died, one of whom was a 16-year-old boy. To stop the outbreak, NIH investigators double-cleaned rooms with bleach and misted hydrogen peroxide in measures far beyond what the CDC recommends.  ↩

The File Drawer Effect

This is not an academics-only esoteric debate. It is about whether new, effective drugs are released. It is about how accurate is our knowledge of reality. Here is astronomer Phil Plait quoted in this excellent essay on Survivorship Bias:

For far too long, studies that fizzled out or showed insignificant results have not been submitted for publication at the same level as studies that end up with positive results, or even worse, they’ve been rejected by prominent journals. Left unchecked, over time you end up with science journals that only present the survivors of the journal process – studies showing significance. Psychologists are calling it the File Drawer Effect. The studies that disprove or weaken the hypotheses of high-profile studies seem to get stuffed in the file drawer, so to speak. Many scientists are pushing for the widespread publication of replication, failure, and insignificance. Only then, they argue, will the science journals and the journalism that reports on them accurately describe the world being explored. Science above all will need to root out survivorship, but it won’t be easy. This particular bias is especially pernicious, said Plait, because it is almost invisible by definition. ”The only way you can spot it is to always ask: what am I missing? Is what I’m seeing all there is? What am I not seeing? Those are incredibly difficult questions to answer, and not always answerable. But if you don’t ask them, then by definition you can’t answer them.”

We subscribe to the AllTrails network – I can’t recommend their work highly enough. See also Publication bias in Wikipedia and All Results Journals.

 

FDA: stop buying antibacterial soap products

Every day, consumers use antibacterial soaps and body washes at home, work, school and in other public settings. Especially because so many consumers use them, FDA believes that there should be clearly demonstrated benefits to balance any potential risks.

In fact, there currently is no evidence that over-the-counter (OTC) antibacterial soap products are any more effective at preventing illness than washing with plain soap and water, says Colleen Rogers, Ph.D., a lead microbiologist at FDA.

Moreover, antibacterial soap products contain chemical ingredients, such as triclosan and triclocarban, which may carry unnecessary risks given that their benefits are unproven.

“New data suggest that the risks associated with long-term, daily use of antibacterial soaps may outweigh the benefits,” Rogers says. There are indications that certain ingredients in these soaps may contribute to bacterial resistance to antibiotics, and may have unanticipated hormonal effects that are of concern to FDA.

(…)

In addition, laboratory studies have raised the possibility that triclosan contributes to making bacteria resistant to antibiotics. Such resistance can have a significant impact on the effectiveness of medical treatments.

Source

 

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.

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…

CDC report: Antibiotic Resistance Threats in the United States, 2013

CDC_antibiotic_resistance_pathways

Every year, more than two million people in the United States get infections that are resistant to antibiotics and at least 23,000 people die as a result, according to a new report issued by the Centers for Disease Control and Prevention (CDC). Press release here, full report with excellent graphics here.

The report, Antibiotic Resistance Threats in the United States, 2013, presents a first-ever snapshot of the burden and threats posed by the antibiotic-resistant germs that have the most impact on human health. This report is also the first time that CDC has ranked these threats into categories of urgent, serious, and concerning.

  • In addition to the illness and deaths caused by resistant bacteria, the report found that C. difficile, a serious diarrheal infection usually associated with antibiotic use, causes at least 250,000 hospitalizations and 14,000 deaths every year.
  • The loss of effective antibiotic treatments will not only cripple the ability to fight routine infectious diseases but will also undermine treatment of infectious complications in patients with other diseases. Many advances in medical treatment, such as joint replacements, organ transplants, and cancer therapies, are dependent on the ability to fight infections with antibiotics. If the ability to effectively treat those infections is lost, the ability to safely offer people many of the life-saving and life-improving modern medical advances will be lost with it.
  • The use of antibiotics is the single most important factor leading to antibiotic resistance around the world. Antibiotics are among the most commonly prescribed drugs used in human medicine. However, up to half of antibiotic use in humans and much of antibiotic use in animals is unnecessary or inappropriate.

If you think you needn’t worry about the rapid growth of antibiotic resistance, then I suggest you need to do a bit of homework. A starting place: Antibiotic resistance: a return to the pre-antibiotic world is coming faster than you think. This isn’t just an issue to be solved by “them”. We are the victims and the pressure for change has to come from “us”.

Thanks to a tweet from @onemedical One Medical Group for the lead to the CDC report. One Medical looks to me to be a promising crack in the broken US primary care model. Not Your Typical Doctor’s Office indeed!

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.