Maryn McKenna

Journalist and Author

Another new bad resistance factor. (Bonus: Another city stigmatized!)

By Leave a Comment

The subcontinent can cease fretting over the naming of that new bacterial resistance factor NDM, for New Delhi. There’s a newer resistance factor in town, and this one stigmatizes… Italy.

Welcome, Verona integron-encoded metallo-beta-lactamase, or VIM.

To be precise, VIM isn’t new — its very first identification was at the Verona University Hospital in 1999 — but it has just been found in the United States for the first time. The CDC said Wednesday evening that it has identified VIM in an American woman who took a Mediterranean cruise this summer, got diarrhea, was hospitalized (twice) in Greece, developed sepsis and C. diff, and eventually was transferred home and hospitalized here for a further 26 days. In the US, she was found to be infected with Klebsiella pneumoniae, a gram-negative bacterium that’s a common cause of serious-hospital acquired infections — urinary tract infections, abdominal infections and pneumonias. This strain, though, was resistant to all the drugs usually used to treat Klebsiella. (The woman did recover.)

To anyone who followed the NDM-1 news a few weeks ago, this should sound familiar. (If you didn’t, here’s my archive. No, go ahead; we’ll wait.) A resident of one country is unexpectedly hospitalized in another. That second country happens to have high rates of a novel, serious resistance factor — in Greece, 50 percent of Klebsiella isolates in ICUs are multi-drug resistant — that clusters in the organisms most likely to cause hospital infections. The person picks up a resistant infection without knowing it, travels home, and transports the novel resistance factor into his or her home country.

And because the gene that directs production of the problematic enzyme resides on a mobile genetic element — meaning it can move easily from one bacterium or species to another — the public health authorities in the unlucky person’s home country begin a very nervous waiting game.

That’s what happened with the identification of NDM-1, which was first noted in a man of South Asian origin, living in Sweden, who was unexpectedly hospitalized in India in 2007 and then hospitalized again in Sweden in 2008. (NDM was found in the US in June.) Like NDM, VIM has spread across the world; within a few years of its original identification it was in France, Spain and Taiwan. Nor are those two enzymes the only bad actors — they’re merely the most recent and notable in successive waves of multi-drug resistance in gram-negative organisms that are washing across the world. (Almost all of them, by the way, are named for their points of origin. GIM, Germany. SPM, Sao Paolo. DIM, Dutch. And so on.)

And those waves (to torture my metaphor until it whimpers) are really just the most visible points of an ocean of gram-negative resistance that has flooded the globe, and certainly the US. And, just to slosh home the point: These resistance mechanisms knock out the drugs of last resort for gram-negatives, the carbepenems, and there are no new drugs to replace them. The drug-development pipeline for gram-positives such as MRSA has a few drops still rolling down it; the pipeline for gram-negatives, as the Infectious Diseases Society of America has documented in several reports, has just about dripped dry.

The CDC on Thursday warned labs and hospitals to start taking action, in ways that will at least require additional staff time and attention, and probably will cost extra money too :

Cases of (carbepenem-resistant Enterobacteriaceae) are a significant, emerging public health problem regardless of the mechanism of carbapenem resistance, and procedures to rapidly recognize and report CRE cases to infection prevention personnel should be in place in all acute and long-term–care facilities. Facilities that have not identified cases of CRE should undertake periodic laboratory reviews to identify cases. Patients with CRE should be managed using contact precautions, and patients exposed to CRE patients (e.g., roommates) should be screened.

The problem with writing about increases in antimicrobial resistance is that, sooner or later, you inevitably end up sounding like Chicken Little. (Or Cassandra. I’m not sure which is worse. Chicken Little is probably cuter.) Every one of these sounds like the worst possible news. Problem is, every one of them is… until the next one comes along.

Image of Klebsiella pneumoniae courtesy of the Public Health Image Library, CDC.

Public service announcement: Throw Your Drugs Away Safely Day

By Leave a Comment

There are people in this world — I’m not pointing fingers — who have extra antibiotics hanging about their houses.

Naturally, this would not be you, any of you, since you know that it’s important to finish prescriptions or risk the development of resistant bacteria. You wouldn’t forget to take your regularly scheduled doses. You wouldn’t stop early because it feels like you’re better. And you certainly wouldn’t save some drugs because someone else without insurance might benefit from them.

(Right? Please. These are not smart ideas.)

But let’s say there’s a household with extra drugs lying around. Maybe a doctor did an extra round of tests and switched a prescription to something else mid-course. Maybe someone moved away. Maybe someone died.

In which case: What do you do with them?

It’s not a good idea to just put them in the trash: Kids and pets can too-easily fish them out. (Ask me about the day my cat ate most of an old bottle of ibuprofen. Yes, she’s OK, thanks.) Most people’s impetus is to flush them. That’s an even worse idea. Tossing antibiotics into the toilet takes the risk away from your household, but it transfers the risk to all households, by adding them to wastewater.

A study published by the US Geological Survey in 2002 sampled 139 streams in 30 states and found pharmaceutical residues in 80 percent of them. Some of the sources clearly were agricultural and industrial — but others were what regulators call “pharmaceutical and personal care products,” including human-use antibiotics and other drugs. Pharmaceutical and personal care products, PPCPs for short, are an emerging concern for regulators and environmental scientists. There’s an entire USGS project devoted to them. They may not be denatured by wastewater treatment. They show up in soil. They’re taken up by plants (soybeans, in this study). And they are presumed to contribute to the development of antibiotic resistance, by putting trace amounts of antibiotics into the environment in an uncontrolled and untracked manner. Resistant organisms have been found in wastewater treatment plants, by the way.

So if you want to be responsible about this, what do you do? Getting rid of antibiotics and other drugs properly is harder than you think. The optimal method is incineration. If you happen not to have a burner in your backyard, the Office of National Drug Control Policy thinks you should mix them into used cat litter or coffee grounds and then seal the mess up.

Or you could let the government take care of it for you — which they’ve volunteered to do, this weekend, at sites around the United States.

This Saturday, Sept. 25, the US Department of Justice is staging a National Prescription Drug Take-Back Day (here’s the press release). Candidly, the driver for it isn’t antibiotic misuse: it’s an attempt by the Drug Enforcement Administration to reduce the availability of prescription stimulants, opiates and so on that could be abused, sold or stolen. (Which you might suss out from the list of co-sponsors: White House Office of National Drug Control Policy, Partnership for a Drug-Free America, International Association of Chiefs of Police, National Association of Attorneys General, National Association of Boards of Pharmacy, Federation of State Medical Boards and National District Attorneys Association.)

But they will take “any (prescription) that’s not a liquid, syringe or inhaler,” a DOJ spokesman told me today — antibiotics included.

You can find drop-off sites via a search engine at this page. The sites are supposed to run from 10 a.m. to 2 p.m. local time. The program represents itself as free, anonymous, no questions asked.

So get those pills out of the house. It’s the right thing to do.

Image courtesy of Flickr user hurtingbombz

Brain Amoebas. Organ Transplants. Brrr.

By Leave a Comment

Nightmare scenario: New disease arises. It’s rare enough that there aren’t many known patients, and so it isn’t well-studied — and because it isn’t well-studied, there aren’t agreed-upon treatments or accurate tests for it, and there isn’t a good understanding of situations where the infected might pose an unusual risk to others.

Situations, for instance, like organ transplants.

The CDC’s weekly bulletin today describes that nightmare scenario come true. Last year, four people received the kidneys, heart and liver of a 4-year-old boy who died in Mississippi of encephalitis that was assumed to be a rare reaction to flu infection. Weeks after the transplant, the two kidney recipients developed neurological symptoms — spasms, seizures, visual disturbances — and were hauled back to hospitals for evaluation. MRIs showed ring-shaped lesions in both their brains. That sent investigators back to re-examine the boy’s death — and revealed that while he did have encephalitis, it wasn’t because of flu.

It was because he was infected with a newly recognized pathogen, Balamuthia mandrillaris, a species of amoeba. It had passed to the four recipients via his organs, and grew in them with an assist from the immune-suppressing drugs they were taking to prevent rejection.

There have been only about 200 human cases of Balamuthia in the world since the infection was first recognized in 1990 (it got its name from its first-ever sighting the year before, in a sick mandrill at the San Diego Wild Animal Park). Treatment is prolonged and complex, an IV cocktail of multiple drugs that can drag on for months and optimally includes a drug, miltefosine, that isn’t even available in the United States except under an emergency plea to the Food and Drug Administration. When the amoeba develops in the brain, treatment is often unsuccessful anyway: Most cases of Balamuthia encephalitis are fatal.

And so it was in this cluster. One kidney recipient, a 31-year-old woman, developed her first neurological symptoms 20 days post-transplant and died on day 75. The other, a 27-year-old man, survived with “residual right arm paralysis, bilateral leg weakness, and intermittent vision loss,” the CDC says. The heart and liver recipients, both toddlers, mysteriously did better: They had not yet developed symptoms when the kidney recipients were diagnosed, and were hospitalized for evaluation and given a multi-drug cocktail in time.

Could this have been detected earlier? Probably not: It sounds simply random, rare and sad. The boy who was the donor was from Kentucky but was living with relatives in Mississippi when he first got sick in October 2009. He was diagnosed with the flu, got antivirals, got better, and then a week later developed headaches and seizures; was hospitalized for three days, diagnosed with acute disseminated encephalomyelitis, an immune reaction that can follow on flu, and was discharged. Four days later, his seizures recurred, and he died a week after that, on Nov. 18. In the course of his treatment, he’d been checked for viral, bacterial and fungal infections, and all had come up negative — so the family and hospital let his organs go for transplant. The recipients got them two days after that.

It wasn’t until the kidney recipients fell ill that the boy’s tissue, preserved after donation, was checked by CDC investigators, who found something that wasn’t viral, or bacterial, or fungal. They found the Balamuthia amoebas, distributed throughout his brain.

Balamuthia lives in soil around the world, but no one is confident yet of how people become infected; the predominance of encephalitis cases, and some facial infections in milder cases, suggest the route may be as simple as inhaling dust that contains amoebic cysts. It can only be diagnosed by brain biopsy, usually at autopsy, and so there’s some concern that it may be misdiagnosed and be more common than we know. A few cases in California have been analyzed, because California happens to have an encephalitis registry.

But it’s a funny thing about new, rare diseases: Once you know what to look for, you start seeing it where you wouldn’t have detected it before. And so it is with Balamuthia — while the CDC staff were writing up this cluster, another report came in, of another transplant cluster that happened just a few weeks ago in Arizona. In this case, the donor was a 27-year-old landscaper who died July 21 of what people thought was a stroke. Arizona residents, both men, got his liver, and one kidney and his pancreas; illustrating how far organ-donation networks can reach, his heart went to a man in California, and the other kidney to a man in Utah.

The liver recipient died Aug. 17. The kidney-pancreas recipient died Aug. 30. Their illnesses alerted the transplant network, and the other two donors were put on a multi-drug cocktail. So far, they have survived.

Because I spend so much time thinking about scary diseases, people often ask me if there’s anything that gets to me. I wash my hands a lot. I follow whatever precautions are being taken by scientists I hang around with. Most of the time, in most of my life, I don’t feel like I’m much at risk.

But amoebas, growing in your brain, because you happened to inhale the wrong speck of dust? That squicks me. A lot. Brrr.

Images of Balamuthia courtesy of the Parasite Image Library, CDC

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

By Leave a Comment

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

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

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

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

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

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

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

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

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

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

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

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

Image: photographer unknown.

The "Indian Superbug": Worse Than We Knew

By Leave a Comment

Just about a month ago, the disease-geek world was riveted by news of the “Indian superbug“: common bacteria carrying a newly recognized gene that confers profound multi-drug resistance, and that was linked to travel between Europe and South Asia, especially for medical tourism.

The gene, which directs production of an enzyme called NDM-1 for short, was briefly Bug of the Week, the spur for alarmist headlines in every Internet echo chamber and the target of denunciations by Indian politicians, who vilified the discovery as a Western “pharma conspiracy” spurred by envy of lucrative medical tourism.

And then, just as quickly as it popped into public consciousness, NDM-1 slid back under the news-radar horizon.

Or so it seemed. Researchers though remain deeply concerned about NDM-1, along with a wider array of dire resistance factors of which it has suddenly become the best-known. This week, I’m at ICAAC (the annual Interscience Conference on Antimicrobial Agents and Chemotherapy), an enormous 12,000-person meeting focused on infectious diseases and the drugs to treat them, and talk of NDM-1 is everywhere.

The news is not good. This new resistance factor has been found so far in the United States, Canada, Belgium, the Netherlands, Austria, France, Germany, Oman, Kenya, Australia, Hong Kong and Japan. Most of the isolates, the bacterial samples in which it has been identified, are susceptible to only one or two remaining antibiotics. One was susceptible to none.

“These resistant bugs,” Dr. Patrice Nordmann, a professor of clinical microbiology at the South-Paris Medical School, said in a briefing here, “have already spread all over the world.”

A brief recap:

NDM-1 was first spotted in 2008, in a 59-year-old man of South Asian origin who lived in Sweden. He was hospitalized on a visit home to New Delhi, had surgery, recovered, went back to Sweden and was hospitalized there again. At that point, physicians recognized that he had a urinary tract infection that was unusually drug-resistant. The infection was caused by a common bacterium, Klebsiella pneumoniae, but the Klebsiella possessed an unusual and worrisome ability to disable carbapenems, a class of drugs given for very resistant infections. They named the enzyme and the gene directing its production for the place where the man had apparently acquired it: New Delhi metallo-beta-lactamase, and blaNDM.

In 2009, the United Kingdom’s public-health agency sent out an alert saying the same resistance mechanism was appearing there and increasing rapidly, going from unknown in 2007 to 18 instances in the first half of 2009, most of them in people who had gone to India for medical care or had frequent family travel back and forth. In June this year, the US Centers for Disease Control and Prevention put out a bulletin about NDM-1’s first US appearance, in three patients in three different states (California, Massachusetts and Illinois), again with ties to South Asian medical care.

And then, confirming this really was something to be concerned about, last month the journal Lancet Infectious Diseases published the results of a survey for NDM-1 that the authors conducted with collaborators in India, Pakistan and the UK. They found it widely distributed in Klebsiella and E. coli in South Asia; in UK residents who had family or business ties to South Asia or had gone there for care; and also in people who had never left the UK. Shortly afterward, the World Health Organization warned governments that they should be taking this new arrival seriously.

In the few papers on NDM-1 that got rustled up in time for ICAAC, there are more details on NDM-1’s behavior in patients in Australia, Canada, Kenya and the US; the patients were infected with different organisms, but the organisms all possessed the same gene, and were all susceptible at best to one or two drugs, some new, some old and with toxic side-effects. What connects that handful of reports: much more detail on the mobile genetic elements where the NDM gene resides. It is on more than one plasmid; it can move freely between plasmids; the plasmids have been shown to move not just between individual bacteria, but also between species and genera. Overall, that adds up to a resistance mechanism that is spreading with remarkable speed — and bringing with it, as fellow-travelers on the same plasmids, even more resistance mechanisms that have not yet been delineated.

[HTML1]

(I can’t link to the work presented at ICAAC because it is not online, but the teams are: Nordmann and colleagues from the Hospital Bicetre in Paris; Timothy Walsh and team from University of Cardiff, who made the first identification in 2008; Brandi Limbago and colleagues from the CDC; and JDD Pitout et al. from the University of Calgary.)

But if you know a new resistance mechanism is spreading worldwide, what do you do about it? That’s the larger discussion percolating through the corridors here. Antibiotic resistance has always been a biological occurrence wrapped in layers of science, economics and politics. For NDM-1, the politics are especially difficult.

In South Asia, several of the researchers pointed out, antibiotic overuse is common, diarrheal disease is endemic, and municipal sanitation is available to only about half of the more than 1 billion population. That’s practically a recipe for the rapid spread of genetic material carried by gut bacteria — and the economic realities of the subcontinent make it unlikely that any of those conditions are going to be remedied soon. At the same time, the South Asian diaspora worldwide is millions of people, and no one wants to be in the position of blaming a country or a people for antibiotic Armageddon.

There’s a clear concern that everyday physicians may see cases of this and not know what they are seeing. These infections look like any other — or will, until the point when patients don’t get better. At that point, what appeared to be a simple urinary tract infection, for instance, can climb backward to the kidneys, enter the bloodstream, and turn deadly. “General practitioners are not used to seeing multi-drug resistant bacteria in the community,” Dr. Pitout said. “If this does become common, it will lead to a lot of failure of treatment.”

When H1N1 swine flu became a worldwide concern last year, and H5N1 flu five years before that, the World Health Organization mobilized an intricate network of influenza surveillance labs around the world to detect aberrant isolates and track their movement. Amazingly, there’s no such network for antibiotic resistance, Nordmann said. And though an international network for the detection of antibiotic resistance would have been useful before — to track the movement of MRSA, for instance — the researchers agreed it is critically needed now. But that’s not an easy demand to satisfy. The flu network is substantially supported by the governments of the countries where the labs are located (the US lab in the WHO network is within the flu division of the CDC). Governments may not have the money available, and may not agree this issue is as high a priority as the West believes.

This week, France will begin screening any new hospital patients, checking to see who has been treated in a South Asian hospital and so may be a source of NDM-1. That’s a first step, and a crucial one. “The only practical advice I can give at this moment is for physicians to ask their patients,” Pitout said. “And if you have been treated abroad and you develop a medical emergency and must be treated at home, it is very important to tell your physician.”

Image from the CDC’s Public Health Image Library.

NDM-1: Novel, global, complex and a serious threat

By Leave a Comment

There’s news today in the journal Lancet Infectious Diseases of the further spread of a troubling new resistance problem that I first talked about in June: Gram-negative bacteria carrying a novel resistance factor that has been dubbed New Delhi metallo-beta-lactamase, or NDM-1.

In writing about resistant bacteria, it’s difficult to avoid overusing superlatives — but this resistance mechanism has spread widely, been transported globally, and brings common bacteria up to the brink of untreatable. It already has been found in India and Pakistan, Sweden, the Netherlands, Australia, Canada and the US, and has been distributed not just by travel but specifically by medical tourism. It has the potential to become an extremely serious global threat.

Hospitals want patients to eat antibiotic-free meat

By Leave a Comment

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

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

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

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

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

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

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

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

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

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

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

Past time to pay attention to polio

By Leave a Comment

In the winter of 1999, I stood in an outpatient clinic in a pediatric hospital in New Delhi and listened to a father sobbing over the paralysis of his only son. He was a farmer and lived in Uttar Pradesh; counting walks, minibuses and trains, it had taken him 24 hours to get to the hospital. He had carried the toddler the entire way.

His son had gotten the drops, he insisted: Every time the teams came to his neighborhood — which they did three, four times each year — he or his wife had lined up all their children, the boy and his older sisters. His son had had 11, 12 doses, the man said. How could he have gotten polio? And it was polio, the doctor treating him confirmed, not one of the transient febrile paralyses that exist alongside the disease and make detection and diagnosis so complex in resource-poor settings. She saw this all the time, she confided. The massive polio-eradication campaigns that continually blanketed India had trouble reaching some resistant populations, and those children contracted polio because they were not vaccinated — but children whose parents were compliant, who believed in the drops and made sure their children received them, became paralyzed as well.

I was in India that winter because the long-hoped-for goal of the worldwide eradication of polio was supposed to be achieved the following year, in 2000. The global eradication initiative — led by the WHO, the CDC and a massive volunteer effort by Rotary International — didn’t make that goal that year. Or in 2002, or in 2005. For a variety of reasons, from the biology of the disease in the tropics to political manipulation in service of unrelated ends, several countries have remained stubborn hot spots. And as long as the disease persists within their borders, it can leak outside them and become re-established in any area where vaccination has slowed down because the goal of stopping local transmission appears to have been achieved.

[Read more…]

News break: CDC alert on imported novel resistance

By Leave a Comment

There’s a troubling item in this afternoon’s issue of the CDC’s Morbidity and Mortality Weekly Report or MMWR: The first report in the United States of a novel resistance mechanism that renders gram-negative bacteria extremely drug-resistant and that has been linked to medical care carried out in India or Pakistan.

The short item describes three isolates (E. coli, Klebsiella pneumoniae and Enterobacter cloacae) found in three patients in three states between January and June of this year. All three isolates produced New Delhi metallo-beta-lactamase (NDM-1), which has never been recorded in the US before. Because of that novel mechanism, the three isolates were resistant to the carbapenems usually used on the most serious gram-negative infections, in fact to all beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, monobactams, etc.) except for one monobactam, aztreonam — and they were also resistant to aztreonam through another mechanism that hasn’t been identified yet. All three of the patients found carrying this novel resistance factor had undergone medical care in South Asia recently.

This may be the first finding of this mechanism in the US, but it’s been causing alarm in Europe for at least two years.

[Read more…]

Incentives for making new antibiotics: What would it take?

By Leave a Comment

Let’s play a thought experiment. Imagine that you’re a major pharmaceutical company, a public company, with shareholders that you answer to, and market analysts looking over your shoulder to see whether this quarter’s earnings are up to projections. Imagine that you want to make a new drug. Let’s make it an antibiotic, because — as we talk about here all the time (and SUPERBUG explores in detail) — new antibiotics that can leapfrog over existing drug resistance are very needed. Thus, you imagine, a new antibiotic ought to sell well, even though any individual course of that antibiotic will only be a few weeks by mouth, or maybe a few months by IV if the patient is very sick. You know there’s a big market out there.

But: Imagine — as is generally accepted to be true — that it will take about 10 years, and about $1 billion dollars, to get that novel antibiotic through the development pipeline and into the marketplace. And then imagine that — as has been shown for a number of drugs, most recently the new antibiotic daptomycin — bacteria begin developing resistance to your drug within a year of its deployment in patients. And after that, imagine — as has been cited in a number of papers — that once local resistance to your antibiotic appears in approximately 20% of isolates, physicians will cease prescribing your antibiotic, for fear their patient will be one of that 20%.

So, to recap: 10 years, $1 billion; short course; short market life; rapid obsolescence.

Would you make that investment? Or would you, if you were a pharma company, opt instead to make insulin, which Type 1 diabetics will take every day for the rest of their lives? Or statins, which at this point we’re practically ready to put in the water supply? Or a cancer drug that costs $10,000 per dose? Or Viagra, or Cialis?

If you’re a company that is responsible to its shareholders, or listening to its analysts — or even capable of doing basic math — the answer’s obvious: Antibiotics lose. Which goes a long way to explaining why so many companies have backed off from making antibiotics, and why many of the few antibiotics in the pipeline are “me too” formulations, rather than new compounds with truly new mechanisms of action.

How to respond to this impasse has been an active debate for a while, largely focused on proposals to give market incentives, changes in tax credits, or patent extensions to pharma companies to persuade them to stay in or re-enter the marketplace. The Infectious Diseases Society of America, the specialty society for infectious-disease physicians (many of whom are also academic researchers), has been addressing this through its campaign “10x 20”, which has a goal of getting 10 new compounds into if not through the pipeline by the year 2020.

But, as a new article in the British Medical Journal points out, good incentivizing demands complexity — not just in developing both “push” and “pull” mechanisms (say, tax incentives to fund research v. prizes and wildcard patent extensions), but also in making sure that the incentives can be taken advantage of by companies of all sizes, not just the international mega-pharmas:

The characteristics of an ideal incentive mechanism and the desire for an equitable approach that engages developers of all sizes would suggest that neither push, pull, nor lego-regulatory mechanisms would be optimal to spur the desired investment in antibiotics …. Rather, elements of each should be combined. The exact shape of the ideal package is, however, as yet unclear. (Morel et al.)

And an accompanying editorial emphasizes that new antibiotics are not the only things needed; new diagnostic tests, for instance, need funding as well:

Catchy as 10×20 sounds, the public sector strategy for funding such research and development must prioritise among different health technologies, such as diagnostics and vaccines, to combat antibiotic resistance. For example, three million children die each year from acute respiratory bacterial infections in developing countries, but penicillin sensitive pneumococcal strains have declined to a half, even a quarter, in some countries. A diagnostic test for bacterial pneumonia would save an estimated 405 000 lives a year, by targeting treatment and avoiding overprescription of antibiotics. New vaccines may also reduce reliance on drugs as the use of pneumococcal vaccine has suggested. (So et al.)

This is a hard discussion. I confess, as a longtime reporter, I flinch reflexively at the thought of handing more money to the pharmacos. At the same time, the state of the market demonstrates that the current model is not working. And though I would much prefer we focus on the ecological model of preserving antibiotics as a resource — dialing back on overuse and encouraging rigorous stewardship — it’s clear that we’ll always need new drugs for the most serious, most resistant infections.

So some sort of incentivizing seems necessary. And the multi-layered approach recommended in the BMJ, with appropriate attention paid to incentivizing the development of tests and vaccines as well, seems worth heeding.

Brand-new research: Vast increase MRSA, CA-MRSA diagnoses among kids

By Leave a Comment

I’m on the road today and have what feels like seconds between commitments, but there’s a brand new piece of research this morning that I think you folks should know about. It’s an early-online release from Pediatrics by researchers from 3 states. It uses a database called the Pediatric Health Information Systems analyze diagnosis codes and antibiotic treatment of kids treated for staph at 25 US children’s hospitals  from 1999 to 2008, and it finds:

The incidence of methicillin-resistant S aureus (MRSA) infections during this period increased 10-fold, from 2 to 21 cases per 1000 admissions, whereas the methicillin-susceptible S aureus infection rate remained stable. Among patients with S aureus infections, antibiotics that treat MRSA increased from 52% to 79% of cases, whereas those that treat only methicillin-susceptible S aureus declined from 66% to <30% of cases. Clindamycin showed the greatest increase, from 21% in 1999 to 63% in 2008.

To translate, for those not used to reading scientific literature:

  • a 10-fold increase in MRSA diagnoses over 10 years
  • a 3-fold increase in what was not the most commonly prescribed drug, one useful for the different resistance profile of community infections
  • clindamycin (used in mild and also invasive infections) eclipsing vancomycin (last-resort drug for invasive cases) as the most-used drug — which could be a sign of changes in prescribing patterns, changes in seriousness of the cases seen, or a warning that with so much use, clindamycin resistance could emerge more quickly, as happened when vancomycin came off the shelf in the 1990s and began to be used more.

It will take me a while to download and read the paper (hard to do in the car), but that’s the topline news. Update to come.

A great blog leaves the 'sphere

By Leave a Comment

Constant readers: Well, the bug finally got me, or one of its close cousins did. I’ve been on the road almost nonstop, and after a book event at University of Wisconsin last week, was felled by a violent bout of foodborne illness that was almost certainly staph — not MRSA, but the related strain of staph that causes very rapid food poisoning. (And, umm, thorough. Ick.) So I’ve been out of commission both physically and mentally. And on a plane again tonight. Back soon in both ways, promise.

But there’s important sad news today that I want you all to know about. Revere, the peerless author of the marvelous public health blog Effect Measure, is bowing out of the blogosphere. For more than 5 years now, Revere (a collective voice of an unknown number of public health experts —for simplicity, let’s say “he”) has been a reliable, thoughtful, expert, humorous and deeply knowledgeable guide to the intricacies of public health and public health politics. He has taken a particular interest in the possibility of pandemic flu and has been the unofficial leader of the loosely knit but fiercely loyal group of bloggers and crowdsourcers who call themselves Flublogia. And though few would admit it, Revere’s posts have been consistent agenda-setters in newsrooms all across the planet; insiders knew that, if Revere said something, it would start showing up in newspapers and on wires about 12 hours later.

If you are a Revere reader and missed this news, get over there and leave a note in the quickly lengthening comment string. If you never made the blog’s acquaintance, now would not be too soon.

A good start?

By Leave a Comment

I happened to notice today that the WHO has posted an update to its campaign Save Lives: Clean Your Hands, which aims to get 10,000 hospitals around the world to sign on — by May 5, 2010, which is next week — to a global commitment to improved hand hygiene in hospitals.

As of last week, 8,173 hospitals had signed up (1899 in the United States, FYI).

If I sound skeptical, it’s because we all know that merely supporting hand-washing (or the gel equivalent) is an easy thing to do. If you asked any hospital in the US, you would hear 100% support for hand-washing — including in the hospitals where healthcare workers miss 50% of opportunities to wash their hands. It’s in the granular details of implementation — and the relentless laser-like focus on execution practiced, for instance, by Novant Health Care in North Carolina, whose story is told in SUPERBUG — that change really happens.

Whether this WHO campaign can bring that focus and create that change… we’ll just have to see.

The WHO campaign’s page includes videos, guidelines, and plans for a global survey to be executed on May 5.

Antibiotic resistance in food — some governments pay attention

By Leave a Comment

Folks, I told you Tuesday about a Congressional hearing on antibiotic resistance, featuring NIAID Director Dr. Anthony Fauci and CDC Director Dr. Thomas Frieden. Not much new was said, but it’s encouraging that the hearing was held at all. (Fauci testimony here, Frieden here.)

Coincidentally, constant reader Pat Gardiner of the UK alerted me to a gathering being held on the same day in Ireland, by the quasi-government agency SafeFood—which reports to the North-South Ministerial Council of Ireland, which deals with whole-island issues under the Good Friday agreement, which is more about the Irish political structure than you probably ever wanted to know.

The conference was titled Antimicrobial resistance and food safety and featured government officials and academic researchers from across Ireland. Here’s the agenda, and here’s the press release with the names of key speakers. Even more important, here are links to a report on antibiotic resistance in food that Safefood released in advance of this conference: executive summary and whole thing.  I especially recommend from p.25 in the big report for an accessible discussion of the connections between ag antibiotic use and human health. Key quote among many:

The majority of the evidence acquired through outbreak and epidemiological investigations of sporadic infections, field studies, case reports, ecological and temporal associations and molecular sub-typing studies support the causal link between the use of antimicrobial agents in food animals and human illness. A few papers have questioned this but these have not survived detailed scrutiny.

It’s refreshing to see a government body engage seriously with this emerging issue, which we’ve been talking about for, well, years now, on this blog (sometime this month we passed our 3-year anniversary). I wish, wistfully, that the government doing the discussing was ours.

SUPERBUG on BoingBoing!

By Leave a Comment

I was thrilled to see a review of SUPERBUG on the incredibly important blog BoingBoing.net, written by (my friend and fellow Minneapolis author) Maggie Koerth-Baker.

It’s so exciting to see people completely get the book, and twice that when it is people you know.

Sample quote:

Superbug is not about an entomological caped crusader.

It’s more like a grown-up version of Scary Stories to Tell in the Dark.

The bug in question is MRSA, an antibiotic-resistant bacteria that kills more Americans every year than AIDS. Superbug is the story of how we created our own monster-under-the-bed, how it spreads through hospitals and communities, and why it’s damn near impossible to control. If you have a cut or a pimple while reading this book, you are pretty much guaranteed to freak yourself out. And I mean that in the best possible way.

A blog reaction so perfect I want to print the whole thing…

By Leave a Comment

(…but I won’t, because it’s not fair use or good blogger behavior. But I want to!)

Melissa Graham of Chicago had a great corporate life — and then she re-evaluated, became a chef and caterer, and began organizing in Chicago for sustainable local food, farmers’ markets, and a family-friendly food system. She blogs at the food and food-policy blog The Local Beet. And she’s written a reaction to SUPERBUG that not only completely gets the book, but is emotional and thoughtful and moving besides.

She says, in part:

Before reading Superbug, the question of confinement raised animals was an ethical one for me – whether the misery inflicted upon animals and, for that matter, the humans working in those facilities by the putrid conditions outweighed the need to eat cheap meat. Even the environmental degradation resulting from the inevitable careless management of CAFOs seemed a distant and intangible casualty. For me, Superbug has changed the argument from one of ethics to a moral imperative. In every hamburger of unknown origin, I see Tony Love’s face or even worse that of Carlos Don IV.

Carlos was another healthy kid who left on a school trip to the mountain and returned with a 104°F fever. The first doctor diagnosed Carlos with walking pneumonia so his mother kept him home bundled and hydrated until she realized that he was beginning to hallucinate. She rushed Carlos to the hospital and the doctor’s ultimately diagnosed his condition as MRSA. A long slow death march ensued during which Carlos’s lungs dissolved and clotting choked off the blood to his lower intestines, legs and arms. In two weeks, he was dead.

After reading Carlos’s story late in the evening, I woke a bewildered little locavore from a dead sleep to scrub his hands clean. I hugged him as tightly as I could.

…[recently] I had the pleasure to hear Ruth Reichl speak and she implored the audience to stop eating confinement raised animals. As she put it, if everyone stopped buying them and eating them, the practice would be history. Knowing what I now know, I think it’s our moral duty.

To give the post the traffic it deserves, please go here.

Quick alert: Congressional hearing Wednesday

By Leave a Comment

Constant readers, I’m on the road again: Georgia Center for the Book tonight in Decatur, 7:15 p.m. But if you can’t make that, take a look at this: The Energy and Commerce Subcommittee of the US House of Representatives has announced a hearing for Wednesday on “Antibiotic resistance and the threat to public health.”

This is not a hearing on PAMTA, but apparently a broader hearing on the whole issue, featuring two VIPs: Dr. Anthony Fauci of NIH and Dr. Tom Frieden of the CDC. To my eye, this indicates that official, policy interest in this issue is (finally, at last) ramping up.

The hearing page is here and the preliminary memo on it is here.

SUPERBUG interest from collegial fellow bloggers

By Leave a Comment

I haven’t been posting it all here — because, you know, that’s why the book has its own website — but SUPERBUG has been getting lots of positive press and reviews. (Yay us.)

But a piece over the weekend was especially meaningful to me and I wanted to call it out: Flu blogger and DailyKos diarist DemfromCT featured the book on his DailyKos page. (And, behold the power of networks: 178 comments this morning. Wow.)

Liz Borkowski at The Pump Handle kindly reproduced Dem’s post.

This builds, of course, on early, consistent and indefatigable support from flu blogger Mike Coston of Avian Flu Diary.

As the book’s acknowledgments say (p. 218!), I am so grateful for our blog community’s support. Sincere thanks to all.

Catching up to MRSA news (not about me)

By Leave a Comment

Constant readers: I’m looking forward to having the breathing space to get back to in-depth blogging. Meanwhile, though, news is zipping by — so here’s a quick list of recent things worth reading.

“Cows on Drugs” — a superb history of the 30-year-old fight to get unnecessary antibiotics out of food animals. Note, written by a former commissioner of the Food and Drug Administration, not exactly a wild-eyed radical:

More than 30 years ago, when I was commissioner of the United States Food and Drug Administration, we proposed eliminating the use of penicillin and two other antibiotics to promote growth in animals raised for food. When agribusiness interests persuaded Congress not to approve that regulation, we saw firsthand how strong politics can trump wise policy and good science.Even back then, this nontherapeutic use of antibiotics was being linked to the evolution of antibiotic resistance in bacteria that infect humans. To the leading microbiologists on the F.D.A.’s advisory committee, it was clearly a very bad idea to fatten animals with the same antibiotics used to treat people. But the American Meat Institute and its lobbyists in Washington blocked the F.D.A. proposal.

Antibiotic resistance in your kitchen, playroom, car... — After years of begging from health advocates, the FDA and EPA are taking a second look at the chemical compound triclosan, an antibacterial that is put into, well, almost anything you can name: soaps, hand sanitizers, cutting boards, toys. Triclosan is suspected of interfering with hormone regulation in the body, and also increases resistance in organisms in our environment. (When I ask you to use hand sanitizers that contain only alcohol or salts, not antibacterials, triclosan is one of the things I’m thinking of.) The FDA will report its findings in a year. I’d rather see it happen sooner, but it’s a great move.

No progress on hospital-acquired infections — The Agency for Healthcare Research and Quality, part of the Department of Health and Human Services, has published its 2009 National Healthcare Quality Report. The news is not good. To quote the agency’s own language: “Very little progress has been made on eliminating health care-associated infections.” This is all hospital-acquired infections, not just MRSA, but MRSA is a leading organism. The ugly details:

  • Post-operative bloodstream infections up 8%
  • Post-operative catheter-associated urinary-tract infections up 3.6%
  • “Selected infections due to medical care” up by 1.6%
  • Bloodstream infections as a result of central lines unchanged.

(NB, three professional organizations — the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, and the Association for Professionals in Infection Control — put out a statement in response to this report saying it “presents an outdated and incomplete picture on healthcare-associated infections (HAIs) in our healthcare system.” The gist of the statement seems to be that they’ve got better numbers coming… soon. When there’s actual data, I’ll let you know.)