Maryn McKenna

Journalist and Author

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

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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

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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.

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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

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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

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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.

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(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.

Antibiotic resistance: Scandinavia gets it

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Odd but interesting fact: Scandinavia takes antibiotic resistance incredibly seriously. Denmark has one of the most thorough programs for preventing antibiotic misuse in agriculture; Norway has very tough regulations regarding antibiotic stewardship in hospitals (as captured in this AP story last year). Sweden has pressed the issue as well; drug resistance was a major issue for the Swedish Presidency of the European Union in the last half of 2009 and led to a major conference there on creating incentives to bring antibiotic manufacturers back into the market.

The presidency has since been relinquished to more southern countries (Spain in the first half of this year and now Belgium) but the Swedish focus on resistance persists, pushed along by the nonprofit organization ReAct, based at Uppsala University. Earlier this week, ReAct hosted a three-day international conference on antibiotic resistance in Uppsala. They haven’t posted the full conference report yet, but they have come out with a closing press release, which says some interesting things (emphases mine):

At a historic three day conference at Uppsala University, Sweden,
190 delegates representing 45 countries and many leading stake holders – civil society, academia, industry, governments, authorities, supranational organizations – agreed on Wednesday to turn a new page and move towards concerted action on antibiotic resistance…
The new signals from the Uppsala meeting include:
– A shared conviction that antibiotic resistance is a universal problem.
Like global warming, it requires joint action, not least by governmental alliances.
– A clear signal from the pharmaceutical industry that
return of investment on research and development of new antibiotics and diagnostic tools will have to be de-linked from market sales in order to boost necessary innovation while yet limiting the use of antibiotics. This requires a new business model where private and public sectors cooperate.
– A strong recommendation to all stakeholders to
speed up the efforts to limit unnecessary use of antibiotics, while at the same time making the medicines affordable and accessible in developing countries.
– A commitment to
improve the monitoring of antibiotic resistance across the world, through shared data and increased efforts. A global network of surveillance will require common methods, and is crucial for both prudent use and needs driven development of new agents.

The release also mentions some promising events coming next year:

– A final report from TATFAR, The Transatlantic Task Force on Antibiotic Resistance.
– A policy meeting on antibiotic resistance in Delhi, India.
– A WHO Action Plan on Antibiotic Resistance.
– A number of regional initiatives, including in Southeast Asia, Africa and The Middle East.

(Hmm. Surely it is time for me to go back to India…)

People who’ve worked in this field for a long time will know, of course, that up-front commitments are easy to make; it’s downstream action, carried out over the long term, that makes a difference. But this looks like a promising start: Even just stimulating international recognition of the program is an encouraging beginning.

Until the final conference report is posted, you can see video of the opening and final sessions here.

Every once in a while: Some stuff about me

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Drowning in work here, folks, which is a pity because there’s lots of news to talk about. Back soon. Meanwhile: I try not to do this very often, because most of what we have to talk about is so much more interesting than me — but my week at UGA, which is capped by an appearance at the Decatur Book Festival, has generated some ink. So here’s some amusements for your morning coffee:

  • A very kind Q&A with me, done by excellent pal Barth Anderson, operator of the feisty food-policy site Fair Food Fight
  • Another Q&A by my former colleague Phil Kloer, for the great arts blog Arts Critic ATL
  • And a video about one of my speeches at UGa, done by student TV station WNEG-TV. (The last line of the report? I didn’t say that. But otherwise, well done.)

On the road this week, and a reading rec

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Constant readers, I’m teaching this week at the University of Georgia’s Grady College of Journalism and New Media Institute, so blogging will be light. If you’re in the Athens or Atlanta area, please come say hello, I’ll also be speaking publicly:

  • Tuesday: 4 p.m., Room 175 of the University of Georgia’s Coverdell Center for Biomedical and Health Sciences, Athens.
  • Wednesday: 6 p.m., the Vaccine Dinner Club of Emory University (Whitehead Health Science Center Administration Building), Atlanta.
  • Thursday: 4:15 p.m., Athens-Clarke County Library, Baxter Street, Athens.

Here’s a press release that UGa kindly put out about the events.

Meanwhile, some reading: When we’re talking about MRSA control, we often talk, somewhat lightly, about isolating people within a hospital or nursing home in order to control MRSA’s spread. For instance, isolation is the key technique on which “search and destroy” hinges.

In today’s New York Times, Dr. Abigail Zuger writes a thoughtful column on the historic roots and present-day challenges of putting patients into isolation. It’s very much worth reading, particularly for understanding why tending to patients in isolation is such a time-burden for health care staff. Also, her description of how C. diff spreads will make you want to wash your hands immediately.

More soon.

New CDC flu numbers: This may not go well

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(Constant readers: Apologies for the slow blogging. Casa Superbug’s little medical crisis from a week ago has recurred, and things are a bit distracting. Back to normal soon, I hope.)

In public health, one of the numbers you hear most often — and especially so the past few years — is
36,000. That’s the number of deaths that the CDC estimates occur in an average year from influenza.

Or rather, estimated. Because today, in its weekly bulletin
MMWR and also in a teleconference for the press, the CDC announced that it is discarding that widely used number, in favor of newer numbers from newer studies that take into account the wide variation in illness and death from one flu season to the next.

The new estimate is:
23,607. Or, a range that goes
from 3,349 to 48,614. Or, in the language recommended by a CDC scientist and a communications specialist in the press call, ”
tens of thousands of people [who] may die each year in an average flu season.”

If that sounds difficult to communicate in a concise manner, well, the reporters on the CDC call today clearly thought so too. And while reporting study results forthrightly is transparent, and more precise numbers are almost always better, I can’t help but wonder whether this attempt at precision and transparency will not be received well. After all, we are only a few months (or a few weeks, depending whose end date you accept) away from the dribbling conclusion of a worldwide pandemic that was taken so not-seriously by the public that, in the US, 71 million doses of H1N1 vaccine went unused — and in Europe, some public representatives alleged that the entire emergency was a concoction by pharmaceutical companies.

Given that history, putting out a public message that
flu kills fewer people than we thought — but is, still, a serious disease that should be planned for and vaccinated against — sounds like a hard sell.

Here’s how today’s new numbers came about:

The mortality rate from flu has always been difficult to assess: People die of influenza directly, but they also die of underlying conditions — heart disease or chronic obstructive pulmonary disease, among others — that might not kill the person if influenza were not putting an extra strain on the system. In either case, but especially in the latter, the death may not be attributed to flu, particularly if the victim has not been tested for the presence of the flu virus.

So, to arrive at an estimate, the CDC has used a statistical model. As explained in the briefing today by Dr. David Shay of the CDC’s Influenza Division:

We have two categories that we look at… One is death certificates that have an underlying diagnosis of pneumonia or influenza. 99% of those deaths are actually coded as pneumonia. So, that’s to make an estimate of deaths in a particular season from pneumonia that are associated with flu. And typically, that’s about 8.5% of deaths over the time period that we looked at…  The broader category of respiratory and circulatory deaths we think encompasses the full picture of influenza-associated deaths, including things such as people who might die because of worsening chronic obstructive pulmonary disease or worsening congestive heart failure that results in death after an infection. And we estimate that about 2% of that broader category in any typical year is associated with influenza.

One other factor affects flu mortality: Which flu strain type is dominant in the season being measures. Flu is generally taken to cause the most severe disease, and the greatest number of deaths, in the elderly; but some strains cause more severe disease than others, and some (H1N1 “swine” flu, for instance) attack the young, who are healthier and less likely to die, more than they do the old. Again, Shay:

[I]t’s important to keep in context, which we don’t really describe in this article because of space, that there’s at least four factors that affect sort of flu mortality in any particular year, and those four would be the specific strain or influenza strains that are in circulation, sort of the length of the season or how long influenza is circulating in the united states, how many people get sick, because of course, the more people get sick, there is more likely to be more serious outcomes, and finally, who gets sick.

In the study released today, the CDC did two things: It
broadened the range of flu seasons from which it took data to feed into the statistical model, and it
took a second look at the years on which the previous model, the one that produced the 36,000-death estimate, was based.

When the range of years was broadened to 31 flu seasons (1976-77 to 2006-07), here’s what shook out:

  • For deaths from influenza and pneumonia:
    from 961 in 1986-87 to 14,715 in 2003-04, an average of 6,309
  • For deaths from respiratory and circulatory complications:
    from 3,349 in 1986-87 to 48,614 in 2003-04, an average of 23,607.

(When asked which number should be used for shorthand, Shay said: “The broader category of respiratory and circulatory deaths we think encompasses the full picture of influenza-associated deaths.”)

When the 36,000-death estimate was re-examined, Shay said:

The 36,000 number that’s often used pertains to a very specific time period from 1990 to 1999. And in that decade, where we had prominent circulation of H3N2 viruses, they were prominent in eight of the nine seasons that are contained within the data that were used to make that estimate, and those are, as you know, typically more severe seasons. We had a high mortality for that nine-year period.

According to the MMWR analysis, mortality rates in the H3N2 years were 2.7 times higher than in years when other types were dominant.

So that’s the rationale behind today’s dialed-down numbers. Here’s the potential problem with it: It just took me about 1,000 words to (somewhat talkily) explain. It requires patience and detail to impart, which in the current media environment are in very short supply. As one of the participants on the call said today:

I’m really scratching my head here wondering what I’m going to use, because we really don’t have a lot of time … to present a lot of numbers, and I think in a sense to say that the range is 3,000 or 3,300 to 49,000 raises a lot of questions, and I think we don’t have time to answer those questions in every report. And I also wonder if it’s not a bit misleading to use 3,300 as the bottom number since it’s been 20 years since it was that low, and even in the last 20 years, the mortality has never been much below 12,000.

You see the problem.

To repeat: This is an effort at transparency and accountability; those are worth applauding. But it’s also a nuanced and difficult health-communication message, launched into a zeitgeist already tuned toward conspiracy theories and a media marketplace with little time or expertise to counter them.

Pessimistically, I wonder how long it will be before this message gets transformed into something like, “See? I told you so. Flu isn’t that big a deal after all.” I hope the CDC is prepared when it does.

(Here’s today’s MMWR article, the transcript of the press briefing, and a Q&A on the new calculation. The cite is: Morbidity and Mortality Weekly Report, “Estimates of Deaths Associated with Seasonal Influenza — United States, 1976–2007.” August 27, 2010. 59(33);1057-1062)

NDM-1: The World Health Organization warns governments

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The World Health Organization released a statement this afternoon, prompted by news of the NDM-1 multi-resistance gene. It’s worth taking a look: The agency recommends that countries around the world pay serious attention to the emergence of this resistance factor.

WHO calls for  broad action within countries, from
hospital infection-control and antibiotic-stewardship programs, to
increased surveillance for the emergence of resistance, to
legislative control of over-the-counter sales. Those sound like (and are) minimal and rational suggestions — but they have the potential to be quite controversial in some countries, from India where OTC antibiotic purchases are a major economic sector, to the US where best practices for hospital control of resistant organisms continue to be, umm, vociferously debated.

The WHO says:

Those called upon to be alert to the problem of antimicrobial resistance and take appropriate action include consumers, prescribers and dispensers, veterinarians, managers of hospitals and diagnostic laboratories, patients and visitors to healthcare facilities, as well as national governments, the pharmaceutical industry, professional societies, and international agencies.

WHO strongly recommends that governments focus control and prevention efforts in four main areas:

  • surveillance for antimicrobial resistance;
  • rational antibiotic use, including education of healthcare workers and the public in the appropriate use of antibiotics;
  • introducing or enforcing legislation related to stopping the selling of antibiotics without prescription; and
  • strict adherence to infection prevention and control measures, including the use of hand-washing measures, particularly in healthcare facilities.

The WHO has been working on antibiotic resistance for a while now, though the effort seems to be continually obscured by urgent news of outbreaks such as SARS, H5N1, H1N1 and so on. Here’s their short fact sheet, detailed program page,  and Global Strategy for Containment of Antibiotic Resistance (sadly 9 years old, so it predates the emergence of community MRSA, not to mention NDM-1).

NDM-1: The early warnings

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Sorry to drop out of sight, constant readers; a little medical emergency at Casa Superbug, but all better now. There are some new developments regarding the novel resistance factor NDM-1, which renders Gram-negative bacteria resistant to almost all antibiotics:

  • Germany has announced its first identifications — plural, apparently. (Bloomberg News)
  • Vietnam says it has also recorded its presence.  (Thanh Nien Daily, h/t H5N1)
  • And France says that it will begin testing for the gene’s presence in bacteria carried by patients being admitted to hospitals, in hopes of keeping the plasmid from transferring to other bacterial species and creating a wider resistance problem. (Agence France Presse) This is a reasonable fear; it is analogous to the process by which MRSA became vancomycin-resistant (VRSA), by acquiring the gene for vancomycin resistance from VRE, vancomycin-resistant Enterococcus. But there’s much more to be said about what it will take for a hospital to keep this bug from entering or spreading; more on that in a future post.

Before we  get too much further from the initial news, I want to go back over
the history of NDM-1’s discovery — because, as with so many superbugs that take the public by surprise (recall the furor when the CDC’s estimate of 19,000 MRSA deaths a year was published in late 2007), it turns out that there have actually been alarm bells ringing on this for a while. Largely, of course, unheard.

The first finding was in an older man of South Asian origin, living in Sweden, who went back to India in 2007, was hospitalized in New Delhi as a result of longstanding health problems, returned to his new home, was hospitalized there also in January 2008, and was discovered there to be carrying this resistance factor. The first public description of his case was made in
October 2008, during a poster session at the annual ICAAC meeting (Interscience Conference on Antimicrobial Agents and Chemotherapy). That was later expanded to a journal article that was published in Antimicrobial Agents and Chemotherapy in
December 2009; the full text is online in PubMed Central.

In the interim, though, the UK’s Health Protection Agency published its first alert, in
July 2009, describing 19 patients carrying this resistance  in 2008 and the first half of 2009, 9 of whom had received medical care in South Asia:

One UK patient, who developed a bloodstream infection with an E. coli that produced NDM-1 enzyme had received treatment for a haematological malignancy in both India and the UK; two others had undergone cosmetic surgery in India and one of these presented to a UK hospital with a wound infection that grew a mixed microbial flora including K. pneumoniae with NDM-1 enzyme; others had received renal or liver transplantation in Pakistan.

Meanwhile, other researchers in Europe were becoming alert to the threat that NDM-1 posed if it were to spread widely; English researchers warned of it in
September 2009, and Scandinavian researchers did the same in
November 2009.

And in
June 2010, the CDC published its first report and warning of NDM-1 in patients in the US, noting that all three, who lived in different states, had received medical care in India.

But what’s important to note is that,  despite the surprise and indignation coming from South Asia after the publication of last week’s Lancet Infectious Diseases papers (article, editorial) describing the spread of NDM-1, the existence of that resistance factor has been discussed in Indian medicine since sometime last year.

From
August to November 2009. a team of physicians at the Hinduja National Hospital and Medical Research Centre in Mumbai surveyed their ICU patients, and found 22 isolates carrying NDM-1. Their paper was submitted very quickly, in
December 2009, and published in March 2010 in the Journal of the Association of Physicians of India:

We sought to identify NDM-1 positive strains among the carbapenem resistant Enterobacteriaceae isolates at our tertiary care centre. In a short span of 3 months, we identified 22 such organisms. The physicians at our institute follow the hospital antibiotic policy and do not indiscriminately use carbapenems. However being a tertiary centre we receive transfer in cases / referrals from other hospitals… The identification of NDM-1 in 22 of 24 isolates is a worrisome development indeed. NDM-1 being present among Enterobacteriaceae has the potential for further dissemination in the community. Such dissemination may endanger patients undergoing major treatment at centres in India and this may have adverse implications for medical tourism. Besides stringent infection control in hospitals, good sanitation in the community is also needed to contain the spread of such clones. (Deshpande et al., JAPI 2010)

News of their finding must have percolated through Indian medicine, because in
January 2010 — before their paper was published — a worried letter discussing NDM-1, by a South Asian scientist working at the Royal Infirmary of Edinburgh, was published in the Indian Journal of Medical Microbiology:

The virtual nonexistence of antibiotic policies and guidelines in India to help doctors make rational choices with regard to antibiotic treatment is a major driver of the emergence and spread of multidrug resistance in India. This is augmented by the unethical and irresponsible marketing practices of the pharmaceutical industry, and encouraged by the silence and apathy of the regulating authorities. Poor microbiology services in most parts of the country add to the problem. (Krishna, IJMM 2010, DOI: 10.4103/0255-0857.66477)

 And in
March 2010, Dr. K. Abdul Ghafur of the Apollo Hospital in Chennai published a passionate and despairing call to arms (“An obituary — on the death of antibiotics!“) alongside the Mumbai team’s findings. The full text is online and it is worth reading in its entirety:

Our country, India, is the world leader in antibiotic resistance, in no other country antibiotics been misused to such an extent. Microbes are the ultimate warriors. They have sophisticated weapons and use ingenious methods of attacks. They have always been many steps ahead of us. Even in the twenty first century with all the developments in the modern medicine, when we face microbes, we feel helpless. Whatever weapons we had in the form of antibiotics, we ourselves have ruined them. Indian medical community has to be ashamed of the NDM-1 (“New Delhi Metallo-1”) gene. Even though we have not contributed to carbapenem development, we have contributed a resistance gene with a glamorous name. The overuse of antibiotics is embedded in our Indian gene. It is an Indian tradition. (Ghafur, JAPI 2010)

That Ghafur’s plea went unheard is all the more striking — because for almost a decade, Indian researchers had been reporting, in their own journals, a steady and troubling expansion of carbapenem resistance in Indian hospitals. More on that when I post next.

More on NDM-1

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One of the frustrations of being a working journalist and a blogger is that, when a big blog-story breaks, you’re likely already to be working on something else. And so it is, unfortunately, with NDM-1: I’m on a magazine assignment and will be off interviewing people when I should be blogging.

(This s a great time to recommend that, for any breaking infectious disease news, you follow Crof at H5N1 (@crof) and Michael Coston at Avian Flu Diary (@Fla_Medic), who are dedicated, thoughtful, nimble and smart.)

Since I last posted, there’s been lots of additional coverage of the “Indian superbug.” Much of it, blog and media, is just echo chamber cannibalizing of the earliest reports (including but certainly not only mine), but there are some important new developments worth noting, which I’ll list below.

There are also some important points that are getting lost in the echo-chamber bounce: First, it is not correct to say that every person who acquired this was seeking cheap medical care or engaged in medical tourism; a few of them were treated on an emergency basis while traveling, and a few have no apparent healthcare tie. So this is not a situation of people seeking to save money and, as some commenters seem to be suggesting, receiving their karmic payback. (C’mon: Seriously?) Second, it is also not correct to say that every case of this has been linked to a hospital — it’s quite clear in the Lancet ID paper that in South Asia, a number of the cases were community infections. So it is not just a case of hospitals that are dirty or have poor infection control (which by the way is a problem in the US as well, right?); NDM-1 is already a community bug, which will make detection and defense much more complex.

OK, curated list:

First, if you’re interested in more from me, CNBC asked me to write up a piece about NDM-1, which ran Thursday; and Friday morning I was on the WNYC-FM (and nationally syndicated) radio show The Takeaway.

Second, the list of potential victims of NDM-1 is growing. Most of them have survived, so marking their cases is really a way of measuring the resistance factor’s previously undetected spread:

The UK has released a new statement, updating its earlier warning, and says it has found “around 50” cases carrying NDM-1, an update from the Lancet ID paper. (Side note: This statement, and the earlier warnings, came from the UK’s Health Protection Agency. The UK has just announced that it will be shutting down that agency in a cost-cutting measure. Great timing.)

The government of Hong Kong has announced that it has seen one case of NDM-1, but the patient recovered.

Canada has disclosed that it has had two cases, not the one mentioned in the Lancet ID editorial, in two different provinces.

Australia says that it has had three cases scattered across the country.

Belgium has announced one death.

And finally — sadly but probably not surprisingly — India is objecting to the stigma of being characterized as the source of NDM-1. The study’s first author has disassociated himself from the paper and members of the government are claiming a “pharma conspiracy.” Medical tourism has become a significant industry in India, and it is true  some of these reports cast doubt on its safety. But still, I find this reaction disappointing.

Evading the stigma of an emerging disease is not a new impulse: Recall how the government of China suppressed for 6 months the news of the start of the SARS epidemic. They did not stop the epidemic, of course — it eventually sicked more than 8000 people across the globe and killed about 775 — but their suppression of the details of its spread kept other jurisdictions from mounting a defense in time. From my teaching gigs in Hong Kong I can testify how much bitterness endures in Hong Kong over this.

China’s actions in 2002-03 led to the enactment of the new International Health Regulations by the WHO, which specify that, because expanding epidemics take no notice of borders, it is inappropriate for any government to attempt to impede the free flow of information about their spread. India is a signatory to the IHRs.

I am not suggesting that India is attempting any suppression of news about NDM-1 — there’s no evidence of that — but the volatile language being used does concern me. I acknowledge that India is an extremely open society, with degrees of political expression that can sound surprising from this distance. But let’s hope the government takes its commitment to the IHRs as seriously as any signatory should.

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

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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.

News break: Hospital-acquired MRSA trending down – but why?

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There’s good news today in the Journal of the American Medical Association: A 4-year study by the CDC and its partners in the Active Bacterial Core Surveillance System reports significant declines in invasive MRSA infections contracted in hospitals. The study, which covers 2005 through 2008, finds a decline of 9.4% per year among infections that were contracted in hospitals and also diagnosed there, and a parallel decline of 5.7% per year in what the CDC calls “hospital-acquired community-onset” infections, ones that were acquired in the hospital but didn’t become evident until after the patient was discharged. Overall, the decline over the study period of hospital-onset infections was 28%, and the decline in hospital-acquired community-onset infections was 17%.

MRSA is the leading organism in the vast national epidemic of hospital-acquired infections (HAIs), which conservatively sicken 1.7 million Americans per year and kills 99,000 of them. (Those numbers date back a decade to an Institute of Medicine report, and have been challenged by Consumers’ Union as an underestimate.) So any solid indication that the epidemic is decreasing is good news. And the CDC study is a solid indication, built on a population-based survey that covers about 15 million people in 9 geographical areas.

So it’s a great pity that we don’t really know why MRSA has declined in this fashion. The study can’t tell us. And because we don’t know, we’ll find it harder than it ought to be to keep the trend going in the appropriate direction.

Here’s the problem: Though it is about healthcare infections, this study doesn’t use data from hospitals. The study itself says: “National data describing changes in incidence in US healthcare institutions are not available.” The data that hospitals report on infections that occur within their walls or result from their actions, contained in the CDC’s National Healthcare Safety Network,  is voluntary, partial and anonymous; in fact, to participate, hospitals are guaranteed confidentiality. The only surveillance systems in the US where hospitals are not anonymous are the various states where legislators, out of exasperation or in response to citizen pressure, have passed laws mandating that infections be reported.

So the declines in MRSA incidence that are reported in this study can’t be linked to specific practices — and that’s important, because for more than a decade, American healthcare has been locked in a ferocious argument over the best way to reduce MRSA and other HAIs in hospitals.

On the one hand, there are institutions such as the Pittsburgh VA (in a project partially funded by the CDC and since adopted across the entire VA) and Evanston Northwestern Healthcare (now called Northshore University Health System) that follow some variant of “active surveillance and testing” or simply “search and destroy,” which tests incoming patients for MRSA carriage and isolates and treats them until they are clear. On the other hand, there are institutions that reject “search and destroy” as too MRSA-specific (and too dependent on expensive rapid-test technology) and opt instead for broader infection-control programs with special emphasis on hand hygiene and antibiotic stewardship. (This paper by physicians from Virginia Commonwealth University summarizes the issues well.) The patients whose data ended up in the JAMA CDC study might have attended hospitals that followed either of these paths, or neither. There’s no way to know.

In addition, a significant proportion of the decline in the CDC study fell into the category of bloodstream infections — which are now also being targeted by the checklist approach espoused by Macarthur Fellow Dr. Peter Pronovost and New Yorker writer and surgeon Dr. Atul Gawande, and adopted patchily across the US. Plus, there’s a further confounder: Since 2009, the Center for Medicare and Medicaid Services has been applying a carrot-and-stick approach — refusal to reimburse for the extra care needed — to certain preventable hospital-caused conditions, including central-line associated bloodstream infections (which are caused by a variety of organisms including MRSA). How successful that has been, or how much influence it has exerted, has not been assessed.

So, to recap: MRSA appears to be declining in hospitals; that’s good. From this study, we can’t say why: That’s frustrating. And, one more point: If we had truly accountable, truly transparent hospital reporting for preventable infections and other medical errors, we would not be in this data fog. Surely it’s past time to clear the air.

Cite:
Kallen AJ, Mu Y, Bulens S et al. Health Care–Associated Invasive MRSA Infections, 2005-2008. JAMA. 2010;304(6):641-647. doi:10.1001/jama.2010.1115
Accompanying editorial:
Perencevich EN, Diekema DJ. Decline in Invasive MRSA Infection: Where to Go From Here? JAMA. 2010;304(6):687-689. doi:10.1001/jama.2010.1125

Unintended consequences: C. diff death after Lyme treatment

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The ongoing fight over long-term Lyme disease treatment has to be one of the most ferocious in health care. If you don’t live in the Northeast or upper Midwest, Lyme disease may not be on your radar, so here’s a super-quick version: There are patients and physicians  who say that Lyme disease symptoms persist following the 28 days of antibiotic treatment that is the standard recommendation of the CDC and the Infectious Diseases Society of America, and also say that patients benefit from additional antibiotic regimens — sometimes IV, sometimes oral — that can last months more. The CDC, IDSA and some other medical authorities say there is no evidence to support these regimens. The ongoing bitterness has extended to antitrust charges by the Connecticut Attorney General that forced a re-evaluation of the IDSA guidelines, which physicians follow and insurance companies refer to when authorizing payment. The disagreements have continued into this year.

I’ve been curious about the long-term Lyme regimens from the antibiotic-resistance POV: whether giving Lyme patients such long courses of antibiotics would encourage the development or spread of resistant organisms. (NB, I don’t know of any research that would answer that question, but if anyone does, cites would be welcome.)

Today, though, I spotted a new paper that describes an unintended consequence I hadn’t thought of: the death of a Lyme patient from Clostridium difficile or C.diff, an infection that becomes more likely after long courses of antibiotics.

Quick lesson: C. diff (here’s the CDC info page) is a toxin-producing bacteria that causes a life-threatening infection of the gut. It’s normally resident in the intestines, but can roar out of control when prolonged courses of antibiotics wipe out the gut’s complex and very abundant population of bacteria. (Ed Yong’s post from a few days ago has excellent detail on the gut microbiome.) C. diff is rising in incidence, becoming drug-resistant, and also is extraordinarily difficult to eradicate from hospital environments — because it is spore-forming and thus protected against the alcohol in the hand gels that hospitals have encouraged in order to balance the need for hand hygiene with the time consumed by hand washing.

The paper, a letter to Clinical Infectious Diseases by representatives of the Minnesota Department of Health (Holzbauer et al., DOI: 10.1086/654808), describes the experience of a 52-year-old woman who had Lyme-like symptoms for about 5 years. She consulted a doctor in June 2009, was tested for Lyme, and was put on 5 weeks of doxycycline. She got better, but then her symptoms returned, and she sought care from a different physician who prescribed an additional 2- to 4-month course of two other antibiotics.

Five weeks after initiating this therapy, the patient developed diarrhea for 3 days and received a diagnosis of C. difficile colitis. … The patient was started on oral metronidazole therapy but was hospitalized 2 days later with severe abdominal pain secondary to diffuse colitis and abdominal ascites. The next morning, she experienced cardiac arrest twice and succumbed to cardiac arrest during an emergency [removal of her colon].

I’ve been talking to Lyme patients recently, including some who decided to take long-term antibiotic regimens. Some of them describe themselves as sick enough to take any risk in an attempt to get better. I wonder whether it’s made clear to them how substantial the risks might be.

Update: The French case — not MRSA but so interesting

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I’m flattered to have as a regular reader Dr. Peter Davies, a professor of swine health and production in the University of Minnesota’s Department of Veterinary Population Medicine. (Disclosure: I worked part-time at U Minn from mid-2006 to mid-2010, but in a different school.) In a comment on my previous post, he points out — perils of reading on a smartphone — an important point where I erred: The staph strain involved in the death of the French 14-year-old was not MRSA, but MSSA, drug-sensitive staph, that had picked up a resistance factor.

Unpacking that a bit: At a minimum, MRSA is resistant to all beta-lactam antibiotics — penicillin, the semi-synthetic penicillins (including methicillin, what the M in MRSA stands for), several generations of cephalosporins, monobactams, and carbapenems. It is also separately, but variably, resistant to macrolides (such as erythromycin), lincosamides (clindamycin), aminoglycosides (gentamicin), fluoroquinolones (ciprofloxacin) and tetracycline.

Livestock-associated MRSA, known as ST398 for its performance on a particular test (multi-locus sequence typing) was first identified as having a tie to pig-farming because it was also resistant to tetracycline, which was being given to the pigs on the farms where the first human carriers worked. (Hence its jocular name, “pig MRSA,” though it’s since been found in other animals.)

The ST398 strain involved in the French girl’s death does not have that broad array of resistance. Chiefly, it was not resistant to beta-lactams, and so can’t be considered MRSA. On analysis, it was resistant to the macrolides, of which the best-known are erythromycin and azithromycin (Zithromax or Z-Pak). Here’s something else intriguing: On another test (spa typing), the ST398 strain in the French girl was one known as t571; the ST398 that has spread from pigs to humans in the European Union, and subsequently to Canada and the United States, is usually t034.

Here’s why this is all so interesting: MSSA ST398 t571 was reported just a few years ago in New York City, in a Bronx community that has close ties to the Dominican Republic, and also in the towns in the Dominican Republic where those Bronx residents come from and visit. (Here’s my initial post on that finding from a medical meeting, and subsequent post when the paper was published.) In that case, the ST398 was fully drug-sensitive — and there was no visible link to pigs, though the authors speculated that livestock, perhaps poultry, might be playing a role on either side of the “air bridge” connecting the two communities.

In the paper (Bhat, Dumortier, Taylor et al., EID 2009, DOI: 10.3201/eid1502.080609), the authors expressed concern that, given staph’s promiscuous ability to acquire resistance — and the fact that ST398 is not regularly surveilled for —  the ST398 in New York could become an undetected resistant strain:

Given ST398’s history of rapid dissemination in the Netherlands, its potential for the acquisition of methicillin resistance, and its ability to cause infections in both community and hospital settings, monitoring the prevalence of this strain in northern Manhattan and the Dominican Republic will be important to understand more about its virulence and its ability to spread in these communities.

And now it appears it has become resistant — but in France, not New York City or the Dominican Republic, and to macrolides, not  beta-lactams. It’s one more reminder of staph’s genius at acquiring genetic defenses, and of how our lack of attention to its mutability and spread continues to allow it to take us by surprise.

News break: "Pig MRSA" ST398 involved in the death of a child?

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The latest postings to the website of the CDC journal Emerging Infectious Diseases include a sad and very troubling letter from physicians in Lyon and Paris, reporting the death from necrotizing pneumonia of a previously healthy 14-year-old girl. That would be sad under any conditions, but here’s what makes the death so troubling: It appears to have been caused by MRSA — but not by the community strain, USA300, that has been implicated in a number of deaths from necrotizing pneumonia. (Several such stories are told in SUPERBUG the book.)

Instead, her death appears to have been caused by infection with MRSA ST398 — the livestock-associated strain that was first noted in pigs raised with antibiotics, and the pig-farm workers caring for them, in the Netherlands 6 years ago, and that has since spread across the European Union, Canada and into the United States. (My 3-year archive of ST398 posts is here.)

This may be the first death associated with ST398, though I can’t say that for sure as I am away from my big computer and working without my database. I’ll update later today and confirm or knock that down.

The physicians say that the girl came in with flu-like symptoms and abdominal pain, was put on IV antibiotics (cefotaxime and amikacin), underwent an exploratory laparotomy that showed nothing, and shortly afterward developed acute respiratory distress and was put on a vent. A chest X-ray was shadowy on both sides. She went rapidly downhill and died 6 days later.

On analysis, the staph strain infecting her was ST398; there was no indication where she had picked it up. The strain had an unusual characteristic: It possessed the ability to make the cell-destroying toxin Panton-Valentine leukocidin, PVL for short, a genetic trick that until now has been a property only of community MRSA strains such as USA300. Though its role is disputed, PVL has been linked to community MRSA’s ability to start infections on intact skin, and to the cellular damage that destroys children’s lungs in cases of pneumonia caused by USA300. Until now, ST398 has been PVL-negative.

The physicians’ letter is short and there’s much more to find out about this case. But if the report and analysis are correct, this is bad news. One of the repeated themes in the 50-year evolution of MRSA has been its ability — all staph’s ability — to promiscuously swap and share the bits of DNA that confer resistance and enhance virulence. Another, since the emergence of ST398, has been the potential peril of a staph strain adapting and mutating in the millions of farm animals around the world that are routinely given antibiotics — and that for the most part are not checked to see whether they harbor resistant organisms. If this report (and my interpretation) are correct, then those two trends are converging in a way that cannot bode well.

Advice for science writers, from science writers

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Ed Yong, an incisive and prolific science blogger-writer-communications officer, opened up his blog to the science-writing community earlier today, with this invitation:

Every now and then, I get an email from someone who’s keen to get into science writing and wants to know how I started. Whenever I reply, and I always try to, I’m always left with the nagging feeling that my experience is but one of a multitude of routes that people have taken. Science writing (whether you want to call it journalism, blogging, communication and so on) is a diverse field, as are the people working in it. It would be far more illuminating for a newbie to see a variety of stories rather than just one.
…I will be asking science writers around the world to do what they do best – tell a story – about the thing they know best – themselves. This will be a perpetual thread that I hope will act as a lasting resource for the writers of tomorrow to take inspiration from.

That was about 18 hours ago. So far there are 59 comment/stories posted, from some of the brightest and sharpest writers working today, with more to come tomorrow, I am sure. (Also, umm, me. I didn’t get in til #51, because I was trying to catch a plane.) Collectively, the comment string is both a peek behind the curtain of how science writers and authors work and think — and think about their work — as well as a trove of advice for anyone else who wants to try this odd and taxing profession.

A selection:

Mark Henderson (#2), science editor of the Times of London: “If you can’t find great stories from everything that’s pouring out of the world’s laboratories, you’re not much of a journalist.”

Jonah Lehrer (#4), author of How We Decide and Proust Was a Neuroscientist: “Writing is a craft. There are no born writers. One has to practice and practice and practice.”

Maggie Koerth-Baker (#5), BoingBoing.com: “Think of yourself as a business, ask to be paid what you’re worth and stick to your guns, always turn things in on time, learn that editing is not your enemy, and work really, really hard at writing nuanced, factual stories that are still fun to read. Luck helps those who help themselves.”

Raima Larter (#16), writer and former chemistry professor: ” I don’t think you can go wrong when you make your choices based on what most excites you. Passion can go a long way in carrying you forward in any career.”

John Pavlus (#21), writer/filmmaker: “BE curious and ACT curious. Everything else will work itself out from there.”

TR Gregory (#29), an evolutionary biologist who has started a companion thread on his own blog: ” There is a lot of frustration among scientists and educators with the way new studies are portrayed in the media, but when someone is recognized as an honest and skilled communicator, he or she will be among the ones that scientists hope will discuss their research.”

Brendan Maher (#34), features editor, Nature: “Humility and self-assured enthusiasm can coexist.”

Eric Michael Johnson (#41), blogger at The Primate Diaries: ” Take risks. Make mistakes. Fall flat on your face. The difference between wanting to be a writer and actually being one is in how often you pick yourself back up.”

(Stripped of the biographical material, here’s my contribution: “Work nights and weekends. Seek mentors. Stay alert to serendipity. When someone wants to tell you a story, listen. Develop expertise. Distrust everyone’s motives, including your own. Always ask another question. Talk to people face to face. Rejoice in complexity, in systems and in persons, and accept that it takes its time revealing its intricacies. Try to tell the truth.”)

Whooping cough: Back, with a vengeance

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A few years ago, I went to India on a reporting trip. When I came back, I had a troublesome cough. I figured I’d picked up a bronchitis aggravated by New Delhi’s smog-laden air, or by the dung smoke from the fires in the villages where I’d spent most of my time. The cough got worse instead of better. It was especially bad at night: I’d lie down to sleep and that would trigger a paroxysm. Sometimes I’d cough until I couldn’t breathe. A few times, I vomited. Eventually my side began to hurt. (Months later, I discovered I’d cracked a rib.)

As a medical reporter, I spent most of my time around doctors and nurses, but I had a rule about never bothering them — first because I was pretty healthy, and second because no one wants to be the guy at the cocktail party who finds out someone’s a doc and backs them into the corner of the buffet table. But one day, worn out by the spasms, I mentioned my symptoms to a friend. His eyes got big. He went and got a textbook.

I didn’t have bronchitis. I had pertussis — whooping cough.

This made no sense, of course. Between a day job as Scary Disease Girl and a childhood spent moving between continents, I am pretty much the most vaccinated person on the planet.  I’d had my full series of pertussis vaccinations as a child. Surely I was protected?

Actually, no — and unless you’ve had a booster, neither are you. The immunity created by the 5-dose childhood series wanes over time; by the age of 12, even fully vaccinated people are vulnerable to pertussis again. Since 2006, the Advisory Committee on Immunization Practices has been recommending a single additional pertussis (Tdap) booster for anyone between the ages of 11 and 64. That may seem like overkill — adult cases of pertussis in previously vaccinated people are often milder than the child version; after all, I survived my bout. But as with so many vaccines, the beneficiary here isn’t just the adult taking the booster. Even more, it’s the more vulnerable person to whom that adult might pass the disease: an elderly person with age-related immune decay; someone with a chronic disease; an infant too young to be vaccinated. In those people, the disease can and does kill — as it did an 18-day-old infant, Nelyn Baker, whom I wrote about in 2004.

Because vaccine immunity fades, pertussis is always with us: in good years, about 1,000 cases across the United States. Lately, though, we’re in bad years. Pertussis cases are rising dramatically, in Alabama, Georgia, Arkansas, Texas, South Carolina, Michigan, Oregon and Ohio. The worst by far is California, where so far this year almost 1,500 cases of pertussis have been reported and another 700 are suspected — compared to 258 for the same time period in 2009.

“We are facing what could be the worst year for pertussis that this state has seen in more than 50 years,” Dr. Gilberto Chávez of the California Department of Public Health said last week in a statement put out by the agency’s Center for Infectious Disease.

The worst news in this upsetting trend is this: We’re doing it to ourselves. As far as anyone can tell, the rise in pertussis is not due to any change in the organism, or to any mysterious error among the manufacturers who make pertussis vaccines. It’s due to vaccine refusal, to parents turning away from vaccines because they think the vaccines are more harmful than the diseases they prevent — or, more selfishly, because they think the wall of immunity created by other vaccinated children will protect their unimmunized ones.

That’s an incorrect assumption, by the way. Work published last year by several scientists at Kaiser Permanente of Colorado found that unvaccinated children were 23 times more likely to contract pertussis than vaccinated ones. (Glanz, McClure, Magid et al., Pediatrics 2009, doi:10.1542/peds.2008-2150.) And yet, as numerous stories (LA Times, MedPage Today) have pointed out, California’s epidemic has blossomed in a state that gives some of the most generous “personal belief exemptions” from vaccination — and the epidemic’s worst hot spots neatly correlate with the most concentrated areas of vaccine refusal.

Pertussis is an awful disease. A child in the throes of a paroxysm sounds like nothing else on earth. Children turn blue, give themselves black eyes, die. We kept it down to manageable levels with the help of a vaccine. That we would willingly bring it back it is beyond belief.

(For a physician’s take on pertussis, see this post by my fellow former Scibling Pal MD. The CDC’s information page on pertussis is here and the National Network on Immunization Information explains the vaccination schedule here. H/t to the infectious-disease mailing list ProMED for starting me thinking.)