Maryn McKenna

Journalist and Author

MRSA in meat: How much? Which? And more bad news.

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(Sorry for the radio silence, constant listeners. It’s been a challenging few weeks at Casa Superbug, with a death in the family and the chaos afterward of catching up to the rest of life. But back now, with some interesting stuff planned for later this week.)

Last week was the General Meeting of the American Society for Microbiology (ASM). This is the conference at which, several years ago, Tara Smith’s team at the University of Iowa first announced they had found MRSA ST398 in pigs in the United States, so it always bears watching for new MRSA news, and this year it didn’t disappoint.

First: I’ve complained persistently because the federal system that monitors antibiotic-resistant bacteria in animals and food, NARMS (National Antimicrobial Resistance Monitoring System) doesn’t include MRSA among the pathogens that it tracks. It is possible that might be changing — because at ASM, a team from the Food and Drug Administration reported the results of a pilot study that looked for MRSA in retail meat in the US and found it.

[Read more…]

Drug-resistant bacteria in bedbugs

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Being Scary Disease Girl, I seem to have earned a reputation for never wincing in the face of weird disease threats.

But this, I admit, makes me go squick:

Researchers in Vancouver, BC have found bedbugs there carrying drug-resistant staph, MRSA, and vancomycin-resistant enterococci, VRE.

(Deep breath.)

(Another deep breath.)

OK, details: [Read more…]

Farm Antibiotics: 'Pig Staph' in a Daycare Worker

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It’s been just about seven years since an alert epidemiologist in the Dutch town of Nijmegen identified an aberrant strain of MRSA, drug-resistant staph, in a toddler who was going in for surgery to fix a hole in her heart. The strain was odd because it didn’t behave normally on the standard identifying tests, and because it had an unusual resistance factor — to tetracycline, a drug that it should not have been resistant to, because the Netherlands had such low rates of MRSA that tetracycline wasn’t being used against the bacterium there.

Pursuing the source of the strain, researchers at Radboud University found it in the toddler’s parents and sister, and in the family’s friends. Not knowing where else to look, they asked what the parents and their friends did for a living; discovered they were all pig farmers; and went to their farms, and checked the pigs, and found it being carried by them, too. Suddenly, that strange resistance pattern made sense: The Netherlands uses more antibiotics in pig agriculture than any other country in the European Union, and the drug that it uses the most is tetracycline. Clearly, the aberrant strain — known as MRSA ST398 for its performance on a particular identifying test — at some point had wandered into pigs, become resistant to the drugs being given to the pigs, and then crossed back to humans, carrying that new resistance factor as it went.

[Read more…]

Turning grief into action: Moms and antibiotic misuse

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In December 2007, I flew to Chicago to meet the team of researchers who spotted the first known cases of community-associated MRSA in the US in the mid-1990s, and who have been agitating ever since for recognition and action to beat back the rising tide of antibiotic resistance. It was grey and snowy outside their shabby suite of offices, carved out of University of Chicago’s long-replaced children’s hospital. I sat in a green-tinged conference room piled with stacks of articles while Everly Macario — a Harvard-trained ScD in public health, the daughter and sister of physicians — described how MRSA killed her toddler son Simon in less than 24 hours.

“We have no idea where he got it,” she told me. “We have no idea why he was susceptible.”

Simon Sparrow was 17 months old in April 2004, a big, sturdy child with no health problems except a touch of asthma. The day before he died, he woke up feverish and disoriented, startling his parents with a cry unlike anything they had heard from him before. It was a busy morning — his older sister had a stomach virus — but they got him to the pediatric ER, got him checked, and brought him home when doctors found nothing unusual going on.

A few hours later, Everly was working at home, watching both kids, and Simon’s breathing changed. Her husband James, a history professor, had driven a few hours away to give a speech. She called a friend who is a pediatrician, held the phone up to Simon’s nose and mouth so she could hear, and then got back on the line.

“Hang up,” her friend said. “Call 911.” [Read more…]

Bacterial music-video festival (tornado edition)

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We had scary-bad weather in the Southeast the past two days. Thankfully, there was no serious damage where I am, but the devastation to the north and west is appalling, with about 180 300 deaths so far. Please spare a thought for them.

It’s going to take me a while to haul my working materials back out from the storm shelter, and by storm shelter, I mean first-floor closet under the stairs behind the washing machine, which was about the only place that would have been protected from shattering glass and flying roof materials.

So in the meantime: This morning, Twitter tossed up a UK hospital’s attempt to energize its staff to wash their hands more frequently. It’s sweet, funny, and — apologies to the participants — unavoidably snark-inducing. Have a look: [Read more…]

World Health Day: Time to tackle resistance

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Tomorrow, Thursday, is World Health Day, an annual observance that the World Health Organization uses to focus attention on some critical global-health issue. This year, they’ve chosen antimicrobial resistance as the issue that most needs highlighting. Noting the choice, the Lancet editorialized: “Resistance has joined the front rank of global health concerns.”

On the day, the WHO and some other agencies and organizations will be announcing plans and strategies. I’ll cover those tomorrow. For today, a scene-setter: Why you should care.

Having spent the last couple of years immersed in antibiotic resistance (because, you know, I wrote a book about it), I’m often puzzled why it doesn’t excite more alarm. I’ve concluded our situation is similar to the overused analogy of the frog in the slowly warming water: We don’t realize how bad things have gotten, even when we’re in imminent danger of death.

So here’s a round-up to remind us, drawn just from recent news.

In hospitals: Very large hospital systems are using more broad-spectrum last-resort drugs. Last weekend, representatives of the Veterans Health Administration disclosed that over 5 years, vancomycin use has gone up 79 percent, and carbapenem use, 102 percent. Vancomycin is the only affordable drug of last resort for MRSA; carbapenems are the drugs of last resort for gram-negative infections such as Klebsiella. The use of those drugs is growing because organisms are becoming multi-resistant to less-powerful drugs, but they are becoming resistant to the big guns too. Carbapenem resistance in Acinetobacter, a bacterium that afflicts ICU patients and gravely wounded military members, rose from 5 percent of isolates in US hospitals in 2000 to 40 percent in 2009. Israeli scientists reported this month that carbapenem-resistant Klebsiella pneumoniae (CRKP, subject of my Scientific American article this month) caused a nationwide outbreak in 2007 and 2008, sickening 1,275 patients in 27 hospitals before it was brought under control. [Read more…]

Farm worker infections with MRSA — the first numbers

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Since the first identification in 2004 of MRSA ST398, also known as “pig MRSA” or livestock-associated MRSA (archives of posts here and here), that drug-resistant organism has been found being carried asymptomatically by farm workers and veterinarians, and causing illness in health care workers, hospital patients, and people with no known ties to agriculture. One of the persistent data gaps, though, has been whether farm workers themselves have been made sick by it.

It’s a difficult question to answer for a nested set of reasons: First, in most of the states, MRSA (methicillin-resistant Staphylococcus aureus, or drug-resistant staph) is not a reportable disease; that is, a doctor who diagnoses it in a patient is under no obligation to tell any public health authority about that patient’s case. And second, the testing required to distinguish livestock-associated MRSA from community-acquired or hospital-acquired is not something that primary-care medical personnel have access to; you have to go to a state laboratory or an academic medical center to do the appropriate molecular typing. Those tests are expensive to perform, and their results primarily are useful to public health, not to individual medical practitioners. So finding out where that nascent epidemic is going has been unusually challenging.

Comes now a team from the University of Iowa — the same team that first identified ST398 in pigs and pig-farm personnel in the United States — to start to fill the gap. [Read more…]

News break: First guidelines for treating MRSA

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For my book SUPERBUG: The Fatal Menace of MRSA (came out last March; paperback will be out in February), I spent several years talking to about 100 victims of antibiotic-resistant staph, and family members of victims who did not survive their infections. There were some striking things about their stories.

One was the variability of the bug, which can cause anything from mild one-time skin infections to lethal necrotizing pneumonia, adding up to almost 19,000 deaths, 369,000 hospitalizations and possibly 7 million medical office visits a year. The other was the variability of the patients’ treatment. Some had the good luck to find physicians who knew about the bug, understood the layers of testing needed to determine the best antibiotics to use, and were sensitive to the possibilities of over- and under-treatment. Others were not so lucky: They went to doctors who didn’t recognize the infection, didn’t prescribe drugs that worked, didn’t have anything to offer when the infection recurred — a whole panoply of errors.

It was a lesson for me in how long it can take news of a new medical development to percolate through the clinical community, especially to primary-care practitioners — people who don’t have a channel for new news because they don’t work for an academic medical center or belong to a specialty society that puts out a journal or at least a substantial newsletter. But it was also a lesson on how few agreed-upon standards of practice there were for treating MRSA. For many presentations, there was no evidence refer to; clinicians were thrown back onto poring through the literature, or on making educated guesses based on their past experience.

As of this week, that should change. The Infectious Diseases Society of America has publshed the first-ever clinical practice guidelines for treating MRSA in adults and children. It’s a substantial document, 38 pages (in the advance access section of Clinical Infectious Diseases) and should be a tremendous resource for patients and their physicians. (I know of one patient who printed it out yesterday and took it to an office visit — only to find the physician had just downloaded a copy himself.) [Read more…]

"Pig MRSA": New human infections in France

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It’s one of the touchiest topics under the broad category of antibiotic resistance: Whether the drug-resistant organisms that emerge on farms as a result of antibiotic use stay on farms, or pose a risk to humans who have no connection to agriculture.

That drug resistance emerges under any selective pressure is basic biology: Resistance is an inevitable process. That they emerge on farms when antibiotics are used broadly — that is, in growth-promoting or prophylactic ways, not to treat disease in individual animals — really isn’t in dispute any more. It’s now a question of economics and politics, not science. (See this bibliography, stretching back to 1969; and the news I broke yesterday of FDA’s estimate of US farms using almost 29 million pounds of antibiotics last year.)

So the argument over farm antibiotic use now tends to focus on whether the resistant organisms that emerge on farms are only an issue within a farm’s confines, or rather pose a broader human health threat — and that’s where the continuing story of the “third epidemic” of MRSA becomes so important. Recapping, this is a strain known as MRSA ST398 that emerged in pigs and passed to pig farmers in the Netherlands in 2004, subsequently spread across the European Union, and crossed to Canada and then to the United States. (Key posts on ST398: here, here, here and this archive at my old site. Yes, it will be moved soon, promise.)

Most of the identifications of MRSA ST398 in humans, including those first identifications above, were colonizations, the term for symptomless carriage of staph in the nostrils and on the skin; in other words, it wasn’t making people sick. News of actual illnesses has been rare — especially illnesses among people who have no contact with farming, such as the post-surgical infections found in Canada earlier this year.

But they’re getting a little less rare, as demonstrated by a letter just posted ahead-of-print to the journal Clinical Infectious Diseases. It recounts the finding, via annual surveys of bloodstream infections, of four cases of ST398 in four different hospitals in France. One may have been due to animal exposure. Three were hospital-acquired.

Examination of patient histories revealed exposure to animals in 1 case, a fatal idiopathic community-acquired bloodstream infection in an 84-year-old man who lived on a farm at which 1 pig was being raised. The remaining cases were hospital-acquired and included 1 case of catheter-associated infection observed in a 58-year-old man with advanced multiple myeloma, 1 case following elective digestive tract surgery in a 69-year-old woman, and 1 case following cardiac surgery in a 68-year-old man.

There’s an especially interesting thing about these cases. In Europe and the US, ST398 has particular characteristics: It is resistant to tetracycline (the drug most commonly given to pigs) and does not manufacture the toxin Panton-Valentine leukocidin or PVL, which is suspected to be a cause of community-strain MRSA’s uncommon virulence. (See this story, from the book SUPERBUG, of how PVL-positive pneumonia almost killed a toddler.) The strain in the French cases, though, does manufacture PVL, and shares some virulence characteristics with the dominant community strain, USA300. It is less like the European strain of livestock-associated MRSA and more like a livestock-associated strain that appears to be emerging in China, ST9 (more on that here).

The argument against the significance of these cases is likely to be that they are, again, just one data-point, and may be just rare and random. That is worth considering. But it is also worth considering that they continue to be found.

And, also, that the community epidemic of MRSA was first flagged in a discovery of 25 cases in children in Chicago back in 1998, a finding that was also dismissed at the time as rare and random — and that grew into an epidemic of millions of cases a year.

(H/t to constant reader Pat Gardiner for flagging this paper for me.)

Cite: van der Mee-Marquet N et al. Emergence of Unusual Bloodstream Infections Associated with Pig-Borne–Like Staphylococcus aureus ST398 in France. Clin Infect Dis. (2011) 52 (1): 152-153. doi: 10.1093/cid/ciq053

Image via Flickr user johnmuk under CC

Alarm over "pig MRSA" — but not in the US

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There’s some new news out — along with a fair amount of public reaction — regarding “pig MRSA” or, to use the technical term, MRSA ST398, the “third epidemic” strain that emerged in pigs in the Netherlands in 2004 and has since appeared, in animals, retail meat, and humans, across the European Union, in Canada, and in the United States. (My last post on it is here, and a long archive of my posts on it starts here.)

I wish I could say the attention to ST398 was being paid in the United States, where there is almost certainly more MRSA in livestock than has been recorded, given that the only published surveillance, from 2009, covered only Iowa and Illinois. Unfortunately, there is still no indication that federal agencies have any intention to test for the presence of the organism in animals or in meat. In fact, the major surveillance mechanism for drug-resistant organisms in meat animals, retail meat and meat-eaters in the US, the National Antimicrobial Resistance Monitoring System or NARMS, doesn’t test for MRSA at all; it handles only enteric or gut-borne bacteria such as Salmonella and Campylobacter. (NARMS IS shared among three agencies: the CDC handles drug-resistant foodborne bacteria in humans, the FDA looks for the same bacteria in food, and the USDA looks for those bacteria being carried by livestock.)

Instead, as so often seems to happen with antibiotic resistance, the country paying attention is in Scandinavia — in this case, Denmark. The annual report from Denmark’s surveillance scheme, DANMAP (Danish Integrated Antimicrobial Resistance Monitoring and Research Programme) is out. Denmark does surveil for MRSA, and here’s what they found: 13% of pigs, at slaughter, were positive for MRSA ST398.
[Read more…]

News break: A new type of MRSA spreads in Ohio

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The annual meeting of the Infectious Diseases Society of America is taking place this week in Vancouver. This afternoon, one of the researchers presenting there released a startling bit of news: the spread in Ohio (and likely elsewhere in the United States) of a MRSA strain that is common in the rest of the world but so unusual in the US that it was last seen here in the 1990s and has never caused infections here.

The strain is ST239, sometimes called the Brazilian clone, and it’s serious stuff: It causes major epidemics and is responsible for something like 90 percent of all the MRSA infections in hospitals in Asia. Its hallmark is that it very multi-drug resistant — including to just about all the oral antibiotics that are used against MRSA.

Brief recap — disease geeks, go on ahead and we’ll catch up: MRSA stands for methicillin-resistant Staphylococcus aureus, the most common drug-resistant infection in the world (and, shameless self-promotion alert, the subject of my recent book). All MRSA strains, at a minimum, are indifferent to the beta-lactam antibiotics, a group of drugs that share a four-cornered arrangement of atoms at the center of their base molecule. That structure allows the beta-lactam drugs to disrupt staph’s cell membrane, killing the bacterium. When staph evolved a work-around for that attack, it became resistant not just to methicillin, which hasn’t been sold for years, but to all the other beta-lactams as well — of which there are dozens; they are the fundamental, basic antibiotics used in medicine every day. Over the years, MRSA has also gained the ability to defuse the attack of additional drugs and drug families, by exchanging with other bacteria bits of DNA containing additional resistance genes. At the same time, the pace of new-drug approvals has slowed dramatically.

OK, back to today’s news.

At IDSA this afternoon, Dr. Shu-Hua Wang, an assistant professor of medicine at Ohio State University, revealed the results of an analysis of MRSA strains that showed up in a surveillance network that links Ohio State and seven rural hospitals nearby. Between January 2007 and January 2010, 7 percent of the 1126 MRSA strains they found in sick patients turned out to be ST239 — the first ST239 infections ever recorded in the US.

The infections were serious: half of the patients had bloodstream infections and one-fourth had pneumonia. And they were unusually difficult to treat: The bacterial samples were indifferent not only to the beta-lactams, but to a wide array of additional drugs: clindamycin, tetracycline, trimethoprim/sulfamethoxazole (TMP/SMX, usually called Bactrim or Septra), moxifloxacin, and gentamicin. They were susceptible only to vancomycin, the MRSA drug of last resort for decades, and one newer drug, linezolid (Zyvox).

That is a dismaying list. Here’s why: In the search for drugs that still work against MRSA, medicine has increasingly turned to older drugs — ones that until recently were never been used against the bug, because there were newer, better drugs available. Tetracycline and TMP/SMX are two of the great remaining hopes for treating MRSA infections without rolling out the really big-gun drugs that should be reserved for life-threatening emergencies. If the resistance factors carried by ST239 knock out the older generics, MRSA infections will become yet harder to treat. As appears to have happened in Ohio:

“Twenty-two percent of the patients experienced relapse and failure of their drug regimens,” Wang said in a briefing for the media. “Another 22 percent died within 30 days.”

The 77 patients infected with ST239 tended to be male and older, and they were apparently already ill: 74 percent had been hospitalized before, 44 percent had had surgery, 29 percent had been in a nursing home, 17 percent had been on dialysis. Where the ST239 first came from and how it spread isn’t clear, Wang said, except that the surveillance network results show the earliest cases to have been treated at Ohio State. It may have spread to the rural hospitals from there.

The most worrisome implication of today’s news may not be the appearance of ST239 itself — it is so common in the rest of the world that its return to the US may just have been a matter of time — but rather the possibility that public health may not be able to keep track of it. In everyday medicine, isolates are tested enough to identify the organism and to determine its susceptibility to antibiotics; those results deliver enough information to determine a patient’s  best treatment. Multi-locus sequence typing, the test that identified ST239 in the Ohio patients, is expensive and complex and delivers more information than a clinician really needs; it’s most used in academic research labs. So it is entirely possible that patients could become infected with this strain without the strain being detected, unless the physician treating them happened to put together the puzzle pieces of the unusual resistance pattern.

This possibility seems to have been on Wang’s mind in Vancouver. To track the spread of ST239, “Increased molecular surveillance is needed,” she said. But she offered some workarounds — less expensive, more commonly used assays — whose results could be used to cast a net of detection for the spread of this new strain.

MRSA image from the Public Health Image Library, CDC; poster previously sold by Threadless, original design by Olly Moss

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.

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

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.

Bad news: From MRSA to LRSA

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Via the Journal of the American Medical Association, a report from Spain: the first recorded outbreak, in a Madrid hospital, of Staphylococcus aureus resistant to linezolid (Zyvox), one of only a few drugs still available to treat very serious infections of drug-resistant staph, MRSA. This is bad news.

Background: The M in MRSA stands for methicillin, the first of the semi-synthetic penicillins, created by Beecham Laboratories in 1960 in response to a worldwide 1950s outbreak of penicillin-resistant staph. The central feature of the chemical structure of both penicillin and methicillin is an arrangement of four atoms, known as the beta-lactam ring, that governs both drugs’ ability to interfere with bacterial cell-wall synthesis. That structure was copied into the formulas of a number of other drug families — the cephalosporins, carbapenems and monobactams — and so MRSA is resistant to them as well. And in addition, the bug has picked up resistance to yet other drug families through horizontal transfer; so increasing the census of new drugs that can treat resistant staph infections is a high priority for drug development. It’s especially critical for severe infections such as ventilator-associated pneumonia, osteomyelitis, endocarditis and bacteremia, since all the remaining last-resort drugs have challenges from toxicities to ineffectiveness in certain organs.

Linezolid is a relatively new drug, out since 2000 (and, as a downside, still under patent and, according to patients who have been prescribed it, very expensive). It was the first of a new drug class, the oxazolidinones; since there were no “me too” similarities to older drugs, clinicians hoped that resistance to linezolid would be slow in coming.

No such luck.

The first recognized case of linezolid resistance in staph was recorded in 2001. Still, there have been relatively few cases of LRSA, or staph that possesses both linezolid and beta-lactam resistance: 8 cases in the US to date, 2 in Germany and 1 each in Brazil, Colombia and the UK.They have all been caused by a particular point mutation, G2576T.

This Spanish outbreak, though, had a different cause, the importation of the cfr gene, which also mediates resistance to the older drugs clindamycin and chloramphenicol, apparently on a plasmid, possibly from a staph strain common in cows. The outbreak caused by this new mechanism was as large as the entire known burden of LRSA to date: 12 patients, over 10 weeks in 2008, in 3 linked ICUs, pls 3 patients who were not in intensive care, but had had previous ICU stays. Six of the patients had ventilator-associated pneumonia and 3 were bacteremic. Six died — though the authors are careful to say that all of these patients were critically ill, with brain tumor and esophageal cancer among other problems, and that LRSA was not directly responsible for all of the deaths.

More bad news: There were actually 4 clones of LRSA within this outbreak, with slightly different resistance patterns. Troublingly, one of the 4 had reduced sensitivity to glycopeptides; the chief glycopeptide is vancomycin, which has been the go-to drug for MRSA for 50 years.

The hospital checked its staff and the ICU environments, and found nothing of significance; there was no reservoir in the hospital that was passing this newly resistant strain to patients. With no obvious solution there, they dialed back sharply on their linezolid use, going from more than 200 doses per day in April 2008 to 25 doses per day in June. That aggressive antibiotic stewardship appears to have put the brakes on the outbreak, and after June, no additional cases were recorded.

An accompanying editorial underlines how critical antibiotic stewardship was in controlling this outbreak, while also pointing out how very liberal the hospital was in prescribing linezolid before the outbreak began — suggesting that if the institution had used its antibiotics more conservatively from the start, this outbreak might not have arisen, or at least not have been as large.

No one doubts the importance of infection-control practices in limiting outbreaks with antibiotic-resistant organisms, but optimizing antibiotic use remains essential for successful control of such outbreaks…No longer can clinicians’ unrestricted use of antibiotics and ignoring suggestions from those who attempt to improve or alter antibiotic use be tolerated. Clinicians must understand the sense of urgency about the appropriate use of antibiotics.

Indeed.

(NB, this outbreak was also written up a few months ago in Clinical Infectious Diseases, and was a late-breaker paper at the 2008 ICAAC meeting.)

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

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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.

"Pig MRSA" causing human infections

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Hi, everyone. Apologies for dropping out of sight! As SUPERBUG’s publication draws closer (and it’s very close now), I keep finding new tasks that I have do to. Last week’s was to go to New York to shoot a video for the Simon & Schuster website — and while there, I got caught in Snowpocalypse, got delayed coming home, and picked up a nasty cold. So I’m a bit behind.

But there’s exciting news tonight to start us up again: “pig MRSA,” ST398, causing human infections in Canada and Denmark.

“Infections” is important, because up til now, most evidence for  the spread of MRSA ST398 in humans has been through detection of colonization, the symptomless carriage of MRSA on the skin and in the nostrils. The first finding of ST398 in the Netherlands was via colonization; so was its first identification in humans in Canada, and also in the United States just about a year ago.

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Antibiotics and farming — how superbugs happen

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Constant readers: There’s an important new paper that’s been out for a week that I haven’t gotten to you. I apologize; it’s been busy. (Let’s not even talk about the important paper that’s been out for two weeks. Maybe over the weekend…)

We’ve talked for ages now about the potential dangers of unrestricted antibiotic use in agriculture, and how it’s analogous to the inappropriate antibiotic use that human health authorities disapprove of in humans. The main culprits, in farming, are subtherapeutic dosing, also known as growth promotion — that’s giving routine smaller-than-treatment doses to animals to increase their weight — and prophylactic dosing, which is giving a treatment dose to an entire herd or flock either routinely, if there is thought to be a disease threat, or when there is known to be disease in some members of the herd/flock. In either case, animals are getting antibiotics when they do not need them — when they are not sick. And just as in humans who take antibiotics when they are not sick, or take too-low doses when they are sick (such as not finishing a prescription), these practices in animals encourage the development of resistant bacteria.

(Necessary comment here: No one, to my knowledge, objects to giving the appropriate doses of antibiotics to animals that are sick. Why would you?)

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Bad news in the President's budget request

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It’s been a few days since the rollout of the White House’s proposed 2011 budget request, time enough for people to dig deep into the minutiae and figure out what that massive document really says. The Infectious Diseases Society of America has done the drilling for the health and infectious disease line items, and I’m sorry to say the news is not good.

Worst first: The proposed budget would cut funding for the CDC’s antimicrobial resistance programs by 50%, $8.6 million. That means that only 20 state or local health departments, or health care institutions, will get money from CDC for surveillance and control of resistant bugs. That’s only 40% of what was funded this year, when 48 health departments and health systems were funded. Which is very disturbing: If there’s one thing almost everyone agrees on with regard to MRSA, it’s that we need more surveillance, not less.

In addition, all state grants in the Get Smart About Antibiotics program, which runs campaigns to reduce inappropriate use, get zeroed out.

There are other cuts as well to infectious-disease program at CDC and elsewhere in HHS, including to to a major childhood immunization program and to pandemic defenses. And funding for HIV/AIDS, TB and other NIH research programs barely tiptoe upward.But these frank cuts in programs to combat antimicrobial resistance, at a time when MRSA is burgeoning, Gram negative organisms such as Acinetobacter are gaining ground, and drug development is stalling, surely cannot be smart.

The IDSA analyis is here.