Maryn McKenna

Journalist and Author

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.

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.

But comes now a team of public and university scientists from Canada to say that ST398 is also causing infections in Canada. They analyzed 3,687 MRSA isolates that had been collected from patients seen for infections in Manitoba and Saskatchewan. Five were ST398. That is an exceedingly low percentage, of course. But it is striking, and odd, that the infections were present at all:

The earliest identified LA-MRSA isolate (08 BA 2176) associated with an infection was obtained from a postoperative surgical site. … This patient is unlikely to have had any recent direct contact with livestock because she had been confined to her home with limited mobility for several years before her hospitalization. Additional nasal swabs from this patient remained positive for this strain for at least 7 months. …
The isolate submitted to the NML by Sunnybrook Health Sciences Centre… was from a 59-year-old man from Ontario. He had been hospitalized in December 2007 for treatment of metastatic squamous cell carcinoma of the larynx. In the previous year, he had undergone a total laryngectomy, neck node dissection, and tracheostomy. …. He was unaware of any animal contact and had no history of exposure to pigs or pig farms. A review of the medical records and standard epidemiologic investigations determined that this was not a nosocomial or healthcare-associated isolate.

Just to underline, we have here a MRSA strain that is strongly associated with close contact with pigs, or with pig meat, and that has spread far enough from farms to be present in people who had no connection with pigs. You can argue that its very low prevalence means that it is not so much a threat as a curiosity. But I’d counter-argue that this is significant: because it establishes that this strain is spreading; because it demonstrates that the strain is causing infections, not just colonization; and because it inserts, into the swarm of isolates that make up MRSA, additional resistance factors that can be traded and exchanged unpredictably among the bacteria — and are likely not to be detected because our surveillance in animals is so sparse.

The authors say:

…additional surveillance efforts are required to monitor the emergence and clinical relevance of this MRSA strain in Canada, including communities, the environment, livestock, farmers, and production facility workers. Whether these strains pose a major threat to human health in light of the low livestock density and continued spread of epidemic hospital and community strains of MRSA in Canada remains unknown.

There’s also a new and tantalizing report from Denmark that appears to describe not only human infections, but human to human transmission, resulting in a very serious pneumonia in a baby. I can’t access the full-text even through my university account, but the abstract says:

Carriage of pig-associated methicillin-resistant Staphylococcus aureus (MRSA) is known to occur in pig farmers. Zoonotic lineages of MRSA have been considered of low virulence and with limited capacity for inter-human spread. We present a case of family transmission of pig-associated MRSA ST398, which resulted in a severe infection in a newborn.

Not good.

The cites for these are:
Golding GR, Bryden L, Levett PN, McDonald RR, Wong A, Wylie J, et al. Livestock-associated methicillin-resistant Staphylococcus aureus sequence type 398 in humans, Canada. Emerg Infect Dis; [Epub ahead of print] DOI: 10.3201/eid1604.091435
Hartmeyer GN, Gahrn-Hansen B, Skov RL, Kolmos HJ. Pig-associated methicillin-resistant Staphylococcus aureus: Family transmission and severe pneumonia in a newborn. Scand J Inf Dis. Epub Feb. 3, 2010 ahead of print.

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?)

The interesting research question is how, exactly, resistance develops. (My real scientist readers may want to take a break, or cut me a break, for the next few sentences. Please.) The classical assumption has been that, through a variety of stimuli and the random copying errors of reproduction, bacteria are constantly acquiring small mutations. Some of those may give the bugs an advantage when they are exposed to a drug, some slight difference that allows the bacteria to disarm or turn aside that drug’s particular method of assault — so that the weak die, the strong survive, and the strong then reproduce more abundantly into that extra living space freed up by the death of the weak. The survivors and their descendants retain that mutation, because it gave them an advantage against the drug. And because bacteria can share resistance factors not only vertically mother-to-daughter, but horizontally in the same generation, once the resistance has emerged, it is likely to spread.

But no matter how quickly it spreads, that process I’ve just described involves acquiring resistance to just one drug or drug family at a time. Provocative new research from Boston University’s medical school and deoartment of biomedical engineering now suggests, though, that multi-drug resistance can be acquired in one pass, through a different mutational process triggered by sublethal doses of antibiotics — the same sort of doses that are given to animals on farms.

In earlier work, the authors found that antibiotics attack bacteria not only in the ways they are designed to (the beta-lactams such as methicillin, for instance, interfere with staph’s ability to make new cell walls as the bug reproduces, causing the daughter cells to burst and die), but also in an unexpected way. They stimulate the production of free radicals, oxygen molecules with an extra electron, that bind to and damage the bacteria’s DNA.

That research used lethal doses of antibiotics, and ascertained that the free-radical production killed the bacteria. In the new research, the team uses sublethal doses, and here’s what they find: The same free-radical production doesn’t kill the bacteria, but it acts as a dramatic stimulus to mutation, triggering production of a wide variety of mutations — what the researchers, in a press release, called “a zoo of mutants.” The plentiful, scattershot mutations included ones that created resistance to a number of different drugs — in some cases, even though no mutation was present that created resistance to the drug being administered.

You can easily see how this is applicable to factory farming: The sublethal dosing applied experimentally is analogous to the subtherapeutic dosing used in agriculture. Is it applicable to MRSA? Yes, absolutely. The two organisms the researchers used to test their hypothesis were S. aureus and E. coli.

making the implication clear, senior author James J. Collins said on the paper’s release:

“These findings drive home the need for tighter regulations on the use of antibiotics, especially in agriculture; for doctors to be more disciplined in their prescription of antibiotics; and for patients to be more disciplined in following their prescriptions.”

The cite is: Kohanski MA, DePristo MA and Collins, JJ. Sublethal Antibiotic Treatment Leads to Multidrug Resistance via Radical-Induced Mutagenesis. Molecular Cell, Volume 37, Issue 3, 311-320, 12 February 2010.

UPDATE: There’s a great discussion of the paper at the blog Mental Indigestion.

Postscript: I suppose I’ve been working too long without a break, because while I was reading about this process of creating multiple resistance factors at once, what I heard in my head was Mickey Mouse chirping: “Seven at one blow!”

Antibiotics and farming — CBS follow-up video

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Constant readers, CBS News has posted some follow-up video to its two-part series last week on antibiotics in agriculture. It features Dr. David Kessler, former Commissioner of the Food and Drug Administration (which under its current leadership has vowed to re-examine farm-antibiotic use), and Eric Schlosser, author of Fast Food Nation.

They talk about the protests CBS has received for airing the package, the concerns public health authorities have over the lack of  data on the amounts and types of antibiotics used, and much more. I especially love Schlosser’s comment: “I’m a meat-eater.” It’s important, I think, to say that being critical of antibiotic use does not mean being opposed to animal agriculture, or wanting to see farms shut down. It means being concerned for the health of farm animals, farm families, and everyone affected by growing antibiotic resistance — which is, you know, everyone.

(H/t @EdibleSF for flagging the video’s release.)


Watch CBS News Videos Online

(Hey, that’s my first embedded video!)

CBS antibiotics and farming package, day one

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Constant readers, I hope you saw the CBS News package on antibiotics in farming Tuesday night. (It continues Wednesday.) MRSA played a prominent role, in an account of infections among workers at a chicken plant (the same outbreak, I think, as was described by Prevention magazine last August) and in questions about MRSA in pig farms in the Midwest (with a prominent mention of Tara Smith’s research into “pig MRSA” ST398).

Here’s the 7-minute video and the text version.

Earlier Tuesday, CBS’s Early Show ran an additional package on the death of a Chicago toddler from MRSA. That toddler’s name is Simon Sparrow, and you’ll be able to read his sad story — told by his mother, Everly Macario — in SUPERBUG.

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.

Back again to MRSA in animals, and spreading to humans

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There are two new reports out regarding new findings of “pig MRSA” ST398 (about which we have talked a lot; archive of posts here.)

First, researchers from the Complejo Hospitalario Universitario de Vigo and Complejo Hospitalario de Pontevedra, both in Pontevedra in northwest Spain, report that they have identified that country’s first human cases of infection with ST398. (It was only last fall that Spain reported the first identification of the strain in animals.)

The age of the three patients was 59, 82, and 83 years, respectively. Two patients owned pigs and the other a calf. Two patients were diabetic and were hospitalized because they developed skin and soft-tissue infections by MRSA ST398. The third patient had bronchitis and the strain was isolated from a respiratory secretion submitted to the laboratory from an outpatient clinic. The three patients had had multiple hospital admissions in the last 12 months.

Tellingly, the researchers spotted these particular isolates (out of 44 analyzed at the two hospitals in 2006) because they were resistant to tetracycline. Tetracycline resistance is not common among community strains of MRSA, because the drug isn’t the first-line choice for skin and soft-tissue infections; and when it is given, it’s usually for a short course, so the drug does not exert much selection pressure on the bug. But tetracycline is a very common animal antibiotic, and tetracycline resistance is a hallmark of ST398; it is one of the factors that led the Dutch researchers who first identified the strain to take a second look at the bug.

Second, researchers from several institutions in Italy report a very troubling case of ST398 infection that produced necrotizing fasciitis — better known as flesh-eating disease.

In early April 2008, a 52-year-old man was admitted to an intensive care unit in Manerbio, Italy, because of severe sepsis and a large ulcerative and suppurative lesion on the right side of his neck. His medical history was unremarkable. He was a worker at a dairy farm, was obese, and did not report any previous contact with the healthcare system.

Necrotizing fasciitis is a terrible disease: If doctors don’t respond very quickly, it can kill, whle the emergency surgery that forestalls death often carves away large areas of flesh or sacrifices entire limbs. This patient was fortunate: He was in the hospital for 31 days, but recovered and went home.

The Italian researchers are alert to, and troubled by, the larger meaning of this case:

… cattle-to-human transmission cannot be proven. However, because our patient did not have any other potential risk factor, dairy cows were probably the source of the human infection. … It is difficult to prevent persons with constant exposure to MRSA in their work or home setting from becoming MRSA carriers. Revisiting policies for the use of antimicrobial drugs on livestock farms, as well as improving hygiene measures, may therefore be necessary in infection control programs.

Cites for these papers:

Potel C et al. First human isolates of methicillin-resistant Staphylococcus aureus sequence type 398 in Spain. Eur J Clin Microbiol Infect Dis. 2010 Jan 23. [Epub ahead of print] DOI 10.1007/s10096-009-0860-z

Soavi L, Stellini R, Signorini L, Antonini B, Pedroni P, Zanetti L, et al. Methicillin-resistant Staphylococcus aureus ST398, Italy [letter]. Emerg Infect Dis 2010 Feb