MRSA research round-up: hospitals, vitamins, pets

Because I've been so behind, there's so much to cover! So let's dive in:

In today's Archives of Surgery, researchers from Seattle's Harborview Medical Center report that one simple addition to the routine of caring for trauma patients made a significant difference to the patients' likelihood of acquiring a hospital-associated infection: bathing them once a day with the antiseptic chlorhexidine (in an impregnated wipe). Patients who were bathed with the antiseptic wipe, compared with patients wiped down with an inert solution, had one-fourth the likelihood of developing a catheter-related bloodstream infection and one-third the likelihood of ventilator-associated MRSA pneumonia. Cite: Evans HL et al. Effect of Chlorhexidine Whole-Body Bathing on Hospital-Acquired Infections Among Trauma Patients. Arch Surg. 2010;145(3):240-246.

How important are hospital-acquired infections? Here's a piece of research from a few weeks ago that I sadly failed to blog at the time: Just two categories of HAIs, sepsis and pneumonia, account for 48,000 deaths and $8.1 billion in health care costs in a single year. Writing in the Archives of Internal Medicine, researchers from the nonprofit project Extending the Cure analyzed 69 million hospital-discharge records issued in 40 states between 1998 and 2006. Hospital charges and number of days that patients had to stay in the hospital were 40% higher because of those infections, many of which are caused by MRSA — and all of which are completely preventable. Cite: Eber, MR et al. Clinical and Economic Outcomes Attributable to Health care-Associated Sepsis and Pneumonia. Arch Intern Med. 2010; 170(4): 347-53.

 What else could reduce the rate of MRSA infections? How about Vitamin D? South Carolina scientists analyze data from the NHANES (National Health and Nutrition Examination Survey 2001-2004), a massive database overseen by the CDC, and find an association between low blood levels of Vit. D and the likelihood of MRSA colonization. More than 28% of the population is Vitamin D deficient. MRSA colonization is increasing in the US. Can giving Vit. D decrease MRSA carriage? More research needed. Cite: Matheson EM et al. Vitamin D and methicillin-resistant Staphylococcus aureus nasal carriage. Scand J Infect Dis. 2010 Mar 8. [Epub ahead of print]

And finally: Who else carries MRSA? Some unlucky pet owners have found that animals can harbor human strains, long enough at least to pass the strain back to a human whose colonization has been cleared. So it makes sense to ask whether humans who spend time with pets are carrying the bug. Last month's Veterinary Surgery reports that the answer is Yes. Veterinarians are carrying MRSA in very significant numbers: 17% of vets and 18% of vet technicians at an international veterinary symposium held in San Diego in 2008. Cite: Burstiner, LC et al. Methicillin-Resistant Staphylococcus aureus Colonization in Personnel Attending a Veterinary Surgery Conference. Vet Surg. 2010 Feb;39(2):150-7.

SUPERBUG the book: First excerpt, first interview, and news!

Constant readers: It's two weeks to publication, and I'm starting to lose my grip on everything there is to do. (As you might be able to tell by my radio silence...) I'm very backed up on great research to tell you about.

First, though, let me share some book news:

EXCERPT: The first excerpt of SUPERBUG has been published on Simon and Schuster's website! It looks like the entire Chapter One.


INTERVIEW: I was invited to Chicago the past few days to do a speech for International Women's Day, and ended up doing some sneak-preview media appearances. Here's the sound file of an interview with the fabulous Alison Cuddy of WBEZ-FM.

MORE INTERVIEWS: I'll be listing forthcoming interviews and appearances on my page at BookTour.com. You'll notice there isn't much up there yet: We're still working on publicity. So help me fill this page, OK? Here's how:


TOUR, A PLEA: My publisher, Free Press, doesn't really believe in sending authors around. They have some justification: As I can testify from my last tour, sometimes a book tour mean spending two hours making painful chit-chat in an empty bookstore whose entire population is the staff, the friend who drove you, and a street person who wandered in and is conversing quietly with her demons. (Twenty-Third Street Books, Portland, OR, thanks for asking. I hear they closed.) But that bad experience notwithstanding, I believe there's value in getting out and talking to readers, victims, disease geeks and anyone else interested in this bug, and I'm willing to do it, if you'll help.

So: If you're a clinician, a professor, or a teacher, and you're willing to host SUPERBUG and me at a class, a department brown-bag or a Grand Rounds, please get in touch. Ditto if you run a Cafe Scientifique, have a book club that wants to talk about science or medicine, have a church group, a kid's group, a med-student society... you get the idea. If I can get there, I'll come. I know already that I'll be in and out of Minneapolis and Atlanta, my two home bases, and also in North Carolina, Iowa, Chicago, and I hope San Francisco, Portland and Boston as well. Help me add to the list!

Right, back to research tomorrow.

"Pig MRSA" causing human infections

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

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

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!)

New film on organic farming (for European readers and others)

This is a little outside our usual subject matter, but it follows nicely on the past two days' discussion of the CBS packages on antibiotics in farming, so:

What looks like a marvelous new documentary exploring environmental damage and human illness from pesticides and other farming chemicals is coming out in France, but needs assistance to get onto the international festival circuit. It's called Nos enfants nous accuseront (Our Children Will Hold Us Responsible), and among other things, looks at the efforts of a French village to make all the food served in its schools organic — which, even in food-centric France, is much harder than it sounds.

You can view the trailer here. The more clicks, the more the film will be taken to have support, and the higher its rankings will go for festival consideration.

It comes well-recommended by friends of mine in Paris, so I hope you'll take a look.

CBS antibiotics and farming, day 2 - and more on the Danish experience

Constant readers, I hope you watched the second day of CBS News' series on antibiotic use in farming, and how it promotes the emergence of antibiotic-resistant infections in animal and humans. I found it surprisingly hard-hitting. Here's the video and the text version.

Most of the report explored the farm experience in Denmark, which in 1998 banned its farmers from using small doses of antibiotics to make animals gain weight faster — the practice that's various called subtherapeutic dosing or growth promotion. Important distinction: The country still permits sick animals to be treated with antibiotics; the ban extends only to giving drugs to animals who are not sick.

That ban has often been represented as a failure for Danish farming [NB: See the update below], but research on the results shows that it was actually a success. Here's an article by Laura Rogers of the Pew Charitable Trusts explaining what happened in Denmark from her own on-the-ground reporting:

Antibiotic use on industrial farms has dropped by half while productivity has increased by 47 percent since 1992. Danish swine production has increased from 18.4 million in 1992 to 27.1 million in 2008. A decrease in antibiotic-resistant bacteria in food animals and meat has followed the reduced use of these vital drugs. ...

The average number of pigs produced per sow per year has increased from 21 to 25 (this is an important indicator of swine health and welfare, according to veterinarians). Most important, total antibiotic use has declined by 51 percent since an all-time high in 1992. Plus, the Danish industry group told us that the ban did not increase the cost of meat for the consumer.

 There are multiple scientific papers done by Danish authors backing up her observations. Here are just a few from just last year:

• Antibiotic-resistant organisms in chickens raised in Denmark declined since the ban — but they remain high in chicken meat imported from other countries that do not have such bans, and passed to Danish consumers who ate that imported meat. (Skjot-Rasmussen et al., May 2009)
• Antibiotic resistance in E. coli in pigs increases when pigs are given antibiotics, and those antibiotic-resistant organisms pass to humans (Hammerum et al., April 2009)
• Antibiotic-resistant organisms found in pigs when they are slaughtered increase when pigs receive more antibiotics (Abatih et al., March 2009)

The industry that supports industrial-sized farms has strongly objected to the CBS series. You can see one detailed response here, from Pork Magazine. The Minneapolis-based Institute for Agriculture and Trade Policy predicts that this is likely just the first wave, and that opposition to any change in agricultural practices will grow stronger as a bill to curb unnecessary antibiotic use gains traction in Congress.

And — you knew I had to do this — here comes the obligatory self-promotion: There is a primer on antibiotic use in farming, and an account of the emergence of MRSA ST398 as a result of antibiotic use in pigs, in SUPERBUG. Which is now 41 days away from publication. And is available for pre-order at a discount! But you knew that.)

UPDATE: FairFoodFight has a great post and a long comments conversation about the CBS series, ag antibiotic use, and particularly the World Health Organizaton research that originally made people doubt the "Danish experiment," The WHO report is here and a Pew analysis of it is here.