We met when I was in graduate school. He was a foreign journalist working in America and I interned where he worked. I left town, finished my degree, moved back. We reconnected, got married, and were considered enough of a catch — two sharp young thrusters, an investigative reporter and an editor — to be head-hunted by a large paper in the Midwest.

To defuse romantic nostalgia, it is important to say that he was unsuited to marriage, with outsize appetites for beer and for women who were not me. But he was perfectly adapted to journalism, smart, bold, adored by his staff, and rising up the professional ladder fast enough to leave contrails.

We had not been at that paper very long when stupid actions by his supervisors confronted him with a choice that no one who loves their work wants to make: Stay and be ethically compromised, or leave with intact standards and an empty wallet. He chose to leave, yanking the brakes on his trajectory and blowing up his career.

I’ve always admired that action. I always wondered whether, faced with a similar situation, I’d be that brave.

Which is my way of saying that I’m leaving Scienceblogs.

I am I think the youngest sibling, having arrived 7 weeks ago after 3+ years at Blogger. I was flattered to be asked to join the excellent bloggers here and energized to be in a network. The Pepsi debacle was a grave disappointment. The follow-on revelations of what appear to be earlier questionable actions by Seed Media Group (here, here and here) are disturbing.

But what troubles me most, going forward, is Seed Media’s glacially paced and indifferent communication with its bloggers, whose frustration was captured yesterday by PZ Myers and even more by Bora Z in a masterful must-read analysis. Without open and complete communication — accountability, transparency, sunlight — I can’t feel secure that I won’t be ethically compromised again.

That experience with my ex — which also derailed my career for a while, because of course I left the paper with him — taught me that the pain of an ethically based decision is an almost infallible guide to its correctness. Sacrificing my connection to this community, its mouthy contentiousness, fearsome expertise and generous welcomes — and yeah, its traffic and its page ranks and its reputation — hurts.

And therefore I’m sure it’s the right thing to do.

I‘ll be resuming blogging for the time being at least at my old Blogger site, now renamed Superbugtheblog.com. If Superbug finds a new home, I’ll make the announcement there also.

As of September 2010, SUPERBUG will be joining Wired.com’s new line-up of “all-star science blogs” at this page.

I hope to see some of you there. Thank you for our time together here.

I dislike and resent having to do this: I was flattered to join Sb and I have great respect for my Sciblings.

I acknowledge that Sb’s management, Seed Media Group, made some concessions today, but I am dissatisfied that those changes came only after community protests, when they addressed issues that should — could — have been foreseen.

I’m also not convinced they go far enough, since the central issue of a corporate-sponsored blog that appears (still, functionally) indistinguishable from the independent blogs here has not been addressed. I don’t want, by remaining, to appear to support the decision to publish that blog in its current form, when I don’t support it.

I need to think these things through. So, publication is temporarily suspended.

Dammit.

Constant readers may have noticed by now that my Sciblings here at Sb are in a justified uproar about the inclusion of a new blog, Food Frontiers, sponsored — that means “paid for” — by Pepsi Co. Sb runs on advertising, but this paid space is not in the ad rails and banners, but in the main column. This was sprung on the blog community without advance notice on Tuesday.

A crapstorm ensued.

In addition to the many critical posts you can see if you click “Last 24 hours” up to the left, a number of excellent bloggers have left for good or suspended until this is rethought, including Dave Dobbs, Sharon Astyk, Blake, Laelaps, Rebecca Skloot, MarkCC, Class M, and I’m sure I’ve missed some. These are all significant losses.

Meanwhile, Sb has been excoriated in the Guardian and on the Knight Science Journalism Tracker, WebNewser, Consumerist, Irregular Times (whose headline is: Scienceblogs Loses Online Respect With Pepsi Deal), and the journalism and science Twitterverses are abuzz.

In response to all of which, Seed Media Group, which owns this space, has done some dialing back. They changed the banner of the blog to include the PepsiCo logo, they added a more-clear explanatory note (more about that below), and they admitted they handled this badly. Meanwhile, the Pepsi blog, whose comments according to would-be commenters are heavily moderated and slow to post, is at 121 comments and climbing.

That’s the recap. Here’s my buried lede: I’m not leaving, yet. But I’m watching closely and reserve the right to change my mind on that. And I think this was, and remains, spectacularly crass, naive, and dumb.

I was a newspaper reporter for a long time, and I have no illusions about publications, print or pixel, needing to find funding. The traditional way to do that is via ads. The sneakier but widely accepted way to do it is to run an “advertorial,” something that looks like a story or magazine page but was produced by a single company or other entity and contains content highly favorable to that entity, with no outside comment or other points of view included (e.g., “Dubai is a wonderful place to vacation and locate your business!,” not “Dubai’s economy is crashing and our airport parking lot is choked with abandoned leased cars.”) Most major magazines (including ones I now write for), and newspapers including the New York Times and the Wall Street Journal, accept such pages, and label them as such more or less clearly. The practice is common enough that the American Society of Magazine Editors has specific guidelines for print advertorials, and equally direct guidelines for online pubs that say, in part:

We recommend the following standards (subject to change as the medium evolves):
The home page and all subsequent pages of a publication’s Web site should display the publication’s name and logo prominently, in order to clarify who controls the content of the site.
All online pages should clearly distinguish between editorial and advertising or sponsored content. If any content comes from a source other than the editors, it should be clearly labeled. A magazine’s name or logo should not be used in a way that suggests editorial endorsement of an advertiser. The site’s sponsorship policies should be clearly noted, either in text accompanying the article or on a disclosure page (see item 8), to clarify that the sponsor had no input regarding the content.
Hypertext links that appear within the editorial content of a site, including those within graphics, should be at the discretion of the editors. If links are paid for by advertisers, that should be disclosed to users.
Special advertising or “advertorial” features should be labelled as such.

My feeling is that the Pepsi blog fails to meet these best practices in a manner that is at least sloppy. For instance, the logo, which was added after the crapstorm began, is small; the sponsorship language is not sufficiently detailed; and the placement within Sb and involvement of Sb’s editors (first graf of first post, by Sb editor Evan Lerner: “On behalf of the team here at ScienceBlogs, I’d like to welcome you to Food Frontiers, a new project presented by PepsiCo.“) implies Sb’s endorsement of the content.

In addition, it is probably disingenuous. For instance: The clarifying statement that has been added to the left rail now says: “All editorial content is written by PepsiCo’s scientists or scientists invited by PepsiCo and/or ScienceBlogs. All posts carry a byline above the fold indicating the scientist’s affiliation and conflicts of interest.” Yet the person who has identified himself as the blog’s editor — that is presumably the person who final-vets posts before they are published — is a member of Pepsi’s “sustainability communications team,” which is not a science position, but sounds like some form of public affairs (social media, social engagement). In addition, the first post on the blog said that future content would include “We have some exciting things planned for this project, including a video series that will begin with a look at the role the food industry plays in health issues.” Scientists don’t script and produce corporate video. PR departments do.

Summing up: By including this corporate-written blog in its stable of otherwise independent blogs, and especially by presenting it in the same format as the independent blogs, with insufficient labeling and transparency, Sb has imperiled the credibility of all of its bloggers. The ethical shadow is particularly acute for the bloggers who write about obesity and food culture, but the question of conflict of interest, and influence over content, could now be asked of any of us.

There may have been a way to do this better: open the concept for discussion in advance of launching the blog, sequester the blog in a separate section, design the page differently to clarify its inevitably advertorial content, remove any PR management from the posts. This was not that way.

Last week, the Food and Drug Adminstration took the first (baby, mincing, tentative) steps to address the problem of antibiotics being used in animal agriculture, not to treat disease, but to make animals grow up to market weight faster. This practice — variously called subtherapeutic dosing, growth promotion, and “for production purposes” in the FDA’s exceedingly careful language — has been fully banned in the European Union for 4 years, and some aspects of the practice have been banned longer.

The simple reason for the ban: There’s decades of good science and real-world experience showing that it contributes to the development of drug-resistant organisms in farm animals and the farm environment, organisms that leave farms in the animals and in their manure, and also contaminate the environment beyond farm borders via leakage into groundwater and dust blowing off manure lagoons.That movement off the farm is critical because many of the drugs used in agriculture are the same, or close analogs, of drugs used in human medicine; so resistance that develops on the farm endangers human health as well. (MRSA ST398, livestock-associated MRSA, is the latest example of this. Find a long archive of posts on ST398 here.)

Just to be clear, growth-promoters don’t treat disease; they’re given to healthy animals solely for the purpose of getting them up to sale weight and to market faster. The ways in which antibiotics are given to livestock to treat or prevent disease have their own issues, but those are not part of the FDA effort. (Historical note: The growth-promoting effect of trace amounts of antibiotics was first recognized in 1947, when scientists at Lederle were looking for something to do with the leftover fermentation mash from the manufacture of chlortetracycline, fed it to chickens, and discovered they thrived on it. Stuart Levy’s The Antibiotic Paradox tells this story in detail.)

In human medicine, when we give antibiotics to people who are not sick with a bacterial illness, we call it inappropriate use — and aim massive education campaigns at the practice in an attempt to dial it down. In contract, the animal side has had a free pass for a long time, to the extent that it remains unclear how many antibiotics are used in farming in the US (best estimate: about 70% of all antibiotic use in the US per year), and there is no organized surveillance that would look at what organisms are emerging in animals from that use.

The FDA has been trying to put curbs on growth promoters since the 1970s, always without success; the lobbying against it, by agriculture and also by pharmaceutical interests, is reliably intense. There’s been a parallel effort in Congress to limit the use in animals of drugs that have close analogs in human medicine, via the Preservation of Antibiotics for Medical Treatment Act, or PAMTA, authored by Rep. Louise Slaughter (D-NY), Congress’s only microbiologist. PAMTA has been introduced in several Congresses but this year finally gained some traction. Last year, the Obama administration signaled, in testimony by then-new assistant FDA commissioner Joshua Sharfstein, that it might be friendly to the idea of dialing back on growth-promoter antibiotic use, and it looked as though the long logjam might finally be broken.

Well, OK: Not broken, exactly. Just shifted a little, and maybe showing a tiny bit of light.

On Tuesday, the FDA released a “draft guidance” that proposes animal ag do two things: stop using growth-promoting subtherapeutic dosing, and administer antibiotics to animals under the supervision of a veterinarian. That’s the good news.

The bad news: It’s only a guidance, not a regulation. In other words, it has no force in law. It’s more like a request — though in a press conference last week, Sharfstein suggested it might also be a shot across agriculture’s collective bow:

We have the regulatory mechanisms and the industry knows that. But we are also interested in what things can be done just voluntarily that they would do them. And I think it’ll be interesting to see how the industry responds to this and how – what direction their comments take. …We’re not handcuffed to the steering wheel of a particular strategy at this point. We really want to understand what people think. And but we’re also – I’m not ruling out anything that we could do to accomplish these important public health goals. (Transcript)

Reactions to the FDA announcement were predictable — effectively “No science, more research needed”: Here’s the National Cattlemen’s Beef Association, the National Pork Producers Council, and a standing statement by the Animal Health Institute. (Supporting the FDA move: the Pew Charitable Trusts, the New York Times.)

The draft guidance stays open for public comment for 60 days, until Aug. 30. The required Federal Register posting is here, with the mailing address. Electronic comments can be left at Regulations.gov; the docket number for the guidance is FDA-2010-D-0094; 33 comments have been posted already.

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

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

Most recently, it has leaked to Tajikistan, a country that has been polio-free since 2002 but shares borders with three of the four countries — India, Pakistan and Afghanistan (Nigeria is the fourth) — where polio remains endemic. As of the last count, 183 children were confirmed to have polio; authorities generally estimate that for every child detected with polio, 200 others may be infected silently and can pass on the disease.

There is so much to say about polio eradication; it is an impossibly complex and expensive task, fraught with cultural complexities and burdened with an endgame of clean-up that will stretch years beyond eradication itself. It is so complex that major public health figures have periodically thrown up their hands and declared eradication unachievable. It is one of the most expensive public health campaigns every attempted, with billions spent so far (and yet chronically short of funds). And because most of the West remains fully vaccinated, polio lurks far below the radar horizon of our concern.

I say all this — which is kind of opening the floodgates for me, because I’ve wanted to talk about polio for years, but it is a damn hard story to sell to editors — because CMAJ, the Canadian Medical Association Journal, has published a great editorial calling for the West to take the threat of polio seriously again.

Although the rates of poliovirus immunization in most of Europe exceed 90%, neither the Ukraine nor Georgia has reached this target. Furthermore, regions of Canada and some European countries have very low rates of vaccine uptake. Infants and toddlers are often not vaccinated on time because of a lack of appreciation of the seriousness of poliomyelitis. Community immunization rates may also be adversely influenced by concerns about vaccine safety, religious beliefs barring vaccination and antivaccine or antigovernment sentiments… There are no cures for poliomyelitis — prevention through vaccination is our best and only defence. We are only one asymptomatic infected traveller away from an outbreak because of low vaccination rates. (MacDonald and Hebert)

Since the year 2000, there have been two recurrences of polio in the US: one in Minnesota, sparked by the vaccine virus, and one in Arizona contracted by a college student traveling abroad. The college student, and the children in the Minnesota community, had never been vaccinated because of religious or cultural exemptions. So our protections are not as impermeable as we think.

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

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

The first identification of NDM-1 was in 2008, in a 59-year-old resident of Sweden who was of South Asian origin and had returned to India for several months. The man was not well — he had long-standing type 2 diabetes and had experienced a number of strokes — and while in India he was hospitalized for an abscess, underwent surgery, developed bedsores and was treated for them as well. He returned to Sweden and was hospitalized there in January 2008, where physicians found him to be suffering from a urinary tract infection caused by a Klebsiella strain carrying this never-seen resistance mechanism.

Last July, the UK’s Health Protection Agency put out a national alert about NDM-1, warning that the novel mechanism had gone from never-seen in 2007, to 4 isolates in 2008, to 18 in the first half of 2009. They were not an outbreak, but represented repeated importations: The isolates were clonally diverse and had been collected at 17 different hospitals. They were, instead, a sign that long-standing two-way population movement between England and South Asia – augmented by elective medical tourism (two patients had gone to India for cosmetic surgery) — was bringing the high rates of antibiotic resistance in India back to a UK medical system that is already challenged by serious infection-control problems.

And now it’s here. The special challenge of NDM-1 (which as today’s finding suggests is on a mobile genetic element that has carried the resistance mechanism between species) is not only that it adds to an accumulating rogues’ gallery of resistance factors that are rapidly making gram-negative bacteria ferociously drug-resistant, but also that there are so few drugs under development for gram-negatives that truly untreatable infections are not far off. The UK clearly is already struggling with attempting to use drugs that are old and toxic, untested against these organisms (and therefore with no agreed-upon dosing), or wrong for the organ systems affected:

Treatment presents major challenges. Most isolates with NDM-1 enzyme are resistant to all standard intravenous antibiotics for treatment of severe infections. Polymyxin is usually active in vitro … but of uncertain clinical efficacy, especially in pneumonia, owing to poor lung penetration. Tigecycline is often active in vitro, but has low serum levels, is unsuitable for urinary infections and, more generally, is of unproven efficacy in severe infections.

The CDC’s alert today asks any clinicians who come up against carbapenem-resistant gram-negatives to ask about contact with India or Pakistan as part of history-taking, and to forward isolates through state public health labs to the the CDC.

Update + fodder: I flipped over to my RSS reader and also discovered this paper posted overnight by Clinical Infectious Diseases, about extended-spectrum beta-lactamases in a particular strain of E. coli (“an important new public health threat”), and this one in Emerging Infectious Diseases, about carbapenem resistance moving between Klebsiella and E. coli.

On Tuesday night, I’ll be discussing antibiotic use in US agriculture at Fair Food Fight Night (a regular event sponsored by the food-policy blog Fair Food Fight) with Thom Petersen of the Minnesota Farmers Union and Fair Food Fight’s proprietor, novelist and food-policy writer Barth Anderson. 7 p.m. at the Cheeky Monkey Deli, 525 Selby, St. Paul.

On Wednesday, I get the chair at the head of the table for Brown Bag Lunch with a Journalist, noon at the East Lake Public Library, 2727 E. Lake St., Minneapolis, sponsored by the awesome Twin Cities Daily Planet. It’s an intimate room, so very crunchy foodstuffs may not be the most excellent choice.

In the all-star annuals of resistant bugs, A. baumanii is an underappreciated player. If people — other than, you know, disease geeks — recognize it, that is because it’s become known in the past few years for its propensity to attack wounded veterans shipped to military hospitals from Iraq and Afghanistan, earning it the nickname “Iraqibacter.” (Important note: Steve Silberman of Wired magazine took an early look at this phenomenon in 2007, in a great story that analyzed the epidemiology of Iraqibacter to show that military infection control, not the environment of Iraq, was to blame for the bug’s rapid emergence.) A. baumanii is a nasty bug, causing not just wound infections but pneumonia, urinary tract infections, meningitis and bacteremia. Even more nasty, it collects resistance factors like baseball cards, and is commonly resistant to at least 4 antibiotic classes. The most resistant strains are susceptible only to the so-toxic-we-put-it-back-on-the-shelf-decades-ago antibiotic colistin.

This is a particular concern because A. baumanii is a Gram-negative bacterium — and while the drug-development pipeline for Gram-positives such as MRSA has slowed practically to a trickle, the one for Gram-negatives has dripped itself dry. As the Infectious Diseases Society of America and Jerome Groopman of the New Yorker highlighted back in 2008, drugs for Gram-negatives are barely on the agenda for the few companies still conducting antibiotic development.

So, the first piece of bad news. In Infection Control and Hospital Epidemiology (ICHE), a team from Brooke Army Medical Center in San Antonio take a look at their incidence of resistant Ab and find it exploding. Between 2001 and 2008, the percentage of A. baumanii isolates that were resistant to at least 3 classes of drugs went from 4% to 55%; of all the isolates, 17% (127) were resistant to at least 4 drug classes, and one was resistant to, well, everything.

How does A. baumanii spread so fast? A second paper in ICHE suggests a reason: The bug seems to do a better job than other resistant pathogens of contaminating the gear and hands of health care workers. A study done at University of Maryland found that when health care workers took care of A. baumanii patients, they ended up with contaminated gowns and gloves 39% of the time, and with contaminated hands (after glove removal) 4.5% of the time. Those are higher rates than for MRSA (18.5% of encounters) or VRE (8.5%).

A review article in Clinical Infectious Diseases reminds us why we should care about this: It examines the drugs to which some strains of A. baumanii are still susceptible, and finds all of them significantly toxic to different organs (kidneys, liver, pancreas, red blood cells, ) at the doses necessary to wipe out the bug.

Which is all troubling by itself. But a paper and editorial also appearing in Clinical Infectious Diseases make the case for A. baumanii as a bigger threat than has been understood. The bug’s recent epidemiology has shown a distinct split, between the highly resistant forms affecting veterans, most of them being treated in the military evacuation chain, and less-resistant forms affecting civilians in hospitals (including in the Brooks data in the paper above). The severe wounds, aggressive treatment and rapid multiple transfers of personnel in the military system inadvertently created an environment that not only put A. baumanii under great selective pressure, but also spread it with startling efficiency.

The paper, reporting data from 4 community hospitals near Detroit, shows that the civilian medical system – that would be the one that most of us live in — has duplicated that churning as well. Between 2003 and 2008, all A. baumanii in their network increased 25%. A. baumanii resistant to the first 2 front-line drugs went from 2% to 33% of isolates. And “pan-resistant” A. baumanii — resistant to all 8 drugs available for it, an essentially untreatable strain — went from nonexistent to 14% of all the isolates that network found.

The effect on the patients was dramatic, of course: The more resistant their strains were, the more likely they were to never go home from the hospital, but (if they did not die there) to be discharged instead to a nursing home, long-term acute care facility, or hospice. But the larger point is that they carried that multiply-resistant strain with them, distributing it throughout the region: Patients came to those 4 hospitals, carrying A. baumanii, from 17 different nursing homes; from the 4 hospitals, carrying A. baumanii, they were transferred out to 28 different nursing homes.

This is a smart analysis, and devastating in its implications. American hospitals do a debatable job right now of handling infection control — but overwhelmingly, they are handling infection control as individual institutions, not as competitors in a local market, and certainly not as members of a geographic region. Yet this data demonstrates clearly that cooperation between hospitals and other healthcare institutions – most of which don’t have hospitals’ infection-control budgets or personnel — is going to be essential if we want to put the brakes on Acinetobacter before it soars in the civilian medical system in the same way it did in the military one.

Problems with drug resistance have moved from the patient’s bedside to threaten global public health. Drug resistance has dramatically increased the costs of fighting tuberculosis (TB) and malaria, has slowed gains against childhood dysentery and pneumonia, and threatens to undermine the push to treat people living with HIV/AIDS effectively. Global health funders and development agencies have cause to worry about whether their investments in access to drugs, and global health programming more broadly, are being undone by the relentless advance of drug resistance.

It calls out a sustained lack of leadership:

Past efforts to energize global action to more comprehensively address drug resistance have been sidetracked by poor timing or over-stretched budgets… In an unfortunate coincidence of timing, a WHO Strategy on Antimicrobial Resistance was launched on September 11, 2001. As a result, the action plan prepared for the Strategy did not get carried out, and over time the interest in cross-cutting drug resistance at WHO withered, even while disease-specific attention grew. For many years, the U.S. Government provided support for research, technical support, surveillance, and policy development on drug resistance in developing countries through an annual budget appropriation to the U.S. Agency for International Development (USAID). That support has become narrowed to programming in only a few areas.

It recommends 4 specific steps:

1. Improve surveillance by collecting and sharing resistance information across networks of laboratories
2. Secure the drug supply chain to ensure quality products and practices
3. Strengthen national drug regulatory authorities in developing countries
4. Catalyze research and innovation to speed the development of resistance-fighting technologies

A policy brief is here and the full report is here.

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.)