Maryn McKenna

Journalist and Author

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. [Read more…]

Once again, flu and bacterial co-infection

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With the H1N1 pandemic trending down, it may seem that the question of how much bacterial co-infection affects the outcome of flu is less important than it was. But though the pandemic is subsiding — for ever, for this season, or just until a third wave, who can say — researchers are just now getting enough good data to be able to make solid observations about what happened during the past 10 months.

Case in point: Writing in the journal Public Library of Science (PLoS) ONE, a team of researchers from Australia has pinpointed the incidence of MRSA co-infection during flu in two hospitals in Perth last summer, which was the Australian winter and the height of their flu season. Of 252 patients admitted for H1N1 infection, 3 were identified during treatment as having MRSA pneumonia. They survived, but two other patients who died were found to have MRSA pneumonia during post-mortem exams. [Read more…]

News round-up!

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As promised, lots to catch up on — so here’s a quick round-up of some great reading that I have been stashing and that you may have missed in the past few weeks.

BBC News: Disinfectants may train bacteria to resist antibiotics
The BBC Health page (bookmark it!) translates a paper from the journal Microbiology on Pseudomonas aeruginosa’s newly recognized ability to pump the active ingredient in disinfectants out of its cells — and then to apply that same ability to the antibiotic Ciprofloxacin, even when it has never been exposed to Cipro before. Money quote: “... Residue from incorrectly diluted disinfectants left on hospital surfaces could promote the growth of antibiotic-resistant bacteria.”

Associated Press:  Solution to killer superbug found in Norway
In the latest installment in a 6-month series, AP writers Martha Mendoza and Margie Mason examine Norway’s success in forcing down rates of hospital MRSA. chiefly by extremely strict control of antibiotics dispensed in hospitals. I have some disagreements with this story; I don’t think they account for how much easier it is to do antibiotic stewardship, as it’s called, in a single-payer health system such as Norway or their second example, England, compared to the extremely complex US system. But I’m very glad to see the AP (and the Nieman Foundation at Harvard, where Mason was a fellow) support public exploration of antibiotic resistance, which I obviously feel gets insufficient attention. (Stay tuned for SUPERBUG’s discussion of one US stewardship program that has worked and may be replicable.)

Time: Should weight factor into antibiotic dosage?
Time.com looks at a provocative new paper in the Lancet that questions whether standard prescribed dosing of antibiotics isn’t really a form of inappropriate use. Money quote: “Dosage according to body mass is standard in anesthetics, pediatrics, oncology and other fields, [but] when it comes to antibiotics and antimicrobials the dosing guidelines are too broad… and may undermine a medications efficacy. …In the face of both widespread obesity and the increasing prevalence of antibiotic-resistance, tailoring dosage for optimal results is increasingly important.”

And finally, new today:
Science Daily: Bacteria Are More Capable of Complex Decision-Making Than Thought
University of Tennessee researchers explore the ability of a bacterium (the soil bacterium Azospirillum brasilense) to sense changes in its environment, process that information and make surprisingly complex decisions in response.

Warning on ST398: Monitor this now

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Drawing your attention: I have a story up tonight at CIDRAP on a new paper by Dr. Jan Kluytmans, a Dutch physician and microbiologist and one of the lead researchers tracking “pig MRSA,” ST398. (All past stories on ST398 here.) It’s a review paper, which is to say that it summarizes key existing findings rather than presenting original research.

Still, it’s important reading because Kluytmans is one of the few scientists who have some history with this bug and understand how quickly and unpredictably it has spread across borders and oceans, from pigs to other livestock, to pig farmers and veterinarians, into health care workers and hospital patients who have no known livestock contact, and now into retail meat in Europe, Canada and the United States.

Take-away: A plea and warning for better surveillance, so that we can track not only the bug’s vast range, but also its evolution as it moves into new ecological niches — including humans who are buying that retail meat and possibly becoming colonized with it as they prep it for cooking in their home kitchens.

To honor fair use (and in hopes you’ll kindly click over to CIDRAP), I won’t quote much, but here’s the walk-off:

Because the novel strain has spread so widely and has already been identified as a cause of hospital outbreaks, it should not be allowed to spread further without surveillance, Kluytmans argues.”It is unlikely that this reservoir will be eradicated easily,” he writes. “Considering the potential implications of the reservoir in food production animals and the widespread presence in meat, the epidemiology of [MRSA] ST398 in humans needs to be monitored carefully.”

The cite is: Kluytmans JAJW. Methicillin-resistant Staphylococcus aureus in food products: cause for concern or case for complacency? Clin Microbiol Infect 2010 Jan;16(1):11-5. The abstract is here.

MRSA in pets – a closer look

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From the research team at the University of Guelph Ontario Veterinary College — who have probably done more than any other group to elucidate MRSA in companion animals — comes a look at MRSA infections in dogs.

In order to get better data, the team used a study model that is much-employed in human epidemiology — and has often been used for MRSA — but under-employed in veterinary medicine: a case-control study matching MRSA infections against MSSA, or drug-sensitive staph. Studies matching MRSA against MSSA have been able, for instance, to show that certain (human) MRSA infections have higher death rates, keep patients in the hospital longer, and cause more healthcare expense.

The Guelph team used the same method to compare the presentation and outcome for 40 MRSA-infected dogs and 80 dogs with MSSA who were seen between 2001 and 2007 in three veterinary hospitals, in Guelph, Philadelphia and Boston. Their verdict:

MRSA is an emerging problem in dogs, and the risk factors for MRSA infections are similar to those in humans, particularly the use of IV catheters and both beta-lactam and fluoroquinolone antibiotics.

The researchers were not able to say whether MRSA in dogs causes more deaths than MSSA, because the infections that were recorded by the hospitals were mostly superficial ones in skin and ears:

Infection types for which death would be a more realistic possible outcome were limited… Comparison of mortality rates between patients with MRSA or MSSA infections would be best performed among on ly those with invasive infections and should be considered for future studies. Here, mortality rate information was obtained retrospectively and only recorded up to the time of discharge. Therefore, whether dogs died from their infections after discharge from the referral hospital, causing an underestimate of deaths, is unknown.

Dr. Scott Weese, senior author of this paper and chief of the Guelph group, has an excellent blog on infections in companion animals, called Worms and Germs. (It’s in the blogroll.) And if you are looking for further information on MRSA in pets, the best resource I know of is the UK-based, but international, Bella Moss Foundation, named for a dog that died of a MRSA infection.

One surgical infection with MRSA: $61,000

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From a multi-state, public-private research team — Duke University, Wayne State University, and the Durham, NC VA — comes a precise and alarming calculation of MRSA’s costs in hospitals: For one post-surgery infection, $61,681.

The group compared the course, costs and final outcome of three matched groups of patients from one tertiary-care center and six community hospitals in one infection-control network run by Duke. The three groups were: patients with a MRSA surgical-site infection; patients with a surgical-site infection (SSI) due to MSSA, drug-sensitive staph; and surgery patients who did not experience infections, matched to the other two groups by hospital, type of procedure, and year when the procedure took place. (This same cohort has been described in an earlier prospective study that looked at risks for MRSA SSIs.) Altogether, there were 150 patients with MRSA SSIs, 128 with MSSA SSIs, and 231 uninfected surgery patients to serve as controls.

Here’s what they found. Patients with post-surgical MRSA infections:

  • stayed in the hospital 23 days longer
  • incurred an average extra cost of $61,681
  • were more likely to be readmitted to the hospital within 90 days
  • were more likely to die before 90 days had passed.

The authors write:

Our study represents the largest study to date of outcomes due to SSI due to MRSA. Our findings confirm that SSIs due to MRSA lead to significant patient suffering and provide quantitative estimates of the staggering costs of these infections. SSI due to MRSA led to a 7-fold increased risk of death, a 35-fold increased risk of hospital readmission, more than 3 weeks of additional hospitalization, and more than $60,000 of additional charges compared to uninfected controls.

For just the patients in this study, the excess costs (across 7 hospitals) totalled $19 million.

This is a highly useful study on several axes. First, remarkably, there has not been agreement over whether and how much of a problem MRSA poses in post-surgical settings, particularly when compared to drug-sensitive staph. This study provides careful, thoughtful, well-documented proof that combating MRSA infection is worthwhile. (NB, MRSA infections did not increase the risk of death relative to MSSA infections, which should remind us both of the often-forgotten virulence of MSSA, and also that MRSA’s perils can lie in extended illness and disability as much or more as in early death.) Second, by putting a very specific number on the cost of a post-surgical MRSA infection, it gives healthcare administrators a benchmark against which they can judge the cost of a prevention program. We’ve all heard complaints that prevention programs can be costly and their benefit is hard to measure in a bottom-line way. With this very specific number, that complaint should no longer be valid.

There’s a final point that is implied in the paper but not called out, so let me call it out on the authors’ behalf. These results are very likely an under-estimate of MRSA’s costs. That’s because, first, the specific procedures the patients underwent were cardiothoracic and orthopedic; those are not the surgical procedures most likely to be followed by a MRSA infection. And second, data collection for this study ceased in 2003, about a year after the first emergence of USA300 and several years before that very successful community strain began its current move into hospitals. However much MRSA was extant in 2003, there is more now.

The cite is: Anderson DJ, Kaye KS, Chen LF, Schmader KE, Choi Y, et al. 2009 Clinical and Financial Outcomes Due to Methicillin Resistant Staphylococcus aureus Surgical Site Infection: A Multi-Center Matched Outcomes Study. PLoS ONE 4(12): e8305. doi:10.1371/journal.pone.0008305

Antibiotics in animals – a warning from the poultry world

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Constant reader Pat Gardiner guided me to an enlightening post at the website of the agricultural magazine World Poultry that questions the routine use of antibiotics in food animals. It’s written by Wiebe van der Sluis, a Netherlands journalist from a farming background, founder of World Poultry and also the magazines Pig Progress and Poultry Processing.

The Netherlands, let’s recall, is the place where MRSA ST398 first emerged, and also the place where that livestock-MRSA strain has caused the most serious human cases and triggered the largest changes in hospital infection-control practices. In the Netherlands, swine farmers and veterinarians are considered serious infection risks because of their exposure to animals, and are pre-emptively isolated when they check into hospitals until they can be checked for MRSA colonization.

Van der Sluis takes seriously the tie between the use of antibiotics in animals and the emergence of MRSA:

Although most of the time MRSA is linked to pig production, it is also related to the veal and poultry industry. The industry, therefore, cannot shrug its shoulders and move on if nothing was wrong. In this case it would be wise to redefine the term prudent use of antibiotics. Time is up for those who use antibiotics to cover up bad management, poor housing conditions or insufficient health care. The standard rule should be: Do not use antibiotics unless there is a serious health issue and no other remedy applies. Veterinary practitioners, who usually authorise producers to use antibiotics, should also take responsibility and prevent unnecessary antibiotic use and the development of antibiotic resistance in animals and humans.

It’s unusual in the US context so hear someone so immersed in agriculture speak so candidly about antibiotic use. It’s refreshing.

Bad news from California: MRSA quadrupled

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Via the Fresno Business Journal and the Torrance Daily Breeze come reports of a new study by California’s Office of Statewide Health Planning and Development: Known MRSA cases in the state’s hospitals increased four-fold between 1999 and 2007, from 13,000 to 52,000 cases per year.

From the Torrance paper:

The good news is that the percentage of people who die of MRSA has decreased, from about 35 percent in 1999 to 24 percent in 2007. The raw number of deaths, however, more than doubled to about 12,500. (Byline: Melissa Evans)

From the Fresno paper (no byline):

Fresno, Kings, Madera and Tulare counties were among 38 counties in California that had 61 to 80% of patients with staph infections.
Only one county, Sierra, fared worse. Eight-one to 100% of patients ended up with staph infections in that county’s hospitals.
In 1999, Kings and Madera counties were in the 0 to 20% range and Fresno and Tulare counties were in the 21 to 40% range.

100%??



NEJM: Antibiotics for pneumonia in H1N1

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The New England Journal of Medicine has been running an open-access blog on H1N1 flu, and they’ve put up a post on when to give antibiotics to prevent secondary bacterial pneumonia, including MRSA pneumonia, in flu patients.

There’s a table of key clinical points to consider, and these important points are made:

For the child or adult admitted to a hospital intensive care unit in respiratory distress, we believe that empirical initial therapy with broad-spectrum antibiotics to include coverage for MRSA, as well as Streptococcus pneumoniae and other common respiratory pathogens, is appropriate.
For the previously healthy child or adult with influenza who requires admission to a community hospital and has features that suggest a secondary pneumonia (Table 1), we would recommend empirical treatment with a drug such as intravenous second- or third-generation cephalosporin, after an effort has been made to prove the association with influenza and to get adequate lower respiratory tract specimens for Gram’s stain and bacterial culture.
If the Gram’s stain suggests the presence of staphylococci or if there is a rapidly progressive or necrotizing pneumonia, an additional antimicrobial agent to cover MRSA is appropriate. …
We do not believe that initial coverage for MRSA is indicated in all patients who are thought to have secondary bacterial pneumonia.

So, to recap:

  • Development of apparent pneumonia in the presence of flu should be met with antibiotics that will treat drug-sensitive bacteria, along with a test to show which bacteria are causing the illness.
  • If staph is present (or the pneumonia appears very serious), then the antibiotics should be upped to one that can control MRSA.
  • But if the pneumonia is serious enough to send a patient straight to the ICU, then drugs that can quell MRSA should be started right away.

For anyone concerned about pneumonia in the aftermath of H1N1, this is worth bookmarking.

Antibiotics – the EU pipeline is empty too

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We’ve talked before about the shrinking number of drugs available to treat MRSA and about the challenges of getting new drugs to market. Well, it’s not just a problem in the United States.

A new report from the European Centre for Disease Prevention and Control (ECDC) and the European Medicines Agency (EMEA) — that’s the CDC and the FDA of the European Union — analyzes the bench-to-market “pipeline” of new drug development in the EU and finds… not good news. Out of 167 antibacterial agents that are somewhere in the pipeline of development, only 15 look likely to improve treatment of resistant organisms over drugs that already exist — and 10 of those 15 are in early-stage trials and will not come to market anytime soon.

That leaves 5 potential new drugs, for an epidemic of antibiotic resistance that, just in the EU, causes 25,000 deaths and $1.5 billion Euros ($2.27 billion) in extra healthcare spending each year.

(Within that epidemic of resistance, by the way, the single most common organism is MRSA.)

It’s worth understanding how the agencies conducted their analysis. When we look for new drugs to treat resistant organisms, we ideally need several things:

  • a formula or molecule that is new (and not just an improved version of an existing one, because if bacteria have developed resistance against the existing one, they have a head start in developing resistance against the new one)
  • a new mechanism or target on the bacterial cell, and not an improved version of an existing one (ditto)
  • evidence that it works in living organisms, and not just in lab dishes (in vivo, not just in vitro)
  • evidence that it can be given internally, not just topically (necessary for addressing the most serious infections)
  • and some indication that it is making its way through the regulatory approval process in time to achieve some practical good.

Here’s what the EU pipeline looks like:

  • 167 agents in process
  • 90 that have shown effectiveness in vivo
  • 66 that are new substances
  • 27 that have a new target or mechanism
  • 15 that can be administered systemically

If you’re wondering whether you should be depressed, the answer is Yes.

… it is unclear if any of these identified agents will ever reach the market, and if they do, they may be indicated for use in a very limited range of infections.

The agencies call for a concerted government effort to turn this around, and ask for quick action because it takes years to get drugs through the pipeline:

…a European and global strategy to address this serious problem is urgently needed, and measures that spur new antibacterial drug development need to be put in place.

This echoes a call that has already been made in this country by the Infectious Diseases Society of America, which has asked for changes in incentives to drug-makers, and has backed what’s known as the STAAR Act (STrategies to Address Antimicrobial Resistance). With this latest EU report — which comes on the heels of a US-ER agreement to work cooperatively on resistance — the IDSA is asking for an international commitment to bringing forth 10 new drugs in 10 years, what they are calling 10 x ’20.

"Pig MRSA" in the EU – long-awaited survey

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It’s not very likely that people will be eating much pork today — OK, maybe some pancetta in the Brussels sprouts — and that’s good, because there’s lots of news today about MRSA in pigs.

(In fact, there’s a ton of news just this week. Make it stop.)

The European Food Safety Authority has published a long-awaited, European Union-wide survey looking for the presence of MRSA in pigs. Here’s the key points: Investigators found MRSA on 1 out of 4 farms where pigs were being raised and in 17 of the 24 EU states. (Two non-member states were included in the analysis.)

Strictly speaking, this is not a survey of MRSA in pigs; the study samples not the pigs themselves, but the dust in pig-raising sheds. The sites were 1,421 breeding farms and 3,176 farms where pig are raised to slaughter age. By far the most common strain was MRSA ST398, though other strains were detected, including some known human strains. The prevalence in various countries went from a low of 0 to as high as 46% of farms. (Highest, in descending order: Spain, Germany, Belgium, Italy, Portugal. The Netherlands, where St398 was first identified, had a prevalence of 12.8%. Countries reporting no MRSA: Bulgaria, Cyprus, Denmark, Estonia, Finland, Hungary, Ireland, Latvia. Lithuania, Luxembourg, Sweden, the United Kingdom, Norway and Switzerland.)

The report closes by recommending comprehensive monitoring of pigs for MRSA, as well as monitoring of poultry and cattle.

About the potential of ST398 crossing to humans, it has this to say:

In humans, colonisation with MRSA ST398 originating from pigs has been identified as an occupational health risk for farmers and veterinarians and their families. Although MRSA ST398 represents only a small proportion of the total number of reports of human MRSA infections in the EU… in some countries with a low prevalence of human MRSA infection, CC398 is a major contributor to the overall MRSA burden.
In most cases, colonisation with MRSA ST398 in humans is not associated with disease, although clinical cases associated with MRSA ST398 have been reported. MRSA ST398 can be introduced into hospitals via colonised farmers and other persons in a region with intensive pig farming. Therefore, MRSA ST398 may add substantially to the MRSA introduced in health care settings. However, it seems that the capacity for dissemination in humans (patient-to-patient transmission) of livestock-origin MRSA, in particular ST398, is lower as compared to hospital-associated MRSA).
… Food may be contaminated by MRSA (including ST398), however there is currently no evidence for increased risk of human colonisation or infection following contact or consumption of food contaminated by ST398 both in the community and in hospital.

Britain’s Soil Association, which pressed for the study to be done, has released a statement quoting the food safety agency warning that the testing method may have underestimated MRSA’s presence on farms, and warning that if ST398 is not yet in England, it is certainly soon to arrive. Germany’s Federal Institute for Risk Assessment also released a statement, admitting that ST398 in German pig stocks is “widespread.”

The report is here, executive summary here, and press release here. All well worth reading.

New MRSA pig strain in China

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Via Emerging Infectious Diseases comes the full version of a piece of research I posted on in September that was presented at the London conference Methicillin-resistant Staphylococci in Animals: Veterinary and Public Health Implications. A new MRSA variant — not ST398 — has been spotted in pigs in China.

Luca Guardabassi and Arshnee Moodley of the University of Copenhagen and Margie O’Donoghue, Jeff Ho, and Maureen Boost of the Hong Kong Polytechnic University report that they found a pig-adapted MRSA strain in 16 of 100 pig carcasses collected at 2 wet markets in Hong Kong. By multi-locus sequence typing, the strain is ST9, previously found in pigs in France; by PFGE, they fall into categories that tend to carry the community-strain cassettes SCCmec IV and V.

Here’s the bad news: This strain possesses resistance factors that resemble human hospital-associated MRSA more than they do ST398.

Twelve isolates displayed a typical multiple resistance pattern, including resistance to chloramphenicol, ciprofloxacin, clindamycin, cotrimoxazole, erythromycin, gentamicin, and tetracyline. The remaining 4 isolates were additionally resistant to fusidic acid. … All isolates were negative for Panton-Valentine leukocidin and susceptible to vancomycin and linezolid.

The further bad news, of course, is that this is being found in Hong Kong, adjacent to China, which is the world’s single largest producer of pork, raising tens of millions of tons of pig meat per year. Most of the pigs sold in Hong Kong come from the Chinese mainland, not from the SAR. Pig surveillance for MRSA in China is practically non-existent (which is not much of a criticism since it does not exist in the United States, either). A human infection with ST9 has already been recorded in Guangzhou, the province adjacent to Hong Kong.

The question, for this strain as for all MRSA strains in pigs, is what is its zoonotic potential? Here again, the news is not good. According to Maureen Boost, who presented this research at the London conference, the isolates were obtained by the researchers from intact heads from butchered pigs; the researchers took the snouts to the lab and and swabbed them there. Pig snout happens to be a desirable meat in China; it is bought in markets, taken home and made into soup. Boiling in broth would probably kill MRSA bacteria — but home butchering of a pig snout could pass the bug on to the human cutting it up, or to that human’s kitchen environment, long before the snout ever got into the pot.

The cite is: Guardabassi L, O’Donoghue M, Moodley A, Ho J, Boost M. Novel lineage methicillin-resistant Staphylococcus aureus, Hong Kong. Emerg Infect Dis. 2009 Dec. DOI: 10.3201/eid1512.090378

 

Community MRSA rates rising, and epidemics converging

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A study published Tuesday in Emerging Infectious Diseases makes me happy, despite its grim import, because it confirms something that I will say in SUPERBUG: Community MRSA strains are moving into hospitals, blurring the lines between the two epidemics.

The study is by researchers at the excellent Extending the Cure project of Resources for the Future, a group that focuses on applying rational economic analysis (think Freakonomics) to the problem of reducing inappropriate antibiotic use. (Here’s a post from last year about their work.)

Briefly, the researchers used a nationally representative, commercial (that is, not federal) database of isolates submitted to clinical microbiology labs, separated out MRSA isolates, divided them into whether they originated from hospitals or outpatient settings (doctors’ offices, ambulatory surgery centers, ERs), and analysed them by resistance profile, which has been a good (thogh not perfect) indicator of whether strains are hospital or community types (HA-MRSA or CA-MRSA). They cut the data several different ways and found:

  • Between 1999 and 2006, the percentage of staph isolates from outpatient settings that were MRSA almost doubled, increasing 10% every year and ending up at 52.9%. Among inpatients, the increase was 25%, from 46.7% to 58.5%.
  • Among outpatients, the proportion of MRSA isolates that were CA-MRSA increased 7-fold, going from 3.6% of all MRSA to 28.2%. Among inpatients, CA-MRSA also increased 7-fold, going from 3.3% of MRSA isolates to 19.8%.
  • Over those 7 years, HA-MRSA did not significantly decrease, indicating that CA-MRSA infections are not replacing HA-MRSA, but adding to the overall epidemic.

So what does this mean? There are a number of significant aspects — let’s say, bad news, good news, bad news.

Bad: CA-MRSA strains are entering hospitals in an undetected manner. That could simply be because patients entering the hospital are colonized by the bug and carry it with them. But it could also be because healthcare staff who move back and forth between outpatient and in-patient settings — say, an ambulatory surgical center and a med-surg ward — could be carrying the bug with them as well.

Good: If they are detected (analyzed genotypically or for drug sensitivity), CA-MRSA strains are less expensive to treat because they are resistant to fewer drugs, and some of the drugs to which they are susceptible are older generics, meaning that they are cheaper.

Very Bad: The entrance of CA-MRSA strains into hospitals risks the trading of resistance factors and genetic determinants of transmissibility and colonization aptitude in a setting where bacteria are under great selective pressure. Several research teams have already seen this: In several parts of the country, CA-MRSA strains have become resistant to multiple drug families.

Is there a response? The work of Extending the Cure focuses on developing incentives that will drive changes in behavior around antibiotic use. These results, lead author Eili Klein told me, call for developing incentives for creating rapid diagnostic tests that will identify not just that a bug is MRSA, but what strain it is, so that it can be treated appropriately and not overtreated.

The results also underline the need for something that is particularly important to me: enhanced, appropriately funded surveillance that will define the true size of the MRSA epidemic and delineate the behavior of the various strains within it. Right now, surveillance is patchy and incomplete, done partially by various CDC initiatives and partially by the major MRSA research teams at academic medical centers. As we’ve discussed, there is no national requirement for surveillance of patients, and very few state requirements; there is no incentive for insurance companies to pay for surveillance, since it benefits public health, not the patient whose treatment the insurance is paying for; and there is a strong disincentive for hospitals to disclose surveillance results, because they will be tarred as dirty or problematic. Yet to know what to do about the MRSA epidemic, we first have to know the size and character of what we are dealing with, and we do not now.

The cite is: Klein E, Smith DL, Laxminarayan R. Community-associated methicillin-resistant Staphylococcus aureus in outpatients, United States, 1999–2006. Emerg Infect Dis. DOI: 10.3201/eid1512.081341

Antibiotic resistance: international news

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Constant readers, we’ve often talked about MRSA and other resistant pathogens as a global problem (cf. these posts for resistance issues in Europe and these for resistance around the world).

But now there has been formal recognition that resistant bacteria respect no borders. On Nov. 3, the US government and the European Union signed an agreement to form a joint task force to investigate and combat antibiotic resistance. From the Joint Declaration, posted on WhiteHouse.gov:

[We therefore agree}… To establish a transatlantic task force on urgent antimicrobial resistance issues focused on appropriate therapeutic use of antimicrobial drugs in the medical and veterinary communities, prevention of both healthcare- and community-associated drug-resistant infections, and strategies for improving the pipeline of new antimicrobial drugs, which could be better addressed by intensified cooperation between us.

You may not have heard much about it here, but in Europe, this declaration was big news. Here’s a story from the Swedish newspaper Arbetarbladet (Sweden currently holds the EU Presidency) and another from the Irish Times. But while it merited barely a blink in the US mainstream media, US nonprofits were deeply involved in the declaration, notably the Infectious Diseases Society of America and the Pew Charitable Trusts:

“Antimicrobial resistance and the lack of new antimicrobial agents to effectively treat resistant infections are problems that no country can deal with alone — they threaten the very foundation of medical care,” said Richard Whitley, MD, FIDSA, president of the Infectious Diseases Society of America (IDSA). “Without effective antimicrobial drugs, modern medical treatments such as operations, transplants, intensive care, cancer treatment and care of premature babies will become very risky if not impossible.” Dr. Whitley joined with Javier Garau, MD, president of European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Shelley A. Hearne, managing director of the Pew Health Group in welcoming the multi-country initiative.
…”Antibiotic resistant bacteria respect no political borders, so we must work together to combat them,” Dr. Hearne said. “Resistance takes a terrible toll on health worldwide and is measured in lives lost, greater suffering and higher health care costs. One way that U.S. leaders can demonstrate their commitment to solving this issue is by immediately joining the EU in banning non-judicious antibiotic uses in food animal production.” (Pew press release)

This fresh focus on the problem of resistance will be sharpened in Europe this week with the celebration of European Antibiotic Awareness Day. (We should be so lucky.) More on that on Wednesday.

It's World Pneumonia Day

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Readers, we talk all the time here about the unexpected and deadly attack of MRSA pneumonia, both on its own and as a sequela of influenza infection. But we should acknowledge that MRSA pneumonia is part of an epidemic of pneumonia, an under-appreciated disease of severe lung inflammation that takes the lives of 2 million children each year around the world.

Today, Nov. 2, has been declared World Pneumonia Day by an enormous coalition of global health organizations that includes UNICEF and Save the Children. (Mis amigos Latinos sabrán que está hoy también Dia de los Muertos. Fitting, no?) From their press release: “Pneumonia takes the lives of more children under 5 than measles, malaria and AIDS combined. The disease takes the life of one child every 15 seconds, and accounts for 20% of all deaths of children under 5 worldwide.”

World Pneumonia Day is being marked by events around the globe (here’s a clickable map) and by the release of a World Health Organization report, the Global Action Plan for Prevention and Control of Pneumonia. The plan has three main goals, aimed at the recourse-poor countries where most pneumonia deaths occur:

  • promote breastfeeding to ensure children’s nutrition and good immune status
  • protect immunity by guaranteeing the distribution in the developing world of the pneumonia vaccines we take for granted in the industrialized world, against Haemophilus influenzae and Strep pneumoniae (pneumococcus)
  • treat children when they need it by making sure that there is adequate, local primary care and — important for our purposes especially — also making sure that antibiotics are used appropriately, but not overused.

The international organization GAVI (formerly known as the Global Alliance for Vaccines and Immunization, now going just by its acronym) has announced plans to immunize 130 million children worldwide against pneumonia and other diseases by 2015.

I want to underline that pneumonia is of interest to us for several reasons: not just because we are concerned for MRSA pneumonia, but also because we are in the midst of the H1N1 pandemic, and as we have talked about before, bacterial infections appear to be playing a role in a significant percentage of the deaths. There is no MRSA vaccine, but there are Hib and pneumo vaccines, which might have prevented some of those deaths. So increasing the administration of pneumonia vaccines could affect the course of this pandemic right now, as well as the fates of children all over the world who have not contracted this flu but will be in danger of bacterial pneumonia in the future.

Get Smart About Antibiotics Week, Oct. 5-11 (now!)

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Every year, the CDC sponsors a week-long observance called Get Smart About Antibiotics Week, intended to bring attention to this issue of antibiotic misuse that all of us here are so concerned about, and to link the efforts of federal and state agencies, nonprofit groups, and anyone else with an interest.

Today marks the start of the 2009 week, and of course it comes as a crucial time: With the H1N1 flu pandemic causing so many people to seek care for upper respiratory illnesses, the possibility of antibiotics being misprescribed for a viral illness is greater than usual.

The homepage for the CDC campaign is here. There is an abundant list of materials, images, campaign strategies and suggestions for framing the conversation, along with graphics (I’ve lifted the one at left from a poster aimed at parents of young children), PSA sound files, and cute little web widgets such as the image at right above (sorry for the poor layout skills, it’s a busy morning).

Since this comes from the CDC and is therefore taxpayer-funded, all of it is open-access. So go, already.

Guest Q&A: Jeanine Thomas and World MRSA Day

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I want to introduce you all to a MRSA campaigner, Jeanine Thomas of Chicago. Jeanine — whose story will be told in SUPERBUG — is the founder of World MRSA Day, a worldwide event of activism and grieving that will take place Friday, Oct. 2. There will be simultaneous observances in the UK, and a candlelight vigil in Salt Lake City that evening.

Tomorrow, Oct. 1, Jeanine will be at Loyola University in Chicago to lead a press conference, commemoration for MRSA victims, and award ceremony for notable MRSA campaigners, and to urge those harmed by MRSA to observe October as MRSA Awareness Month.

In advance of the observances, I asked Jeanine to talk to SUPERBUG about her experience and her activism.

Tell us about your personal experience with MRSA.
I was infected with MRSA after ankle surgery in 2000. I came back to the ER — my incisions were black and oozing a large amount of pus and I was in teribble pain — and was admitted. Three days later my culture came back positive for MRSA. I was not put on the right antibiotic; the infection went into my bloodstream and bone marrow and I went into septic shock and multiple organ failure in the middle of the night. The night nurses were able to pull me back and save me. I had seven more surgeries to save my leg from amputation, spent a month in the hospital, and then was confined to bed on a cocktail of antibiotics for 5 more months. I also contracted C. difficile. I now have a destroyed ankle joint and a severely compromised immune system.

You started a MRSA patients’ group. Tell us about the group and why you did that.
I started MRSA Survivors Network in 2003 to give support, raise awareness and educate others. There was so little out there about this disease. I never wanted anyone else to go through what I had.

You used your experience with MRSA to help pass patients-rights legislation in Illinois. Please talk a little about the bill.
In 2003, I helped push the “Hospital Report Card Act” that then-state senator Obama introduced, to have infection rates reported. As the consumer representative on the state board for the HRCA, I saw that state health officials and doctors did not even want to have MRSA reported as a disease. So I decided I must take action and in 2006 we introduced the “MRSA Screening and Reporting Act.” It passed in 2007, the first in the country, and mandated that all ICU and other at-risk patients be screened for MRSA and infection rates reported. Since then, the Illinois Hospital Association has reported that inpatient infection rates have dropped, but they see many more CA-MRSA cases because of the screening.

How and why did you come up with the idea for World MRSA Day?
In January of 2009 I was thinking of ways to raise awareness and the idea of launching World MRSA Day and a MRSA Awareness Month popped into my head. There are awareness days for every other diisease and as MRSA is pandemic, we need global awareness. I did not know how successful I could be the first year during a recession, but the response was surprising, and I was able to launch the campaigns.

Tell us what you hope will change in the aftermath of having had this worldwide event.
I hope that awareness of MRSA as an epidemic in the US and a pandemic sweeping the globe will be revealed, and that action from the World Health Organization, Department of Health and Human Services, the CDC, governments and health departments will happen. I want all of them to declare MRSA an epidemic. This should have happened years ago, but let’s move forward now. Their inaction has caused this disease to proliferate. I also want the public to be aware of MRSA as we are all in this together and every single person on this planet is at risk. Prevention is key to saving lives.

More evidence of MRSA involvement in H1N1 flu

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When the H1N1 pandemic started at the end of last April, few of the case-patients seemed to have any secondary bacterial infections. This was unusual: In the 3 20th-c pandemics, the only ones for which there are good records, bacterial pneumonias seem to have accounted for a high percentage of illness and death. But H1N1 was unusual in a number of ways, and so health authorities wrote down the lack of bacterial infections as one more quirk of this novel strain.

Comes now the CDC to say that while that may have been the case in the spring, it is not now. In a conference call conducted Monday for doctors, which I covered for CIDRAP, the agency said that out of 77 deaths for which it had excellent autopsy data (a small subset of the deaths so far), 22, or 29%, had some bacterial co-involvement. Among the 22, the leading bacterium was S. pneumoniae (or Pneumococcus), but S. aureus was the second leading cause, with 7 cases, and 5 of those cases were MRSA.

(There is not yet anything online from that call to link to. A transcript is promised, and the CDC reps conducting the call said the data will be out soon in the MMWR. I’ll update when possible.)

In fact, there is an emerging literature on the role of bacterial infections in illness and deaths in this flu, and an emerging consensus that bacterial infections are playing a bigger and more serious role than was thought at first. At the ICAAC meeting two weeks ago (more on that soon), KK Johnson et al of the Women’s and Children’s Hospital of Buffalo, N.Y., along with researchers from two other institutions, described two severe and ultimately fatal infections with H1N1 complicated by community-strain MRSA. The victims were children, a 9-year-old girl and a 15-year-old boy, who arrived at the emergency room several days after being seen for mild flu symptoms. Both children died of necrotizing pneumonia, one 11 days after being hospitalized and one 3 days. Cite (no link available): K.K. Johnson, H. Faden, P. Joshi, J. F. Fasanello, L. J. Hernan, B.P.Fuhrman, R.C.Welliver, J.K. Sharp and J. J. Schentag, “Two Fatal Pediatric Cases of Pandemic H1N1/09 Influenza Complicated by Community-Acquired Methicillin-Resistant Staphylococcus aureus (CA-MRSA),” poster G1-1558a.

Finally, there is one recent paper that is online, and it describes MRSA necrotizing pneumonia plus flu in an adult, not a child. It comes from Hong Kong, from a group that were the first to describe SARS pneumonia and thus have a lot of experience in surfing the early wave sof a pandemic. In this new paper in the Journal of Infection, they describe the death from necrotizing pneumonia of a healthy 42-year-old man who was in the hospital only 48 hours. They believe this is the first H1N1+MRSA death to be recorded in the medical literature, and so they use the opportunity to issue a warning to doctors: If a flu patient arrives with what appears to be secondary pneumonia, drugs that can treat MRSA must be prescribed, or the infection will flourish unchecked and death will result. The cite is: Cheng VCC, et al., Fatal co-infection with swine origin influenza virus A/H1N1 and community-acquired methicillin-resistant Staphylococcus aureus, J Infect (2009), doi:10.1016/j.jinf.2009.08.021.

We’ve been talking since the beginning of this pandemic, and before that, about the unique hazards of MRSA + flu coinfection. (Archive of posts here.) It’s important ot understand that the bacterial pneumonias now being recorded are not only due to MRSA; Pneumococcus is playing a role as well. That is important because, unlike MRSA, we have vaccines against Pneumococcus; in the United States, one vaccine is approved for children and a second related one for adults. With no MRSA vaccine anywhere, and no H1N1 vaccine yet, it is worth considering whether to take a pneumococcal vaccine for additional protection as this pandemic unfolds.

New news on MRSA and animals

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Constant readers, I’ve been behind the Great Firewall of China for two weeks, unable to post. (Apparently Blogger is not always unavailable there, but access has tightened up in advance of the National Day celebrations on Oct. 1.) I left with a file of things to post in my spare time — and so now we’re way behind, with lots to catch up on.

Latest news first, though. A few days ago, an intriguing conference was held in London: Methicillin-resistant Staphylococci in Animals: Veterinary and Public Health Implications. It was co-sponsored by the American Society for Microbiology and the European Society of Clinical Microbiology and Infectious Diseases, and it was the first conference ever convened to examine the behavior in animals of MRSA and other staph species, including our old friend, ST398.

I have the abstracts (which have not otherwise been published), and wow, there was a ton of news.

Here’s the biggest: An investigation by a team at University of Iowa (the same group that first identified ST398 in pigs and pig farmers in the United States) found significant amounts of MRSA in pigs and in human workers on 4 out of 7 conventional farms, but no MRSA on 6 organic farms. MRSA was present — as a colonizing organism, not causing illness — in 23% of the 168 pigs sampled on the conventional farms, and 58% of 45 humans who worked on those farms. “These results suggest a significant number of U.S. swine may be colonized with MRSA, adding to the concern about domestic animal species as a reservoir of this bacterium,” the abstract says. “Furthermore, occupational exposure to these colonized pigs may spread the bacteria from the farm to the community via a high number of colonized swine workers.” (Author: Abby L. Harper, MPH, University of Iowa)

A partial list of the other findings announced:

  • MRSA ST398, which emerged as an animal and human pathogen in the Netherlands, is now causing human colonization and illnesses in other countries. Denmark, which like the Netherlands has a very low background rate of MRSA, has detected 109 cases since 2003, 35 of them with actual infections. Two of the infections were very serious: one pneumonia in a newborn baby, and one septic arthritis in an adult that led to sepsis and multi-organ failure. (J. Larsen, National Centre for Antimicrobials and Infection Control, Denmark)
  • Meanwhile, the Netherlands — which conducts routine screening for MRSA carriage on hospital admission — has seen its annual count of MRSA detections rise from 16 per year between 2002 ad 2006 to 148 per year between 2006 and 2008, with 81% of the current cases due to ST398. (M. Wulf, PAMM Laboratory, the Netherlands) UPDATE: Coilin Nunan of the Soil Association in the UK corrects me (thanks, Coilin!): This study covers only the southeastern pig-farming areas, or about 40% of the MRSA cases in the country.
  • MRSA ST398 spreads from infected to uninfected pigs during transport to slaughterhouses and while being held at slaughterhouses. (E. M. Broens, Wageningen University, the Netherlands)
  • More than 15% of slaughterhouse workers who handle live pigs — but none of those who handled pig carcasses after slaughter — were carrying MRSA 398, and 25% of environmental samples such as dust taken from different parts of slaughterhouses were carrying the organism as well. (B. A. van Cleef, RIVM [National Institute for Public Health and the Environment], the Netherlands)
  • Along with the pig-origin ST398, recognized human strains of MRSA can also colonize pigs, according to a study on one Norwegian farm, but human strains are less successful at persisting in pigs and tend to die out after months. (M. Sunde, National Veterinary Institute, Norway)
  • Animal-origin MRSA is rising in China, the world’s largest producer of pork, but the problematic strain there is ST9, not ST398. That MRSA strain was found on 5 out of 9 farms in Sichuan province in mainland China, and in 33.5% of 260 pigs slaughtered in Hong Kong, where more than 90% of pork comes from the mainland. (J. A. Wagenaar, Central Veterinary Institute, the Netherlands; and M. V. Boost, Hong Kong Polytechnic University)
  • And an intriguing finding for those concerned about humane slaughter methods: Broiler chickens were significantly more likely to carry MRSA, and transmit it to slaughterhouse workers, if they were killed by the traditional method of electrical shock followed by throat-slitting, and less likely to carry or transmit the bug if they were killed by carbon dioxide asphyxiation, which has been held out as a more humane method of killing. (M. N. Mulders, RIVM [National Institute for Public Health and the Environment], the Netherlands)

UPDATE: I’m still a bit jet-lagged and forgot to mention that, of course, we have a long archive of coverage of ST398 and other strains in animals. Find them here.