MRSA and H1N1 "swine" flu - still not a lot of evidence

Hello again, constant readers. It's busy out there.

The CDC said Wednesday that new infections with the novel H1N1 virus (Formerly Known As Swine Flu) may be trending down. Nevertheless, there is still a lot of rumor and speculation out there regarding what role MRSA pneumonia may have played in serious cases.

The CDC commented on this in its May 19th press briefing:

Q: Is anybody looking for, and is anybody finding any evidence of, coinfection with MRSA?
A: We′re very interested in that question. As you know, the seasonal influenza in children we′ve been tracking pediatric deaths, and we have seen MRSA among seasonal flu cases in children at a higher rate than we had expected. MRSA is a big problem in the United States right now in terms of the community associated resistant staff or its infections. So far as we′ve been looking at the patients with the H1N1 virus, we don′t have evidence of coinfection. Not everybody has been tested for bacterial infections. But among the ones that have been tested, we aren′t seeing an important role for bacterial coinfection, including MRSA. I think this is an important issue for us to continue to follow, whether bacterial co-infections or bacterial pneumonias following the illness are featured. It′s a feature we′re interested in but haven′t seen this turn up yet.

We've talked a number of times before here about MRSA necrotizing pneumonia, and about the apparent importance of secondary bacterial infections to the death rates in prior flu pandemics.

But for anyone who needs a refresher, I recommend an excellent new paper by researchers at Emory University, published last week in the journal Lancet Infectious Diseases. It recounts the clinical course of two people who were treated at Atlanta's Grady Memorial Hospital for MRSA pneumonia. Both were adults, and both survived, but their courses were complicated; the clinicians note that they did not improve until they were given additional antibiotics aimed at shutting down MRSA's toxinproduction, a step that is not universally considered by doctors treating a MRSA patient.

The cite is: Hidron, AI et al. Emergence of community-acquired methicillin-resistant Staphylococcus aureus strain USA300 as a cause of necrotising community-acquired pneumonia. Lancet Infect Dis. 2009 Jun;9(6):384-92. The abstract is here.

ST398 found again — in Italy

There's a letter in the upcoming issue of Emerging Infectious Diseases (hat tip Pat Gardiner) alerting the medical community that "pig MRSA" ST398 has been found in Italy, adding t the steadily enlarging list of countries where this strain has been identified.

(NB: Because most of these surveys are one-offs, we don't yet know whether ST398 is truly expanding its range, or has always been there, but no one looked until now.)

Angelo Pan and colleagues of the Cremona Hospital and other institutions report that a pig-farm worker was discovered to have a severe pyomyositis (abscess buried in muscle):

The case-patient was a 58-year-old man admitted to a surgical department in Cremona, Italy, on July 30, 2007, because of a 1-week history of fever and intense pain in his right buttock. He worked on a pig farm, was obese, consumed high volumes of wine (1.5 L/day), was taking medication for hypertension, and had not had recent (<5 years) contact with the healthcare system. At the time of hospital admission, he was moderately ill, oriented, and cooperative. His right buttock was extremely painful. He reported neither recent trauma nor anything that would explain infection. ...
Based on clinical and magnetic resonance imaging data, the diagnosis was cellulitis, pyomyositis, and pelvic multiloculated abscess of the buttock. A needle aspiration of the abscess, guided by computed tomography, was performed. Because of persistent fever (38.5°C), oral ciprofloxacin was added to the patient's treatment regimen on day 3. Blood and abscess cultures yielded MRSA that was sensitive to glycopeptides, rifampin, linezolid, gentamicin, and mupirocin and resistant to co-trimoxazole, macrolides, clindamycin, and fluoroquinolones. After treatment was switched to vancomycin plus rifampin, the patient's general condition improved; he was discharged from the hospital after 24 days.

An investigation was launched, and the results were intriguing:

Two fellow workers were colonized with S. aureus, 1 with methicillin-sensitive S. aureus (MSSA) and the other with MRSA. The pig farm, a farrow-to-finish production farm with 3,500 pigs, was screened for MRSA ... Dust swabs were taken from 5 areas of the farm; 7 MRSA isolates were detected.
The isolate from the patient belonged to spa type t899, was ST398, carried an SCCmec type IVa cassette, and was PVL negative. The isolate from the MRSA-colonized worker was a t108 strain carrying SCCmec type V. The isolate from the MSSA-colonized worker was identified as t899. The dust swabs yielded 7 isolates: 2 belonged to t899 and carried SCCmec IVa; 5 belonged to t108 and carryied SCCmec V. The isolates obtained from the patient, farrowing area 7, and gestation area 1 were indistinguishable (i.e., same spa type, SCCmec type, and ST profile; Table), thus confirming the animal origin of transmission.

So, we have:

• A high rate of carriage on the farm (3 of 4 workers with ST398, either MR or MS)
• A strain-type that is both MRSA and MSSA, suggesting that in its drug-sensitive state it can acquire resistance factors rather easily
• A PVL-negative strain that nevertheless causes invasive disease requiring more than 3 weeks hospitalization

None of these are good news.

The authors very sensibly call for more public-health attention to this strain, which — we have contended before — is long overdue:

...attention should be given to the emergence of MRSA strains among animals, and continuous surveillance in humans should monitor the extent of disease from MRSA ST398, especially in areas of intensive animal farming. Collaboration between infectious disease specialists, microbiologists, and epidemiologists, on both the human and the veterinary sides, should be strengthened and readied for appropriate action whenever complex, zoonotic, public health issues occur.

The cite is: Pan A, Battisti A, Zoncada A, Bernieri F, Boldini M, Franco A, et al. Community-acquired methicillin-resistant Staphylococcus aureus ST398 infection, Italy [letter]. Emerg Infect Dis [serial on the Internet]. 2009 May. DOI: 10.3201/eid1505.081417

MRSA research at Society for Healthcare Epidemiology of America meeting

As promised, a round-up of some of the research presented at the annual meeting of the Society for Healthcare Epidemiology of America (SHEA), held last weekend in San Diego. (Disclosure: I was on the faculty for the meeting; in exchange for co-hosting a session, SHEA will be reimbursing me for airfare and hotel. I wasn't otherwise paid, though.) There were 143 presentations on MRSA; here are a few.

I'm going to put in links to the online abstracts — I have SHEA's permission to do this — but I can't guarantee how long they will stay up. For those outside the science world, what happens at these meetings is that research is presented, in slide/PowerPoint sessions or in a poster, as a preliminary step to getting it published in a journal. Once a journal expresses interest, a cone of silence descends, the researchers are asked not to discuss the research until the paper is printed, and the abstract will probably be taken offline.

So, efforts to control hospital MRSA are showing some success:

• Invasive hospital-onset MRSA infections declined 16% from 2005 to 2007, and hospital-associated community-onset infections went down almost 9% — probably, though not provably, because of in-hospital prevention campaigns. (A. Kallen et al.)
• MRSA control in a small ICU (22 beds) leads to MRSA reductions throughout a 270-bed Montana community hospital. (P.J. Chang et al.)

But those efforts face some complexities:

• Swabbing the nose and culturing the swab, the classic test to check for MRSA colonization, misses 30% of positive patients because they are colonized in the groin or armpit. (C. Crnich et al.)
• If a hospital does not use AST (active surveillance and testing, or "search and destroy") it may seriously underestimate its MRSA incidence, though it may be able to detect general trends. (P.J. Chang et al.)
• But medical centers of similar size and situation that did v. did not use AST achieved similar reductions in hospital infections. (K. Kirkland et al.)
  

Community strains are moving into hospitals:

• Most of the cases of MRSA colonization identified in a Delaware healthcare system were found so soon after admission that they must have begun out in the community and were not due to hospital transmission. (K. Riches et al.)
• The proportion of MRSA bloodstream infections caused by community strains (proven microbioogically) doubled at Chicago's main public hospital between 2000 and 2007. (K. Popovich et al.)
• One out of every 7 ICU cases of MRSA in Atlanta's major public hospital involved a community strain. (H. Blumberg et al.)
• The number of MRSA infections brought to a Chicago-area ER increased 566% between 2002 and 2007, and was seasonally clustered (D. Buchapalli et al.)

And at the same time, hospital strains are moving out into the community:

• Hospital-associated community-onset cases accounted for 58% of all invasive MRSA in the US between 2005 and 2007, with patients undergoing dialysis or those who have been in long-term care the most vulnerable. (J. Duffy et al.)

New newspaper series on HA-MRSA

The Seattle Times this morning launched an three-day investigative project on incidence of HA-MRSA in Washington State that is worth reading.

As readers here already know, MRSA is not a reportable disease, and there are no diagnosis codes that directly correspond to MSRA that make infection or death easily trackable through hospital records or death certificates. The Times' team came up with some innovative data-drilling techniques and apparently did a massive amount of number-crunching to come up with the incidence estimates that underpin their reporting. They use those to challenge hospitals' reluctance to undertake surveillance and treatment that would wipe out MRSA on colonized patients and thus reduce the likelihood of MRSA infecting those patients or spreading to others via healthcare workers who neglect infection control. (NB, Michael Berens, the series' co-author, did a huge project on nosocomial infections when he was at the Chicago Tribune a number of years ago.)

I am puzzled by one thing I am seeing on the story's web page — one of the items in the break-out box that sums the story up very quickly to attract eyeballs to it. It says: "About 85 percent of people infected with MRSA get the germ at a hospital or other health-care facility. " That figure doesn't make sense to me; it sounds as though it is a mis-translation of the CDC finding a year ago (in the Klevens JAMA paper) that approximately 85% of invasive cases of MRSA have hospital-associated risk factors. Constant readers will remember that estimate has been challenged by researchers on community MRSA, who believe that CA-MRSA accounts for a much larger proportion of the current epidemic than has been acknowledged, and think that the wide spread of the community strain is the actual driver of the overall epidemic. I can't see where in the text the Times team has done the math to support that assertion, so if anyone else spots it, or knows the reference it comes from, please let me know.

UK grapples with community MRSA

Regular readers in the US will have noticed that the MRSA situation here is quite different from Europe. In the UK, for instance, hospital MRSA has been an enormous scandal, but community MRSA — both skin and soft-tissue infections, and fatal invasive infections such as necrotizing pneumonia — has been much less of a concern.

That appears to be changing. Today, the BBC's Radio 4 broadcast a documentary, "The Bug That Can Kill Within Hours," that focuses on fears of a dramatic rise in the UK of cases of serious community MRSA. According to the UK's Health Protection Agency, lab-confirmed cases of community MRSA strains hit 1,361 in 2007, three times what they were the year before. (Soundfile here, starts automatically.)

The documentary refers to CA-MRSA as "PVL-MRSA," a recognition of the fact that most of the community strains produce the toxin Panton-Valentine leukocidin, or PVL. (PVL is known to destroy white blood cells, but whether it is responsible for the virulence of CA-MRSA is a hotly disputed question in MRSA research.) Aside from the difference in terminology, any of the statements from the accompanying BBC website story could have been said here any time in the past 10 years:

Professor Brian Duerdan, the Inspector of Infection Control at the Department of Health, admits however that many aspects of this virulent bug are a mystery.
"We do know that it spreads in the community amongst close contacts, families, people who share the same sporting events. But we still need to know a lot more about its exact prevalence in the community," he said.

People who have been tracking the relentless expansion of CA-MRSA, espeially its dominant clone USA 300, are likely to find some of the statements in the documentary both troubling and poignant. The UK is beginning to deal with some of the wuestiosn that the US has struggled with: how much surveillance to do, how to spend scarce research dollars, and what the consequences may be if CA-MRSA is not focused on now.

Hugh Pennington, Emeritus Professor at the University of Aberdeen, and President of MRSA Action, told the BBC that the HPA lacks the resources to keep proper surveillance on outbreaks of infection from this strain of bugs.
"The scandal here is that we know what to do, the technology's there to spot these things as they are appearing and we know how to react to them.
"It would be quite wrong if we allow these things to develop and of course history tells us that it we do neglect these bugs, we neglect them at our peril."

Indeed.

Emergency medicine in crisis (important for MRSA also)

Constant readers may remember that, before I began this MRSA project, I spent a year as a media fellow with the Henry J. Kaiser Family Foundation, researching overcrowding and stress in emergency rooms. (Some stories from that project here, here and here.)

So I was particularly interested in and saddened by a post on the excellent blog Health Beat (now in the blogroll!) that explores in good detail why emergency rooms are so crowded and especially what the loss of experienced emergency nurses is doing to the quality of emergency care.

Why is this important for MRSA? Well, if you or a family member is struck with what looks like one of the dramatic presentations of MRSA — bone infection, rapidly progressing pneumonia, even a serious skin infection — where are you likely to take that problem? Yes, to the ER. Even if you have insurance; an increasing number of studies are pointing out that the vast majority of people waiting for care are not the uninsured or undocumented, but insured people who can't get care from their regular doctors.

So be prepared.

MRSA colonization - the long-term risk

One of the ongoing puzzles of MRSA's behavior is the significance of colonization, that situation of MRSA living on the skin — or in the nostrils or other locations close to the body's external surface — without causing illness. It's not known how frequently MRSA colonization occurs, for one thing: The long-standing estimate of 1% of the population has been challenged by a number of recent studies.

Another persistent question has been whether the risk of illness and death changes as colonization continues. It has been established that up to one-third of newly colonized carriers will become seriously ill within a year of their acquiring the bug (Huang, SS. et al., Society for Healthcare Epidemiology of America Annual Meeting 2006, abstract 157 - not online that I can find)— but what happens beyond that? Does the risk of illness persist or decrease?

In Clinical Infectious Diseases, the same team that defined the risks of recent colonization report that there are significant risks to long-term carriage as well: 27% of invasive illness in the second year and 16% thereafter, based on a review of 281 patients who were followed for at least one and up to four years at Brigham & Women's Hospital, a Harvard Medical School teaching hospital. These patients become very ill, and in addition use a significant amount of health-care resources:

At our hospital, there are 2–3 times as many hospital admissions involving patients previously known to harbor MRSA than there are hospital admissions of individuals who are newly detected as MRSA carriers each year.

What is the precipitating event that tips MRSA carriage over into MRSA illness? It may be health care. In other words, the long-term carriers do not become ill with MRSA disease and then come to the hospital. Instead, they come to the hospital for some other reason, and the surgery, IV placement, dialysis etc. they receive allows their MRSA strain to slip past the protective barrier of their skin and begin an invasive infection.

We submit that these high risks of MRSA infection among culture-positive prevalent carriers are not only preferentially detected because of hospitalization but may, in fact, be incurred because of the device-related, wound-related, and immunologic declines associated with a current illness.

This raises the question of whether any admitted patient found to be colonized should undergo the routine known as decolonization before any other procedures are performed — and whether institutions and insurance companies will be open to the additional hospital days and drug costs that will represent.

The cite is: Datta, R. and Huang, SS. Risk of Infection and Death due to Methicillin-Resistant Staphylococcus aureus in Long-Term Carriers. Clinical Infectious Diseases. 2008 47:176-81.

A staph vaccine: How much would it help?

One more post on research from the meeting of the Society for Healthcare Epidemiology of America: Many MRSA researchers believe that the only way to truly control the pathogen — especially out in the community — will be through a vaccine.

Lay aside for the moment how problematic introducing a new vaccine can be these days, since the cost issues, along with shifts in the public's willingness to accept new vaccines, are ferocious hurdles. And lay aside also the difficulties that pharma companies have already faced in attempting to develop a staph vaccine.

But if such a vaccine were achieved, how many people could it help? Researchers from the Centers for Disease Control and Prevention attempted to answer that question in research presented at SHEA.

Background assumptions, part 1: The number of invasive MRSA infections now tops an estimated 105,000/year (a recalculation of the 94,000/year estimate from last October); more than 40% of invasive infections occur in those over 65; more than 50% are associated with a recent hospitalization; and 15% of MRSA infections recur at least once. And background assumptions part 2: A vaccine would have an efficacy rate of 40-75%, and an acceptance rate similar to flu-vaccine uptake: 20-50% among those 15-44, 35-70% among those 45-64, and 50-70% among those 65 and older.

Given those assumptions, Cynthia Lucero, MD and colleague predicted:

• If given only to those 65 and older, a vaccine would prevent from 12,720 to 32,270 invasive MRSA infections;
• If given to those over 65 and also those 15 and older who have already had an invasive infection, a vaccine would prevent 14,130 to 38,310 invasive MRSA infections;
• And if given to those over 65 and also anyone over 15 who is being discharged from a hospital, a vaccine would prevent from 17,240 to 49,940 invasive MRSA infections.

The best bang for the buck, the agency said, would be the middle strategy: It would prevent from 660 to 1,170 cases for every million doses of vaccine used. And since the vaccine would also cover methicillin-sensitive staph, it would likely prevent an equal number of serious MSSA cases as well.

The CDC is not by law allowed to lobby — or even, for the most part, allowed to offer a professional opinion unless Congress has asked it to do so. So these numbers are purely a thought experiment. But they're also a strong argument for the broad usefulness of a staph vaccine if one could be achieved.

"Leaky" hospitals redux: When HA is CA

The CDC work below and several other papers published recently attribute a good proportion of CA-MRSA to hospital strains that have left the institution in a colonized patient and sickened that patient at some point post-discharge. But several papers presented at the annual meeting of the Society for Healthcare Epidemiology of America underline that MRSA traffic is two-way: Community strains can enter the hospital and cause outbreaks there as well.

Cases in point:

• Between 2004 and 2007, the Medical University of South Carolina in Charleston identified 272 hospital-acquired infections that were caused by USA300, the dominant CA-MRSA clone. That's 21.3% of all HAIs in that hospital in those years. (Lead author K Hardman)
• At Johns Hopkins University in Baltimore, nine out of 757 patients admitted to the pediatric intensive care unit became colonized or infected with MRSA 48 hours or longer after they were admitted. Six of the nine were found to have USA300, and one developed invasive MRSA disease. (Lead author AM Milstone, MD)
• And at New York-Presbyterian Hospital, a 5-day-old baby who had not yet left the hospital became infected with USA300, the first casualty in a complex outbreak involving several MRSA strains that eventually comprised 21 infants (12 colonized and nine with infection; 14 of the 21 with USA300) and 10 mothers (five infected Caesarean incisions, two with breast abscesses, two with mastitis and one with a skin infection; six out of 10 with USA300). (Lead author Jean-Marie Cannon, RN)
  

New news on invasive MRSA rates: headed down?

I am at the annual conference of the Society for Healthcare Epidemiology of America, where authentic news was released Sunday, in a very quiet way.

Last fall, a team of authors from the Centers for Disease Control and Prevention published a paper in the Journal of the American Medical Association that for the first time estimated the burden of invasive MRSA disease in the United States. Using data from the Active Bacterial Core Surveillance System — which comprises nine sites around the country and takes in about 14 million people — the team estimated that the annual incidence of invasive MRSA in the US is 94,360 cases, including 18,650 deaths. In an important (and to some researchers controversial) contribution to defining MRSA disease, the team also estimated that 13.7% of the invasive infections were community-associated, 26.6% were hospital-acquired (which they called "hospital-onset"), and by far the largest proportion, 58.4%, were a new category they called "hospital-acquired, community-onset" — the patients acquired the bug while in the hospital, but did not develop disease until after they were discharged. (Cite: Klevens RM et al., Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA, 2007 Oct 17;298(15):1763-71. Full text here.)

The important event Sunday was the first release of an update to that data, adding a second year of analysis. The news: Hospital-acquired infections declined in a small but significant way, by 8.1% — though community-associated and community-onset cases did not change.

The original paper analyzed data from July 20o4, when the ABC system expanded from a pilot program to the full nine sites, through December 2005. The update both reslices that data and adds fresh numbers: It compares calendar year 2005 to calendar year 2006. It finds small downward trends as well in community-onset and community-associated cases, but judges those trends not statistically significant. But Dr. Scott Fridkin, who presented these numbers and was an author on last fall's paper, said the dip in nosocomial cases is statistically robust and a true decline, though adding a third year of data will make the analysis yet more solid.

The decline is intriguing and raises the question: If infection-control interventions in hospitals are pushing down rates of hospital-acquired cases, then why are "hospital-acquired/community-onset" cases not down as well?

As usual with conference papers, the abstract is not online; the CDC says it will be posted today and I'll update when they do. (NB: The data presented at the conference is actually an update of the data in the abstract, and so when the abstract goes up the numbers will not match; the decline presented today is a few percentage points smaller, due to a re-cut of the data after the abstract was written.)

UPDATE 8 April 08: The abstract is now online here.

(Financial disclosure: I am at SHEA for book research and to participate in a session on interactions between researchers and media. In exchange for that session, the organization paid my airfare.)