If there was any lingering doubt about the scope or severity of methicillin-resistant S. aureus (MRSA) in the United States, it was dispelled by two developments last month. The first: a report in the Oct. 17 Journal of the American Medical Association, in which CDC researchers identified 5,287 cases of invasive MRSA infection and 988 deaths in 2005. Based on their data, collected from 9 locations through the CDC's Active Bacterial Core laboratory surveillance system from July 2004 through December 2005, the incidence of invasive MRSA infections in 2005 was 31.8 per 100,000 people -- nearly 3 times as high as the CDC's previous estimates. The researchers projected that 94,360 patients developed invasive MRSA infections in 2005, and that 18,650 of them -- nearly 20% -- died. If the study's projections are correct, the number of deaths annually from MRSA would exceed those from HIV/AIDS, emphysema or homicide. The second development -- presented in more personal rather than statistical terms -- was the news reports of a string of community-associated MRSA infections in schools in several states, including Virginia, West Virginia, Maryland, Georgia and New York. Among the cases, CA-MRSA was deemed the likely cause of death for 2 previously healthy teenagers. The developments prompted sobering assessments by infectious-disease specialists, who used words like "astounding" and "we should be very worried" to characterize the public-health problem.
MRSA goes outpatient
The overall burden of MRSA infections still falls disproportionately on hospitals and nursing homes. The JAMA report -- the first comprehensive, national estimate of invasive MRSA infections -- confirmed that the majority of invasive MRSA infections (85%) are healthcare-associated (originating in inpatient settings). Furthermore, the majority of all MRSA infections, whether community-associated or healthcare-associated, are noninvasive. Still, the report's findings and the highly publicized recent cases make clear that MRSA isn't just a hospital problem anymore. Because the JAMA study tracked only invasive MRSA infections, its estimates are "only the tip of the drug-resistance iceberg," according to the accompanying editorial by Elizabeth Bancroft, MD. There is no single reliable estimate for the prevalence of all MRSA infections nationally, as the CDC does not do comprehensive surveillance of CA-MRSA infections. But an April 2005 study from the CDC's Emerging Infections Program Network, based on surveillance in Baltimore, Atlanta and in 12 Minnesota hospitals, reported that the annual incidence of community-associated MRSA was 25.7 cases per 100,000 in Atlanta and 18.0 per 100,000 in Baltimore. And the rates have undoubtedly increased since then. "MRSA is everywhere. Most doctors know about it, but they may not have known know how big the problem is," says Henry F. Chambers, MD, professor of medicine and chief of infectious diseases at the University of California, San Francisco, who studies the prevalence of and treatments for community-associated MRSA. "The hospital isn't the epicenter of the problem anymore -- now it's the community," adds Robert S. Daum, MD, professor of pediatrics at the University of Chicago, who has done extensive research on the topic. "The whole paradigm has changed, but some doctors are still working under the old paradigm."
CA-MRSA brings new risk factors
While MRSA infections were once limited almost exclusively to patients with recent healthcare exposure, the rise of CA-MRSA has brought new risk factors. The following populations are especially vulnerable to CA-MRSA infections:
- children under 2 years and elderly patients
- athletes, particularly those playing contact sports
- military recruits
- children in daycare centers
- those living in households with poor hygiene and close contact
- black Americans
- Native Americans
- men who have sex with men
Perhaps the most striking feature of CA-MRSA is that it now routinely infects healthy children and adults with no recent healthcare exposure and none of the above-listed risk factors. "This isn't your father's MRSA," says Loren Miller, MD, associate professor of medicine in the Division of Infectious Diseases at Harbor-UCLA Medical Center. "A decade ago, if you had told us [doctors] that a healthy person who hadn't been in the hospital had MRSA, we wouldn't believe you -- it was unheard of. The scary thing is that now anyone can get it."
Heightened vigilance required For physicians, this new era calls for heightened vigilance and a stronger clinical suspicion that any skin or soft-tissue infection (SSTI), or any systemic infection consistent with a staph infection, could be caused by MRSA. Listed below are the clinical conditions most commonly associated with invasive MRSA infection, according to the JAMA report, including each condition's prevalence among all the invasive MRSA infections classified in the study, and the crude mortality rate. Other manifestations of invasive MRSA infection include pyomyositis, empyema, necrotizing fasciitis, and purpura fulminans.
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Most patients with invasive MRSA infections have severe enough symptoms that they will go directly to the emergency department. For patients with suspected MRSA infections who present in outpatient settings, cultures should be taken from appropriate tissues and antibiotic susceptibility testing performed. Physicians should be particularly alert for cases of pneumonia following the flu, as these could be MRSA-caused, and for sudden-onset joint or bone pain -- including a limp in children -- accompanied by fever, as these could be signs of MRSA-caused osteomyelitis. The decision to hospitalize a patient with a MRSA infection will depend on the physician's judgment about the patient's health and the severity of the illness, though detailed guidance on the subject is beyond the scope of this article.
Biggest impact on management of SSTIs In terms of day-to-day clinical practice, CA-MRSA has the biggest implications for management of skin and soft-tissue infections, since they constitute 80-90% of all CA-MRSA infections. SSTIs are the 3rd-most-common type of infection seen in primary-care practice, after upper respiratory infections and urinary tract infections. In 2003, there were close to 12 million outpatient visits for skin infections typical of S. aureus, according to a 2006 study by CDC researchers. According to another 2006 study, from the EMERGEncy ID Net surveillance network, MRSA was the most common identifiable cause of skin and soft-tissue infections among patients presenting to emergency departments in 11 U.S. cities, representing 60% of all cases in the study. Based on these findings, there are several million cases of CA-MRSA-caused skin and soft-tissue infections each year in the United States. "The take-home message is that that skin infections nowadays should be assumed to be MRSA until proven otherwise," Miller says. "I've told this to primary-care physicians and a lot of them have had trouble believing it, because it's such a radical change from what they're used to treating."
