Emergence of MRSA USA300 Clone

Abstract & Commentary

By Robert Muder, MD, Hospital Epidemiologist, Pittsburgh VA Medical Center, is Associate Editor for Infectious Disease Alert.

Dr. Muder does research for Aventis and Pharmacia.

Synopsis: Active, prospective laboratory-based surveillance of community-onset staphylococcal skin and soft-tissue infections at an Atlanta hospital found that 72% were caused by MRSA. Of these, 90% were due to the MRSA USA300 clone, which is genetically distinct from the predominant hospital associated MRSA clonal types.

Source: King MD, et al. Emergence of Community-Acquired Methicillin-Resistant Staphylococcus aureus USA300 Clone as the Predominant Cause of Skin and Soft-Tissue Infections. Ann Intern Med. 2006:144:309-317.

King and colleagues conducted prospective, laboratory-based surveillance of all community-onset staphylococcal skin and soft-tissue infections presenting to Grady Memorial Hospital and its affiliated clinics for a 3.5-month period in 2003. They included all infections with Staphylococcus aureus isolated at an outpatient visit or within 72 hours of admission. A community-acquired MRSA isolate was defined as one that demonstrated the USA300 or USA400 pulsed field type or, if the isolate was unavailable for typing, demonstrated resistance only to β-lactam antibiotics and erythromycin. They identified 389 episodes, of which 279 (72%) were caused by MRSA. Two hundred forty-four (87%) isolates causing MRSA infection were community-acquired, using the stated definition. Of the 159 isolates that were identified as community acquired by pulsed-field typing, 157 (99%) were USA300; the remaining 2 were USA400. Multivariate analysis of risk factors for community-acquired MRSA identified black race, female sex, and absence of hospitalization within the previous 6 months as significant.


Until the late 1990s, MRSA was primarily identified as a cause of nosocomial infection. However, reports of localized outbreaks of MRSA among persons without exposure to hospital began to appear. These occurred among groups of otherwise healthy people who had close physical contact with one another. These included children in day care, athletes, prisoners, military personnel, and Native Americans living on reservations. These outbreaks were typically caused by a single clonal strain of MRSA belonging to one of 2 clonal types, USA300 or USA400.1 These strains are phenotypically and genetically distinct from existing hospital associated. Community-acquired strains are usually susceptible to multiple antimicrobials except for β-lactams and erythromycin. Methicillin resistance is caused by a distinct methicillin resistance gene cassette, SCCmecIV, previously not found in hospital strains. In addition, many community-acquired strains carry the Panton-Valentine leukocidin (PVL), an exotoxin that is highly toxic to leukocytes and other cells. Its precise pathogenic significance is uncertain, but presence of PVL is associated with severe skin and soft-tissue infections and necrotizing pneumonia in otherwise healthy adults and children. PVL is rarely found in hospital strains of MRSA.

The report that the majority of community-onset staphylococcal infections encountered at a single facility were due to community-acquired strains of MRSA (USA300) is highly disturbing. The significance of this report for the rest of the United States is not yet entirely clear, as it came from a single institution that primarily serves a poor urban population. Although there is no single source of data on the prevalence of community-acquired MRSA in the United States, a review of the literature indicates that it is widespread. A population-based study performed by the CDC in 2001-2002 found that the incidence of community-onset MRSA infections was 25.7/100,000 population in Atlanta and 18.0/100,000 in Baltimore.2 At a single hospital in Houston, 66% of all community-onset infections leading to hospitalization of children were caused by MRSA.3 Eighty percent were skin or soft-tissue infections, 11% were pneumonia, and 6% were bone and joint infections. Fourteen isolates were subjected to pulsed field typing, and all were USA300.

How widespread USA300 is in the United States is unclear. In the same issue of the Annals of Internal Medicine, Graham and colleagues reported the results of a US population-based study of nasal carriage of S. aureus involving nearly 10,000 participants.3 Only 0.84% of patients were colonized with MRSA, and half of the isolates were SCCmecIV strains. This suggests that USA300 MRSA strains are not widespread. That conclusion may be premature, however. The epidemiology of USA300 outbreaks suggests that close contact with an infected person, rather than nasal carriage, is the immediate precursor to infection. Surveys of nasal carriage might dramatically underestimate the contribution of USA300 MRSA to cases of staphylococcal infection.

β-lactam antibiotics have been the drug of choice for community-acquired staphylococcal infections since the discovery of penicillin, but it's clear that this is no longer the case in regions in which community-acquired MRSA has taken hold. For relatively uncomplicated skin and soft-tissue abscesses, incision and drainage alone may be adequate. Purely empiric antimicrobial therapy of suspected staphylococcal soft-tissue infections is not appropriate; therapy should definitely be guided by culture and susceptibility testing. Optimal therapy is uncertain, as there are no randomized trials of therapy. Although most USA300 strains are susceptible to clindamycin by in vitro testing, approximately 10% have inducible clindamycin resistance that is not detected by standard disk diffusion or microtiter assays. Trimethoprim/sulfamethoxazole or minocycline may be reasonable choices as oral therapy for outpatients. Oral linezolid would likely be effective, but it is fairly expensive. Based on a poor track record in treating MRSA infections, quinolones are best avoided regardless of susceptibility testing.


  1. Rybak MJ, LaPlante KL. Community-Associated Methicillin-Resistant Staphylococcus aureus: A Review. Pharmacotherapy. 2005;25:74-85.
  2. Fridkin SK, et al. Methicillin-Resistant Staphylococcus aureus Disease in Three Communities. N Engl J Med. 2005;352:1436-1444. Erratum in: N Engl J Med. 2005;352:2362.
  3. Graham PL, et al. A US Population-Based Survey of Staphylococcus aureus Colonization. Ann Intern Med. 2006;144:318-325.