Background: Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections have been increasing since the 1990s, when four fatal cases were reported in Native American children. Although community-acquired MRSA occurs worldwide, the problem is of special concern in the United States where it accounts for up to 60 to 75 percent of all reported S. aureus infections. Most of these infections are relatively minor soft-tissue and skin infections, with or without purulence. However, they can also cause more serious infections, including pneumonia, pelvic osteomyelitis, septic thrombophlebitis, and necrotizing fasciitis.
Because community-acquired MRSA is resistant to traditional S. aureus treatments such as antistaphylococcal penicillins (e.g., dicloxacillin) and cephalosporins (e.g., cephalexin [Keflex], cefadroxil [formerly Duricef]), U.S. physicians have prescribed a variety of other antibiotics to treat these infections (see accompanying table). The National Institutes of Health has initiated several clinical trials examining the effectiveness of alternative antibiotics, but there are currently no randomized prospective trials of agents used to treat skin and soft-tissue infections from community-acquired MRSA. Until such data are complete, only anecdotal and retrospective data are available to guide treatment recommendations.
Recommendations: Community-acquired MRSA skin and soft-tissue infections, such as pustules, furuncles, and small abscesses, usually respond to incision and drainage. This may be sufficient to treat small, uncomplicated purulent lesions, although clear evidence is lacking. More complicated lesions (i.e., those with surrounding cellulitis or no drainable foci) are usually treated with antimicrobial agents. Patients with fever or other systemic symptoms are also usually treated with antimicrobial agents.
Trimethoprim/sulfamethoxazole (TMP/SMX; Bactrim, Septra) is the agent most commonly used to treat adults with community-acquired MRSA infections in the United States. In vitro evidence suggests TMP/SMX has greater bactericidal activity against community-acquired MRSA than linezolid (Zyvox), rifampin (Rifadin), clindamycin (Cleocin), or minocycline (Minocin). A retrospective review showed TMP/SMX to be effective for skin and soft-tissue infections. However, because TMP/SMX may inadequately treat group A streptococci, combining it with another antimicrobial may be preferred when the specific organism is unknown. The ideal dosage of TMP/SMX for treating community-acquired MRSA is unknown, although one small study reported higher success rates when two double-strength pills were given twice daily, compared with one pill twice daily.
Clindamycin is widely used in children for community-acquired MRSA skin and soft-tissue infections, and is anecdotally reported to be effective. Resistance to clindamycin varies widely, from less than 12 percent in San Francisco, Calif., to as much as 76 percent in Boston, Mass. Routine microbiologic testing may falsely report community-acquired MRSA isolates to be sensitive to clindamycin because of the inducible expression of the MLSB gene, which methylates the binding site and renders the organism resistant. This can be avoided by ordering tests, such as the double-disk D-test, to detect this type of inducible resistance.
Long-acting tetracyclines (i.e., minocycline and doxycycline [Vibramycin]) were successfully used in Japan for MRSA infections before the availability of vancomycin. A clinical review found response rates between 80 to 100 percent with these agents, and one small prospective trial reported a 100 percent response rate in doxycycline-treated patients after incision and drainage of MRSA abscesses. However, resistance of community-acquired MRSA to these agents has been reported on both coasts in the United States.
Rifampin has excellent in vitro activity against community-acquired MRSA, but it cannot be used by itself because of rapid development of resistance, which can occur during active treatment. Combining rifampin with TMP/SMX, or fusidic acid where available, may be more effective than using either agent alone. Linezolid is the only oral agent with demonstrated effectiveness against MRSA in controlled trials, but its use has been restricted because it is expensive.
Parenteral therapy is available for serious community-acquired MRSA infections. Vancomycin remains the first choice for MRSA therapy. There have been reports of resistance to vancomycin through a heteroresistance mechanism, but this is not easily identified with clinical microbiology testing and requires special detection techniques. Although daptomycin (Cubicin) has not been widely studied for treatment of community-acquired MRSA, it has recently been approved for treating bacteremia and right-sided endocarditis caused by S. aureus (including MRSA). However, MRSA strains with heteroresistance to vancomycin may exhibit a similar effect with daptomycin. Daptomycin should also be avoided in patients with community-acquired MRSA-associated pneumonia because it is inactivated by pulmonary surfactant.
Linezolid has been demonstrated to be effective in MRSA infections in clinical controlled trials. It may be especially useful in serious skin and soft-tissue infections, such as necrotizing fasciitis, because of its ability to inhibit toxin production. However, a reasonable alternative would be to use vancomycin with clindamycin for this purpose. Although linezolid may prove useful for community-acquired MRSA-associated pneumonia, there are no studies examining this to date. Tigecycline (Tygacil) has been shown to be noninferior to vancomycin for serious MRSA infections, but the number of patients studied to date has been relatively small.