Background: Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) is the most commonly identified organism in skin and soft tissue infections (SSTIs) in many regions of the United States. However, because most SSTIs (e.g., impetigo, cellulitis, small abscesses) are treated without drainage or culture, the true prevalence is not known. Traditional first-line empiric therapy has included betalactam drugs, which cover group A Streptococcus and methicillin-sensitive S. aureus, but not community-acquired MRSA. Trimethoprim/sulfamethoxazole (Bactrim, Septra) covers MRSA but not group A Streptococcus. More recent guidelines include consideration of MRSA coverage in endemic regions. Elliott and colleagues compared the treatment failure rates among betalactams, clindamycin (Cleocin), and trimethoprim/sulfamethoxazole to better assess the effectiveness of empiric MRSA coverage in SSTIs that will not be cultured.

The Study: This nested case-control trial included children from five urban primary care practices in an MRSA-endemic region whose SSTIs were not cultured or drained on the day of the index visit. Patients placed on oral monotherapy were included for review, and those placed on topical antibiotics or on more than one oral antibiotic were excluded. Treatment failure was defined as hospitalization with SSTI as the admitting diagnosis, a subsequent drainage procedure, an antibiotic change not related to allergy or intolerance, or extension of antibiotic use because of inadequate clinical response, all within 28 days following the diagnosis. Treatment failures were identified by chart review. Each patient with confirmed treatment failure was matched with four control participants who were treated successfully in the same calendar quarter.

Results: Between January 1, 2004, and March 31, 2007, a total of 2,096 children met the inclusion definition for nondrained, non-cultured SSTIs, and 104 (5.0 percent) had a treatment failure. Of those, 28 (26.9 percent) required admission, 21 (20.2 percent) required outpatient drainage, 21 (20.2 percent) received a prolonged course of the initial antibiotic, and 34 (32.7 percent) received an additional antibiotic prescription. The average failure rate remained constant at 5.7 percent during the three years of the study, with the proportion of empiric community-acquired MRSA coverage increasing dramatically. Treatment with trimethoprim/sulfamethoxazole or clindamycin increased from 16.4 percent of all prescriptions at the study onset, to 62.2 percent in 2007. The use of trimethoprim/sulfamethoxazole was associated with an increase in the odds of treatment failure compared with betalactam drugs (odds ratio [OR] = 2.35). However, clindamycin did not have notably increased odds of treatment failure compared with betalactams (OR = 1.40). Other risk factors for treatment failure included white race, antibiotic use within the previous six months, an index visit in the emergency department, the presence of fever, and induration or abscess.

Conclusion: In this retrospective study, empiric community-acquired MRSA coverage through the monotherapeutic use of trimethoprim/sulfamethoxazole for SSTIs did not improve clinical outcomes and was associated with increased odds of treatment failure. Therefore, betalactams may remain the treatment of choice for uncultured SSTIs, regardless of the region's community-acquired MRSA prevalence.

editor's note: Current guidelines for treating SSTIs include drainage and culture whenever possible and antimicrobial therapy tailored to culture and sensitivity results. MRSA coverage should be considered for persons with systemic or severe local symptoms, immunosuppression, or failure to respond to incision and drainage. For infections that cannot be cultured, the Centers for Disease Control and Prevention recommends coverage for Streptococcus and other suspected pathogens, which may include MRSA. Recommended agents for MRSA coverage include trimethoprim/sulfamethoxazole, clindamycin, and doxycycline.¹—a.c.f.