Background—Skin and skin-structure infections are common in ambulatory settings. However, the efficacy of various antibiotic regimens in the era of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) is unclear.
Methods—We enrolled outpatients with uncomplicated skin infections who had cellulitis, abscesses larger than 5 cm in diameter (smaller for younger children), or both. Patients were enrolled at four study sites. All abscesses underwent incision and drainage. Patients were randomly assigned in a 1:1 ratio to receive either clindamycin or trimethoprim–sulfamethoxazole (TMP-SMX) for 10 days. Patients and investigators were unaware of the treatment assignments and microbiologic test results. The primary outcome was clinical cure 7 to 10 days after the end of treatment.
Results—A total of 524 patients were enrolled (264 in the clindamycin group and 260 in the TMP-SMX group), including 155 children (29.6%). One hundred sixty patients (30.5%) had an abscess, 280 (53.4%) had cellulitis, and 82 (15.6%) had mixed infection, defined as at least one abscess lesion and one cellulitis lesion. S. aureus was isolated from the lesions of 217 patients (41.4%); the isolates in 167 (77.0%) of these patients were MRSA. The proportion of patients cured was similar in the two treatment groups in the intention-to-treat population (80.3% in the clindamycin group and 77.7% in the TMP-SMX group; difference, −2.6 percentage points; 95% confidence interval [CI], −10.2 to 4.9; P = 0.52) and in the populations of patients who could be evaluated (466 patients; 89.5% in the clindamycin group and 88.2% in the TMP-SMX group; difference, −1.2 percentage points; 95% CI, −7.6 to 5.1; P = 0.77). Cure rates did not differ significantly between the two treatments in the subgroups of children, adults, and patients with abscess versus cellulitis. The proportion of patients with adverse events was similar in the two groups.
Conclusions—We found no significant difference between clindamycin and TMP-SMX, with respect to either efficacy or side-effect profile, for the treatment of uncomplicated skin infections, including both cellulitis and abscesses. (Funded by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, National Institutes of Health; ClinicalTrials.gov number, NCT00730028.)
Study Design and Population
We performed a multicenter, prospective, randomized, double-blind clinical trial of clindamycin versus TMP-SMX for the treatment of uncomplicated skin infections. Patients were eligible if they had two or more of the following signs or symptoms for 24 or more hours: erythema, swelling or induration, local warmth, purulent drainage, and tenderness to pain or palpation. Patients were categorized as having cellulitis (defined as inflammation of the skin and associated skin structures without signs of a drainable fluid collection), abscess (defined as a circumscribed, drainable collection of pus), or both (if lesions of both cellulitis and abscess were present). Exclusion criteria were superficial skin infections (e.g., impetigo), skin infection at a body site that requires specialized management (e.g., perirectal, genital, or hand infection), a human or animal bite at the infection site, high fever (oral temperature, >38.5°C [>38.0°C in children 6 to 11 months of age]), receipt of immunosuppressive medications or the presence of an immunocompromising condition such as diabetes or chronic renal failure, morbid obesity (body-mass index [the weight in kilograms divided by the square of the height in meters], >40), surgical-site or prostheticdevice infection, and receipt of antibacterial therapy with antistaphylococcal activity in the previous 14 days. Patients were ineligible if they lived in a long-term care facility, had cancer or an inflammatory disorder that required treatment in the previous 12 months, or had major surgery in the previous 12 months. All the inclusion and exclusion criteria are listed in Table S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org. The full protocol and statistical-analysis plan are also available at NEJM.org.