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Clin Infect Dis. 2013 Jun;56(12):1754-62. doi: 10.1093/cid/cit122. Epub 2013 Mar 1.

Clinical trial: comparative effectiveness of cephalexin plus trimethoprim-sulfamethoxazole versus cephalexin alone for treatment of uncomplicated cellulitis: a randomized controlled trial.

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Department of Emergency Medicine, Brigham and Women's Hospital, Boston, MA, USA.



Community-associated methicillin-resistant S. aureus (CA-MRSA) is the most common organism isolated from purulent skin infections. Antibiotics are usually not beneficial for skin abscess, and national guidelines do not recommend CA-MRSA coverage for cellulitis, except purulent cellulitis, which is uncommon. Despite this, antibiotics targeting CA-MRSA are prescribed commonly and increasingly for skin infections, perhaps due, in part, to lack of experimental evidence among cellulitis patients. We test the hypothesis that antibiotics targeting CA-MRSA are beneficial in the treatment of cellulitis.


We performed a randomized, multicenter, double-blind, placebo-controlled trial from 2007 to 2011. We enrolled patients with cellulitis, no abscesses, symptoms for <1 week, and no diabetes, immunosuppression, peripheral vascular disease, or hospitalization ( NCT00676130). All participants received cephalexin. Additionally, each was randomized to trimethoprim-sulfamethoxazole or placebo. We provided 14 days of antibiotics and instructed participants to continue therapy for ≥1 week, then stop 3 days after they felt the infection to be cured. Our main outcome measure was the risk difference for treatment success, determined in person at 2 weeks, with telephone and medical record confirmation at 1 month.


We enrolled 153 participants, and 146 had outcome data for intent-to-treat analysis. Median age was 29, range 3-74. Of intervention participants, 62/73 (85%) were cured versus 60/73 controls (82%), a risk difference of 2.7% (95% confidence interval, -9.3% to 15%; P = .66). No covariates predicted treatment response, including nasal MRSA colonization and purulence at enrollment.


Among patients diagnosed with cellulitis without abscess, the addition of trimethoprim-sulfamethoxazole to cephalexin did not improve outcomes overall or by subgroup.




cellulitis; cephalexin; community-associated methicillin-resistant Staphylococcus aureus; comparative effectiveness; trimethoprim-sulfamethoxazole

[Indexed for MEDLINE]

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