Treating Uncomplicated Cellulitis: Is Adding TMP/SMX Beneficial?

MRSA cell
MRSA cell
Adding trimethoprim-sulfamethoxazole to cephalexin treatment for cellulitis does not benefit outcomes compared to cephalexin alone.

In uncomplicated cellulitis, adding trimethoprim-sulfamethoxazole to cephalexin treatment, does not appear to benefit clinical outcomes compared to cephalexin alone, according to a study published in JAMA.1

A total of 496 emergency department outpatients with cellulitis and no wound, purulent drainage, or abscess were included in a double-blind, randomized superiority trial. Participants were administered either cephalexin 500 mg 4 times daily plus trimethoprim-sulfamethoxazole 320mg/1600mg twice daily (n=248), or cephalexin plus placebo (n=248). In both arms, treatments were administered for 7 days.

Clinical cure was defined as an absence of the following features at follow-up: fever, increase in erythema (>25%), swelling, or tenderness at days 3-4; no decrease in erythema, swelling, or tenderness at days 8–10; and more than minimal erythema, swelling, or tenderness at days 14-21. 

A total of 411 (82.2%) patients were included in the per-protocol analysis. For this population, clinical cure was demonstrated in 182 (83.5%) of 218 patients for the cephalexin plus trimethoprim-sulfamethoxazole group vs 165 (85.5%) of 193 in the cephalexin and placebo group (difference −2.0%; 95% CI, −9.7% to 5.7%; =.50).

However, analysis of the intention-to-treat population found a greater percentage of those in the cephalexin plus trimethoprim-sulfamethoxazole group reached clinical cure (189 of 248; 76.2%) than those in the cephalexin plus placebo group (171 of 248; 69%), (difference 7.3%; 95% CI, −1.0% to 15.5%; =.07).

The rate of skin infections in the US has risen with the emergence of methicillin-resistant Staphlococcus aureus (MRSA). A 2006 report in the New England Journal of Medicine found that MRSA was the most common cause of purulent skin infections in the US.2 Although this research found no cure improvements with the inclusion of trimethoprim-sulfamethoxazole in the per-protocol analysis, it did find an increase in cure rates in the modified intention-to-treat analysis, which lead the authors to conclude that, “further research may be needed.”

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  1. Moran GJ, Krishnadasan A, Mower WR, et al. Effect of cephalexin plus trimethoprim-sulfamethoxazole vs cephalexin alone on clinical cure of uncomplicated cellulitis: a randomized clinical trial. JAMA. 2017;317:2088-2096. doi: 10.1001/jama.2017.5653
  2. Moran GJ, Krishnadasan A, Gorwitz RJ, et al; EMERGEncy ID Net Study Group. Methicillin-resistant S aureus infections among patients in the emergency department. N Engl J Med. 2006;355:666-674. doi: 10.1056/NEJMoa055356

This article originally appeared on MPR