Treating Uncomplicated Cellulitis: Is Adding TMP/SMX Beneficial?

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%; P =.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%; P =.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.”

References

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