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Am Fam Physician. 2017;96(6):399

Clinical Question

Does the addition of trimethoprim/sulfamethoxazole (TMP/SMX) to cephalexin (Keflex) increase the rate of cure for uncomplicated cellulitis?

Bottom Line

Compared with cephalexin alone, covering for methicillin-resistant Staphylococcus aureus (MRSA) and streptococci with cephalexin plus TMP/SMX does not improve rates of clinical cure when treating nonpurulent cellulitis. However, a trend favoring the combination regimen was found in a modified intention-to-treat population in this study, so further research may be required. (Level of Evidence = 1b)


Guidelines from the Infectious Diseases Society of America recommend treating nonpurulent cellulitis with an antibiotic that is active only against streptococci. However, in practice, clinicians often prescribe an antibiotic regimen that includes activity against MRSA. Using concealed allocation, these investigators randomized 500 patients who presented to the emergency department with nonpurulent, uncomplicated cellulitis to receive a seven-day course of cephalexin plus TMP/SMX or cephalexin plus matching placebo. Bedside ultrasonography was used to exclude patients with abscess. The primary outcome was clinical cure at 14 to 21 days in the per-protocol group (those who took at least 75% of the study medication during the first five days and had an in-person follow-up at 14 to 21 days, or those who took at least 75% of the study medication during the first 48 hours but had clinical failure). No significant difference was detected, with approximately 85% clinical cure in both groups.

In the modified intention-to-treat population of patients who took at least one dose of study medication and were followed up at 14 to 21 days, there was a trend toward greater clinical cure in the cephalexin plus TMP/SMX group (76% vs. 69%; difference = 7.3%; 95% confidence interval, −1.0% to 15.5%; P = .07). Although this difference was not statistically significant, the 95% confidence interval includes the minimal clinically important difference of 10%, suggesting a possible benefit. Adverse events, which were reported as mild 90% of the time, were not different between the two groups.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Concealed

Setting: Emergency department

Reference: MoranGJKrishnadasanAMowerWRet alEffect of cephalexin plus trimethoprim-sulfamethoxazole vs cephalexin alone on clinical cure of uncomplicated cellulitis: a randomized clinical trial. JAMA2017;317(20):2088–2096.

POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see Copyright Wiley-Blackwell. Used with permission.

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