Cephalexin 500 mg Four Times Daily vs. 1000 mg Three Times Daily for the Treatment of Uncomplicated Cellulitis

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ID: 332388
2026
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Abstract
Abstract Background Cephalexin is a commonly prescribed agent for uncomplicated cellulitis. The currently recommended cellulitis dosing for cephalexin is 500 mg four times daily (QID), although QID dosing can be burdensome and literature has suggested that increased dosing frequency leads to decreased adherence. In practice, some clinicians have moved to prescribing cephalexin 1000 mg three times daily (TID) to improve feasibility and adherence. Methods This retrospective, multicenter cohort study evaluated adult patients who were diagnosed with uncomplicated lower extremity cellulitis and prescribed either cephalexin 500 mg QID or 1000 mg TID for a total of 5 to 10 days. The primary outcome was to compare treatment failure, defined as a composite of change in antimicrobial selection due to documented lack of efficacy or intolerable adverse reaction, or retreatment of cellulitis within 30 days of completion of initial therapy. Results 300 patients were included (QID, n=150; TID, n=150). There was no difference in treatment failure between groups (QID 6.7% vs. TID: 5.3%, p=0.627). Time to treatment failure was similar between groups (QID 7 days [IQR 3–8 days] vs. TID 5 days [IQR 2.5–8 days], p=0.633). There was no difference in unplanned revisit or hospitalization within 30 days between groups (QID 4% vs. TID 2.7%, p=0.52). Adverse reactions were uncommon and similar between groups (QID 0% vs. TID 0.7%, p=1.0). Conclusion Cephalexin 1000 mg TID was well-tolerated and as effective as cephalexin dosed 500 mg QID for the treatment of uncomplicated cellulitis. A thrice-daily dosing strategy may improve patient adherence.
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Authors Erin T Ruiter, Kristen M. Johnson, Ashlyn M. Kiebach, Lauren T. Harven, Andrew P. Jameson, Lisa E. Dumkow
Journal Open forum infectious diseases
Year 2026
DOI
10.1093/ofid/ofag681
URL
https://doi.org/10.1093/ofid/ofag681
Keywords Keywords not found

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