Two Times Versus Four Times Daily Cephalexin Dosing for the Treatment of Uncomplicated Urinary Tract Infections in Females

BACKGROUND: The current treatment guidelines of the Infectious Diseases Society of America recommend β-lactam antibiotics as alternative rather than first-line agents for the treatment of uncomplicated urinary tract infection (uUTI). Cephalexin is a commonly prescribed first-generation cephalosporin with excellent bioavailability and urinary penetration; however, little data exist to support optimal dosing for uUTI. METHODS: This retrospective multicenter cohort study included adult female patients who received 5 to 7 days of cephalexin for symptomatic uUTI with a cefazolin-susceptible urine culture. The primary objective was to compare uUTI treatment failure (eg, continued or recurrent symptoms within 30 days) between patients treated with cephalexin 500 mg twice daily (BID group) and 500 mg 4 times daily (QID group) in the outpatient setting. Secondary outcomes included time to treatment failure, reported adverse events within 7 days of treatment, and occurrence of Clostridioides difficile within 30 days of treatment. RESULTS: A total of 261 patients were included (BID, n = 173; QID, n = 88). Baseline characteristics were similar between the groups. Escherichia coli was the most commonly isolated pathogen (85.4%). There was no difference in treatment failure observed between the groups (BID 12.7% vs QID 17%, P = .343), including failure while undergoing therapy (BID 2.3% vs QID 5.7%, P = .438) or recurrence within 30 days (BID 10.4% vs QID 11.3%, P = .438). No differences in reported adverse events (BID 4.6% vs QID 5.6%, P = .103) were observed between groups. CONCLUSIONS: Twice-daily cephalexin is as effective as 4-times-daily dosing for uUTI. A twice-daily dosing strategy may improve patient adherence.