A historical cohort study from San Francisco General Hospital evaluated patients ≥18 years old that were hospitalized and received at least one dose of ceftriaxone. In a multivariable analysis, for every day a patient also received doxycycline the rate of Clostridium difficile infection was 27% lower than for those who did not receive doxycycline (hazard ratio, 0.73%; 95% confidence interval, 0.56-0.96).