Clostridioides difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea; however, its association with antituberculous therapy (ATT) remains underrecognized. This review examines the risk, mechanisms, and clinical implications of CDI in patients with active tuberculosis (TB). Although ATT is traditionally considered low risk, prolonged exposure, particularly to rifampicin, may lead to cumulative disruption of gut microbiota and loss of colonization resistance. A characteristic feature of CDI in this setting is delayed onset, typically occurring several weeks to months after ATT initiation, which complicates timely diagnosis. Rifampicin plays a dual role, contributing to microbiota alterations and selection of resistant strains, while potentially affecting the pharmacokinetics of co-administered drugs. CDI in TB patients is associated with increased morbidity and mortality, with reported mortality rates up to 9.9%. Fidaxomicin is preferred due to its microbiota-sparing effect and lower recurrence rates, although cost remains a major limitation in high TB-burden settings, since vancomycin is an appropriate alternative. Management requires an individualized approach that balances the risk of CDI recurrence against the necessity of maintaining effective TB therapy.
Javorac et al. (Fri,) studied this question.