Antibiotic Therapy in Acute Infectious Diarrhea and Clostridioides difficile Infection: Clinical Indications, Antimicrobial Stewardship, and Evidence Gaps

Background: Most acute gastrointestinal infections are self-limiting, but antibiotics remain essential for selected patients with severe, invasive, or high-risk disease. This narrative review examines when antibiotics should be started or withheld in adults and children with suspected or confirmed bacterial gastrointestinal infection, which regimens should be selected, and how treatment should be reassessed after diagnostic and susceptibility results become available. Methods: PubMed and Scopus were searched for relevant English-language evidence published from 1 January 2014 through 28 August 2026. Google Scholar was used for supplementary citation tracking, and landmark earlier studies and major international guidelines were also considered. The search informed a narrative synthesis and was not conducted as a systematic review. Sixty-one sources were included. Results: The evidence base is uneven. Recommendations concerning rehydration, avoidance of antibiotics in Shiga toxin-producing Escherichia coli infection, and treatment of Clostridioides difficile infection (CDI) are comparatively consistent. By contrast, treatment thresholds and durations for several enteric infections rely largely on observational evidence, indirect evidence, or expert consensus. Antibiotics should generally be withheld in uncomplicated watery diarrhea and used selectively for dysentery, severe travelers’ diarrhea, cholera, enteric fever, invasive salmonellosis, and CDI. Regimen selection should reflect host risk, illness severity, travel exposure, and local susceptibility data. Therapy should be narrowed or discontinued after diagnostic clarification whenever appropriate. Conclusions: The principal stewardship priorities are appropriate patient selection, culture and susceptibility testing when the results may change management, and use of the shortest effective regimen supported by the available evidence.