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A man who has sex with men, living with HIV and having a history of previous syphilis, presented to our outpatient STI service with gastrointestinal symptoms following use of multiple antibiotics intended as postexposure prophylaxis (PEP) for STI prevention.1 2 He was receiving antiretroviral treatment with intramuscular cabotegravir and rilpivirine long-acting, with stable HIV RNA suppression (<50 copies/mL) and a high CD4 count (>1000 cells/µL). He reported engaging in condomless receptive and insertive oro-anal sex with >100 partners in the previous week and taking different antibiotics for STI PEP, but deviating from the recommended use and dosing schedule. These included doxycycline (200 mg two times per day daily for three consecutive days), azithromycin (1 g for 2 days) and amoxicillin/clavulanate (2 g for 2 days). He presented with a history of five episodes per day of liquid stools containing blood and mucus, abdominal tenderness, malaise and fever. Clinical examination revealed dehydration with pharyngeal hyperaemia, bilateral reactive inguinal lymphadenopathy and mild abdominal tenderness. Laboratory tests showed mild leucocytosis, normal electrolytes, negative tests for gonorrhoea, chlamydia, syphilis and hepatitis C, and no gastrointestinal parasites. Stool analysis was positive for C. difficile toxin. Outpatient treatment with fidaxomicin (200 mg two times per day daily for 10 days) was prescribed in view of the microbiological results and clinical symptoms, the underlying HIV infection, the potential difficulties with adherence to other regimens and the risk of relapse.