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Peritoneal dialysis (PD) associated peritonitis is the leading cause of PD discontinuation and haemodialysis transfer. Current guidelines strongly recommend prompt initiation of empiric broad-spectrum intraperitoneal antibiotics, with suspected peritonitis. Clostridium difficile colitis is one of the most common healthcare-associated infections, with increased morbidity and mortality among end-stage kidney disease patients. Clinical presentation is mainly characterised by diarrhoea of varying severity, which may eventually evolve into toxic megacolon and paralytic ileus. However, PD patients with Clostridium difficile infection (CDI) may also have colitis-triggered peritonitis, presenting challenging scenario for antibiotic treatment strategy, since broad-spectrum antibiotics against peritonitis may worsen CDI-related colitis, while inappropriate or discontinuation of antibiotic therapy may worsen peritonitis. Currently, guidelines on peritonitis management do not include such challenging clinical situations, although increasingly common. We herein describe a case of a patient, with culture-negative PD associated peritonitis and CDI, presenting with diarrhoea, abdominal pain and cloudy effluent.