Enteropathogenic Escherichia coli and Bacterial Overgrowth Co-infection Exacerbating Immune Checkpoint Inhibitor-Induced Colitis

Immune checkpoint inhibitor-induced colitis (ICIC) is a common gastrointestinal immune-related adverse event, particularly with combined ipilimumab-nivolumab therapy. We present a case of a 53-year-old man with metastatic mucosal melanoma receiving combination immunotherapy who developed severe diarrhea (>20 stools/day), profound hypokalemia (2.2 mmol/L), metabolic acidosis, and QTc prolongation. Multiplex stool PCR detected enteropathogenic <i>Escherichia coli</i> (EPEC), while colonoscopy with biopsy confirmed ICIC. Despite high-dose corticosteroids, the patient required >1,900 mEq potassium supplementation over 8 days. Stool studies revealed an osmotic gap of 123 mOsm/kg, and persistent bloating prompted empiric treatment for suspected small intestinal bacterial overgrowth (SIBO) with rifaximin. Clinical improvement occurred only after addressing all three pathologic processes: immune-mediated inflammation, EPEC infection, and bacterial overgrowth. This case demonstrates that enteric pathogens and bacterial overgrowth can significantly exacerbate ICIC, resulting in severe electrolyte derangements and prolonged clinical course. Clinicians should maintain high suspicion for co-infections in patients with ICIC who demonstrate disproportionate fluid and electrolyte losses or inadequate response to immunosuppression. Comprehensive diagnostic evaluation, including stool testing, endoscopic assessment, and physiologic profiling of diarrhea, enables targeted multimodal therapy beyond corticosteroid monotherapy.