S5047 Fulminant C. difficile Colitis Mimicking Typhlitis in a Patient Undergoing BiTE Therapy: Diagnostic and Therapeutic Challenges in a Neutropenic Host

Introduction: Typhlitis is a well-known complication in immunocompromised patients presenting with right-sided abdominal pain and neutropenia. However, fulminant Clostridioides difficile infection (CDI) can initially present similarly, particularly in patients without diarrhea. We present a diagnostically challenging case of fulminant CDI mimicking typhlitis in a neutropenic patient undergoing bispecific T-cell engager (BiTE) therapy. Case Description/Methods: A 65-year-old man with multiple myeloma was admitted for Talquetamab ramp-up in preparation for CAR-T. After each dose, he developed progressive altered mental status consistent with Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS), treated with dexamethasone. He was started on empiric cefepime on Hospital Day 7 due to neutropenia and concern for infectious encephalopathy—an established risk factor for CDI. On Day 18, he developed right lower quadrant pain without diarrhea. He was hemodynamically stable but neutropenic. Computed tomography (CT) imaging showed cecal and ascending colitis, concerning for typhlitis, prompting antibiotic broadening for anaerobic coverage. On Day 21, he was transferred to the ICU for worsening ICANS. He remained tenuous with increasing abdominal pain and rebound tenderness. Repeat CT showed pancolitis, raising concern for fulminant colitis. Despite only 1 loose stool, CDI polymerase chain reaction was sent (outside institutional criteria), and he was empirically started on oral/rectal vancomycin and intravenous metronidazole. GI, ID, and surgical services were consulted. Due to rising lactate, worsening vitals, and imaging suggestive of toxic megacolon, he underwent emergent total colectomy. Postoperatively, he stabilized. Pathology confirmed pseudomembranous colitis without features of typhlitis. Discussion: This case highlights the need for clinical judgment in complex immunocompromised patients. Though right-sided colitis in neutropenic hosts suggests typhlitis, early CDI must be considered, particularly with recent antibiotic exposure. Strict reliance on ≥3 loose stools for CDI testing may delay diagnosis in critically ill patients. Here, imaging and systemic decline guided empiric therapy and testing, which proved lifesaving. Steroid use for ICANS complicated decisions, as corticosteroids are generally contraindicated in infectious colitis. Multidisciplinary ICU management enabled timely diagnosis, surgery, and recovery despite fulminant disease in a pancytopenic patient.