INTRODUCTION: Patient with acute myeloid leukemia (AML) are at increased risk of developing Clostridium difficile (C. Diff) colitis due to routine use of prophylactic antibiotics, the use of chemotherapy and neutropenia. These factors also add additional challenges to successful treatment. We report a case of fulminant C. Diff pancolitis to highlight these challenges. CASE DESCRIPTION/METHODS: 65 year old male was found to have pancytopenia on routine blood work at primary care office after experiencing 15 pound weight loss over 1 month. He had a history of rheumatoid arthritis that was well controlled on medications and had no other symptoms. His initial CBC showed a WBC 0.4 k/mm3, Hgb 6.9 g/dL, & platelets 8 k/mm3. A subsequent bone marrow biopsy showed 50% myeloblast, flow cytometry and genetic testing showed normal cytogenetics with intermediate risk & (-) FLT 3 mutation. Patient underwent 7 + 3 induction & a 5 + 2 reinduction after day 14 bone marrow showed residual disease. Patient was placed on prophylactic voriconazole, acyclovir & Levaquin but still developed fevers during neutropenic nadir. Blood cultures showed polymicrobial sepsis from a GI source (with growth of Gemella haemolysans & Rothia mucilaginosa). He developed diarrhea & NAAT tested positive for C. Diff. An abdominal X ray showed dilated large bowel loops with ileus a subsequent CT scan confirmed pancolitis (Figures 1 and 2). Patient developed septic shock. He initially responded to fluid resuscitation and was started on oral vancomycin and IV flagyl. After 4 days patient had a PEA arrest and was transferred to ICU after ROSC. Patient passed away soon after as patient family opted for comfort measures. DISCUSSION: Patients with acute myeloid leukemia (AML) are immunocompromised with neutropenia either due to their disease or from the effects of their chemotherapy regimen. Neutropenic patients are at risk for life threatening infections & administration of prophylactic antibiotics is common practice for induction chemotherapy. Many chemotherapy agents have antimicrobial activity altering the gut biome. Research has shown cancer patients have decreased response to therapy, increased time to resolution of diarrhea, and increased relapse rates to C. Diff associated diarrhea. The key is to diagnose & treat early. Severe disease should be distinguished early. The 2018 IDSA guidelines recommends use of algorithms and criteria to aid in this process (Figure 3). Further research is needed to outline the optimum approach to treatment in this patient group.