S5083 The Colitis Conundrum: Recurrent C. difficile and CMV Colitis in a Patient With Underlying Ulcerative Colitis

Introduction: Ulcerative colitis (UC) is a chronic inflammatory condition with complex environmental and genetic influences, complicated by a dysregulated immune response and gut dysbiosis. Clostridioides difficile is a toxin-mediated enterocolitis typically resulting from a deranged microbiome. Cytomegalovirus (CMV) is a ubiquitous herpesvirus that can lead to fulminant colitis in immunocompromised hosts. Case Description/Methods: A 58-year-old man with a history of recurrent C. difficile colitis presented with hematochezia and tenesmus. Prior C. difficile infections were resistant to vancomycin and metronidazole, only improving with fidaxomicin. On this hospitalization, the patient presented with a hemoglobin of 7.2 g/dL, and a sigmoidoscopy revealed severe colitis. Histology demonstrated crypt abscesses consistent with active UC. Strikingly, biopsies also revealed superimposed CMV colitis, prompting treatment with both methylprednisolone and ganciclovir. A sigmoidoscopy 3 months later showed inflamed pseudopolyps. Biopsies confirmed active chronic inflammation with cryptitis, but CMV inclusion bodies were no longer found. He was treated for UC with infliximab but had persistent hematochezia. He was transitioned to Upadacitinib with improvement. One year later, he again developed C. difficile colitis, leading to a UC flare. He was treated with Bezlotoxumab, but follow-up colonoscopy with biopsy showed pancolitis with CMV-infected cells. Alongside Upadacitinib, he started ganciclovir and fecal microbiota spore live-brpk capsules. After 5 months, a repeat colonoscopy finally showed significant mucosal healing. Discussion: UC increases the risk of recurrent C. difficile and CMV due to microbiome disturbance. UC patients often have increased colonic sulfate-reducing bacteria. Because of this, UC patients typically have gut dysbiosis with increased inflammatory expression, which impairs tight junctions and increases bacterial translocation. This patient had failed all other C. difficile treatments in the past. He also failed UC treatment with infliximab. Oftentimes, patients with coinfections in UC require colectomy. Remarkably, the use of fecal live-brpk capsules to restore the microbiome, aggressive therapy with ganciclovir to treat CMV, and rescue therapy with Upadacitinib allowed the patient to reach clinical remission. This case highlights the importance of revitalizing the microbiome in IBD patients to achieve remission. Until the microbiome was optimized, prior therapies targeting CMV and C. difficile were ineffective.