BEZLOTOXUMAB THERAPY FOR RECURRENT CLOSTRIDIUM DIFFICILE INFECTION IN AN ULCERATIVE COLITIS PATIENT

Abstract

INTRODUCTION Clostridium difficile infection (CDI) is the most common infectious cause of nosocomial diarrhea, comprising 10-20% of all cases. CDI is a significant complication for IBD patients. Not only can CDI induce IBD flare, IBD patients also experience significantly higher CDI recurrence when compared to the general population. New monoclonal antibody (mAB) therapies, such as bezlotoxumab, have improved management of recurrent CDI (rCDI). The MODIFY I/II trial included 44 patients with known IBD, 28 of which received bezlotoxumab. Among these 28 patients, there was a 27.2% absolute reduction in the incidence of rCDI. Encouraged by these results, we recently prescribed bezlotoxumab in a UC patient with rCDI and herein report our experience. CASE REPORT A 21-year-old female with a history of ulcerative colitis (UC) diagnosed in 2017 presented for treatment of rCDI. Her first episode of CDI occurred in 2019 during an active UC flare treated with steroids and infliximab induction. CDI was successfully treated with a four-week course of 125mg oral vancomycin twice daily followed by once daily for an additional four weeks. She had a recurrent episode of CDI one year after her initial infection while on vedolizumab for UC treatment. She was treated with 125mg oral vancomycin, four times daily, and tapered down by one dose over a four-month period. Two years after her initial CDI, she developed worsening non-bloody diarrhea, nausea, and anorexia with weight loss. She again tested positive for C. difficile via glutamate dehydrogenase antigen and PCR for toxin B. Fecal calprotectin was 2190 mg/g. She was treated with 14-day course fidaxomicin 200mg BID and a single infusion of bezlotoxumab 10mg/kg. Treatment for UC was not adjusted. At follow up one month later, her symptoms had resolved and fecal calprotectin normalized (17 mg/g). Six months later, she remains asymptomatic. DISCUSSION Recurrent CDI is a frequent culprit for inducing IBD flares, and is difficult to manage. Fecal transplant (FMT) is an option for rCDI, but often entails logistical challenges and risks cross-contamination of endoscopic facilities. Bezlotoxumab is an appealing option for rCDI as a single dose medication with few reported side effects in the MODIFY clinical trials. While the number of IBD patients in the MODIFY trial was small, results were promising. In our patient, bezlotoxumab quickly resolved her rCDI and IBD flare without need for alteration or escalation of her biologic therapy, and she has remained asymptomatic for six months. This case corroborates the prospect that bezlotoxumab positively affects the clinical outcomes of UC patients with rCDI compared to those on repetitive antimicrobial therapy and/or FMT without mAB therapy. Further investigation into the long-term efficacy of this therapy is merited for the IBD patient population in the real-world setting.

Clostridioides difficile infections; new treatments and future perspectives

“…Bezlotoxumab was approved by the FDA in 2016 and is now recommended as an adjunctive to vancomycin for initial treatment of patients with a high risk or recurrence or after a first recurrence [ 17 , 18 ]. More recently, bezlotoxumab has been shown to reduce CDI recurrence in immunocompromised patients [ 44 ] and shows promise in patients with ulcerative colitis [ 45 ]. Although effective at reducing the incidence of recurrence, there is a distinct lack of preventive options.…”