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Bezlotoxumab: A Novel Drug for Reduction of Recurrent Clostridium difficile Infections

Whitaker, Andrea, PharmD*; Cosimi, Reese, A., PharmD, BCPS; Reveles, Kelly, R., PharmD, PhD, BCPS; Evoy, Kirk, E., PharmD, BCACP, BC-ADM, CTTS

Infectious Diseases in Clinical Practice: March 2018 - Volume 26 - Issue 2 - p 60–65
doi: 10.1097/IPC.0000000000000571
Review Articles

The purpose was to review the pharmacology, safety, and efficacy of bezlotoxumab (Zinplava; Merck Sharp & Dohme Corp, Whitehouse Station, NJ) as a novel therapy for prevention of recurrent Clostridium difficile infection (CDI). MEDLINE was searched (1946 to February 2017) using the terms bezlotoxumab, MK6072, MBL-CDB1, and MDX-1388. Additional studies were identified through searching FDA.gov, clinicaltrials.gov, and review of reference lists. Studies included were randomized control trials in English language on bezlotoxumab for recurrent CDI. Animal studies were excluded. Three randomized control trials were identified evaluating bezlotoxumab in adults receiving standard of care therapy for CDI. The primary outcome evaluated in all trials was CDI recurrence. A phase II trial found the combination of bezlotoxumab-actoxumab compared with placebo decreased CDI recurrence at 84 days (7% vs 25%, P < 0.001). Two similar, yet independent phase III trials evaluated recurrent CDI at 12 weeks. Results were consistent between the 2 trials and pooled analysis displayed a reduction in CDI recurrence in the bezlotoxumab group (absolute difference, −10.1%; 95% confidence interval, −14 to −6; P < 0.001) and the bezlotoxumab-actoxumab group (absolute difference, −11.5%; 95% confidence interval, −15.2 to −7.2; P < 0.001) compared with placebo. Initial and sustained clinical cure rates were similar between bezlotoxumab, bezlotoxumab-actoxumab, and placebo. Overall, the adverse effects associated with bezlotoxumab were similar to placebo, with diarrhea, nausea, pyrexia, and headache having a higher occurrence than placebo. In conclusion, bezlotoxumab is safe and effective at reducing CDI recurrence and the use of bezlotoxumab should be considered in patients who are at highest risk for CDI.

Clostridium difficile infection (CDI) incidence has doubled from 2001 to 2010. Despite appropriate therapy, the likelihood of first recurrence is 10–20%, which subsequently increases to 40–65% after the initial recurrence. Bexlotoxumab is a new monoclonal antibody that provides passive immunity against the virulent toxin B produced by C. difficile during an infection. Bezlotoxumab showed a 10% reduction in recurrent CDI infections compared to placebo when used with standard of care antibiotics.

From the *University Health System, †South Texas Veterans Health Care System, and ‡College of Pharmacy, The University of Texas at Austin, Pharmacotherapy Education and Research Center, UT Health Science Center, San Antonio, TX.

Correspondence to: Andrea Whitaker, PharmD, Manchester University, College of Pharmacy, Natural and Health Sciences, 10627 Diebold Road Fort Wayne, IN 46845. E-mail: awhitaker@manchester.edu.

The authors have no funding or conflicts of interest to disclose.

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