Clinical Edge

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Prevention of Recurrent Clostridium difficile

N Engl J Med; ePub 2017 Jan 26; Wilcox, et al

Among patients receiving antibiotic treatment for primary or recurrent Clostridium difficile (C. difficile) infection, those taking bezlotoxumab experienced a substantially lower rate of recurrent infection when compared to placebo, a recent study found. MODIFY I and MODIFY II were 2 double-blind, randomized, placebo-controlled, phase 3 trials that included 2,655 adults with primary or recurrent C. difficile infection receiving oral standard-of-care antibiotics plus either an infusion of bezlotoxumab, actoxumab plus bezlotoxumab, or placebo. Actoxumab alone was given in MODIFY I but discontinued. Researchers found:

  • In both trials, the rate of recurrent C. difficile was significantly lower with bezlotoxumab alone than with placebo and was significantly lower with actoxumab plus bezlotoxumab than with placebo.
  • Rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; rates of sustained cure were 64%, 58%, and 54%, respectively.
  • The addition of actoxumab did not improve efficacy.

Citation:

Wilcox MH, Gerding DN, Poxton IR, et al. Bezlotoxumab for prevention of recurrent Clostridium difficile infection. N Engl J Med. 2017; 376:305-317. doi:10.1056/NEJMoa1602615.

Commentary:

Clostridium difficile has become a common cause of post-antibiotic diarrhea among both hospital inpatients and patients in the community. With current treatment regimens of metronidazole or oral vancomycin, up to 35% of patients develop recurrent C. difficile infection.1,2 Recurrences tend to be more severe, have a higher chance of re-occurrence, and have worse outcomes. Actoxumab and bezlotoxumab are monoclonal antibodies against C. difficile toxins A and B respectively. By binding and neutralizing the circulating antibody, the agent active against the B toxin, bezlotoxumab appears to decrease recurrences of C. difficile. This new method of treatment is promising, and along with other new methods including fecal transplant, will likely have find their optimal value in patients with recurrent C. difficile. —Neil Skolnik, MD

  1. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31:431-455.
  2. Kelly CP, LaMont JT. Clostridium difficile — more difficult than ever. N Engl J Med. 2008;359:1932-40. doi:10.1056/NEJMra0707500.