IV bezlotoxumab reduced recurrent infections in patients with Clostridium difficile infection (CDI) when added to standard antibiotics, a manufacturer-sponsored study reported earlier this year. The study included two double-blind, phase 3 trials funded by Merck in which 2,655 adults receiving oral standard-of-care antibiotics for primary or current CDI were randomized to an infusion of bezlotoxumab (10 mg/kg), actoxumab plus bezlotoxumab (10 mg/kg each), or placebo. In 12 weeks of follow-up, patients in the bezlotoxumab group had significantly lower rates of recurrence than those on placebo, while the actoxumab plus bezlotoxumab group showed similar recurrence rates to bezlotoxumab alone.
The study was published in the Jan. 26 New England Journal of Medicine and was summarized in the Feb. 1 ACP Hospitalist Weekly. The following commentary by Fred Arthur Zar, MD, FACP, was published in the ACP Journal Club section of the May 16 Annals of Internal Medicine.
The trial by Wilcox and colleagues reinforces the results of a previous trial, which found that actoxumab plus bezlotoxumab reduced CDI recurrence rates compared with placebo. It also clarifies that the active antibody was bezlotoxumab, which was approved by the U.S. Food and Drug Administration in 2016 for the treatment of CDI in patients at high risk for relapse. The duration of follow-up to detect recurrence in both trials was 84 days, which was more than adequate compared with other trials that followed patients for relapses up to 21 to 28 days. In the trial by Wilcox and colleagues, bezlotoxumab had a similar frequency of adverse reactions as placebo, and none were allergic in nature, which would be of concern given the 19-day elimination half-life of bezlotoxumab.
Only 1 other treatment, fidaxomicin, reduces recurrences after first CDI better than vancomycin and metronidazole. Fidaxomicin costs about $4400, which is about the same as bezlotoxumab. The high costs merit cost-effectiveness analyses, which have been done for fidaxomicin; it seems to be cost-effective compared with vancomycin for treating severe or recurrent CDI. However, this may not be true for bezlotoxumab because, unlike fidaxomicin, it must be given in addition to oral treatment for CDI and has the additional costs inherent in IV administration. Fecal microbiota therapy has not been extensively studied for treating initial CDI but is effective in recurrent CDI and cost-effective compared with vancomycin.
It seems reasonable to consider either fidaxomicin or bezlotoxumab in patients at high risk for CDI recurrence or those for whom recurrence could be devastating, such as patients who are elderly, have vital organ failure, or are being treated in the critical care unit.