Researchers in the United Kingdom have found that the addition of bezlotoxumab (Zinplava, Merck) to standard antibiotic treatment can reduce the risk of a repeat infection with Clostridium difficile by 37%. Bezlotoxumab is a human monoclonal antibody that works by neutralizing a toxin produced by C. difficile bacteria that can damage the gut wall.
Dr. Mark Wilcox, professor of microbiology at the University of Leeds, led the study, which was published in the New England Journal of Medicine.
“About one in four patients who have been treated with antibiotics for an initial C.diff infection will go on to have a repeat infection,” Wilcox said. “These repeat infections are more difficult to treat; have more severe outcomes for the patient; and are associated with more hospitalizations. It is important to treat the first episodes of C. diff infection optimally, as each recurrence increases the chance of another episode even more.”
Wilcox and his colleagues conducted a randomized, double-blind, placebo-controlled trial involving 2,655 adults at 300 hospitals in 30 countries. All of the participants had primary or recurrent C. difficile infections and were receiving a standard-of-care antibiotic (i.e., metronidazole, vancomycin, or fidaxomicin). The patients were randomly assigned to receive a single infusion of the human monoclonal antibody actoxumab (10 mg/kg of body weight); a single infusion of bezlotoxumab (10 mg/kg of body weight); a single infusion of bezlotoxumab plus actotoxumab (10 mg/kg of body weight), or a single infusion of placebo (saline).
After initial cure of their C. difficile infections, the patients were followed for 12 weeks. Another C. difficile infection developed in 26% of the actoxumab group, in 17% of the bezlotoxumab group; in 15% of the bezlotoxumab/actotoxumab group, and in 27% of the placebo group.
According to Wilcox, the study showed that bezlotoxumab was particularly effective in patients with risk factors for poor outcomes, including older age, an immunocompromised state, and severe infections.