Antibiotic Significantly Cuts Recurrent C. difficile Infection

Researchers have seen a nearly 40% reduction in recurrent Clostridium difficile (C. difficile) infections when using the antibiotic bezlotoxumab.

Researchers from the University of Leeds conducted two phase 3 trials called MODIFY I and MODIFY II to determine if actoxumab or bezlotoxumab were effective in preventing recurrent infection within 12 weeks after infusion. The researchers explained that both actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively.

The two studies included 2,655 adults from 300 hospitals in 30 countries who received standard oral antibiotics for their primary or recurrent C. difficile infections. The participants in the study received either an infusion of bezlotoxumab (10 mg per kg of body weight), actoxumab with bezlotoxumab (10 mg per kg each) or a placebo (saline). In the MODIFY I study, actoxumab alone (10 mg per kg) was administered but discontinued after a planned interim, the researchers explained.

“About one in four patients who have been treated with antibiotics for an initial C. difficile infection will go on to have a repeat infection,” study author Mark H. Wilcox, MD, explained in a press release. “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. difficile infection optimally, as each recurrence increases the chance of another episode even more. Fewer recurrent infections would mean less need to use antibiotics, fewer hospital admissions, reduced costs for the NHS and possibly a reduction in deaths.”

After a follow up period of 12 weeks, the researchers found that about a quarter of the actoxumab patients developed another C. difficile infection, while 15% patients in the actoxumab with bezlotoxumab group developed another infection. For patients in the bezlotoxumab only group, 17% of those patients developed a subsequent infection. About a quarter of the placebo patients developed another C. difficile infection.

About 80% of the patients treated with bezlotoxumab alone were categorized as clinically cured by the researchers, plus 73% of the patients treated with actoxumab plus bezlotoxumab. The researchers also determined that 80 percent of the placebo patients were also clinically cured. The sustained cure rates — which the investigators defined as initial clinical cure without recurrent infection after 12 weeks – were 64%, 58%, and 54%, respectively.

“The studies showed that bezlotoxumab was particularly effective in those patients with risk factors for poor outcome, including older age, immunocompromise, and severe infection,” Wilcox added. “"Doctors should now consider which patients could best benefit from use of bezlotoxumab.”

The most common adverse events in the groups were diarrhea and nausea, and the researchers added that the rates of these adverse events were similar among the groups.

The paper, which was titled “Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection,” was published in the New England Journal of Medicine.

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