Clostridium difficile Recurrence Prevented with Bezlotoxumab

Rachel Lutz

The timing of administrating the drug didn’t seem to matter in terms of efficacy.

Mary Beth Dorr, PhD

Bezlotoxumab is effective in preventing Clostridium difficile (C. difficile) infection recurrence as long as it is administered any time before suspending antibacterial drug treatment, as demonstrated in a recent study.

Researchers from New Jersey conducted a study of 1554 patients with C. difficile infection in order to understand if the timing of bezlotoxumab administration affected clinical outcome with respect to the onset of C. difficile. Between November 2011 and May 2015, there were 781 patients who received bezlotoxumab while 773 patients received a placebo. Of those patients, 649 of them received a transfusion between 0 and 2 days after onset of antibacterial treatment for their C. difficile infection; 469 patients received their transfusion between 3 and 4 days after onset; and 436 patients received their transfusion after 5 or more days. The researchers also reported that baseline characteristics among the bezlotoxumab and placebo groups were generally similar.

In this study researchers defined the initial clinical cure as having no diarrhea during 2 consecutive days following 16 days of antibacterial drug treatment for C. difficile infection. The initial clinical cure rates were similar in all groups, the study authors reported, and treatment administered or timing of administration did not significantly matter.

“Bezlotoxumab, which is an antibody that binds to and neutralizes toxin B (the cause of the symptoms of C. difficile infection), does not treat the original infection—it prevents the infection from coming back after the antibiotic is stopped,” study author Mary Beth Dorr, PhD, told MD Magazine. “The implication of this finding is there can be flexibility for when the infusion is given, which facilitates administration in an outpatient setting. It can be given as early as the day antibiotic treatment is started, or it can be given later in the course of antibiotic treatment, after the patient is feeling better. This flexibility also allows time for the medication to be ordered and for the patient to schedule an appointment at an outpatient infusion center.”

Additionally, investigators said rates of recurrent C. difficile infection were lower with bezlotoxumab compared to placebo across all infusion timing groups, and the adjusted difference between the 2 groups was similar, regardless of the timing of infusions.

In both the groups, the time to resolution of diarrhea was similar, where about 70% of the patients who received antibacterial treatment for 3 or more days prior to their infusion no longer had diarrhea at the time of the infusion. The researchers said 95% of the study participants resolved their diarrhea in both the bezlotoxumab and placebo groups, regardless of the timing of their infusion.

The researchers originally suspected that administration after early onset symptoms could improve outcomes in patients with severe C. difficile infection, however, in their study, only 17% of participants were administered the infusion within the first 2 days of onset, leading to too small of a sample size to further examine this hypothesis.

The paper, titled “Efficacy of bezlotoxumab based on timing of administration relative to start of antibacterial therapy for Clostridium difficile infection,” was published in the Journal of Antimicrobial Chemotherapy.