16 March 2017

New FDA-Approved Drug Proven Effective in Reducing Recurrent C. diff Infections

Among the healthcare associated infections that may arise during a patient’s hospitalization, Clostridium difficile is an especially dangerous ailment due to its easy dissemination and antibiotic resistance. Transmission may occur if medical staff touch surfaces contaminated with feces during and between treatment of patients. The few available antibiotics that can be used to treat the initial infection do not prevent its recurrence in about 20 percent of those affected. To improve the efficacy of current standard-of-care antibiotic treatments, the healthcare community has long sought after an antibiotic that will further reduce the rate of C. diff infection recurrence. According to a study published in the January 2017 New England Journal of Medicine, researchers seem to have found an antibiotic capable of treating recurrent C. diff.

In two extensive, double-blind trials conducted between 2011 and 2015, researchers tested the effects of actoxumab and bezlotoxumab on 2,655 patients receiving standard-of-care antibiotic treatments for their C. diff infections. Actoxumab and bezlotoxumab are human monoclonal antibodies designed to bind to and neutralize C. diff toxins A and B, respectively, thereby preventing infection recurrence. In separate studies known as MODIFY I and MODIFY II, patients were given antibiotic treatments that fell into four test groups: actoxumab-only, bezlotoxumab-only, both actoxumab and bezlotoxumab and a placebo.

At the end of each 12-week study, researchers found that C. diff infection recurred significantly less frequently in patients who received bezlotoxumab alone or both actoxumab and bezlotoxumab when compared with the placebo. In MODIFY I, the rate of recurrence was 17 percent under bezlotoxumab alone and 16 percent under the combined treatment, while recurrence under placebo was 26 percent. MODIFY II showed nearly identical results with 16 percent recurrence under bezlotoxumab, 15 percent under both antibiotics and 26 percent under placebo. 

To confirm that bezlotoxumab was the cause of reduction in infection recurrence, during MODIFY I, researchers compared results of the actoxumab-only group and the placebo group. Patients in these groups demonstrated similarly high recurrence rates of 26 percent and 28 percent. When researchers supplemented patients’ antibiotic treatments with actoxumab, they found high rates of adverse effects such as diarrhea and nausea following frequent C. diff infections. Adverse effects occurred at 67 percent under actoxumab alone, 61 percent under bezlotoxumab alone, 58.6 percent under combined actoxumab and bezlotoxumab and 61.2 percent under placebo. 

Overall, researchers concluded that bezlotoxumab accounted for a significant 38 percent reduction in C. diff infection recurrence when combined with standard-of-care therapy. As a result of MODIFY I and MODIFY II, the U.S. Food and Drug Administration recently approved the use of bezlotoxumab for C. diff infection treatments. While further research is warranted, the findings are a promising development toward the potential eradication of this costly and debilitating healthcare concern.