Fidaxomicin Top Choice for Treating C difficile

Fidaxomicin provides a sustained symptomatic cure for Clostridium difficile infection most frequently, according to a new meta-analysis.

For the meta-analysis, investigators from the University of Leeds in the United Kingdom searched databases such as Medline, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their dates of creation until June 2017 and identified more than 23,000 clinical trials. They then narrowed the search down to 24 relevant randomized controlled trials of treatments for nonrecurrent C difficile infection cases in adults that reported both the primary cure and recurrence rates. These included information on 5000 patients and 13 different treatments. The overall quality of the evidence was rated as “moderate to low.”

The investigators examined the cases further for sustained symptomatic cure rates (defined as the number of patients with resolution of diarrhea, subtracting the number with recurrence or death). The most effective and sustainable treatments for C difficile infection were then compared and ranked.

According to the results, fidaxomicin and teicoplanin were significantly better than vancomycin in reaching sustained symptomatic cures. Furthermore, teicoplanin, ridinilazole, fidaxomicin, surotomycin, and vancomycin were all better than metronidazole in achieving sustained symptomatic cures. (Metronidazole ranked 11th of the 13 options included in the analysis.) Teicoplanin and fidaxomicin were both better than bacitracin in the same measures, and tolevamar was found to be inferior to all drugs except for LFF571 and bacitracin.

“Among the treatments for non-multiply recurrent infections by C difficile, the highest quality evidence indicates that fidaxomicin provides a sustained symptomatic cure most frequently,” the investigators wrote. “Fidaxomicin is a better treatment option than vancomycin for all patients except those with severe infections with C difficile and could be considered as a first-line therapy. Metronidazole should not be recommended for treatment of C difficile.”

In a related editorial, Herbert L. DuPont, MD, from the University of Texas Medical School and Public Health, Houston, agreed that metronidazole should not be widely used, except as a last resort. He described a situation where despite its inferiority, metronidazole could be used if oral drugs cannot be used and then it could be administered intravenously with other treatments.

Additionally, he noted that in the United States, medical practitioners are too often focused on the least expensive approved drug, which may, in fact, cost our societies more in the long run.

He concluded that, “Future research [on treatments for C difficile] should include the study of intermittent and tapering drug dosing or the administration of longer term (3—4 weeks or longer) low-dose (sub-therapeutic) suppressive drug administration with various drugs for C difficile treatment, after a standard course of treatment to prevent future recurrences.”

The studies, “Search for the optimal antimicrobial therapy of Clostridium difficile infection” and “Comparative efficacy of treatments for Clostridium difficile infection: a systematic review and network meta-analysis,” were published in The Lancet Infectious Diseases.