For the treatment of Clostridium difficile (C difficile) infection, fidaxomicin was found to be more effective than metronidazole in providing a long-term cure, according to a study published in The Lancet

A team of investigators from the United Kingdom conducted a systematic review and network meta-analysis of MEDLINE, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and for trials conducted until June 30, 2017, to compare various treatments of C difficile.  Included trials involved patients who aged ≥18 years and had confirmed infections of C difficile, defined as active diarrhea and a positive C difficile nucleic acid amplification test, a positive C difficile cytotoxin assay result, a stool culture that showed C difficile, or pseudomembranes identified on colonoscopy. 

The primary outcome was sustained symptomatic cure, which was determined by subtracting the number of patients with recurrence or who died during follow-up from the number of patients with a cure of diarrhea at the end of treatment. Secondary outcomes included primary cure of diarrhea and recurrence rate of diarrhea.

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A total of 24 studies that included 5361 patients were included in the meta-analyses (mean study sample size, 223 patients). All studies were published between 1983 and 2017. Most listed follow-up time between 21 and 30 days; one study reported outcomes at 56 days, and another reported outcomes at 90 days. The most frequent treatment was vancomycin (n=2107 participants), followed by fidaxomicin (n=881) and metronidazole (n=563). Duration of treatment ranged from 4 to 25 days.

Teicoplanin (odds ratio [OR] 0.37) and fidaxomicin (OR 0.67) were found to be significantly more effective than vancomycin in achieving sustained symptomatic cure. Vancomycin, teicoplanin, ridinidazole, fidaxomicin, and surotomycin were all more effective than metronidazole. No treatment was found to be significantly superior to vancomycin for primary symptomatic cure. Significantly fewer associated recurrences were reported with fidaxomicin compared with vancomycin and metronidazole.

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“The findings of this network meta-analysis suggest that, of the currently approved treatments, fidaxomicin has the strongest evidence for being the most effective treatment in providing a long-term cure against C difficile,” the authors concluded. “Apart from affordability, there is little evidence to support use of metronidazole as a first-line treatment against infections with C difficile.”

Please refer to the article for a full list of author disclosures.


Beinortas T, Burr NE, Wilcox MH, Subramanian V. Comparative efficacy of treatments for Clostridium difficile infection: a systematic review and network meta-analysis [published online July 16, 2018]. Lancet.