Beinortas T, et al. - In this random effects network meta-analysis, researchers compared and ranked treatments for non-multiply recurrent infections with Clostridium difficile in adults. By the highest quality evidence, most frequent symptomatic cure was offered by fidaxomicin. Furthermore, fidaxomicin demonstrated better therapeutic efficacy than vancomycin in all patients except for those with severe infections with C difficile and could be considered as a first-line therapy. Findings suggested not to go for metronidazole to treat C difficile.

Methods

• This meta-analysis was performed within a frequentist setting to obtain direct and indirect comparisons of trials.
• From the inception until June 30, 2017, MEDLINE, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched for published and unpublished trials.
• Researchers included randomised controlled trials of treatments for non-multiply recurrent infections with confirmed C difficile in adults (at least 18 years) that reported both primary cure and recurrence rates.
• Using the Cochrane Risk of Bias tool, they appraised trial methods.
• They extracted the total numbers of patients with primary cure and recurrence.
• They sought for sustained symptomatic cure, defined as the number of patients with resolution of diarrhoea minus the number with recurrence or death.

Results

• The analysis included 24 trials, comprising 5,361 patients and 13 different treatments, of 23,004 studies screened.
• The overall quality of evidence was rated as moderate to low.
• Fidaxomicin (odds ratio 0·67, 95% CI 0·55–0·82) and teicoplanin (0·37, 0·14–0·94) were significantly better than vancomycin in terms of providing sustained symptomatic cure.
• Compared with metronidazole, teicoplanin (0·27, 0·10–0·70), ridinilazole (0·41, 0·19–0·88), fidaxomicin (0·49, 0·35–0·68), surotomycin (0·66, 0·45–0·97), and vancomycin (0·73, 0·56–0·95) were found to be better.
• According to findings, bacitracin was found inferior to teicoplanin (0·22, 0·06–0·77) and fidaxomicin (0·40, 0·17–0·94), and tolevamer was found to be inferior to all drugs except for LFF571 (0·50, 0·18–1·39) and bacitracin (0·67, 0·28–1·58).
• A low global heterogeneity of the entire network was reported (Cochran's Q=15·70; p=0·47).