A network meta-analysis of randomized controlled trials has identified fecal microbiota transplantation as the most effective treatment for Clostridioides difficile infections, particularly in recurrent cases.
In the study, published in The Lancet Regional Health–Europe, investigators analyzed data from 73 randomized controlled trials involving 27,959 adult patients. They found that fidaxomicin outperformed vancomycin in recurrent C difficile infections, while probiotics showed no statistically significant benefit for prevention.
The meta-analysis compared 28 C difficile infection treatments across five networks. Fecal microbiota transplantation (FMT) demonstrated the highest overall cure rate (P-score: .9952) and was the most effective for recurrent C difficile infections (P-score: .9836). Among antibiotic therapies for recurrent C difficile infections, fidaxomicin (P-score: .6734) was significantly more effective compared with vancomycin (P-score: .3677) and tolevamer (P-score: .0365).
For nonrecurrent C difficile infections, ridinilazole, fidaxomicin, FMT, and nitazoxanide showed comparable efficacy. In preventing recurrence, ridinilazole (P-score: .7671) and fidaxomicin (P-score: .7627) emerged as the most effective.
FMT administration via oral and colonoscopic routes yielded similar efficacy. Probiotics, however, did not demonstrate effectiveness in preventing C difficile infections compared with placebo in network meta-analyses. A subgroup analysis suggested that Lactobacillaceae species were more effective than placebo for prevention.
The systematic review included randomized controlled trials published up to August 19, 2024, sourced from MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. The investigators applied a frequentist random-effects meta-analysis, reporting odds ratios with 95% confidence intervals. The study was preregistered in PROSPERO (CRD42022371210).
Risk of bias among the included studies ranged from low to high, with noted heterogeneity in therapeutic doses, treatment durations, and follow-up periods.
"Our findings could inform [C difficile infection] treatment guidelines, prioritizing FMT, especially in recurrent cases, and fidaxomicin in nonrecurrent cases. Our data may urge the reconsideration of probiotic administration with preventative aims," said lead study author Dániel Steve Bednárik, of the Centre for Translational Medicine at Semmelweis University in Hungary, and colleagues.
The investigators emphasized the need for further research to optimize FMT protocols and assess its long-term safety and efficacy.
No conflicts of interest were disclosed in the study.
