Clin Microbiol Infect. 2023 Sep 8:S1198-743X(23)00420-2. doi: 10.1016/j.cmi.2023.09.002. Online ahead of print.
BACKGROUND: Current practice guidelines favour fidaxomicin over vancomycin and exclude metronidazole from the recommended standard regimen for Clostridioides difficile infection (CDI), based on lower recurrence rates with fidaxomicin, giving little weight to mortality or the clinical implications of recurrences.
OBJECTIVES: To compile the effects of metronidazole, glycopeptides (vancomycin or teicoplanin) and fidaxomicin for CDI on mortality and other patient-relevant outcomes.
DATA SOURCES: PubMed, the Cochrane Library, ClinicalTrials.gov, conference proceedings and Google Scholar, until August 2023 STUDY ELIGIBILITY: Randomised controlled trials (RCTs).
PARTICIPANTS: Adult patients experiencing primary or recurrent CDI.
INTERVENTIONS: Glycopeptides versus fidaxomicin or metronidazole (comparators).
RISK OF BIAS ASSESSMENT: We used the RoB 2 tool for randomised trials, focusing on the outcome of all-cause mortality.
DATA SYNTHESIS: Random effects meta-analyses were performed for dichotomous outcomes. Outcomes were summarized preferentially for all randomized patients.
RESULTS: Thirteen trials were included. There was no significant difference in all-cause mortality (RR<1 favouring the comparator) between vancomycin and fidaxomicin (RR 0.86, 95% CI 0.64 to 1.14, 8 RCTs, 1951 patients) or metronidazole (RR 0.78, 95% CI 0.46 to 1.32, 4 RCTs, 808 patients), with low and very low certainty of evidence, respectively. No significant difference in initial treatment failure between fidaxomicin and vancomycin was found, however, initial treatment failure was higher with metronidazole (RR 1.58, 95% CI 1.10 to 2.27, 5 RCTs, 843 patients). No study reported on symptomatic recurrence necessitating re-treatment among all randomized patients. Among initially-cured patients, symptomatic recurrence necessitating re-treatment was lower with fidaxomicin than with vancomycin (RR 0.54, 95% CI 0.42 to 0.71, 6 RCTs, 1617 patients). None of the studies reported on other CDI complications or the burden of infection on daily activities.
CONCLUSIONS: Setting patient-relevant outcomes for CDI independently of the RCT definitions and results might lead to less confidence in the guidance for CDI management.