Dose addition of intravenous metronidazole to oral vancomycin improve outcomes in Clostridioides difficile infection?

Abstract

Abstract Background Guidelines recommend adding intravenous (IV) metronidazole to oral vancomycin for fulminant Clostridioides difficile infection (CDI). This study compared dual therapy with IV metronidazole and oral vancomycin versus vancomycin monotherapy. It assessed prevalence of use and effectiveness of dual therapy in non-fulminant and fulminant CDI. Methods This was a two-center retrospective study conducted from 2010 to 2018. Adult inpatients were included if they had a positive C. difficile PCR performed on an unformed stool and received oral vancomycin within two days (either before or after) of testing. Patients were classified as having received dual therapy if IV metronidazole was given within the same time window, and otherwise as having received vancomycin monotherapy. The primary outcome was  death or colectomy within 90 days after the index test. Logistic regression modeling was used to adjust for CDI severity and other established predictors of CDI outcomes. CDI recurrence was examined as a secondary outcome, adjusting for death as a competing risk. Results The study included 2,114 patients (dual therapy: 993; monotherapy: 1,121) of whom 23% met the primary outcome. There was no association between dual therapy and the primary outcome (adjusted OR (aOR) 1.07, 95% CI 0.79-1.45) which remained true when the analysis was restricted to patients with fulminant CDI (aOR 1.17, 95% CI 0.65-2.10). There was also no association between dual therapy and CDI recurrence. Conclusions Dual therapy with IV metronidazole and oral vancomycin was common for non-fulminant and fulminant CDI, but was not associated with improved outcomes compared to vancomycin alone.