Does Addition of Intravenous Metronidazole to Oral Vancomycin Improve Outcomes in Clostridioides difficile Infection?

Background: Guidelines recommend adding intravenous (IV) metronidazole to oral vancomycin for fulminant Clostridioides difficile infection (CDI). In this study, we compared dual therapy with IV metronidazole and vancomycin vs vancomycin monotherapy. We assessed prevalence of use and effectiveness of dual therapy in nonfulminant and fulminant CDI.

Methods: This was a 2-center retrospective study conducted from 2010 to 2018. Adult inpatients were included if they had a positive C. difficile polymerase chain reaction (PCR) performed on an unformed stool and received vancomycin within 2 days of testing. Patients were classified as having received dual therapy if IV metronidazole was given within the same time window, and otherwise classified as 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 2114 patients (dual therapy, 993; monotherapy, 1121); 23% met the primary outcome. There was no association between dual therapy and the primary outcome (adjusted odds ratio [aOR], 1.07; 95% confidence interval [CI], .79-1.45), which remained true when the analysis was restricted to patients with fulminant CDI (aOR, 1.17; 95% CI, .65-2.10). There was also no association between dual therapy and CDI recurrence.

Conclusions: Dual therapy with IV metronidazole and vancomycin was common for nonfulminant and fulminant CDI but was not associated with improved outcomes compared with vancomycin alone.