ABSTRACT
Aim: Recent guidelines recommended removing metronidazole as a therapeutic option for Clostridioides difficile infections (CDI). However, superiority of vancomycin over metronidazole in mild CDI is not established and use of vancomycin might lead to emergence of vancomycin-resistant enterococci (VRE). Patients & methods: A retrospective cohort study and efficacy analyses were conducted at Shamir Medical Center, Israel (2010-2015), among adults with acute CDI. Results: A total of 409 patients were enrolled. In multivariable analyses, metronidazole was noninferior to vancomycin for mild CDI, but vancomycin was an independent predictor for post-CDI VRE acquisition. Conclusion: A significant independent association was evident between treatment with vancomycin and, later, acquisition of VRE. In first episodes of mild acute CDI, metronidazole should be considered a valid therapeutic option.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Clostridium Infections/drug therapy , Drug Administration Schedule , Metronidazole/therapeutic use , Acute Disease/therapy , Adult , Aged , Aged, 80 and over , Clostridioides difficile/drug effects , Clostridium Infections/mortality , Female , Humans , Israel , Male , Middle Aged , Practice Guidelines as Topic , Retrospective Studies , Time Factors , Treatment Outcome , Vancomycin/pharmacology , Vancomycin/therapeutic use , Vancomycin-Resistant Enterococci/drug effects , Young AdultABSTRACT
BACKGROUND: The epidemiology of Clostridium difficile infections (CDI) have evolved dramatically in the past decade. Vancomycin is the treatment of choice for moderate to severe CDI. However, controlled comparative data pertaining to mild CDI is lacking. Furthermore, the potential impact of vancomycin treatment on subsequent vancomycin-resistant Enterococcus (VRE) isolation remains unknown. METHODS: A retrospective cohort analysis was executed at the Assaf Harofeh Medical Center, from 2013 to 2015. Adult patients (>18 years) with a first episode of acute CDI, determined per pre-established criteria, were enrolled. The efficacy of vancomycin vs. metronidazole among patients with mild CDI, and the independent association of oral vancomycin treatment during the acute CDI and later (up to 18 months) VRE isolation, was analyzed by logistic regression. RESULTS: A total of 260 patients with CDI were enrolled. The majority were elderly (75%), and 56% had moderate to severe disease. Among 75 patients with mild disease, no differences were observed in terms of clinical outcomes between vancomycin or metronidazole treatment. Metronidazole remained non-inferior even after incorporating a prediction score to control for confounders associated with being a "vancomycin case". In multivariable analysis, oral vancomycin treatment during the acute CDI was the strongest independent predictor for later isolation of VRE (aOR=74, p=0.004). CONCLUSIONS: Our study suggests that metronidazole should remain the recommended treatment of choice for mild CDI, due to clinical non-inferiority and an apparent association between vancomycin therapy and subsequent VRE isolation on an individual patient level analysis.
