206 Oral Vancomycin Prophylaxis for the Primary and Secondary Prevention of Clostridium difficile Infection: A Systematic Review and Meta-Analysis

Abstract

INTRODUCTION: Clostridium difficile infection (CDI) is the leading cause of infectious healthcare-associated diarrhea. It is a major cause of in-hospital morbidity and increased healthcare costs. Past research has identified populations at high risk of CDI. However, there is no current consensus on CDI prophylaxis. Oral vancomycin prophylaxis (OVP) has been suggested for the primary and secondary prevention of CDI. Therefore, we have conducted a comprehensive systematic review and meta-analysis to investigate the role of OVP in CDI prevention in published literature. METHODS: A computerized search of MEDLINE, EMBASE and Cochrane databases from inception to March 2019 for publications investigating OVP for CDI prevention. Results were screened for relevance and eligibility criteria. Relevant data was extracted and analyzed using Comprehensive Meta Analysis software. Publication bias was assessed for using Egger's test. P < 0.05 was considered significant. RESULTS: Six retrospective cohort studies with total of 1263 patients published between 2016–2019 were included. OVP use was associated with lower CDI (OR 0.175, CI 0.06–0.52) with considerable heterogeneity (I2 67%). OVP use was associated with lower CDI in immunocompromised (OR 0.072 CI 0.01–0.92) (I2 30.8%) as well as immunocompetent (OR 0.22, CI 0.07–0.69) (I2 71%) patients. The reduction in CDI was noted when OVP was used for primary (OR 0.04, CI 0.01–0.27) (I2 0%) as well as secondary (OR 0.27, CI 0.10–0.76) (I2 64%) prevention. Meta regression analysis showed that total daily dose of OVP was correlated to OR of CDI and was able to explain 100% of heterogeneity noted between studies. Only two studies evaluated the risk of VRE emergence in treated populations and found no significant increase. No publication bias was found using Egger's test. CONCLUSION: Our results suggest that the use of OVP was associated with lower CDI rates in at-risk populations. Higher daily doses of OVP were associated with higher rates of CDI suggesting that a lower OVP dose might be more effective for CDI prevention. While it might be prudent for physicians to prescribe OVP for high risk patients, the total daily dose, duration of treatment and long term side-effects are yet to be determined. These questions should be further evaluated with randomized controlled trials.