Efficacy of oral vancomycin prophylaxis for prevention of Clostridioides difficile infection: a systematic review and meta-analysis

Abstract

Background: Prevention of recurrent Clostridioides difficile infection (CDI) is a challenge in clinical practice, particularly in patients who need systemic antimicrobial therapy. We aimed to evaluate the role of oral vancomycin prophylaxis (OVP) in prevention of primary or future CDI in patients on systemic antimicrobial therapy. Methods: A systematic search of MEDLINE, Embase, and Web of Science was performed from 2000 to January 2020. We included case-control or cohort studies that included patients on systemic antimicrobial therapy who did or did not receive oral vancomycin prophylaxis (OVP) and were evaluated for development of CDI. Odds ratio (OR) estimates with 95% confidence intervals (CI) were calculated. Results: Four studies including 1352 patients evaluated OVP for primary CDI prevention, with CDI occurring in 29/402 patients on OVP (7.4%) compared with 10.4% (99/950) without OVP. Meta-analysis revealed no significant decrease in risk of CDI in patients who received OVP (OR, 0.18; 95% CI, 0.03–1.03; p = 0.06). There was significant heterogeneity with I2 = 76%. Ten studies including 9258 patients evaluated OVP for secondary CDI prevention. Future CDI occurred in 91/713 patients on OVP (13.3%) compared with 21.9% (1875/8545) who did not receive OVP. Meta-analysis revealed a statistically significant decreased risk of future CDI (OR, 0.34; 95% CI, 0.20–0.59; p < 0.00001). Significant heterogeneity was seen with I2 = 59%. Discussion: Based on observational data, OVP appears to decrease the risk of future CDI in patients with prior CDI who require systemic antimicrobial therapy. However, OVP was not effective for primary prevention of CDI.

Oral Vancomycin Prophylaxis for Primary and Secondary Prevention of Clostridioides difficile Infection in Patients Treated with Systemic Antibiotic Therapy: A Systematic Review, Meta-Analysis and Trial Sequential Analysis

“…There are key differences between the present work and the two previous meta-analyses [ 44 , 45 ]. Babar and colleagues included fewer studies and, performing several meta-regression analyses, did not investigate the impact of OVP duration [ 44 ].…”

“…To the best of our knowledge, this is the first systematic review and meta-analysis with trial sequential analysis addressing the clinical question of the effectiveness of OVP in CDI prevention in persons undergoing SAT. Two earlier meta-analyses have been published on the topic [ 44 , 45 ] that informed a recent guideline endorsed by the American College of Gastroenterology (ACG) [ 46 ]. ACG experts conditionally recommend OVP for secondary CDI prevention in high-risk patients undergoing SAT, although the recommendation is supported by low-quality evidence [ 46 ].…”

“…On the other hand, among the many variables tested, they showed that higher doses of OVP may magnify the risk of CDI, also accounting for 100% of heterogeneity among studies [ 44 ]; this finding is coherent with results of our work, since from subgroup analysis the lowest OVP dosage (125 mg once daily) emerged as the best. Tariq and collaborators included 14 studies, but one-third (5 out of 14) were conference presentations [ 45 ]. In the former meta-analysis, the OR for CDI onset associated with OVP use was 0.26 (95% CI 0.13–0.52), in the latter 0.34 (95% CI 0.20–0.59).…”

“…The strengths of our work include a comprehensive literature search with rigorous inclusion criteria, excluding works not published in full. Furthermore, as opposed to previous meta-analyses on the topic [ 44 , 45 ], we followed a detailed statistical framework to deal with zero-event studies [ 13 ] and performed a TSA, a powerful tool to assess the conclusiveness of meta-analyses [ 66 ]. Furthermore, we conducted several sensitivity and quantitative bias analyses, eventually carefully assessing the available evidence according to the GRADE system.…”

My Treatment Approach to Clostridioides difficile Infection

“…However, oral vancomycin prophylaxis was not effective for primary prevention of C difficile infection. 65 Scientifically, vancomycin does not eliminate C difficile spores but does eliminate the vegetative forms. In addition, it is a broadspectrum antibiotic leading to widespread microbiome perturbation and could potentially increase the risk of C difficile infection.…”