Abstract
Background: Clostridioides difficile infection (CDI) is associated with substantial morbidity and mortality as well as high propensity of recurrence. Systemic antibiotic therapy (SAT) represents the top inciting factor of CDI, both primary and recurrent (rCDI). Among the many strategies aimed to prevent CDI in high-risk subjects undergoing SAT, oral vancomycin prophylaxis (OVP) appears promising under a cost-effectiveness perspective. Methods: A systematic review with meta-analysis and trial sequential analysis (TSA) of studies assessing the efficacy and the safety of OVP to prevent primary CDI and rCDI in persons undergoing SAT was carried out. PubMed and EMBASE were searched until 30 September 2021. The protocol was pre-registered on PROSPERO (CRD42019145543). Results: Eleven studies met the inclusion criteria, only one being a randomized controlled trial (RCT). Overall, 929 subjects received OVP and 2011 represented the comparator group (no active prophylaxis). OVP exerted a strong protective effect for CDI occurrence: odds ratio 0.14, 95% confidence interval 0.04–0.38. Moderate heterogeneity was observed: I2 54%. This effect was confirmed throughout several subgroup analyses, including prevention of primary CDI versus rCDI. TSA results pointed at the conclusive nature of the evidence. Results were robust to a variety of sensitivity and quantitative bias analyses, although the underlying evidence was deemed as low quality. No differences between the two groups were highlighted regarding the onset of vancomycin-resistant Enterococcus infections. Conclusions: OVP appears to be an efficacious option for prevention of CDI in high-risk subjects undergoing SAT. Nevertheless, additional data from RCTs are needed to establish OVP as good clinical practice and define optimal dosage and duration.
Highlights
Clostridioides difficile infection (CDI) is a leading cause of antibiotic-associated diarrhea (AAD), being implicated in 10–25% cases of AAD, as well as most cases of pseudomembranous colitis [1]
American College of Gastroenterology (ACG) experts conditionally recommend oral vancomycin prophylaxis (OVP) for secondary CDI prevention in high-risk patients undergoing Systemic antibiotic therapy (SAT), the recommendation is supported by low-quality evidence [46]
The ESCMID committee does not support the routine use of anti-CDI antibiotics during SAT, leaving a window open for very select patients with a history of multiple recurrent CDI (rCDI) incited by SAT, always after careful balancing of the risks and benefits, preferably with the support of an infectious disease or a clinical microbiology specialist [48]
Summary
Clostridioides (formerly known as Clostridium) difficile infection (CDI) is a leading cause of antibiotic-associated diarrhea (AAD), being implicated in 10–25% cases of AAD, as well as most cases of pseudomembranous colitis [1]. Colonization is favored by the profound modification in the intestinal microbiota, that, in turn, may depend on either exogenous or host-related risk factors [4]. Among the former, pharmacological agents such as antibiotics and gastric acid suppressants (proton pump inhibitors, H2-receptor antagonists) stand out along with corticosteroids and nonsteroidal anti-inflammatory drugs; other exogenous determinants include invasive procedures and abdominal surgery [4]. Among the many strategies aimed to prevent CDI in high-risk subjects undergoing SAT, oral vancomycin prophylaxis (OVP) appears promising under a cost-effectiveness perspective. Conclusions: OVP appears to be an efficacious option for prevention of CDI in high-risk subjects undergoing SAT. Additional data from RCTs are needed to establish OVP as good clinical practice and define optimal dosage and duration
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