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Antibiotics and hospital-associated Clostridioides difficile infection: systematic review and meta-analysis 2020 update.

Background: Clostridioides difficile infection (CDI) is the most common cause of healthcare facility associated (HCFA) infectious diarrhoea in high income countries. Antibiotic use is the most important modifiable risk factor for CDI. The most recent systematic review covered studies published until 31st December 2012. Objectives: To update the evidence for epidemiological associations between specific antibiotic classes and HCFA CDI for the period 1st January 2013 to 31st December 2020. Data sources: PubMed, Scopus, Web of Science Core Collection, WorldCat, and Proquest Dissertations and Theses. Study eligibility criteria, participants and exposures: Eligible studies were those conducted among adult hospital inpatients, measured exposure to individual antibiotics or antibiotic classes, included a comparison group, and measured the occurrence of HCFA CDI as an outcome. Study appraisal and synthesis methods: The Newcastle Ottawa Scale for the Assessment of Quality was used to appraise study quality. To assess the association between each antibiotic class and HACDI, a pooled random effects meta-analysis was undertaken. Metaregression and sub-group analysis was used to investigate study characteristics identified a priori as potential sources of heterogeneity. Results: Carbapenems, and 3rd and 4th generation cephalosporin antibiotics remain most strongly associated with HCFA CDI, with cases more than twice as likely to have recent exposure to these antibiotics prior to developing CDI. Modest associations were observed for fluoroquinolones clindamycin, and betalactamase inhibitor combination penicillin antibiotics. Limitations: Individual study effect sizes were variable and heterogeneity was observed for most antibiotic classes. Availability of a single reviewer to select, extract and critically appraise the studies. Conclusions: This review provides the most up to date synthesis of evidence in relation to the risk of HCFA CDI associated with exposure to specific antibiotic classes. Studies were predominantly conducted in North America or Europe and more studies outside of these settings are needed.