Prognostic factors for severe and recurrent Clostridioides difficile infection: a systematic review

Abstract Background Clostridioides difficile infection (CDI), its subsequent recurrences (rCDI), and severe CDI (sCDI) provide a significant burden for both patients and the healthcare system. Identifying patients diagnosed with initial CDI who are at increased risk of developing sCDI/rCDI could lead to more cost-effective therapeutic choices. Objectives In this systematic review we aimed to identify clinical prognostic factors associated with an increased risk of developing sCDI or rCDI. Methods . Data sources PubMed, Embase, Emcare, Web of Science and COCHRANE Library databases were searched from database inception through March, 2021. Study eligibility criteria Cohort and case-control studies. Participants Patients ≥18 years diagnosed with CDI. Exposure Clinical or laboratory factors analyzed to predict sCDI/rCDI. Assessment risk of bias Quality in Prognostic Research (QUIPS) tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool modified for prognostic studies. Methods of data synthesis Study selection was performed by two independent reviewers. Overview tables of prognostic factors were constructed to assess the number of studies and the respective effect direction and statistical significance of an association. Results 136 studies were included for final analysis. Higher age and the presence of multiple comorbidities were prognostic factors for sCDI. Identified risk factors for rCDI were higher age, healthcare-associated CDI, prior hospitalization, PPIs started during/after CDI diagnosis and previous rCDI. Conclusions Prognostic factors for sCDI and rCDI could aid clinicians to make treatment decisions based on risk stratification. We suggest that future studies use standardized definitions for sCDI/rCDI and systematically collect and report the risk factors assessed in this review, to allow for meaningful meta-analysis on risk factors using data of high-quality trials.