GRADING prognostic factors for severe and recurrentClostridioides difficileinfection: expected and unexpected findings. A systematic review

AbstractBackgroundClostridioides difficileinfection (CDI), its subsequent recurrences (rCDI), and severe CDI (sCDI) provide a significant burden for both patients and the healthcare system. Treatment consists of oral antibiotics. Fidaxomicin, bezlotoxumab and fecal microbiota transplantion (FMT) reduce the number of recurrences compared to vancomycin, but are more costly. Identifying patients diagnosed with initial CDI who are at increased risk of developing sCDI/rCDI could lead to more cost-effective therapeutic choices.ObjectivesIn this systematic review we aimed to identify clinical prognostic factors associated with an increased risk of developing sCDI or rCDI.MethodsPubMed, Embase, Emcare, Web of Science and COCHRANE Library databases were searched from database inception through March, 2021. Study selection was performed by two independent reviewers on the basis of predefined selection criteria; conflicts were resolved by consensus. Cohort and case-control studies providing an analysis of clinical or laboratory data to predict sCDI/rCDI in patients ≥18 years diagnosed with CDI, were included. Risk of bias was assessed with the Quality in Prognostic Research (QUIPS) tool and the quality of evidence by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool, modified for prognostic studies. Overview tables of prognostic factors were constructed to assess the number of studies and the respective direction of an association (positive, negative, or no association).Results and conclusions136 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. Some variables that were found as risk factors for sCDI/rCDI in previous reviews were not confirmed in the current review, which can be attributed to differences in methodology. Risk stratification for sCDI/rCDI may contribute to a more personalized and optimal treatment for patients with CDI.