External Validation and Comparison of Clostridioides difficile Severity Scoring Systems

Abstract

Background Many models have been developed to predict severe outcomes from Clostridioides difficile infection. These models are usually developed at a single institution and largely are not externally validated. This aim of this study was to validate previously published risk scores in a multicenter cohort of patients with CDI. Methods Retrospective study on four separate inpatient cohorts with CDI from three distinct sites: The Universities of Michigan (2010-2012 and 2016), Chicago (2012), and Wisconsin (2012). The primary composite outcome was admission to an intensive care unit, colectomy, and/or death attributed to CDI within 30 days of positive testing. Both within each cohort and combined across all cohorts, published CDI severity scores were assessed and compared to each other and the IDSA guideline definitions of severe and fulminant CDI. Results A total of 3,646 patients were included for analysis. Including the two IDSA guideline definitions, fourteen scores were assessed. Performance of scores varied within each cohort and in the combined set (mean area under the receiver operator characteristic curve(AUC 0.61, range 0.53-0.66). Only half of the scores had performance at or better than IDSA severe and fulminant definitions (AUCs 0.64 and 0.63, respectively). Most of the scoring systems had more false than true positives in the combined set (mean: 81.5%, range:0-91.5%). Conclusions No published CDI severity score showed stable, good predictive ability for adverse outcomes across multiple cohorts/institutions or in a combined multicenter cohort.

The gut bacterial community potentiates Clostridioides difficile infection severity

“…Furthermore, there is variation in the genome, growth rate, sporulation, germination, and toxin production in different isolates of a strain (34)(35)(36)(37). This variation may help explain why severe CDI prediction tools often miss identifying many patients with CDI that will develop severe disease (3,23,38,39). Therefore, it is necessary to gain a full understanding of all factors contributing to disease variation to improve our ability to predict severity.…”

“…Since these measures are CDI outcomes, they have limited ability to predict risk of severe CDI when the infection is first detected. Schemes have been developed to score a patient’s risk for severe CDI outcomes based on clinical factors but have not been robust for broad application (3). Thus, we have limited ability to prevent patients from developing severe CDI.…”

A Predictive Model to Identify Complicated Clostridiodes difficile Infection

“…While several CDI severity and complication scoring systems have been developed previously, they generally were developed from single centers and were not externally validated [5][6][7][8][9][10][11][12][13][14]. Our group recently published the largest external validation of published CDI severity scoring systems and found that all models yielded AUC scores below 70% suggesting that current models are not generalizable and cannot reliably predict severe complications from CDI [15].…”

“…We conducted a multi-center retrospective longitudinal cohort study at four geographically and temporally distinct cohorts, including the University of Michigan (2010)(2011)(2012)(2015)(2016), University of Wisconsin (2014Wisconsin ( -2015, and University of Chicago (2013)(2014)(2015), as previously described by Perry et al [15]. Adult subjects ≥18 years who were diagnosed with CDI were included in our analysis.…”

“…Current risk scores developed to identify patients at high risk for complicated CDI, have limited generalizability due to being developed in small, single-center cohorts or having not undergone rigorous external or prospective validation [5][6][7][8][9][10][11][12][13][14]. Recently, our group demonstrated that published CDI severity scoring systems performed poorly when tested on a large, multicenter cohort within the US [15]. Thus, an accurate prediction model that can be easily applied early after CDI diagnosis is needed to identify patients at risk for complicated CDI and to facilitate effective therapy that minimizes the risk for adverse CDI outcomes.…”