Derivation and internal validation of the multivariate toxigenic C. difficile diarrhea model and risk score for emergency room and hospitalized patients with diarrhea

Abstract

Background: Many factors have been associated with the risk of toxigenic C. difficile diarrhea (TCdD). This study derived and internally validated a multivariate model for estimating the risk of TCdD in patients with diarrhea using readily available clinical factors.

Methods: A random sample of 3,050 symptomatic emergency department or hospitalized patients undergoing testing for toxigenic C. difficile at a single teaching hospital between 2014 and 2018 was created. Unformed stool samples positive for both glutamate dehydrogenase antigen by enzyme immunoassay and tcdB gene by polymerase chain reaction were classified as TCdD positive. The TCdD Model was created using logistic regression and was modified to the TCdD Risk Score to facilitate its use.

Results: 8.1% of patients were TCdD positive. TCdD risk increased with abdominal pain (adjusted odds ratio 1.3; 95% CI, 1.0-1.8), previous C. difficile diarrhea (2.5, 1.1-6.1), and prior antibiotic exposure, especially when sampled in the emergency department (4.2, 2.5-7.0) versus the hospital (1.7, 1.3-2.3). TCdD risk also increased when testing occurred earlier during the hospitalization encounter, when age and white cell count increased concurrently, and with decreased eosinophil count. In internal validation, the TCdD Model had moderate discrimination (optimism-corrected C-statistic 0.65, 0.62-0.68) and good calibration (optimism-corrected Integrated Calibration Index [ICI] 0.017, 0.001-0.022). Performance decreased slightly for the TCdD Risk Score (C-statistic 0.63, 0.62-0.63; ICI 0.038, 0.004-0.038).

Conclusions: TCdD risk can be predicted using readily available clinical risk factors with modest accuracy.

Figure 1.

Adjusted association of hospital day and eosinophil count on toxigenic C. difficile diarrhea (TCdD). The adjusted association of hospital day of sample (A) and eosinophil count (B) with TCdD is presented. In both plots, the association is presented as the adjusted odds ratio (vertical axis) accounting for all other variables in the TCdD Model (Appendix B) relative to midpoint values (day 9 and eosinophil count of 0.25).

Figure 2.

Interaction of patient age and white cell count on adjusted toxigenic C. difficile diarrhea (TCdD) risk. This heat map presents the adjusted likelihood of TCdD risk as a function of patient age (horizontal axis) and WBC count (left vertical axis). TCdD risk is expressed as an adjusted odds ratio (right vertical axis) relative to that of a 60-year-old patient with a WBC count of 11 (with an adjusted odds ratio of 1.0, presented as white). Adjusted odds ratios less than 1.0 (indicating lower TCDD risk) are blue; adjusted odds ratios exceeding 1.0 (indicating higher TCdD risk) are red. See Appendix B for the entire TCdD Risk Model.

Figure 3.

Calibration plot of toxigenic C. difficile diarrhea (TCdD) model and score. This figure plots the observed TCdD probability (vertical axis) against the expected TCdD probability (horizontal axis) TCdD Model (Appendix B, blue) and the TCdD probability risk score (Table 4, black). Optimism-adjusted fit statistics in the internal validation population (top left) were calculated on 1,000 bootstrap samples.