Clostridioides difficile Toxin B PCR Cycle Threshold as a Predictor of Toxin Testing in Stool Specimens from Hospitalized Adults

Rapid, accurate detection of Clostridioides difficile toxin may potentially be predicted by toxin B PCR cycle threshold (tcdB C(t)). We investigated the validity of this approach in an inpatient adult population. Patients who tested positive by C. difficile PCR (Cepheid GeneXpert) from December 2016 to October 2020 (n = 368) at a tertiary medical center were included. All stool samples were further tested by rapid glutamate dehydrogenase (GDH)/toxin B EIA and cell cytotoxin neutralization assay (CCNA). Receiver operating characteristic curves were analyzed. The area under the curve for tcdB C(t) predicting toxin result by EIA was 0.795 (95% confidence interval (CI) 0.747–0.843) and by CCNA was 0.771 (95% CI 0.720–0.822). The Youden C(t) cutoff for CCNA was ≤27.8 cycles (sensitivity 65.0%, specificity 77.2%). For specimens with C(t) ≤ 25.0 cycles (n = 115), CCNA toxin was positive in >90%. The negative predictive value of tcdB C(t) for CCNA was no greater than 80% regardless of cutoff chosen. In summary, very low C(t) values (≤25.0) could have limited value as a rapid indicator of positive toxin status by CCNA in our patient population. A broad distribution of C(t) values for toxin-negative and toxin-positive specimens precluded more robust prediction. Additional data are needed before broader application of C(t) values from qualitatively designed assays to clinical laboratory reporting.