Toxin B PCR Amplification Cycle Threshold Adds Little to Clinical Variables for Predicting Outcomes in <i>Clostridium difficile</i> Infection: a Retrospective Cohort Study

Abstract

The objective of the present study was to evaluate the value of the PCR cycle threshold (<i>C_T</i> ) for predicting the recurrence/severity of infection compared to that of toxin detection plus clinical variables. First episodes of <i>Clostridium difficile</i> infection (CDI) diagnosed during 2015 at our institution were included. Samples were tested for glutamate dehydrogenase (GDH) and toxin A/B by use of a single enzyme immunoassay (EIA). The Xpert <i>C. difficile</i> PCR assay was performed on GDH-positive samples. Medical data were reviewed by investigators blinded to diagnostic results for comparison of patients with and without recurrence or a poor outcome (severe/severe-complicated CDI episodes and all-cause death). We generated two sets of predictive models by incorporating the presence of a positive toxin EIA ("EIA-including model") or the optimal PCR <i>C_T</i> cutoff value ("PCR-including model") into the clinical variables. Among 227 episodes of CDI included in the study, the rates of recurrence and poor outcome were 15.8% and 30.8%, respectively. The mean PCR <i>C_T</i> was lower for episodes with recurrence (24.00 ± 3.28 versus 26.02 ± 4.54; <i>P</i> = 0.002) or a poor outcome (24.9 ± 4.24 versus 26.05 ± 4.47; <i>P</i> = 0.07). The optimal cutoff value for recurrence was 25.65 (sensitivity, 77.8% [95% confidence interval {CI}, 60.9 to 89.9]; and specificity, 46.6% [95% CI, 39.4 to 53.9]). The area under the receiver operator characteristics curve (auROC) for the "PCR-including model" was similar to that for the "EIA-including model" (0.785 versus 0.775, respectively). The optimal PCR <i>C_T</i> value for poor outcome was 27.55 (sensitivity, 78.6% [95% CI, 67.1 to 87.5]; and specificity, 35.7% [95% CI, 28.2 to 43.7]). The auROC of the "PCR-including model" was again similar to that of the "EIA-including model" (0.804 versus 0.801). Despite the inverse correlation between PCR <i>C_T</i> and the risk of CDI recurrence/severity, this determination does not meaningfully increase the predictive value of clinical variables plus toxin EIA.