Dual Reporting of Clostridioides difficile PCR and Predicted Toxin Result Based on PCR Cycle Threshold Reduces Treatment of Toxin-Negative Patients without Increases in Adverse Outcomes

Abstract

Nucleic acid amplification tests are commonly used to diagnose Clostridioides difficile infection (CDI). Two-step testing with a toxin enzyme immunoassay is recommended to discriminate between infection and colonization but requires additional resources. Prior studies showed that PCR cycle threshold (CT) can predict toxin positivity with high negative predictive value. Starting in October 2016, the predicted toxin result (CT-toxin) based on a validated cutoff was routinely reported at our facility. To evaluate the clinical efficacy of this reporting, all adult patients with positive GeneXpert PCR results from October 2016 through October 2017 underwent a chart review to measure the recurrence of or conversion to a CT-toxin+ result and 30-day all-cause mortality. There were 482 positive PCR tests in 430 unique patients, 282 CT-toxin+ and 200 CT-toxin−. Patient characteristics were similar at testing, though CT-toxin+ patients had higher white blood cell (WBC) counts (12.5 × 103 versus 9.3 × 103 cells/μl; P = 0.001). All cases (n = 21) of fulminant CDI had a CT-toxin+ result. Index CT-toxin+ patients were significantly more likely to have a CT-toxin+ result within 90 days than CT-toxin− patients (17.4% [n = 49] versus 8.0% [n = 16], respectively; P = 0.003). Thirty-day all-cause mortality was higher in CT-toxin− patients (11.1% versus 6.8%; P = 0.1), though no deaths in CT-toxin− patients were directly attributable to CDI. Of the 200 CT-toxin− patients, 51.5% (n = 103) were treated for CDI. The rates of conversion to a CT-toxin+ result (8.8% versus 7.2%; P = 0.8) and all-cause mortality (8.8% versus 13.4%; P = 0.3) were similar between treated and untreated CT-toxin− patients, respectively. CT-based toxin prediction may identify patients at higher risk for CDI-related complications and reduce treatment among CT-toxin− patients.

Real-time polymerase chain reaction (PCR) cycle threshold and Clostridioides difficile infection outcomes

“…9 The use of PCR Ct to quantify C. difficile burden (and, subsequently, to predict outcomes of CDI) has been studied, with mixed results. 12,13,15,17,20 In our study, among 318 patients with HO-HFA CDI, PCR Ct values at the time of diagnosis were not independently associated with CDI severity or recurrence within 8 weeks but were independently associated with 30-day all-cause mortality. At least 2 previous studies have reported that lower PCR Ct values are associated with increased risk of 30-day mortality, and 1 study has reported that Ct values are not associated with all-cause mortality.…”

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

“…Overlapping distributions of Ct values of 25.0-28.0 were also noted between CCNA-negative and CCNA-positive cases in another comparison [20]. Although others have not found adverse outcomes associated with the implementation of reporting tcdB C t values [21], it is important to note that test performance characteristics may differ by institution.…”

Recent advancement and development of capillary isotachophoresis: A review

“…ITP is a topic of ongoing research, application, and invention. [29] Terzis et al, developed test durations and scale-up attempts for the processed sample amounts that can be restricted by joule heating in ITP. ITP systems spatiotemporal temperature field dynamics of Joule heating, despite their importance.…”