Impact of the Reverse 2-Step Algorithm for Clostridioides difficile Testing in the Microbiology Laboratory on Hospitalized Patients

Evann E Hilt; Byron P Vaughn; Alison L Galdys; Michael D Evans; Patricia Ferrieri

doi:10.1093/ofid/ofae244

Impact of the Reverse 2-Step Algorithm for Clostridioides difficile Testing in the Microbiology Laboratory on Hospitalized Patients

Open Forum Infect Dis. 2024 Apr 27;11(5):ofae244. doi: 10.1093/ofid/ofae244. eCollection 2024 May.

Authors

Evann E Hilt¹, Byron P Vaughn², Alison L Galdys³, Michael D Evans⁴, Patricia Ferrieri¹

Affiliations

¹ Infectious Diseases Diagnostic Laboratory, Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
² Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
³ Division of Infectious Disease and International Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
⁴ Clinical and Translational Science Institute, University of Minnesota, Minneapolis, Minnesota, USA.

Abstract

Background: Multistep laboratory testing is recommended for the diagnosis of Clostridioides difficile infection (CDI). The aim of this study was to present the impact of multistep CDI diagnostic testing in an academic hospital system and evaluate the toxin B gene polymerase chain reaction (PCR) cycle threshold (Ct) values of PCR-positive tests.

Methods: In October 2022, our system began reflex testing all PCR-positive stool samples with the C. DIFF QUIK CHEK COMPLETE (Techlab), an enzyme immunoassay-based test with results for the glutamate dehydrogenase antigen (GDH) and C difficile toxin A/B. Hospital-onset (HO) CDI and CDI antibiotic use before and after testing were tracked. Ct values were obtained from the Infectious Diseases Diagnostic Laboratory. Receiver operating curve analysis was used to examine the sensitivity and specificity for identifying GDH⁺/toxin⁺ and GDH^-/toxin^- at various Ct thresholds.

Results: The HO-CDI rate decreased from 0.352 cases per 1000 patient-days to 0.115 cases per 1000 patient-days post-reflex testing (P < .005). Anti-CDI antibiotics use decreased, but the decrease was not commensurate with CDI rates following reflex testing. PCR⁺/GDH⁺/toxin⁺ samples had a lower mean Ct value than PCR⁺/GDH^-/toxin^- samples (23.3 vs 33.5, P < .0001). A Ct value of 28.65 could distinguish between those 2 groups. Fifty-four percent of PCR⁺/GDH⁺/toxin^- samples had a Ct value below that cut-off, suggesting the possibility of CDI with a negative toxin test.

Conclusions: Reflex testing for a laboratory diagnosis of CDI results in rapid, systemwide decreases in the rate of HO-CDI. Additional research is needed to distinguish CDI from C difficile colonization in patients with discordant testing.

Keywords: Clostridioides difficile infection; antibiotic stewardship; enzyme immunoassay; molecular diagnostics; nucleic acid amplification tests.

Grants and funding

UL1 TR002494/TR/NCATS NIH HHS/United States