Sequential introduction of a multistep testing algorithm and nucleic acid amplification testing leading to an increase in Clostridioides difficile detection and a trend toward increased strain diversity

Abstract

Background: Most clinical microbiology laboratories have replaced toxin immunoassay (EIA) alone with multistep testing (MST) protocols or nucleic acid amplification testing (NAAT) alone for the detection of C. difficile. Objective: Study the effect of changing testing strategies on C. difficile detection and strain diversity. Design: Retrospective study. Setting: A Veterans’ Affairs hospital. Methods: Initially, toxin EIA testing was replaced by an MST approach utilizing a glutamate dehydrogenase (GDH) and toxin EIA followed by tcdB NAAT for discordant results. After 18 months, MST was replaced by a NAAT-only strategy. Available patient stool specimens were cultured for C. difficile. Restriction endonuclease analysis (REA) strain typing and quantitative in vitro toxin testing were performed on recovered isolates. Results: Before MST (toxin EIA), 79 of 708 specimens (11%) were positive, and after MST (MST-A), 121 of 517 specimens (23%) were positive (P < .0001). Prior to NAAT-only testing (MST-B), 80 of the 490 specimens (16%) were positive by MST, and after NAAT-only testing was implemented, 67 of the 368 specimens (18%) were positive (P = nonsignificant). After replacing toxin EIA testing, REA strain group diversity increased (8, 13, 13, and 10 REA groups in the toxin EIA, MST-A, MST-B, and NAAT-only periods, respectively) and in vitro toxin concentration decreased. The average log10 toxin concentration of the isolates were 2.08, 1.88, 1.20 and 1.55 ng/mL for the same periods, respectively. Conclusions: MST and NAAT had similar detection rates for C. difficile. Compared to toxin testing alone, they detected increased diversity of C. difficile strains, many of which were low toxin producing.

Characteristics and outcomes of Clostridioides difficile infection after a change in the diagnostic testing algorithm

“…1,2 Testing strategies for CDI also evolved over this period. [3][4][5] In 2009, polymerase chain reaction (PCR) testing primarily targeting the gene for toxin B (tcdB) was approved for commercial use in the detection of C. difficile. 6 Utilization of PCR provided clinicians with a rapid and highly sensitive test for C. difficile 6 but also led to increased CDI rates reported for many institutions.…”

“…7,9 In response, many institutions have readopted a 2-step testing algorithm utilizing either GDH plus a toxin EIA or PCR plus a toxin EIA. 4 Additionally, recent data suggest that the presence of C. difficile toxin by EIA is associated with increased severity and risk of recurrence but not other CDI-related complications or mortality. 8 In September 2019, our hospital changed the testing algorithm for C. difficile from PCR alone to PCR followed by toxin A/B EIA.…”