Potential underreporting of treated patients using a Clostridioides difficile testing algorithm that screens with a nucleic acid amplification test

Abstract

Objective: Patients tested for Clostridioides difficile infection (CDI) using a 2-step algorithm with a nucleic acid amplification test (NAAT) followed by toxin assay are not reported to the National Healthcare Safety Network as a laboratory-identified CDI event if they are NAAT positive (+)/toxin negative (−). We compared NAAT+/toxin− and NAAT+/toxin+ patients and identified factors associated with CDI treatment among NAAT+/toxin− patients. Design: Retrospective observational study. Setting: The study was conducted across 36 laboratories at 5 Emerging Infections Program sites. Patients: We defined a CDI case as a positive test detected by this 2-step algorithm during 2018–2020 in a patient aged ≥1 year with no positive test in the previous 8 weeks. Methods: We used multivariable logistic regression to compare CDI-related complications and recurrence between NAAT+/toxin− and NAAT+/toxin+ cases. We used a mixed-effects logistic model to identify factors associated with treatment in NAAT+/toxin− cases. Results: Of 1,801 cases, 1,252 were NAAT+/toxin−, and 549 were NAAT+/toxin+. CDI treatment was given to 866 (71.5%) of 1,212 NAAT+/toxin− cases versus 510 (95.9%) of 532 NAAT+/toxin+ cases (P < .0001). NAAT+/toxin− status was protective for recurrence (adjusted odds ratio [aOR], 0.65; 95% CI, 0.55–0.77) but not CDI-related complications (aOR, 1.05; 95% CI, 0.87–1.28). Among NAAT+/toxin− cases, white blood cell count ≥15,000/µL (aOR, 1.87; 95% CI, 1.28–2.74), ≥3 unformed stools for ≥1 day (aOR, 1.90; 95% CI, 1.40–2.59), and diagnosis by a laboratory that provided no or neutral interpretive comments (aOR, 3.23; 95% CI, 2.23–4.68) were predictors of CDI treatment. Conclusion: Use of this 2-step algorithm likely results in underreporting of some NAAT+/toxin− cases with clinically relevant CDI. Disease severity and laboratory interpretive comments influence treatment decisions for NAAT+/toxin− cases.