Clinical Outcomes and Management of NAAT-Positive/Toxin-Negative Clostridioides difficile Infection: A Systematic Review and Meta-Analysis
Connor Prosty, Ryan Hanula, Khaled Katergi, Yves Longtin, Emily G McDonald, Todd C Lee- Infectious Diseases
- Microbiology (medical)
Abstract
Background
Standalone nucleic acid amplification tests (NAATs) are frequently used to diagnose Clostridioides difficile infections (CDI), although they may be unable to distinguish colonization from disease. A two-stage algorithm pairing NAATs with toxin immunoassays (Toxin) may improve specificity. We evaluated clinical outcomes of patients who were NAAT+/Toxin + versus NAAT+/Toxin- and treated versus untreated NAAT+/Toxin- cases through systematic review and meta-analysis.
Methods
We searched EMBASE and MEDLINE from inception to April 1, 2023 for articles comparing CDI outcomes among symptomatic patients tested by NAAT and Toxin tests. The risk differences (RD) of all-cause mortality and CDI recurrence were computed by random effects meta-analysis between patients who were NAAT+/Toxin + and NAAT+/Toxin-, as well as between patients who were NAAT+/Toxin- and treated or untreated.
Results
Twenty-six observational studies comprising 12737 patients were included. 30-Day all-cause mortality was not significantly different between those who were NAAT+/Toxin + (8.4%) and NAAT+/Toxin- (6.7%) (RD = 0.41%, 95%Confidence interval [95%CI]=-0.67, 1.49). Recurrence at 60 days was significantly higher among patients who were NAAT+/Toxin + (19.8%) versus NAAT+/Toxin- (11.0%) (RD = 7.65%, 95%CI = 4.60, 10.71). Among treated compared to untreated NAAT+/Toxin- cases, the all-cause 30-day mortalities were 5.0% and 12.7%, respectively (RD = -7.45%, 95%CI = -12.29, -2.60), but 60-day recurrence was not significantly different (11.6% versus 7.0%, respectively; RD = 5.25%, 95%CI -1.71, 12.22).
Conclusion
Treatment of patients who were NAAT+/Toxin- was associated with reduced all-cause mortality, but not recurrence. While subject to the inherent limitations of observational studies, these results suggest that some patients who are NAAT+/Toxin- may benefit from treatment.