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Meta-Analysis
. 2024 Feb 17;78(2):430-438.
doi: 10.1093/cid/ciad523.

Clinical Outcomes and Management of NAAT-Positive/Toxin-Negative Clostridioides difficile Infection: A Systematic Review and Meta-Analysis

Connor Prosty  1 , Ryan Hanula  2 , Khaled Katergi  3 , Yves Longtin  4 , Emily G McDonald  2   5   6 , Todd C Lee  2   6   7
Affiliations
Meta-Analysis

Clinical Outcomes and Management of NAAT-Positive/Toxin-Negative Clostridioides difficile Infection: A Systematic Review and Meta-Analysis

Connor Prosty et al. Clin Infect Dis. .

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 2-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 12 737 patients were included. The 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 [CI] = -.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% vs 7.0%, respectively; RD = 5.25%, 95% CI -1.71, 12.22).

Conclusions: Treatment of patients who were NAAT+/Toxin- was associated with reduced all-cause mortality but not recurrence. Although subject to the inherent limitations of observational studies, these results suggest that some patients who are NAAT+/Toxin- may benefit from treatment.

Keywords: Clostridioides difficile; PCR; enzyme immunoassay; nucleic acid amplification test; toxin.

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Conflict of interest statement

Potential conflicts of interest. E. G. M. and T. C. L. have operating grants from the Canadian Institutes of Health Research (CIHR) and receive salary support from the Fonds de Recherche du Québec—Santé outside of this work. E. G. M. also reports a role as Board Member for WikiGuidelines for infectious diseases. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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