Risk factors for progression from Clostridioides difficile colonization (NAAT+/toxin–) to infection (toxin+) following symptomatic retesting

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Abstract Objective: To identify host and clinical risk factors contributing to the development of Clostridioides difficile infection (CDI) among colonized patients. Design: Retrospective, matched case-control study. Setting: Duke University Health System, including 3 hospitals and affiliated outpatient clinics. Participants: Adult patients who underwent ≥2 two-step C. difficile tests (nucleic acid amplification test (NAAT) followed by toxin enzyme immunoassay) between 03/15/2020–12/31/2023. Cases were patients with C. difficile colonization (NAAT+/toxin–) who converted to CDI (NAAT+/toxin+) within 90 days; controls were colonized patients who remained toxin-negative. Cases were matched to controls by date of index testing (±1 year). Methods: Data collection encompassed a 90-day “pre-exposure” period preceding index testing and a ≤ 90-day “exposure” period between index and repeat testing. Antibiotic use was stratified by risk for each period. Multivariate conditional logistic regression with forward selection was used to identify predictors of progression. Results: Among 2,212 colonized patients, 71 cases and 133 matched controls were identified. Several host and clinical characteristics were independently associated with progression to CDI in our multivariate model. Notably, high-risk antibiotic use across the pre-exposure and exposure periods was associated with greater odds of progression to CDI compared to other patterns of antibiotic use (adjusted odds ratio 2.70; P = .03). Conclusions: Sustained exposure to high-risk antibiotics was a strong predictor of the progression from C. difficile colonization to infection, underscoring the need for further research on longitudinal stewardship strategies for CDI prevention, particularly among patients previously identified as colonized.

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