Clinical utility of direct disk diffusion testing in guiding antibiotic therapy for Gram-negative bacteremia

Abstract

Objective: Conventional antibiotic susceptibility testing (AST) for bloodstream infections requires ∼48 hours, often delaying optimal therapy. We investigated the clinical impact of implementing direct disk diffusion testing (dDDT) for Gram-negative bacteremia.

Methods: This retrospective cohort study compared patients with Gram-negative bacteremia before (n=212) and after (n=214) dDDT implementation. The primary outcome, 30-day mortality, was assessed using the Kaplan-Meier method, a Kolmogorov-Smirnov test, and a multivariate Cox proportional hazards model, with logistic regression for sensitivity analysis. Secondary analyses on therapy appropriateness and the antibiotic spectrum index (ASI) were performed using a mixed-design ANOVA.

Results: dDDT reduced the mean time to susceptibility results by ∼24 hours (37.6±14.3 hours vs. 61.6±16.3 hours hours). Post-implementation, the appropriateness of therapy for multidrug-resistant organisms (MDROs) significantly improved from 76.5% to 91.2% (p=0.048). ASI analysis confirmed these changes were driven by appropriate escalation for MDROs and de-escalation for non-MDROs. Kaplan-Meier analysis showed lower cumulative mortality post-dDDT (p=0.023), but dDDT was not an independent predictor of 30-day mortality in multivariate analysis (aHR 1.27, 95% CI 0.76-2.14).

Conclusions: dDDT implementation significantly shortens time-to-results and improves antibiotic appropriateness, facilitating timely stewardship. While a trend towards lower mortality was observed, dDDT was not an independent predictor of survival, highlighting the multifactorial nature of patient outcomes.

Summary: Direct disk diffusion testing (dDDT) for Gram-negative bacteremia significantly shortens susceptibility reporting, improves antibiotic appropriateness, and may guide antibiotic stewardship. While a trend towards lower mortality was observed, dDDT was not an independent predictor of survival in this study.

Keywords: Gram-negative bacteremia; antibiotic susceptibility testing; antimicrobial stewardship; direct disk diffusion testing; turnaround time.