Diagnostic performance and antibiotic impact of droplet digital PCR in suspected sepsis: the PROGRESS trial.

Abstract

Currently, tools to dynamically monitor pathogen load and guide antibiotic adjustment in suspected sepsis are limited. In this prospective, multicenter randomized trial (3:1, ddPCR vs standard care), 1,373 patients were followed for 90 days. The primary outcome was diagnostic efficacy; secondary outcomes included mortality and SOFA. ddPCR showed higher detection positivity (54.1% vs 21.6%, p < 2 × 10^-16), faster turnaround, and sensitivity of 80.6%. It increased appropriate antimicrobial coverage (12.91% vs 6.1%, p = 0.0039), and sufficient coverage within 0-3 days was associated with improved outcomes (p = 0.026). Baseline pathogen load >3051 copies/mL, day 3 > 404.1 copies/mL, and day 7 > 1348 copies/mL predicted 28-day mortality. Furthermore, ddPCR-guided early, precision-based adjustment of antimicrobial therapy significantly increased the rate of appropriate antimicrobial coverage, thereby translating into a meaningful improvement in survival outcomes among patients with sepsis. ClinicalTrials.gov: NCT05190861.