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Droplet Digital PCR Improves Sepsis Care in PROGRESS Trial

A multicenter trial shows droplet digital PCR detects pathogens faster and guides earlier antibiotic adjustments to improve sepsis survival.

WHAT YOU NEED TO KNOW
  • Droplet digital PCR achieved a 54.1% detection positivity rate compared to 21.6% for standard care in a 1,373-patient trial.
  • Appropriate antimicrobial coverage rose to 12.91% with ddPCR versus 6.1% under standard treatment.
  • Pathogen loads over 3,051 copies/mL at baseline and 404.1 copies/mL at day three predicted 28-day mortality.

Researchers demonstrated that droplet digital PCR testing substantially outperforms standard care in diagnosing suspected sepsis and directing antibiotic treatment, according to a clinical study published in Nature Communications.

The prospective PROGRESS trial evaluated 1,373 patients across 14 clinical centers, following participants for 90 days under registration NCT05190861. Investigators randomized patients in a 3:1 ratio between droplet digital PCR (ddPCR) and standard care to assess diagnostic efficacy as the primary outcome, alongside secondary measures including Sequential Organ Failure Assessment (SOFA) scores and mortality.

Testing with ddPCR delivered a 54.1% detection positivity rate compared to 21.6% for standard care (p < 2 × 10−16), showing faster turnaround and an overall sensitivity of 80.6%. The platform increased the rate of appropriate antimicrobial coverage to 12.91% compared to 6.1% under standard care (p = 0.0039). Achieving sufficient antimicrobial coverage within zero to three days was linked to improved patient outcomes (p = 0.026).

Pathogen load measurements gathered by the system also functioned as prognostic indicators for patient survival. Baseline pathogen loads exceeding 3,051 copies/mL, day three levels above 404.1 copies/mL, and day seven levels above 1,348 copies/mL predicted 28-day mortality. Early, precision-based adjustments to antimicrobial therapy guided by ddPCR elevated appropriate coverage rates and translated into improved survival outcomes.

Ruilan Wang, Jingwen Ai, and Wenhong Zhang jointly supervised the multicenter study, with equal author contributions from Haocheng Zhang, Ke Lin, Xinlei Xu, and Qiaoyan Yue across institutions including Huashan Hospital at Fudan University. Pilot Gene Technology in Hangzhou, China, provided technical assistance for the ddPCR platform, with support from the National Key Research and Development Program of China and the National Natural Science Foundation of China.

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