Clinical application of ddPCR-assisted antimicrobial stewardship in febrile leukopenia patients

Febrile leukopenia is a common and potentially life-threatening complication in patients with hematological diseases. Rapid identification of causative pathogens is essential for timely antimicrobial management, yet conventional microbiological methods often have limited sensitivity and prolonged turnaround times. This study aimed to evaluate the diagnostic performance of droplet digital polymerase chain reaction (ddPCR) for pathogen detection in febrile leukopenic patients with hematological diseases and to explore its potential association with antimicrobial management. We conducted a retrospective cohort study at The First Affiliated Hospital of Zhejiang Chinese Medical University between March 2024 and March 2025. Febrile patients with hematological diseases and leukopenia (peripheral white blood cell count < 4.0 × 10 9 /L) who underwent ddPCR, blood culture, and routine inflammatory marker testing were included. The primary objective was to evaluate the diagnostic performance of ddPCR compared with conventional microbiological methods. Exploratory analyses assessed antimicrobial modifications following ddPCR testing and associated clinical outcomes. A total of 253 samples (172 inpatients) were analyzed, with 47 in the ddPCR- participated antimicrobial therapy group and 206 in the experienced care group. ddPCR demonstrated significantly higher pathogen detection rate than blood culture, (1,3)-β-D-glucan (G) test, and galactomannan (GM) test. Receiver operating characteristic analysis showed that ddPCR achieved the highest diagnostic performance for clinically adjudicated bloodstream infection (AUC = 0.796, 95% CI: 0.703–0.889), significantly outperforming CRP ( p = 0.011) and IFN ( p = 0.001), while no significant difference was observed compared with PCT ( p = 0.137). Exploratory analyses suggested that antimicrobial modification following ddPCR testing was associated with lower antibiotic expenditure, particularly among patients with hematological malignancies ( p = 0.020). ddPCR provides rapid and sensitive pathogen detection in febrile leukopenic patients with hematological diseases and may complement conventional microbiological methods for early pathogen identification. Its potential role in supporting antimicrobial optimization warrants further investigation in prospective multicenter studies.