Plasma versus whole blood multiplex droplet digital PCR for pathogen detection in ICU patients with clinically suspected sepsis: a prospective multicenter cohort study.

ObjectivesRapid pathogen identification remains challenging in critically ill patients with suspected sepsis. Droplet digital PCR (ddPCR) is a promising molecular diagnostic tool, but it is usually performed on plasma and may miss pathogen signals retained in cellular blood components. We therefore compared plasma and whole-blood ddPCR in ICU patients with clinically suspected sepsis.MethodsIn this prospective multicenter cohort study, ICU patients with clinically suspected sepsis underwent paired plasma and whole-blood ddPCR together with blood culture. Blood culture-negative/ddPCR-positive cases were interpreted using structured clinical adjudication.ResultsAmong 223 patients, 62 (27.8%) had positive blood cultures. Both plasma and whole-blood ddPCR identified substantially more pathogens than blood culture alone and provided microbiological support for 38 and 46 adjudicated definite sepsis cases, respectively, among blood culture-negative patients. Overall performance was similar between matrices, but whole-blood ddPCR showed a higher detection rate for the Candida genus than plasma ddPCR (87.5% vs 31.3%, P = 0.03). Concordant positivity in both matrices was associated with greater disease severity.ConclusionBoth plasma and whole-blood ddPCR complement blood culture in ICU patients with clinically suspected sepsis. Although overall performance was similar, whole-blood ddPCR showed higher detection of the Candida genus in this cohort, a finding that requires validation in larger fungal sepsis cohorts.