Plasma versus Whole Blood Multiplex Droplet Digital PCR for Pathogen Detection in ICU Patients with Clinically Suspected Sepsis: A Prospective Multicenter Cohort Study.

Summary

In 223 ICU patients with clinically suspected sepsis, both plasma and whole-blood ddPCR detected substantially more pathogens than blood culture alone and provided microbiological support in blood culture-negative cases adjudicated as definite sepsis. Overall performance was similar between the two specimen types, but whole-blood ddPCR detected Candida more frequently than plasma ddPCR, suggesting a potentially important advantage for fungal sepsis.

Key Findings

• Among 223 patients, 62 (27.8%) had positive blood cultures.
• Plasma and whole-blood ddPCR provided microbiological support for 38 and 46 blood culture-negative cases, respectively, that were adjudicated as definite sepsis.
• Whole-blood ddPCR detected Candida genus more frequently than plasma ddPCR (87.5% vs. 31.3%, P=0.03).

Clinical Implications

Paired plasma and whole-blood ddPCR may be considered as adjuncts to blood culture when rapid pathogen identification is essential, particularly in suspected fungal sepsis. The findings do not justify replacing blood culture or initiating therapy solely on the basis of ddPCR without clinical interpretation.

Limitations

• The study included 223 patients, and the number of fungal sepsis cases was limited.
• The clinical adjudication of blood culture-negative cases may introduce subjectivity, and the study did not establish whether ddPCR-guided treatment improves outcomes.

Future Directions

Larger prospective studies should evaluate fungal sepsis specifically, determine the incremental diagnostic value and turnaround-time advantages of whole-blood ddPCR, and test whether ddPCR-guided antimicrobial decisions improve mortality, time to effective therapy, and antimicrobial stewardship.