Clinical Scorecard: Comparison of Plasma and Whole Blood Multiplex Droplet Digital PCR for Identifying Pathogens in ICU Patients with Suspected Sepsis: A Prospective Multicenter Cohort Investigation

At a Glance

Key Highlights

• The prospective multicenter study included 223 critically ill adults.

• Blood cultures were positive in 62 patients (27.8%).

• Plasma and whole-blood ddPCR provided additional microbiological support in blood culture–negative cases.

• Overall diagnostic performance did not differ significantly between the 2 matrices.

• Whole-blood ddPCR detected the Candida genus more frequently than plasma ddPCR in this cohort.

• The laboratory ddPCR workflow usually required approximately 2–4 hours.

Guideline-Based Recommendations

This observational study did not establish new clinical guidelines or evaluate a ddPCR-guided treatment strategy.

Diagnosis

• Eligibility required suspected infection with new-onset organ dysfunction, defined as an increase in SOFA score of at least 2 points.

• Patients also required at least 1 specified clinical or laboratory feature suggestive of infection.

• ddPCR should be interpreted alongside blood culture, site-specific cultures, imaging, laboratory findings, and the overall clinical presentation.

• Molecular detection identifies microbial nucleic acids and does not independently establish active infection.

Management

• Plasma and whole-blood ddPCR may complement conventional blood culture in the evaluation of suspected sepsis.

• Whole-blood testing may provide additional value in selected situations, particularly when fungal sepsis is suspected.

• The study did not determine whether ddPCR-guided decisions improved antimicrobial selection or patient outcomes.

• Antimicrobial treatment changes following ddPCR testing were not systematically captured.

Monitoring & Follow-up

• Clinical evaluation included blood counts, inflammatory biomarkers, blood chemistry, and cultures from blood and suspected infection sites.

• Concordant positivity in both matrices was associated with higher procalcitonin than the single-positive and double-negative patterns and with higher lactate, SOFA, and APACHE II values than the double-negative pattern.

• Twenty-eight-day survival did not differ significantly across ddPCR detection patterns.

• The study did not establish a specific follow-up or repeat-testing schedule.

Risks

• Positive ddPCR results may reflect residual microbial DNA, transient circulating DNA, or low-level contamination rather than active infection.

• The predefined panel was limited to 17 bacterial targets and the Candida genus.

• Incorporating ddPCR findings into clinical adjudication may have overestimated diagnostic performance.

• The apparent whole-blood advantage for Candida detection was based on only 16 detection events.

Patient & Prescribing Data

The study enrolled 223 adults with clinically suspected sepsis. All had received empirical antimicrobial therapy before enrollment, for a median of 2 days.

Blood culture, plasma ddPCR, and whole-blood ddPCR were performed in parallel. The study did not systematically evaluate antimicrobial changes, prescribing optimization, or treatment outcomes attributable to ddPCR.

Clinical Best Practices

• Use ddPCR as an adjunct to conventional cultures and clinical assessment rather than as a replacement.

• Interpret positive molecular findings within the complete microbiological and clinical context.

• Consider suspected pathogen biology when selecting plasma or whole blood.

• Recognize that whole blood was not globally superior, despite higher Candida detection in this cohort.

• Apply the findings cautiously pending validation in larger sepsis and invasive-fungal-infection cohorts.

Related Resources & Content

Plasma Versus Whole Blood Multiplex Droplet Digital PCR for Pathogen Detection in ICU Patients With Clinically Suspected Sepsis: A Prospective Multicenter Cohort Study — Wu Z, Wang X, Xia J, et al. International Journal of Infectious Diseases. 2026;171:109015. doi:10.1016/j.ijid.2026.109015.