Evaluation of Droplet Digital PCR Rapid Detection Method and Precise Diagnosis and Treatment for Suspected Sepsis

• droplet digital PCR method (Diagnostic test): The droplet digital PCR method can detect nucleic acids from the most common pathogens (approximately 90%) responsible for BSIs according to Chinet2020 and takes about 4 hours to perform, reporting within the first 24h of suspected sepsis/septic shock.
• blood culture (Diagnostic test): Blood culture is a conventional microbiological method of pathogen detection. Results from blood cultures are usually not available until 24 to 72 hours after sampling.

Primary outcomes

• Sensitivity [Up to 96 hours post blood collection]: The primary endpoint of estimated sensitivity will be determined by comparing positive blood culture results with the concomitantly collected ddPCR results from the prospective clinical specimens.
• Specificity [Up to 96 hours post blood collection]: The primary endpoint of estimated specificity will be determined by comparing negative blood culture results with the concomitantly collected ddPCR results from the prospective clinical specimens.

Secondary outcomes

• Time to the change to the targeted antimicrobial therapy [At time point of change to the targeted antimicrobial therapy, up to 96 hours post blood collection]
• Number of patients with targeted antimicrobial therapy [Up to the end of study participation, an average of 1 year]
• Time to identification of a potential pathogen [At time point of identification of a potential pathogen, up to 96 hours post blood collection]
• Duration of antimicrobials [Up to the end of study participation, an average of 1 year]
• Change in condition severity [Up to the end of study participation, an average of 1 year]: The sequential organ failure assessment score (SOFA score), previously known as the sepsis-related organ failure assessment score, higher scores mean worse outcome.
• Days in intensive care unit (ICU) [Up to the end of study participation, an average of 1 year]
• Ventilation duration in ICU (hours) [Up to the end of study participation, an average of 1 year]
• Days in hospital (from study inclusion) [Up to the end of study participation, an average of 1 year]
• All-cause death [Up to the end of study participation, an average of 1 year]
• Treatment costs [Up to the end of study participation, an average of 1 year]
• Quality of life of survivors after being discharged [Up to the end of study participation, an average of 1 year]: EQ-5D, a standardised measure of health-related quality of life developed by the EuroQol Group.The EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. The number of levels in these dimensions is 5 in the EQ-5D-5L. Higher levels mean worse health states.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1.18 years or older

2.Meet 2 of 4 sepsis criteria

1. Temperature > 38C or < 36C
2. Heart rate > 90 bpm
3. Respiratory rate >20 or PaCO2 <32mmHg
4. WBC >12000/µL or < 4000/µL or > 10% bands

   3.Hospitalized patients who have a diagnostic blood culture ordered as standard of care for suspected sepsis

   4.Informed Consent by patient or legal representative.

   Exclusion Criteria:
   1. Refusal to participate in the study or Failure to comply with treatment or follow-up time
   2. Known breastfeeding or pregnancy
   3. The researcher believes that there are any conditions (social or medical) that allow subjects to participate is unsafe. For example, severe anemia or high risk of bleeding,etc., which are not suitable for taking peripheral blood for testing
   4. Participating in other clinical studies

• Results publication: Zhang H, Lin K, Xu X, Yue Q, Li X, Chen X, Hong L, Chen L, Huang Y, Ye Y, Su T, Pan J, Li W, Xiao S, Geng X, Zheng J, Jiang L, Chen J, Zhang S, Liu Y, Li L, Yin J, Du H, Zhou A, Ke L, Huang Q, Chen L, Feng T, Wang R, Ai J, Zhang W. Diagnostic performance and antibiotic impact of droplet digital PCR in suspected sepsis: the PROGRESS trial. Nat Commun. 2026 Aug 20;17(1):9921. doi: 10.1038/s41467-026-76767-y. PMID 42749736
• Results publication: Zhao Y, Lin K, Zhang H, Zhang Y, Li S, Zhang S, Zhang W, Zhou A, Zhuang Y, Chen J, Wu C, Zhou W, He X, Yue Q, Zhang M, Huang Y, Li L, Hong L, Cai F, Huang L, Ruan Z, Xu S, Zhang Y, Chen X, Chen J, Ye Y, Bian T, Li J, Yin J, Li X, Jiang L, Lei C, Liu J, Zhang Y, Jin J, Ai J, Pan J, Zhang W. Prognostic value of poly-microorganisms detected by droplet digital PCR and pathogen load kinetics in sepsis patients: a multi-center prospective cohort study. Microbiol Spectr. 2024 May 2;12(5):e0255823. doi: 10.1128/spectrum.02558-23. Epub 2024 Mar 25. PMID 38526296
• Results publication: Zhao Y, Lin K, Zhang H, Yuan G, Zhang Y, Pan J, Hong L, Huang Y, Ye Y, Huang L, Chen X, Liu J, Li X, He X, Yue Q, Zhang H, Zhou A, Zhuang Y, Chen J, Wu C, Zhou W, Cai F, Zhang S, Li L, Li S, Bian T, Li J, Yin J, Ruan Z, Xu S, Zhang Y, Chen J, Zhang Y, Han J, Su T, Tu F, Jiang L, Lei C, Du Q, Ai J, Zhang W. Evaluation of droplet digital PCR rapid detection method and precise diagnosis and treatment for suspected sepsis (PROGRESS): a study protocol for a multi-center pragmatic randomized controlled trial. BMC Infect Dis. 2022 Jul 19;22(1):630. doi: 10.1186/s12879-022-07557-2. PMID 35854212