Prognostic value of poly-microorganisms detected by droplet digital PCR and pathogen load kinetics in sepsis patients: a multi-center prospective cohort study

• Published in: Microbiology spectrum Vol. 12; no. 5; p. e0255823
• Main Authors: Zhao, Yuanhan, Lin, Ke, Zhang, Haocheng, Zhang, Yanliang, Li, Shaling, Zhang, Shengguo, Zhang, Wei, Zhou, Aiming, Zhuang, Yangyang, Chen, Jie, Wu, Caixia, Zhou, Wei, He, Xiaoju, Yue, Qiaoyan, Zhang, Meng, Huang, Yan, Li, Liang, Hong, Liang, Cai, Fujing, Huang, Lisu, Ruan, Zhengshang, Xu, Shanshan, Zhang, Yan, Chen, Xiaohua, Ye, Ying, Bian, Tingting, Li, Jiabin, Yin, Jun, Li, Xiang, Jiang, Lijing, Lei, Chen, Liu, Jun, Zhang, Ying, Jin, Jialin, Ai, Jingwen, Pan, Jingye, Zhang, Wenhong
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 02-05-2024
• Subjects: Aged; Aged, 80 and over; Bacteria - classification; Bacteria - genetics; Bacteria - isolation & purification; Bacterial Load - methods; Computational Biology; droplet digital polymerase chain reaction; Female; Humans; Kinetics; Male; Middle Aged; mortality; pathogen load; Polymerase Chain Reaction - methods; polymicrobial infection; Prognosis; Prospective Studies; Research Article; Risk Factors; sepsis; Sepsis - diagnosis; Sepsis - microbiology; Sepsis - mortality; mortality; polymicrobial infection; pathogen load; sepsis; droplet digital polymerase chain reaction
• ISSN: 2165-0497; 2165-0497
• DOI: 10.1128/spectrum.02558-23

This study aimed to investigate the prognostic value of a novel droplet digital polymerase chain reaction (DDPCR) assay in sepsis patients. In this prospective cohort study, univariable and multivariable Cox regressions were used to assess risk factors for 28-day mortality. We also monitored pathogen load together with clinical indicators in a subgroup of the cohort. A total of 107 sepsis patients with positive baseline DDPCR results were included. Detection of poly-microorganisms [adjusted hazard ratio (HR) = 3.19; 95% confidence interval (CI) = 1.34-7.62;
= 0.009], high Charlson Comorbidity Index (CCI) score (adjusted HR = 1.14; 95% CI = 1.01-1.29;
= 0.041), and Sequential Organ Failure Assessment (SOFA) score (adjusted HR = 1.18; 95% CI = 1.05-1.32;
= 0.005) at baseline were independent risk factors for 28-day mortality while initial pathogen load was not associated (adjusted HR = 1.17; 95% CI = 0.82-1.66;
= 0.385). Among 63 patients with serial DDPCR results, an increase in pathogen load at days 6-8 compared to baseline was a risk factor for 28-day mortality (
= 0.008). Also, pathogen load kinetics were significantly different between day-28 survivors and nonsurvivors (
= 0.022), with a decline overtime only in survivors and an increase from days 3 and 4 to days 6-8 in nonsurvivors. Using DDPCR technique, we found that poly-microorganisms detected and increased pathogen load a week after sepsis diagnosis were associated with poor prognosis.IMPORTANCEThis prospective study was initiated to explore the prognostic implications of a novel multiplex PCR assay in sepsis. Notably, our study was the largest cohort of sepsis with droplet digital polymerase chain reaction pathogen monitoring to date, allowing for a comprehensive evaluation of the prognostic significance of both pathogen species and load. We found that detection of poly-microorganisms was an independent risk factors for 28-day mortality. Also, pathogen load increase 1 week after sepsis diagnosis was a risk factor for 28-day mortality, and differential pathogen load kinetics were identified between day-28 survivors and nonsurvivors. Overall, this study demonstrated that pathogen species and load were highly correlated with sepsis prognosis. Patients exhibiting conditions mentioned above face a more adverse prognosis, suggesting the potential need for an escalation of antimicrobial therapy.Registered at ClinicalTrials.gov (NCT05190861).