Department of Infectious Diseases, National Medical Center for Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, China.
Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, China.
Microbiol Spectr. 2024 May 2;12(5):e0255823. doi: 10.1128/spectrum.02558-23. Epub 2024 Mar 25.
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).
本研究旨在探讨新型液滴数字聚合酶链反应（DDPCR）检测在脓毒症患者中的预后价值。在这项前瞻性队列研究中，使用单变量和多变量 Cox 回归评估了 28 天死亡率的风险因素。我们还在队列的一个亚组中监测了病原体负荷以及临床指标。共纳入了 107 例基线 DDPCR 阳性的脓毒症患者。多微生物检测（调整后的危险比[HR] = 3.19；95%置信区间[CI] = 1.34-7.62；P = 0.009）、高 Charlson 合并症指数（CCI）评分（调整后的 HR = 1.14；95%CI = 1.01-1.29；P = 0.041）和序贯器官衰竭评估（SOFA）评分（调整后的 HR = 1.18；95%CI = 1.05-1.32；P = 0.005）是 28 天死亡率的独立风险因素，而初始病原体负荷与死亡率无关（调整后的 HR = 1.17；95%CI = 0.82-1.66；P = 0.385）。在 63 例有连续 DDPCR 结果的患者中，与基线相比，第 6-8 天病原体负荷增加是 28 天死亡率的一个风险因素（P = 0.008）。此外，28 天幸存者和非幸存者之间的病原体负荷动力学有显著差异（P = 0.022），幸存者的病原体负荷随时间下降，而非幸存者的病原体负荷从第 3 天和第 4 天增加到第 6-8 天。使用 DDPCR 技术，我们发现脓毒症诊断后一周内检测到的多微生物和增加的病原体负荷与预后不良有关。
重要性
本前瞻性研究旨在探讨新型多重 PCR 检测在脓毒症中的预后意义。值得注意的是，我们的研究是迄今为止最大的脓毒症使用液滴数字聚合酶链反应病原体监测队列，能够全面评估病原体种类和负荷的预后意义。我们发现，多微生物检测是 28 天死亡率的独立风险因素。此外，脓毒症诊断后 1 周病原体负荷增加是 28 天死亡率的一个风险因素，28 天幸存者和非幸存者之间的病原体负荷动力学存在差异。总体而言，本研究表明病原体种类和负荷与脓毒症预后高度相关。表现出上述情况的患者预后更差，提示可能需要升级抗菌治疗。在 ClinicalTrials.gov（NCT05190861）注册。
