Prognostic value of poly-microorganisms detected by droplet digital PCR and pathogen load kinetics in sepsis patients : a multi-center prospective cohort study
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; P = 0.009], high Charlson Comorbidity Index (CCI) score (adjusted HR = 1.14; 95% CI = 1.01-1.29; P = 0.041), and Sequential Organ Failure Assessment (SOFA) score (adjusted HR = 1.18; 95% CI = 1.05-1.32; P = 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; P = 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 (P = 0.008). Also, pathogen load kinetics were significantly different between day-28 survivors and nonsurvivors (P = 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).
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Microbiology spectrum - (2024) vom: 25. März, Seite e0255823 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhao, Yuanhan [VerfasserIn] |
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| Links: |
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| Themen: |
Droplet digital polymerase chain reaction |
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| Anmerkungen: |
Date Revised 25.03.2024 published: Print-Electronic ClinicalTrials.gov: NCT05190861 Citation Status Publisher |
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| doi: |
10.1128/spectrum.02558-23 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370158644 |
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| 100 | 1 | |a Zhao, Yuanhan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Prognostic value of poly-microorganisms detected by droplet digital PCR and pathogen load kinetics in sepsis patients |b a multi-center prospective cohort study |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Revised 25.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT05190861 | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a 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; P = 0.009], high Charlson Comorbidity Index (CCI) score (adjusted HR = 1.14; 95% CI = 1.01-1.29; P = 0.041), and Sequential Organ Failure Assessment (SOFA) score (adjusted HR = 1.18; 95% CI = 1.05-1.32; P = 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; P = 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 (P = 0.008). Also, pathogen load kinetics were significantly different between day-28 survivors and nonsurvivors (P = 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) | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a droplet digital polymerase chain reaction | |
| 650 | 4 | |a mortality | |
| 650 | 4 | |a pathogen load | |
| 650 | 4 | |a polymicrobial infection | |
| 650 | 4 | |a sepsis | |
| 700 | 1 | |a Lin, Ke |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Haocheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yanliang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Shaling |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Shengguo |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Aiming |e verfasserin |4 aut | |
| 700 | 1 | |a Zhuang, Yangyang |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Caixia |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a He, Xiaoju |e verfasserin |4 aut | |
| 700 | 1 | |a Yue, Qiaoyan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Fujing |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Lisu |e verfasserin |4 aut | |
| 700 | 1 | |a Ruan, Zhengshang |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Shanshan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xiaohua |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Ye, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Bian, Tingting |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jiabin |e verfasserin |4 aut | |
| 700 | 1 | |a Yin, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiang |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Lijing |e verfasserin |4 aut | |
| 700 | 1 | |a Lei, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Jialin |e verfasserin |4 aut | |
| 700 | 1 | |a Ai, Jingwen |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Jingye |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wenhong |e verfasserin |4 aut | |
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