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血浆游离DNA微滴式数字PCR为发热血液病患者提供快速有效的感染性微生物学诊断。

Plasma cell-free DNA Droplet Digital PCR provides rapid and efficient infectious microbiology diagnosis for febrile haematological patients.

作者信息

Li Ying, Xiao Jun, Xia Lihui, Sun Xueqin, Li Jia, Bai Huili

机构信息

The Center for Clinical Molecular Medical Detection, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Front Cell Infect Microbiol. 2025 Feb 19;15:1522426. doi: 10.3389/fcimb.2025.1522426. eCollection 2025.

Abstract

BACKGROUND

Febrile haematological patients are at high risk for potential bloodstream infections, the rapid and accurate identification of pathogens is crucial for clinical diagnosis and treatment. Droplet Digital PCR (ddPCR) is a novel and ultra-sensitively molecular technique for the rapid detection of pathogens. We evaluated the ability of ddPCR to identify infectious etiologies to discuss the applicability of ddPCR in the diagnosis and treatment of infections for febrile haematological patients.

METHODS

This study enrolled and analyzed 89 ddPCR tests performed on 71 febrile haematological patients. We conducted a comparison between ddPCR results, blood culture (BC), and conventional microbiological testing (CMT). Additionally, we analyzed the correlation between ddPCR results and inflammatory factors, as well as their impact on antimicrobial therapy.

RESULTS

DdPCR detected 113 pathogens in 72 plasma samples, while CMT identified 39 pathogens in 32 plasma samples. The detection rate of bacteria and viruses using ddPCR was significantly higher than that of CMT (p <0.0001). The turnaround time (TAT) for pathogenic diagnosis was significantly shorter with ddPCR compared to CMT (p <0.0001). When we used the CMT as reference standard, the sensitivity and specificity of ddPCR were 93.8%, 26.3%, respectively. We observed a positive correlation between the ddPCR results and CRP, PCT and IL-6, and ddPCR (AUC=0.771) has better diagnostic performance. The anti-infective treatment strategies were adjusted for 30 patients based on the positive ddPCR results, with 86.7% (26/30) of these cases demonstrating effectiveness in the anti-infective treatment.

CONCLUSION

DdPCR has the potential to enhance pathogen detection in febrile haematological patients by offering high sensitivity, rapid, precise results, it demonstrates better diagnostic performance compared to inflammatory factors and can contribute to the real-time clinical optimization of antimicrobial regimens, thereby enhancing the efficacy of anti-infective therapy.

摘要

背景

发热血液病患者发生潜在血流感染的风险很高,病原体的快速准确鉴定对临床诊断和治疗至关重要。数字液滴PCR(ddPCR)是一种用于快速检测病原体的新型超灵敏分子技术。我们评估了ddPCR鉴定感染病因的能力,以探讨ddPCR在发热血液病患者感染诊断和治疗中的适用性。

方法

本研究纳入并分析了对71例发热血液病患者进行的89次ddPCR检测。我们对ddPCR结果、血培养(BC)和传统微生物检测(CMT)进行了比较。此外,我们分析了ddPCR结果与炎症因子之间的相关性,以及它们对抗菌治疗的影响。

结果

ddPCR在72份血浆样本中检测到113种病原体,而CMT在32份血浆样本中鉴定出39种病原体。ddPCR检测细菌和病毒的检出率显著高于CMT(p<0.0001)。与CMT相比,ddPCR进行病原诊断的周转时间(TAT)显著缩短(p<0.0001)。以CMT作为参考标准时,ddPCR的灵敏度和特异性分别为93.8%、26.3%。我们观察到ddPCR结果与CRP、PCT和IL-6之间呈正相关,且ddPCR(AUC=0.771)具有更好的诊断性能。基于ddPCR阳性结果,对30例患者调整了抗感染治疗策略,其中86.7%(26/30)的病例抗感染治疗有效。

结论

ddPCR具有提高发热血液病患者病原体检测的潜力,它能提供高灵敏度、快速、精确的结果,与炎症因子相比具有更好的诊断性能,有助于抗菌方案的实时临床优化,从而提高抗感染治疗的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bf1/11880229/d1bc7a02226f/fcimb-15-1522426-g001.jpg

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