Metagenomic next-generation sequencing (mNGS) for detecting pathogens and antimicrobial resistance genes (ARGs), and guiding antimicrobial therapy in cancer patients from Southwest China

IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES
Qian Zhao, Qian Wan, Si-wei Wang, Pei Zhao, Yi Li, Shan-ling Xu, Chen Chen
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引用次数: 0

Abstract

Background

Cancer patients often face etiological diagnosis challenges due to repeated hospitalizations, antibiotic exposure, and conventional microbiology tests (CMTs) limitations (low positivity, long turnaround). Metagenomic next-generation sequencing (mNGS) enables rapid and accurate pathogen detection, however, its clinical utility in cancer patients requires further investigation.

Methods

Two years of mNGS results and clinical data of cancer patients in Sichuan Cancer Hospital were collected. The pathogens and antimicrobial resistance genes (ARGs) were analyzed. The diagnostic performance was evaluated via sensitivity, specificity, accuracy, positive and negative predictive value. The clinical significance in guiding antimicrobial therapy was assessed by comparing outcomes between mNGS-guided and empirical therapy groups. Multivariable logistic regression analysis was performed to explore risk factors for multidrug-resistant organisms (MDROs) and opportunistic pathogens infections in cancer population.

Results

The study included 340 mNGS results from 267 cancer patients. Streptococcus pneumoniae, Pseudomonas aeruginosa, Candida albicans and Epstein-Barr virus were the most common Gram-positive and Gram-negative bacteria, fungus and virus, respectively. The main ARGs were ESBLs and aminoglycoside resistance genes. mNGS showed high pathogen diagnostic sensitivity (97.50%) and moderate ARGs diagnostic sensitivity (64.29%). The mNGS-guided group had lower mortality (29.5% vs. 34.1%, P = 0.65) and shorter duration of mechanical ventilation (39.34 ± 81.15 vs. 42.30 ± 102.39 h, P = 0.88). Age (P = 0.028) and prior 90-day antibiotic use (P = 0.047) independently predicted MDROs infections; immunodeficiency predicted Pneumocystis jirovecii (P = 0.005) and Aspergillus spp. (P = 0.010) infections.

Conclusion

mNGS was reliable for pathogen diagnosis in cancer patients. However, its clinical significance on guiding antimicrobial therapy requires more prospective multicenter studies to confirm.
新一代宏基因组测序(mNGS)检测西南地区肿瘤患者病原菌和耐药基因(ARGs)并指导抗菌药物治疗
背景:由于反复住院、抗生素暴露和传统微生物检测(cmt)的局限性(低阳性、长周期),癌症患者经常面临病因学诊断方面的挑战。新一代宏基因组测序(mNGS)能够快速准确地检测出病原体,但其在癌症患者中的临床应用还有待进一步研究。方法:收集四川省肿瘤医院2年肿瘤患者的mNGS结果及临床资料。分析病原菌及其耐药性基因(ARGs)。通过敏感性、特异性、准确性、阳性预测值和阴性预测值对诊断效果进行评价。通过比较mngs引导组与经验治疗组的疗效,评价其指导抗菌药物治疗的临床意义。采用多变量logistic回归分析探讨癌症人群中耐多药菌(MDROs)和机会致病菌感染的危险因素。结果:该研究包括来自267名癌症患者的340个mNGS结果。最常见的革兰氏阳性菌为肺炎链球菌,最常见的是铜绿假单胞菌,最常见的是白色念珠菌和eb病毒,最常见的是真菌和病毒。主要ARGs为ESBLs和氨基糖苷耐药基因。mNGS诊断敏感性高(97.50%),ARGs诊断敏感性中等(64.29%)。mngs引导组死亡率较低(29.5%∶34.1%,p=0.65),机械通气时间较短(39.34±81.15∶42.30±102.39 h, p= 0.88)。年龄(p=0.028)和之前使用抗生素90天(p=0.047)独立预测MDROs感染;免疫缺陷可预测吉氏肺囊虫(p=0.005)和曲霉(p=0.010)感染。结论:mNGS对肿瘤患者病原菌的诊断是可靠的。然而,其指导抗菌药物治疗的临床意义还需要更多的前瞻性多中心研究来证实。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of global antimicrobial resistance
Journal of global antimicrobial resistance INFECTIOUS DISEASES-PHARMACOLOGY & PHARMACY
CiteScore
8.70
自引率
2.20%
发文量
285
审稿时长
34 weeks
期刊介绍: The Journal of Global Antimicrobial Resistance (JGAR) is a quarterly online journal run by an international Editorial Board that focuses on the global spread of antibiotic-resistant microbes. JGAR is a dedicated journal for all professionals working in research, health care, the environment and animal infection control, aiming to track the resistance threat worldwide and provides a single voice devoted to antimicrobial resistance (AMR). Featuring peer-reviewed and up to date research articles, reviews, short notes and hot topics JGAR covers the key topics related to antibacterial, antiviral, antifungal and antiparasitic resistance.
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