宏基因组下一代测序（mNGS）用于检测西南地区癌症患者体内病原体及抗菌药物耐药基因（ARGs），并指导抗菌药物治疗方案的制定

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 hours, 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