Metagenomic Next-Generation Sequencing Unveils Prognostic Microbial Synergism and Guides Precision Therapy in Candidemia: A Retrospective Cohort Study

Yuhui Chen,1,2 Meng Li,1,2 Xinai Gan,1,2 Yutong Wang,1,2 Xinzhu Tang,1,2 Yongzhao Zhou,3,4 Ting Niu1,5,6 1Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2West China School of Medicine, Sichuan University, Chengdu, People’s Republic of China; 3Integrated Care Management Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 5State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6National Facility for Translational Medicine (Sichuan), West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Ting Niu, Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, No. 37 GuoXueXiang Street, Chengdu, Sichuan Province, 610041, People’s Republic of China, Email [email protected] Yongzhao Zhou, Integrated Care Management Center, West China Hospital, Sichuan University, No. 37 GuoXueXiang Street, Chengdu, Sichuan Province, 610041, People’s Republic of China, Email [email protected]: Candidemia remains a life-threatening infection, compounded by diagnostic delays and limited prognostic tools. While metagenomic next-generation sequencing (mNGS) offers rapid pathogen detection, its prognostic utility and therapeutic impact in candidemia remain unestablished.Patients and Methods: This retrospective cohort study analyzed 97 candidemia patients with positive blood mNGS at West China Hospital (2020– 2024). Multivariable logistic regression and survival analyses identified mortality predictors, while therapeutic impacts were assessed through antifungal regimen modifications.Results: The 28-day mortality was 44.3% (43/97). Blood mNGS outperformed cultures in species identification (5 vs 4 species) and co-infection detection. Bacterial co-detections (HR=2.00, 95% CI:1.15– 3.48; p< 0.05) doubled mortality risk. SOFA score was the strongest mortality predictor (adjusted OR=1.29 per point; p< 0.001). mNGS-guided antifungal initiation reduced mortality by 52.4% in treatment-naïve patients (22.6% vs 75.0%; p< 0.05), though regimen adjustments in pretreated cases showed no benefit (p> 0.05). Notably, Candida species exhibited equivalent virulence (log-rank p> 0.05), and mNGS read counts lacked prognostic value (p> 0.05).Conclusion: mNGS transforms candidemia management by enabling early risk stratification (via SOFA scores and co-infection profiles) and precision therapy initiation. Its capacity to unmask high-risk bacterial synergists and guide time-sensitive interventions supports integration into diagnostic algorithms, particularly for culture-negative cases. Further validation of standardized mNGS protocols is warranted to maximize clinical impact.Keywords: candidemia, metagenomic next-generation sequencing, mNGS, prognostic model, microbial synergism, precision therapy