Impact of intraoperative metagenomic next-generation sequencing on long-term outcomes in patients with blood culture–negative infective endocarditis
L Zhang, S Yang, S Xu, G Ma, X Liu, J Liu, C Zhang, J ZhengAbstract
Background/Introduction
Treatment of infective endocarditis (IE) remains challenging, largely due to difficulties in accurately identifying causative pathogens. Metagenomic next-generation sequencing (mNGS) enables highly sensitive and specific pathogen detection; however, evidence regarding its long-term clinical impact in surgically treated IE patients remains limited.
Purpose
To evaluate the impact of intraoperative mNGS on long-term outcomes in patients with blood culture–negative infective endocarditis (BCNIE) undergoing surgical treatment.
Methods
We retrospectively analyzed patients who underwent surgical treatment for IE between 2013 and 2025, with a median follow-up of 4 years. Patients were classified into mNGS and non-mNGS groups based on intraoperative pathogen testing. Propensity score matching (1:1) was performed to balance baseline characteristics, yielding 90 matched pairs with good covariate balance. Since mNGS testing was implemented at our center starting in 2020, surgical era (before vs. after 2020) was included in the propensity score model to account for potential temporal effects. Overall survival was assessed using Cox proportional hazards models, and endocarditis recurrence was analyzed using Gray’s test.
Results
Among 773 patients undergoing IE surgery, 250 (32.3%) had BCNIE. In patients who underwent mNGS testing, the most commonly identified pathogens were streptococci (38.8%), staphylococci (13.3%), fungi (10%), Coxiella burnetii (5.5%), and Brucella species (4.4%). Antimicrobial therapy was adjusted in 51.1% of cases. In-hospital survival was similar between the mNGS and non-mNGS groups (97.8% vs. 98.1%). After propensity score matching, no significant differences were observed between the two groups in in-hospital mortality (P = 0.725), postoperative complications, or intensive care unit stay. Recurrence rates were also comparable between groups (HR = 0.93; 95% CI 0.41–2.04; P = 0.83). Notably, intraoperative mNGS was associated with significantly improved long-term overall survival (HR = 0.42; 95% CI 0.17–0.99; P = 0.048; Figure 1). Stratified analyses showed that this survival benefit was observed in patients with native valve BCNIE (HR = 0.28; 95% CI 0.09–0.94; P = 0.040) but not in those with prosthetic valve involvement (HR = 1.06; 95% CI 0.22–5.09; P = 0.937; Figure 2).
Conclusions
In patients with BCNIE, intraoperative mNGS facilitates more precise antimicrobial therapy and is associated with improved long-term survival, particularly in those with native valve disease.Figure 1Figure 2