Clinical outcomes in blood culture-negative versus blood culture-positive infective endocarditis: a systematic review and meta-analysis.

Abstract

Blood culture-negative infective endocarditis (BCNIE) remains a diagnostic and therapeutic challenge due to uncertainty in pathogen identification and treatment decisions. Existing literature offers conflicting data on its prognosis. This meta-analysis aims to compare the clinical outcome between BCNIE and blood culture-positive infective endocarditis (BCPIE). Articles from PubMed/MEDLINE, Embase, the Cochrane Library and Scopus published up to January 2025 were screened. Studies reporting the primary outcome (mortality) and secondary outcomes (heart failure and embolic events) were included. A random-effects model was used to compare mortality between BCNIE and BCPIE, and pooled risk ratios (RRs) were calculated. Stratified analyses were performed to explore potential sources of heterogeneity. A total of 35 studies comprising 17 661 patients were included in the meta-analysis. Short-term mortality was comparable between BCNIE and BCPIE (RR=0.95; 95% CI 0.77 to 1.19; I² = 83%) suggesting no meaningful difference in risk. Mortality outcomes were consistent across subgroups based on study design, geographical region, sample size and publication year. Heart failure was more common in BCNIE (RR: 1.33; 95% CI 1.16 to 1.51); whereas, embolic events were less frequent in BCNIE compared with BCPIE (RR: 0.81; 95% CI 0.69 to 0.95). In this study-level meta-analysis, short-term mortality did not differ between BCNIE and BCPIE. However, complication rates varied: heart failure was more common in BCNIE, whereas embolic events were less frequent. These findings suggest that while blood culture status may not influence survival, it may be associated with distinct clinical presentations and complications. CRD420250656399.