Blood Culture Negative vs. Blood Culture Positive Infective Endocarditis: A Multicenter Study of 4,917 Patients

All articles of this category (opens in new window) Background: Identification of causal bacterial strains by preoperative blood cultures is crucial for the diagnosis and management of infective endocarditis (IE). This study compared clinical characteristics and outcomes of surgically treated IE patients with either negative or positive preoperative blood cultures. Methods: The database of the Clinical Multicenter Project for Analysis of Infective Endocarditis in Germany (CAMPAIGN), comprising 4.917 consecutive endocarditis patients treated by open-heart valve surgery between 1994 and 2018. The cohort was stratified regarding identification of causal microorganisms: culture-negative (CNIE) vs. culture-positive infective endocarditis (CPIE). Propensity Score Matching (PSM) was used to minimize differences in baseline characteristics and adjust for cofounders. Results: The study groups comprised 1.870 (38%) patients with CNIE and 3.047 (62%) patients with CPIE. After 1:1 PSM, 1.198 pairs were assigned to either group. Median age of patients in the matched CNIE vs. CPIE groups was 64.0 [IQR: 53.0–73.0] vs. 64.0 [53.7–73.0] years, respectively ( p = 0.452). EuroSCORE II was similar between groups (11.2 [6.5–18.9] vs. 9.6 [4.4–25.2] %; p = 0.120). In the CPIE group, Staphylococcus aureus species accounted for 41.4% of infections, followed by Streptococcus species (26.0%) and Enterococcus species (17.8%). Distribution of valve involvement was similar between groups: aortic valve IE (65.2% vs. 63.4%; p = 0.188), mitral valve IE (41.7% vs. 45.4%; p = 0.070), prosthetic valve endocarditis (PVE; 23.8% vs. 25.1%; p = 0.476). However, patients with CNIE had lower detection rates of vegetations by echocardiography (40.2% vs. 86.6%; p < 0.001) and lower prevalence of septic embolism (22.3% vs. 34.1%; p < 0.001). Postoperative complications such as re-exploration for bleeding (10.1% vs. 15.4%; p < 0.001), new-onset stroke (6.6% vs. 24.7%; p < 0.001), or need for dialysis (13.0% vs. 21.1%; p < 0.001) occurred significantly less frequently in the CNIE group. Mortality rates at 30 days were similar (13.1% vs. 12.8%; p = 0.852). CNIE patients demonstrated significantly lower mortality rates after 1 year (24.0% vs. 32.2%; p < 0.001) and after further follow-up of a median of 4.8 [0.1–5.9] years (28.5% vs. 40.7%; p < 0.001). Conclusion: This analysis of the CAMPAIGN registry demonstrates similar 30-day mortality after surgery for CNIE vs. CPIE. However, patients with CNIE experienced a lower prevalence of perioperative complications and more favorable long-term survival. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany