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Culture-Negative vs. Culture-Positive Infective Endocarditis
Quick Takes
- In an ancillary analysis of data in the ESC-EORP EURO-ENDO registry, approximately 17% of patients with infective endocarditis (IE) had culture-negative IE (CNIE).
- Among patients with a theoretical indication, surgery was performed less frequently among patients with CNIE.
- One-year mortality was not significantly different among CNIE and culture-positive IE (CPIE) patients who underwent surgery, but was higher among CNIE than CPIE patients treated without surgery.
Study Questions:
How do the clinical characteristics and outcomes of patients with culture-negative infective endocarditis (CNIE) compare to those of patients with culture-positive infective endocarditis (CPIE)?
Methods:
The European Society of Cardiology (ESC)-EURObservational Research Programme (EORP) European Endocarditis (EURO-ENDO) registry is an international registry that includes clinical data from patients >18 years of age hospitalized with active IE at one of 156 centers (120 [77%] ESC-affiliated, 36 [23%] outside Europe; 80% high-volume, 20% low-volume) in 40 countries from January 2016–March 2019; follow-up for each patient was up to 1 year after discharge; primary endpoints were 30-day and 1-year mortality. In an ancillary analysis of data in the ESC-EORP EURO-ENDO registry, CPIE was defined as IE with a causative agent identified by blood and/or tissue cultures (or with positive immunoglobulin G antibodies for Coxiella burnetiid), whereas CNIE was defined as IE with negative blood and tissue cultures.
Results:
Overall, 3,113 patients who were diagnosed with IE during the study period were included in the analysis. Of these, 2,590 (83.2%) had CPIE and 523 (16.8%) had CNIE. Clinical presentations were different between patients with CPIE and CNIE (fever, septic shock, and spondylitis were more frequent with CPIE than CNIE; heart murmur and congestive heart failure were more frequent with CNIE than CPIE). Cardiac surgery was performed during the index hospitalization in 1,488 (48.1%) patients, including 1,259 (48.8%) with CPIE and 229 (44.5%) with CNIE. CNIE was a predictor of 1-year mortality (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.04–1.56), whereas surgery was significantly associated with survival (HR, 0.49; 95% CI, 0.41–0.58). A theoretical surgical indication was present in 69.4% (1,797/2,590) of patients with CPIE and 69.0% (360/522) of patients with CNIE; however, surgery was performed in 24.8% (445/1,797) of patients with CPIE and 32.2% (116/360) with CNIE (p = 0.003). One-year mortality was significantly higher in CNIE compared to CPIE patients in the medical subgroup (94/286 patients [32.9%] vs. 380/1,322 patients [28.7%], respectively; p = 0.04), but not significantly different among patients who underwent surgery (CNIE 37/229 patients [16.2%] vs. CPIE 199/1,259 patients [15.8%]; p = 0.09).
Conclusions:
There is a higher long-term mortality among patients with CNIE compared to those with CPIE. This difference was present in patients receiving medical therapy alone but not in those who underwent surgery, with surgery associated with reduced mortality risk. The authors concluded that additional efforts are required both to improve the etiological diagnosis of IE and identify CNIE cases early, before progressive disease potentially contraindicates surgery.
Perspective:
The inability to identify the causative organism in IE may delay and impair targeted therapy, and some studies have found an association between CNIE and increased early and late mortality. This ancillary analysis from the ESC-EORP EURO-ENDO registry found that CNIE was relatively common, accounting for about 17% of all IE hospitalizations; that clinical presentations tended to be different between CNIE and CPIE; that among patients with a theoretical indication, surgery was performed less frequently among patients with CNIE; and that 1-year mortality was not significantly different among CNIE and CPIE patients who underwent surgery, but was higher among CNIE than CPIE patients treated without surgery. Although limited by its observational nature, this study reinforces the variability of IE and its outcomes, and supports the clinical importance of establishing the organism responsible for IE in order to help target appropriate therapy.
Clinical Topics: Cardiac Surgery, Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Prevention, Valvular Heart Disease, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Cardiac Surgery and VHD, Acute Heart Failure, Interventions and Structural Heart Disease
Keywords: Cardiac Surgical Procedures, Endocarditis, Endocarditis, Bacterial, Heart Failure, Heart Murmurs, Heart Valve Diseases, Immunoglobulin G, Myocarditis, Patient Discharge, Secondary Prevention, Shock, Septic, Spondylitis
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