Background: Culture-negative endocarditis is a diagnostic challenge with variable clinical presentation and protean manifestations.
Etiology and diagnosis: The two main causes why endocarditis may be culture-negative are 1. antibiotic treatment prior to obtaining blood cultures, and 2. the presence of fastidious microorganisms with limited or no capacity to grow in routine blood cultures (Table 1). If initial blood cultures remain negative for 48-72 hours, these cultures should be incubated for at least an additional 2-4 weeks. Moreover, subcultures should be plated onto chocolate agar and incubated in an atmosphere of increased CO2 environment to facilitate recovery of fastidious bacteria. Additional techniques for identification of a causative organism include serologic tests and DNA/RNA-based molecular techniques. If the patient is clinically stable, the clinician can wait until culture results from initial samples are known before deciding upon either administering an empiric antibiotic therapy or obtaining further blood cultures. Certain predisposing patient characteristics or epidemiologic exposures may be associated with particular causative microorganisms in culture-negative endocarditis. In the absence of positive blood cultures echocardiography is a crucial tool in the diagnosis and management of culture-negative endocarditis which provides the basis for the visualization of endocarditis-associated cardiac lesions. In this context, transesophageal echocardiography is associated with a significantly higher sensitivity in the detection of vegetations and perivalvular complications and is, therefore, considered the diagnostic imaging method of choice in the diagnosis of culture-negative endocarditis. The Duke criteria have been shown to have a high accuracy in the diagnosis of culture-negative endocarditis. In this context global clinical judgment demonstrated a comparable sensitivity but a lower specificity. Main differential diagnoses include diseases which can mimic the clinical endocarditis syndrome as well as the echocardiographic pattern of culture-negative endocarditis, especially 1. nonbacterial thrombotic endocarditis and 2. valvular sclerosis in the presence of systemic infection (Table 2).
Treatment: The selection of a particular antibiotic regimen in a suspected case of culture-negative endocarditis depends on demographics (e.g., age or geographic area), epidemiologic history (e.g., animal exposures, drug-use history, alcohol abuse, homelessness) and clinical characteristics which may be suggestive of an etiologic organism.