Background: Culture-negative endocarditis is a diagnostic challenge with va
riable 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, an
d 2. the presence of fastidious microorganisms with limited or no capacity
to grow in routine blood cultures (Table 1). If initial blood cultures rema
in negative for 48-72 hours, these cultures should be incubated for at leas
t an additional 2-4 weeks. Moreover, subcultures should be plated onto choc
olate agar and incubated in an atmosphere of increased CO2 environment to f
acilitate recovery of fastidious bacteria. Additional techniques for identi
fication of a causative organism include serologic tests and DNA/RNA-based
molecular techniques. If the patient is clinically stable, the clinician ca
n wait until culture results from initial samples are known before deciding
upon either administering an empiric antibiotic therapy or obtaining furth
er blood cultures. Certain predisposing patient characteristics or epidemio
logic 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 cult
ure-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 t
he detection of vegetations and perivalvular complications and is, therefor
e, considered the diagnostic imaging method of choice in the diagnosis of c
ulture-negative endocarditis. The Duke criteria have been shown to have a h
igh accuracy in the diagnosis of culture-negative endocarditis. In this con
text global clinical judgment demonstrated a comparable sensitivity but a l
ower specificity. Main differential diagnoses include diseases which can mi
mic the clinical endocarditis syndrome as well as the echocardiographic pat
tern of culture-negative endocarditis, especially 1. nonbacterial thromboti
c endocarditis and 2. valvular sclerosis in the presence of systemic infect
ion (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 ma
y be suggestive of an etiologic organism.