Infective endocarditis (IE) is associated with high morbidity and mortality
. This infection is difficult to diagnose and, in some cases, to treat succ
essfully particularly when the causative agent is non-culturable. Blood cul
ture is still the most important laboratory test performed during the diagn
ostic work-up of IE. The bacteraemia associated with the disease is usually
continuous and low grade. In two-thirds of all IE cases the blood cultures
taken will be positive and will usually reveal a variety of aetiological a
gents depending on the patient population. Streptococcus spp. are the main
causative agents in patients who have an intact immune system and possess n
ative heart valves. Staphylococci are the predominant microorganisms in pat
ients with prosthetic heart valves and in intravenous drug abusers. Other m
iscellaneous bacteria and fungi may also cause IE. However between 5 and 24
% of suspected IE cases yield negative blood culture results; there are se
veral possible explanations for this, including prior antibiotic therapy, f
astidious and cell-dependent organisms or fungi. Ultimately the identificat
ion of the causative agent is the cornerstone of successful treatment of IE
through appropriate chemotherapy. Conventional methodologies cannot detect
the causative agent in culture-negative IE cases and hence difficulties ar
ise in the clinical management of such patients. The aim of this review is
to examine: (i) the reasons contributing to culture-negative IE; (ii) diagn
ostic criteria for the classification of IE; (iii) diagnostic methodology o
f IE, particularly trends in the application of molecular-based techniques;
(iv) aetiological agents responsible for culture-negative IE; and (v) trea
tment of IE. (C) 2000 Lippincott Williams & Wilkins.