CLINICAL RESEARCH STUDY
Diagnosis of infectious endocarditis in patients
undergoing valve surgery
Gilbert Greub,
a
Hubert Lepidi,
a
Clarisse Rovery,
a
Jean-Paul Casalta,
a
Gilbert Habib,
b
Frédéric Collard,
c
Pierre-Edouard Fournier,
a
and Didier Raoult
a
a
Unité des Rickettsies, Faculté de Médecine, Université de la Méditerranée, Marseille, France;
b
Service de cardiologie, and
c
Service de chirurgie cardiaque, Hôpital de la Timone, Marseille, France.
PURPOSE: Histologic examination of valve samples is considered as the gold standard for the
diagnosis of infectious endocarditis. Molecular tools are also very promising for patients with
negative-culture endocarditis. Thus, we studied the contribution of valvular histology, culture, and
16S rRNA PCR amplification plus sequencing to the diagnosis of infectious endocarditis in patients
undergoing valve surgery.
SUBJECTS AND METHODS: We performed culture, histological examination, and broad-range
PCR amplification plus sequencing on valve samples taken from 127 patients with infectious
endocarditis and from 118 patients without endocarditis. The sensitivity and specificity of these
tests for the diagnosis of endocarditis in patients undergoing valve surgery were studied.
RESULTS: The sensitivity of PCR was of 61% (64/105) whereas that of histological examination
was of 63% (62/98) and that of valve culture was of only 13% (14/105). All 68 positive PCR results
considered reliable according to an interpretation scheme were from patients with infectious
endocarditis, resulting in a 100% (118/118) specificity of the interpreted molecular approach. The
specificity of histology was also of 100% (118/118) when using stringent criteria (ie, presence of
vegetation, microorganisms, and/or valvular inflammation with mainly polymorphonuclear cells).
PCR identified an etiological agent in 38% (5/13) of definite blood culture-negative infectious
endocarditis.
CONCLUSION: We show that valvular histology with stringent criteria is the gold standard for
the diagnosis of infectious endocarditis. Broad-range amplification of 16S rRNA gene is indicated
for infectious endocarditis of unknown etiology, whereas valve culture is of limited sensitivity.
© 2005 Elsevier Inc. All rights reserved.
KEYWORDS:
Endocarditis;
Etiological diagnosis;
valve analysis;
histopathology;
polymerase chain
reaction
Bacteremia is a common feature of infectious endocar-
ditis, and blood cultures are considered one of the most
important tools to make a diagnosis of endocarditis.
1
How-
ever, blood cultures fail to isolate an etiologic agent in 2.5
to 31% of cases.
2– 4
Culture-negative endocarditis is often
associated with antibiotic use within the previous 2 weeks,
5
or less frequently caused by intracellular pathogen that are
not detected using standard culture approaches.
6,7
Use of
alternative laboratory diagnostic methods are thus needed,
including pathologic examination of valvular samples and
immunohistology,
8
serology,
9
and molecular tools (re-
viewed in
10,11
).
Histologic examination of valve samples is generally
considered as the gold standard and as a criterion of definite
Requests for reprints should be addressed to Gilbert Greub, Institute of
Microbiology, Faculty of Biology and Medicine, Lausanne, Switzerland.
E-mail: didier.raoult@medecine.univ-mrs.fr
0002-9343/$ -see front matter © 2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.amjmed.2004.12.014
The American Journal of Medicine (2005) 118, 230–238