title: Comprehensive diagnostic strategy for blood culture-negative endocarditis: a prospective study of 819 new cases.
abstract: BACKGROUND. Blood culture-negative endocarditis (BCNE) may account for up to 31% of all cases of endocarditis. METHODS. We used a prospective, multimodal strategy incorporating serological, molecular, and histopathological assays to investigate specimens from 819 patients suspected of having BCNE. RESULTS. Diagnosis of endocarditis was first ruled out for 60 patients. Among 759 patients with BCNE, a causative microorganism was identified in 62.7%, and a noninfective etiology in 2.5%. Blood was the most useful specimen, providing a diagnosis for 47.7% of patients by serological analysis (mainly Q fever and Bartonella infections). Broad-range polymerase chain reaction (PCR) of blood and Bartonella-specific Western blot methods diagnosed 7 additional cases. PCR of valvular biopsies identified 109 more etiologies, mostly streptococci, Tropheryma whipplei, Bartonella species, and fungi. Primer extension enrichment reaction and autoimmunohistochemistry identified a microorganism in 5 additional patients. No virus or Chlamydia species were detected. A noninfective cause of endocarditis, particularly neoplasic or autoimmune disease, was determined by histological analysis or by searching for antinuclear antibodies in 19 (2.5%) of the patients. Our diagnostic strategy proved useful and sensitive for BCNE workup. CONCLUSIONS. We highlight the major role of zoonotic agents and the underestimated role of noninfective diseases in BCNE. We propose serological analysis for Coxiella burnetii and Bartonella species, detection of antinuclear antibodies and rheumatoid factor as first-line tests, followed by specific PCR assays for T. whipplei, Bartonella species, and fungi in blood. Broad-spectrum 16S and 18S ribosomal RNA PCR may be performed on valvular biopsies, when available.
authors.affiliation: Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, Centre National de la Recherche Scientifique-Institut de Recherche pour le Développement, Unité Mixte de Recherche 6236, Faculté de Médecine, Université de la Méditerranée, France.
authors.forename: Pierre-Edouard
authors.initials: PE
authors.lastname: Fournier
authors.forename: Franck
authors.initials: F
authors.lastname: Thuny
authors.forename: Hervé
authors.initials: H
authors.lastname: Richet
authors.forename: Hubert
authors.initials: H
authors.lastname: Lepidi
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Casalta
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Arzouni
authors.forename: Max
authors.initials: M
authors.lastname: Maurin
authors.forename: Marie
authors.initials: M
authors.lastname: Célard
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Mainardi
authors.forename: Thierry
authors.initials: T
authors.lastname: Caus
authors.forename: Frédéric
authors.initials: F
authors.lastname: Collart
authors.forename: Gilbert
authors.initials: G
authors.lastname: Habib
authors.forename: Didier
authors.initials: D
authors.lastname: Raoult
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000473:pathology; D001424:Bacterial Infections / Q000175:diagnosis / Q000382:microbiology; D002648:Child; D004696:Endocarditis / Q000175:diagnosis* / Q000209:etiology* / Q000473:pathology; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000175:diagnosis / Q000473:pathology; D057089:Pathology, Molecular / Q000379:methods; D016133:Polymerase Chain Reaction / Q000379:methods; D011446:Prospective Studies; D055815:Young Adult