Blood Culture-Negative Infective Endocarditis (BCNIE)
Definition: No etiology found after 3 separate blood cultures remain negative for 7 days
Etiologies - "True" BCNIE may be due to:
 • Previous administration of antimicrobials reduces recovery rate of bacteria by 35-40%!
 • Infection with highly fastidious bacteria or fungi (grows slow, requires special media)
 • Infection with intra-cellular bacteria
 • Inadequate microbiological techniques
Work-up of BCNIE relies on evaluation of epidemiological factors, history of prior infections, exposure to antimicrobials, clinical course, extracardiac sites, severity.
Etiology will vary with geographic and epidemiological risk factors, but important causes include:
 • Bartonella spp, Brucella spp, Coxiella burnetii, Chlamydia spp, Tropheryma whipplei, Fungi (Aspergillus, Candida), Mycoplasma spp, Legionella spp
Although HACEK organisms (Haemophilus spp., Aggregatibacter spp., Cardiobacterium hominis, Eikenella corrodens, Kingella spp) and nutritionally variant Strep spp (Granulicatella, Abiotrophia) were classically listed under BCNIE, these bacteria should grow and be identified with modern culture methods!!!
BCNIE Diagnostic Strategies:
 • Blood - Depending on local and patient-specific epidemiologic risk factors:
    - Serology for zoonotic agents (especially helpful for Coxiella, Bartonella, Bartonella). See charts
    - Assays for antinuclear antibodies, rheumatoid factor, antiphospholipid syndrome
 • Valve:
    - Standard culture of valve only ~10% sensitive
    - Histopathology with special stains (e.g. Warthin-Starry if Bartonella), immunohistochemistry (for Coxiella, Bartonella, T. whipplel) of explanted valve tissue
    - Valvular 16S (bacteria) and 18S ( fungi) ribosomal RNA PCR 
    - PCR for specific pathogens also exists

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