Blood culture negative endocarditis in the modern era of 16S rRNA sequencing

Abstract

Blood culture negative endocarditis (BCNE) accounts for up to 20% of infective endocarditis. While the most common cause of BCNE remains the initiation of antibiotics prior to culture, intracellular organisms such as Coxiella and Bartonella spp account for a significant proportion of cases. Identifying the infecting organism remains important to ensure optimal antimicrobial treatment. However, these organisms can be difficult to diagnose. We outline a systematic approach to BCNE. Over half of patients with infective endocarditis now undergo early surgery and 16S ribosomal ribonucleic acid (rRNA) polymerase chain reaction (PCR) of excised tissue can be vitally important to secure a diagnosis. Molecular testing is likely to become a key tool in improving outcomes from BCNE and contribute to an improved understanding of the aetiology. We advocate modifying the Duke criteria to incorporate organisms identified on molecular testing, including 16S rRNA PCR, in particular from explanted tissue.

Evaluation of 16S rDNA Heart Tissue PCR as a Complement to Blood Cultures for the Routine Etiological Diagnosis of Infective Endocarditis

“…BCNE rates are highly variable in the literature, ranging from 2.5 to 31% [18]. This variability is conditioned by several factors, such as antimicrobial treatments prior to culture and/or the incidence of noncultivable or fastidious microorganisms [19]. Molecular analysis of heart valves was found to be the only method to establish the etiology of BCNE, giving consistent results in 16 out of 44 patients (36%).…”

Bartonella Endocarditis: A Missed Diagnosis in Medical Practice

“…can take up to 21 days to grow [1]. Histopathological stains of the surgical tissue are neither sensitive nor specific [1,[4][5][6]. In recent years, where molecular testing has become available, polymerase chain reaction (PCR) 16S RNA of the valvular tissue has shown a sensitivity and specificity of 70-98% [1,5,6].…”

“…Histopathological stains of the surgical tissue are neither sensitive nor specific [1,[4][5][6]. In recent years, where molecular testing has become available, polymerase chain reaction (PCR) 16S RNA of the valvular tissue has shown a sensitivity and specificity of 70-98% [1,5,6]. However, microbial DNA can persist for months following infection, in which case a positive PCR does not imply ongoing infection [5].…”

“…In recent years, where molecular testing has become available, polymerase chain reaction (PCR) 16S RNA of the valvular tissue has shown a sensitivity and specificity of 70-98% [1,5,6]. However, microbial DNA can persist for months following infection, in which case a positive PCR does not imply ongoing infection [5]. Serologic testing such as immunofluorescence assays and enzyme-linked immunosorbent assays are the most useful tests for the diagnosis of Bartonella endocarditis, but they are not part of the DUKE criteria yet [1,4,5].…”

“…However, microbial DNA can persist for months following infection, in which case a positive PCR does not imply ongoing infection [5]. Serologic testing such as immunofluorescence assays and enzyme-linked immunosorbent assays are the most useful tests for the diagnosis of Bartonella endocarditis, but they are not part of the DUKE criteria yet [1,4,5]. IgG titers of B. henselae of >1:64 with a four-fold titer rise at least two weeks apart have a sensitivity of 88-98% [1,2].…”