Molecular and Serological Diagnostic Approach to Define the Microbiological Origin of Blood Culture-Negative Infective Endocarditis

Abstract

Blood culture-negative infective endocarditis (BCNIE) poses a significant challenge in determining the best antibiotic regimen for this life-threatening infection, which should be treated with as specific and effective a regimen as feasible. The goal of this study was to determine the prevalence of BCNIE among definite infective endocarditis (IE) cases and to study the impact of a molecular and serological diagnostic approach in defining the microbiological origin of BCNIE. This study included 94 definite IE cases. Serum and blood samples from BCNIE patients were tested using serological, broad-range PCR, and sequencing assays. Valve tissue sections obtained from 42 operated patients were subjected to culture and molecular studies. BCNIE accounted for 63 (67%) of the cases. Of these cases, blood PCR followed by sequencing could diagnose 11 cases. Zoonotic infective endocarditis was detected in 7 (11%) patients by serology and PCR (four Brucella, two Bartonella, and one Coxiella). Sequencing of valve PCR bands revealed 30 positive cases. Therefore, the percentage of BCNIE with unidentified etiology was reduced from 67% to 27.7% through a combination of all diagnostic procedures utilized in our study. Blood and valve PCR and sequencing assays are valuable techniques for the etiological diagnosis of BCNIE, especially in cases with previous antibiotic therapy. However, these tests should be used as part of a larger diagnostic strategy that includes serology, microscopy, and valve culture. The use of an automated blood culture system, and proper blood culture collection before ordering antibiotics, will guide IE etiological diagnosis.

Evaluation of Infective Endocarditis in Children: A 19-Year Retrospective Study in Taiwan

“…Although blood and valve tissue cultures are the gold standard for IE pathogens’ detection, they are very time-consuming and unfeasible for fastidious or intracellular microorganisms [ 14 ]. Many modified criteria and diagnostic techniques, such as imaging, have been introduced in an effort to improve the diagnosis of pathologically proven native valve blood-culture-negative IE [ 15 ]. The value of echocardiography in the diagnosis of patients with culture-negative endocarditis is great since it improves sensitivity and specificity [ 16 , 17 ] and has proven to be a major criterion for endocarditis in 78–98.5% of definite IE cases [ 15 , 17 ].…”

“…Many modified criteria and diagnostic techniques, such as imaging, have been introduced in an effort to improve the diagnosis of pathologically proven native valve blood-culture-negative IE [ 15 ]. The value of echocardiography in the diagnosis of patients with culture-negative endocarditis is great since it improves sensitivity and specificity [ 16 , 17 ] and has proven to be a major criterion for endocarditis in 78–98.5% of definite IE cases [ 15 , 17 ]. Although there are no major microbiological criteria, blood-culture-negative endocarditis has been shown to be associated with younger age, shorter duration of symptoms at time of presentation [ 18 ], more a frequent need for surgical repair [ 19 ], a greater number of intra- and postoperative complications, and consequently, worse outcomes and disease courses [ 20 ].…”

Left‐sided infective endocarditis presenting with pulmonary involvement and liver abscess: A case report

“…The fundamental tools for diagnosing IE are echocardiography and blood cultures 5 . However, in some cases, the blood culture may be negative (blood culture‐negative endocarditis or BCNE), posing a bigger challenge in diagnosis and treatment 6 . The most common causative bacteria for IE are staphylococci (about 40%–45%, mostly S .…”

“…the blood culture may be negative (blood culture-negative endocarditis or BCNE), posing a bigger challenge in diagnosis and treatment. 6 The most common causative bacteria for IE are staphylococci (about 40%-45%, mostly S. aureus), streptococci (about 35%-40%, mainly viridans streptococci), and enterococci (about 10%). Other less frequent pathogens include gram negative bacteria such as the HACEK group (Hemophilus, Aggregatibacter, Cardiobacterium, Eikenella corrodens, and Kingella species) and fungal infections, notably candida and aspergillus.…”