Laboratory Diagnosis of Infective Endocarditis

Abstract

Infective endocarditis is life-threatening; identification of the underlying etiology informs optimized individual patient management. Changing epidemiology, advances in blood culture techniques, and new diagnostics guide the application of laboratory testing for diagnosis of endocarditis. Blood cultures remain the standard test for microbial diagnosis, with directed serological testing (i.e., Q fever serology, Bartonella serology) in culture-negative cases. Histopathology and molecular diagnostics (e.g., 16S rRNA gene PCR/sequencing, Tropheryma whipplei PCR) may be applied to resected valves to aid in diagnosis. Herein, we summarize recent knowledge in this area and propose a microbiologic and pathological algorithm for endocarditis diagnosis.

Keywords: clinical microbiology; endocarditis.

FIG 1

Histopathological findings of endocarditis. (A) Section of mitral valve from a case of streptococcal endocarditis showing focal basophilic bacterial colonies (arrow) at low magnification (×40 total magnification, hematoxylin and eosin [H&E]). (B) Higher magnification of the case shown in (A) demonstrating clearly defined cocci (×1,000 total magnification). (C) Gram stain of streptococcal endocarditis demonstrating Gram-positive cocci mixed with occasional Gram-negative staining organisms (arrows; ×1,000 total magnification, Twort's Gram stain). It is common to see inconsistent staining patterns in Gram-stained tissue sections. (D) Gram stain of Cutibacterium acnes endocarditis from a bioprosthetic aortic valve demonstrating Gram-positive bacilli (×1,000 total magnification, Twort's Gram stain). (E) Grocott-Gomori methenamine silver (GMS) stain of streptococcal endocarditis highlighting the external contours of the cocci. GMS stain often provides increased sensitivity over tissue Gram stain for the detection of bacteria in valvular tissue. (F) Endocarditis caused by Tropheryma whipplei. Note the large foamy macrophages with periodic acid-Schiff [PAS]-positive staining (×1,000 total magnification, PAS stain with diastase).

FIG 2

Diagnostic testing for identification of the microbiological etiology of infective endocarditis. This algorithm is intended for use in patients with clinical and/or echocardiographic findings suggestive of infective endocarditis based on the modified Duke criteria (3). Strong recommendations appear in boldface, with other diagnostic testing considerations shown in standard typeface. ¹, Details on blood culture collection are provided in the text. ², C. burnetii anti-phase I IgG antibody titer of ≥1:800 is considered positive. ³, The sensitivity of T. whipplei PCR from blood in endocarditis is unknown; a negative result should not be used to rule out T. whipplei endocarditis. ⁴, If surgery is not performed, consider testing for noninfectious etiologies. ⁵, Histologic evaluation is used to evaluate for infectious and noninfectious etiologies and for correlation with microbiology test results. ⁶, Ideally, a representative sample of valvular tissue should be specifically collected for molecular testing in a sterile fashion in the operating room. ⁷, If sufficient valvular tissue is available after sampling for histopathological and molecular (microorganism-specific and broad-range) testing, consider culture and microbiology Gram stain. Due to the low sensitivity and specificity of culture, molecular testing should be prioritized over culture. ⁸, PAS-D, periodic acid-Schiff with diastase. Macrophages infected with T. whipplei will stain PAS positive following diastase digestion. ⁹, Examples include Mycoplasma hominis and Cutibacterium (formerly Propionibacterium) acnes PCR. By permission of the Mayo Foundation for Medical Education and Research. All rights reserved.