Abstract

ObjectiveThe present study aimed to prospectively evaluate the role of metagenomic next-generation sequencing (mNGS) in the etiological diagnosis of patients with perioperative infective endocarditis (IE).MethodsFrom May 1st, 2019 to December 31st, 2020, a total of 99 patients with IE were enrolled in the present study according to the modified Duke criteria, etiological, and pathological results. 11 non-IE patients undergoing heart valve surgery in the same period were selected as the control group. A blood culture test was performed immediately after admission, and the valves harvested operatively were examined by blood culture and mNGS.ResultsIn the IE group, there were 29 cases (29.3%) with positive blood culture, 16 cases (16.2%) with positive valve culture, and 85 cases (85.9%) with positive valve mNGS. Compared to culture-based detection, mNGS achieved better performance with a sensitivity, specificity, area under the curve (AUC) of 0.859, 0.727, and 0.793, respectively. The combined approach using culture and mNGS further improved the diagnostic accuracy (sensitivity 89.9%, specificity 72.7%, AUC 0.813). Preoperative white blood cell (P = 0.029) and neutrophils (P = 0.046) were identified as independent factors affecting the detection rate of mNGS. In the mNGS-positive group, 95 strains of pathogens were found and 10 cases were identified with mixed infection. There were 72 gram-positive bacteria and 14 gram-negative bacteria. mNGS positive group displayed higher species richness than mNGS negative group with enrichment of Streptococcus sanguis, Streptococcus buccalis, and Streptococcus griseus. Proteobacteria and Actinomycetes were enriched in mNGS negative group. Notably, six patients showed disconcordant results between culture and mNGS. Rothia aeria was identified in the blood culture, valve culture, and valve mNGS in one patient. Bartonella Quintana and Coxiella burnetii, which were fastidious intracellular bacteria, were found in two blood and valve culture-negative cases.ConclusionsmNGS outperformed the conventional culture method and displayed high accuracy in detecting pathogens in IE patients. This study provided support for the use of mNGS in the etiological diagnosis of IE.

Highlights

  • Infective endocarditis (IE) refers to the inflammation caused by the direct infection of bacteria, fungi, or other microorganisms, which may dwell in natural or artificial heart valves, endocardial surfaces, or cardiac implanted devices

  • In the IE group, there were 29 (29.3%) blood culture-positive cases, 16 (16.2%) valve culture-positive cases, and 85 (85.9%) valve metagenomic next-generation sequencing (mNGS)-positive cases. 14 cases were found to be positive in both valve culture and valve mNGS detection

  • In the nonIE group, there were no positive cases in blood culture or valve culture, but 3 positive cases in valve mNGS (27.3%)

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Summary

Introduction

Infective endocarditis (IE) refers to the inflammation caused by the direct infection of bacteria, fungi, or other microorganisms, which may dwell in natural or artificial heart valves, endocardial surfaces, or cardiac implanted devices. The incidence of IE is as high as 7.6–7.8/100,000. The incidence of IE in the elderly population is even up to 37.9/100,000, and the 90-day mortality rate reaches 24.2%, which seriously endangers human health [2]. 50% of IE patients need surgical treatment. The incidence of blood-culture negative endocarditis is as high as 31–35%. The high false-negative rate and the amount of time blood culture take delay timely diagnosis and treatment, which exert a significantly adverse impact on the prognosis [4–6]. There is an urgent need to improve the accuracy and effectiveness of diagnosis, so as to reduce the mortality of IE patients by early intervention

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