The clinical value of valve metagenomic next-generation sequencing when applied to the etiological diagnosis of infective endocarditis

Abstract

Background: Metagenomic next-generation sequencing (mNGS) is widely applied in the etiological diagnosis of infectious diseases. However, the clinical practice of mNGS in infective endocarditis (IE) is relatively less studied. This research aimed to assess the etiological diagnostic value of valve mNGS in IE.Methods: We retrospectively analyzed 49 IE patients who underwent cardiac valve surgery in Zhongshan Hospital, Fudan University, Shanghai from 1 June 2018 to 30 November 2020. Among these IE patients, 28 were culture positive and 21 were culture negative. The culture results of the culture-positive IE patients were set as gold standard to assess the sensitivity and specificity of valve mNGS in the etiological diagnosis of IE. We studied the positive detection rate of pathogens by valve mNGS among the culture-negative IE patients. During the same period, we also collected the resected valves of 8 patients with non-infective valvular diseases for mNGS as negative controls.Results: The valve mNGS results of the culture-positive IE patients were the exact same as their culture results. Both the sensitivity and specificity of valve mNGS were 100%. The positive detection rate of pathogens by valve mNGS was 100% among the culture-negative IE patients. The stringent mapped reads number of genera (SMRNG), relative abundance of genera, stringent mapped reads number of species (SMRN), relative abundance of species, and coverage rate of valve mNGS results were significantly higher in culture-positive IE participants than in culture-negative IE participants. The valve mNGS results of the 8 participants with non-infective valvular diseases were all negative.Conclusions: Valve mNGS is a promising technology for the etiological diagnosis of IE, especially culture-negative IE, and it may be used to guide precise antibiotic treatment after surgery.

Utility of Metagenomic Next-Generation Sequencing in Infective Endocarditis: A Systematic Review

“…To RK and colleagues, for example, reported that four of eight IE patients underwent revision of antimicrobial regimens, based on mNGS results, to enhance the likelihood of treatment success [ 19 ]. This was also the case in the study of Cai S et al, where antibiotic therapy was de-escalated to cephalosporin and aminoglycosides for six culture-negative IE subjects following pathogen identification by valve mNGS screening of valve tissue [ 15 ]. In addition, mNGS may be also important in enhancing antimicrobial stewardship, and reducing both adverse drug events and selection for antimicrobial resistance.…”

“…However, it remains essential to correlate the mNGS to the clinical context of the patient as there may be false positives as suggested in some studies possibly due to laboratory contamination or detection of normal skin flora [ 15 , 16 , 23 ]. Sequencing results include many parameters that reflect the number of distinct and unique sequences aligned to a microorganism’s genome.…”

“…In the study of Cai S et al, the parameters of all IE valve mNGS included: stringent mapped reads number (SMRN) 10100, stringent mapped reads number of genera (SMRNG) 12072, a relative abundance of genera (RAG) of 95.5%, relative abundance of species (RAS) of 70.1%, and a coverage rate (CV) of 26.6%. However, these parameters were significantly higher in culture-positive IE cases than in those with culture-negative IE ( p < 0.05) [ 15 ]. To consider mNGS positive, there is a certain consensus on the threshold (90%), above which a pathogen is considered causative of infection [ 17 , 18 ].…”

“…Pre-operative peripheral white blood cell (WBC) count and neutrophils have been identified as independent factors affecting the detection rate of mNGS with p values of 0.029 and 0.046, respectively [ 16 ]. Cai S et al also suggested that in patients with an acute course who have high fever, elevated peripheral WBC count, and increased serum inflammatory markers, the sensitivity of blood mNGS may be enhanced in pathogen identification compared to that among patients with a more indolent subacute course of IE [ 15 ]. Other factors affecting the detection rate by mNGS are blood culture positivity and cycle threshold (CT) values at the time of specimen collection [ 18 ].…”

Native valve, prosthetic valve, and cardiac device-related infective endocarditis: A review and update on current innovative diagnostic and therapeutic strategies

“…The remaining 21 patients (42.9%) had negative culture results. For all patients, including culture-negative IE patients, receiving empirical antibiotic treatment, the causative IE pathogen could be detected with mNGS ( Cai et al, 2021 ).…”