Genomic identification of streptococcal strains and relation to clinical characteristics. A substudy to The Partial Oral Treatment of Endocarditis (POET) Trial.

Abstract

The Danish National Partial Oral Treatment of Endocarditis Trial (POET) demonstrated non-inferiority of partly peroral compared to intravenous antibiotic therapy for infective endocarditis (IE) caused by Streptococcus spp, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci. Identifications by whole genome sequencing (WGS) of available streptococcal strains were related to clinical data. Sequences were obtained using Illumina technology (MiseqÒ) followed by core genome analysis and single-nucleotide polymorphism phylogeny examinations. Average nucleotide identification (ANI) calculated using the tool fastANI. Informations on +/- preexisting valve prosthesis, valve surgery and outcome related to obtained identifications. Streptococcal strains (n=123) from 117 patients were WGS examined. Twelve percent were pyogenic group strains and 88% belonged to viridans groups, mainly mitis and bovis groups. Phylogenetic trees were in accordance regarding species and subspecies identifications. High ANI percentages to type strains were found. Respectively 39, 60 and 16 IE cases involved mitral, aortic or both valves. IE caused by pyogenic group or mitis plus bovis group streptococci most frequent affected, respectively, mitral and aortic valves. Thirty-one patients (26%) had a preexisting prosthesis; notably, in 50% of bovis group IE cases. Fifty-six patients had valve surgery done during the current disease; 8% and 93% of patients having, respectively, pyogenic group and mitis group strains as causative agents. Of patients allocated to intravenous or intravenous followed by peroral antibiotic treatment, respectively 26 and 30 had valve surgery done during the current disease. Composite outcome (all-cause mortality, unplanned cardiac surgery, embolic events, or relapse of bacteremia with the primary pathogen) at five-year follow-up comprised in total 39 events. In conclusion, molecular examinations adds on substantially by detailing species and subspecies affiliations. A broad spectrum of streptococcal species and subspecies causing IE were identified with mitis- and bovis group strains dominating. Relating strain identifications to clinical data can assist in planning and treating confirmed/suspected IE patients. Adding WGS identification of streptococci in selected patients groups (e.g. IE) in order to expand number of cases characterized in detail seems ideal and advocates for centralized registration of results to reveal important clinical relations.