title: Tedizolid susceptibility in linezolid- and vancomycin-resistant Enterococcus faecium isolates.
abstract: Vancomycin-resistant enterococci (VRE) are of ever-increasing importance, most notably in high-risk patient populations. Therapy options are often limited for these isolates, and apart from tigecycline and daptomycin, oxazolidinone linezolid is frequently administered. The broad usage of linezolid, however, has driven the emergence of linezolid-resistant VRE strains (LR-VRE), further shortening therapeutic options. Second-generation oxazolidinone tedizolid has the advantage of being active against a specific subset of LR-VRE, i.e. isolates expressing the plasmid-encoded chloramphenicol-florfenicol resistance (cfr) gene. Here we tested tedizolid activity in a collection of 30 LR Enterococcus faecium VRE (MIC range 32-256 mg/l) isolated between 2012 and 2015 from clinical and screening specimens. By pulsed field gel electrophoresis (PFGE) isolates were assigned to 16 clonal lineages. In three cases, linezolid-susceptible progenitor isolates of LR-VRE were isolated, thus demonstrating the de-novo emergence of the linezolid-resistant phenotype. PCR did not detect cfr, cfr(B) or novel oxazolidinone resistance gene optrA in LR-VRE. All isolates, however, carried mutations within the 23S rDNA. Compared to linezolid, tedizolid MICs were lower in all isolates (MIC range 2-32 mg/l), but remained above the FDA tedizolid breakpoint for E. faecalis at 0.5 mg/l. Thus, related to the predominant resistance mechanism, tedizolid is of limited value for treatment of most LR-VRE and represents a therapeutic option only for a limited subset of isolates.
authors.affiliation: Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
authors.forename: E-M
authors.initials: EM
authors.lastname: Klupp
authors.affiliation: Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Both
authors.affiliation: Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Belmar Campos
authors.affiliation: Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Büttner
authors.affiliation: Klinikapotheke, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: König
authors.affiliation: Klinik für Stammzelltransplantation, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Christopeit
authors.affiliation: Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Christner
authors.affiliation: Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Aepfelbacher
authors.affiliation: Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany. rohde@uke.de.
authors.forename: H
authors.initials: H
authors.lastname: Rohde
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000235:genetics; D004275:DNA, Ribosomal / Q000235:genetics; D024881:Drug Resistance, Bacterial; D016984:Enterococcus faecium / Q000187:drug effects* / Q000302:isolation & purification; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology; D006801:Humans; D000069349:Linezolid / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010755:Organophosphates / Q000494:pharmacology*; D010080:Oxazoles / Q000494:pharmacology*; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D065507:Vancomycin-Resistant Enterococci / Q000187:drug effects* / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D004275:DNA, Ribosomal; D010755:Organophosphates; D010080:Oxazoles; D012338:RNA, Ribosomal, 23S; D000069349:Linezolid; C515040:tedizolid phosphate