title: Evaluation of tedizolid against Staphylococcus aureus and enterococci with reduced susceptibility to vancomycin, daptomycin or linezolid.
abstract: OBJECTIVE
  Tedizolid displays potent activity against Gram-positive pathogens. In vitro studies against clinical isolates of Staphylococcus aureus and enterococci demonstrated improved tedizolid activity over linezolid. However, this is not well-characterized against a large collection of resistant isolates, including vancomycin-intermediate S. aureus (VISA), heterogeneous VISA (hVISA), daptomycin-non-susceptible (DNS) S. aureus, linezolid-resistant (LR) S. aureus and VRE. Therefore, our objective was to determine tedizolid activity versus other agents, against MRSA and VRE with various resistance phenotypes.
  
  
  METHODS
  In total, 302 MRSA (75 DNS, 100 VISA, 120 hVISA and 7 LR) and 220 VRE [100 Enterococcus faecalis (all susceptible to daptomycin and linezolid) and 120 E. faecium (25 DNS and 10 LR)] were evaluated. LR isolates were analysed for the cfr gene. MICs of tedizolid, linezolid, ampicillin, clindamycin, daptomycin, gentamicin, levofloxacin, oxacillin, tigecycline, trimethoprim/sulfamethoxazole and vancomycin were determined in accordance with CLSI guidelines.
  
  
  RESULTS
  Tedizolid MIC90 values for hVISA, VISA and DNS were 0.5 mg/L (versus 4, 4 and 2 mg/L, respectively, for linezolid). The tedizolid MIC range for LR MRSA was 0.063-1 mg/L. Two LR MRSA possessed the cfr gene with tedizolid MICs of 0.125 and 0.25 mg/L (linezolid MICs of 16 and 8 mg/L). The tedizolid MIC90 for vancomycin-resistant E. faecalis and E. faecium was 0.25 and 1 mg/L, respectively; three dilutions lower for E. faecalis and two dilutions lower for E. faecium compared with linezolid.
  
  
  CONCLUSIONS
  Tedizolid MICs demonstrate activity against isolates with decreased susceptibility to alternative agents, including linezolid. Tedizolid may be a viable treatment option in clinical situations with MDR Gram-positive pathogens.
authors.affiliation: Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, MI, USA.
authors.forename: Katie E
authors.initials: KE
authors.lastname: Barber
authors.affiliation: Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, MI, USA.
authors.forename: Jordan R
authors.initials: JR
authors.lastname: Smith
authors.affiliation: Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, MI, USA.
authors.forename: Animesh
authors.initials: A
authors.lastname: Raut
authors.affiliation: Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, MI, USA Wayne State University School of Medicine, Detroit, MI, USA m.rybak@wayne.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rybak
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017576:Daptomycin / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D016983:Enterococcus / Q000187:drug effects*; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000302:isolation & purification; 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; D010755:Organophosphates / Q000494:pharmacology*; D010080:Oxazoles / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D010755:Organophosphates; D010080:Oxazoles; D014640:Vancomycin; D000069349:Linezolid; D017576:Daptomycin; C515040:tedizolid phosphate