Early experience with tedizolid: clinical efficacy, pharmacodynamics, and resistance

Pharmacotherapy. 2014 Nov;34(11):1198-208. doi: 10.1002/phar.1491. Epub 2014 Sep 30.


Antimicrobial resistance among gram-positive organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) continues to limit therapeutic options. The oxazolidinones are a synthetic class of agents now commonly relied on for the treatment of serious MRSA and VRE infections. With increasing utilization of linezolid, resistant pathogens have once again begun to emerge. Tedizolid, a next-generation oxazolidinone, possesses a spectrum of activity including MRSA and VRE, with significantly enhanced potency also against linezolid-resistant strains. Preclinical and early clinical studies have reported positive results, demonstrating a favorable pharmacokinetic profile in combination with key potential safety advantages. In two phase III clinical trials, tedizolid was found noninferior to linezolid in the treatment of acute bacterial skin and skin structure infections. Investigations for treatment of ventilator-acquired and health care-associated pneumonia are currently underway. Tedizolid has been subjected to pharmacodynamics studies throughout its development that have highlighted properties unique to this agent. Considerable accumulations in epithelial lining fluid and antimicrobial activity greatly augmented by the presence of granulocytes suggest that slow but bactericidal activity may be possible in some clinical scenarios. Structural distinctions between tedizolid and linezolid suggest that tedizolid has decreased vulnerability to oxazolidinone resistance mechanisms. Tedizolid minimum inhibitory concentrations are essentially unchanged in organisms possessing the chloramphenicol-florfenicol resistance gene, a horizontally transferable linezolid resistance mechanism. Although the clinical experience with tedizolid remains limited, early data suggest a potential role in the treatment of serious infections due to multidrug-resistant gram-positive pathogens.

Keywords: infectious disease; oxazolidinone; pharmacodynamic; resistance; tedizolid.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Drug Resistance, Bacterial*
  • Drug Resistance, Multiple, Bacterial
  • Drugs, Investigational / adverse effects
  • Drugs, Investigational / pharmacokinetics
  • Drugs, Investigational / pharmacology
  • Drugs, Investigational / therapeutic use*
  • Gram-Positive Bacterial Infections / drug therapy
  • Gram-Positive Bacterial Infections / metabolism
  • Gram-Positive Bacterial Infections / microbiology
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Organophosphates / adverse effects
  • Organophosphates / pharmacokinetics
  • Organophosphates / pharmacology
  • Organophosphates / therapeutic use*
  • Oxazoles / adverse effects
  • Oxazoles / pharmacokinetics
  • Oxazoles / pharmacology
  • Oxazoles / therapeutic use*
  • Prodrugs / adverse effects
  • Prodrugs / pharmacokinetics
  • Prodrugs / pharmacology
  • Prodrugs / therapeutic use*
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / metabolism
  • Staphylococcal Infections / microbiology
  • Vancomycin-Resistant Enterococci / drug effects


  • Anti-Bacterial Agents
  • Drugs, Investigational
  • Organophosphates
  • Oxazoles
  • Prodrugs
  • tedizolid phosphate