Purpose: The mechanism of action, pharmacokinetics, pharmacodynamics, and clinical efficacy and safety of an investigational second-generation oxazolidinone are reviewed.
Summary: Tedizolid is a protein synthesis inhibitor in clinical development for the treatment of gram-positive infections. Similar to linezolid, tedizolid works by binding to the 23S ribosomal RNA of the 50S subunit, thereby preventing the formation of the 70S initiation complex and inhibiting protein synthesis. Tedizolid has demonstrated potent in vitro activity against multidrug-resistant gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, and vancomycin-resistant enterococci (VRE), including some linezolid-resistant strains. Tedizolid has a favorable pharmacokinetic profile that allows for once-daily dosing and easy i.v.-to-oral conversion. Unlike linezolid, tedizolid has not been shown to interact with serotonergic agents in clinical studies. Two Phase III studies in patients with acute bacterial skin and skin structure infections have demonstrated the noninferiority of 6 days of tedizolid therapy (200 mg i.v. or orally once daily) relative to 10 days of linezolid therapy. In clinical trials to date, overall rates of treatment-related adverse effects with linezolid and tedizolid were comparable (40.8% versus 43.3%), with nausea being the most commonly reported adverse effect associated with tedizolid use (16% of patients). Planned studies will investigate tedizolid's potential role in the treatment of community-acquired bacterial pneumonia, hospital-acquired/ventilator-associated bacterial pneumonia, and bacteremia.
Conclusion: Tedizolid is an investigational oxazolidinone antibiotic for the treatment of multidrug-resistant gram-positive pathogens such as MRSA, Streptococcus pneumoniae, and VRE, including some linezolid-resistant strains.