New and old oxazolidinones: tedizolid vs. linezolid

Abstract

Tedizolid is a novel oxazolidinone that has been recently approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by Gram-positive pathogens, including MRSA. The mechanism of action of tedizolid is similar to other oxazolidinones – inhibition of bacterial protein synthesis. As with other oxazolidinones, the spontaneous frequency of resistance development to tedizolid is very infrequent and lower than for linezolid. Tedizolid is 4-32 fold more in vitro potent than linezolid against staphylococci, enterococci, and streptococci. Importantly, tedizolid demonstrates activity against linezolid-resistant strains harboring the horizontally transmissible cfr gene, that is one of the main mechanisms of decreased linezolid susceptibility. With its half-life of approximately 12 h, tedizolid is dosed once daily and does not require dosage adjustment in patients with renal or hepatic dysfunction. Two phase III clinical trials have demonstrated non-inferiority of a oncedaily tedizolid 200 mg dose for 6 days versus twice-daily 600 mg 10 days linezolid for the treatment ofABSSSIs. Clinical trials for the treatment of some other infections are currently undergoing. Tedizolid has demonstrated that it is well tolerated and animal studies have shown a lower propensity for neuropathies with long-term use than linezolid. Data from the clinical trials demonstrated that the tedizolid had significantly less impact on hematologic parameters as well as significantly less gastrointestinal adverse effects than linezolid. With its enhanced in vitro activity against multiresistant Gram(+) aerobic bacteria, once-daily dosing, a short 6-day course of therapy, availability of both oral and intravenous routes of administration, and an adverse effect profile that appears to be more favorable than linezolid, tedizolid is a very attractive agent for use in both the hospital and community settings.