title: Potential role of tedizolid phosphate in the treatment of acute bacterial skin infections.
abstract: Tedizolid phosphate (TR-701), a prodrug of tedizolid (TR-700), is a next-generation oxazolidinone that has shown favorable results in the treatment of acute bacterial skin and skin-structure infections in its first Phase III clinical trial. Tedizolid has high bioavailability, penetration, and tissue distribution when administered orally or intravenously. The activity of tedizolid was greater than linezolid against strains of Staphylococcus spp., Streptococcus spp., and Enterococcus spp. in vitro studies, including strains resistant to linezolid and those not susceptible to vancomycin or daptomycin. Its pharmacokinetic characteristics allow for a once-daily administration that leads to a more predictable efficacy and safety profile than those of linezolid. No hematological adverse effects have been reported associated with tedizolid when used at the therapeutic dose of 200 mg in Phase I, II, or III clinical trials of up to 3 weeks of tedizolid administration. Given that the clinical and microbiological efficacy are similar for the 200, 300, and 400 mg doses, the lowest effective dose of 200 mg once daily for 6 days was selected for Phase III studies in acute bacterial skin and skin-structure infections, providing a safe dosing regimen with low potential for development of myelosuppression. Unlike linezolid, tedizolid does not inhibit monoamine oxidase in vivo, therefore interactions with adrenergic, dopaminergic, and serotonergic drugs are not to be expected. In conclusion, tedizolid is a novel antibiotic with potent activity against Gram-positive microorganisms responsible for skin and soft tissue infections, including strains resistant to vancomycin, linezolid, and daptomycin, thus answers a growing therapeutic need.
authors.affiliation: Services of Hospital Pharmacy, Hospital Universitari del Mar, Universitat Autònoma de Barcelona.
authors.forename: Olatz
authors.initials: O
authors.lastname: Urbina
authors.forename: Olivia
authors.initials: O
authors.lastname: Ferrández
authors.forename: Mercè
authors.initials: M
authors.lastname: Espona
authors.forename: Esther
authors.initials: E
authors.lastname: Salas
authors.forename: Irene
authors.initials: I
authors.lastname: Ferrández
authors.forename: Santiago
authors.initials: S
authors.lastname: Grau
mesh_terms: D000208:Acute Disease; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D024881:Drug Resistance, Bacterial; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D010755:Organophosphates / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D010080:Oxazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D017192:Skin Diseases, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D018461:Soft Tissue Infections / Q000188:drug therapy / Q000382:microbiology; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D010755:Organophosphates; D010080:Oxazoles; C515040:tedizolid phosphate
keywords: TR-700; TR-701 FA; linezolid resistance; oxazolidinone; skin and soft tissue infections; tedizolid