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.