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.

Pharmacokinetic/Pharmacodynamic Analysis of Tedizolid Phosphate Compared to Linezolid for the Treatment of Infections Caused by Gram-Positive Bacteria

“…Linezolid, the first representative member of the oxazolidinone family introduced into the pharmaceutical market, shows excellent activity; however, in recent years, resistance to microorganisms (mainly MRSA) has emerged [31]. Due to the limited number of therapeutic options available for ABSSSIs, new therapeutic alternatives have been developed, especially for resistant Gram-positive microorganisms.…”

Flipping the Substrate Creates a Highly Selective Halohydrin Dehalogenase for the Synthesis of Chiral 4-Aryl-2-oxazolidinones from Readily Available Epoxides

“…Chiral 5-substituted 2-oxazolidinones represent a novel chemical class of synthetic antimicrobial agents. For example, linezolid and tedizolid are antibacterial drugs approved by the FDA to effectively treat various Gram-positive bacterial infections, including blood infections, skin and soft tissue infections, and community- and hospital-acquired pneumonia. Optically active 4-substituted 2-oxazolidinones not only bear antibacterial activity but also have important applications as chiral auxiliaries, − ligands, , and intermediates , in the synthesis of complex molecules.…”

New antibiotics for bad bugs: where are we?

“…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 of developing myelosuppression. Unlike linezolid, tedizolid does not inhibit monoamine oxidase in vivo , therefore interactions with adrenergic, dopaminergic, and serotonergic drugs are not to be expected [ 71 ].…”