Tedizolid

• Brand names: Sivextro
• Route: Oral and intravenous

Tedizolid phosphate is a prodrug converted to tedizolid, which binds the 50S ribosomal subunit and prevents formation of the initiation complex.

Additional binding interactions make it four to sixteen times more potent than linezolid in the laboratory, including against some linezolid-resistant strains carrying the cfr gene.

Like linezolid it suppresses staphylococcal toxin production.

• 200 mg once daily, orally or intravenously, for six days in acute bacterial skin and soft-tissue infection.
• Oral bioavailability is about 90%, so intravenous-to-oral switching is straightforward.
• No dose adjustment for kidney or liver impairment, and it can be taken with or without food.
• The monoamine oxidase interaction is weaker than with linezolid, but caution with serotonergic drugs is still advised.

Doses listed are typical adult regimens quoted for reference. The actual dose, route and duration are decided by a clinician for the individual patient.

Tedizolid was designed by Dong-A Pharmaceutical in South Korea and developed by Trius Therapeutics, later Cubist and Merck.

The ESTABLISH-1 and ESTABLISH-2 trials showed a six-day once-daily course was non-inferior to ten days of linezolid.

It was approved by the FDA in 2014 and in Europe the following year.

• Nausea, headache, diarrhoea and vomiting.
• Less thrombocytopenia than linezolid over the standard six-day course, although marrow effects can still occur with prolonged use.
• Peripheral and optic neuropathy have been reported with long off-label courses.

• Skin infection caused by streptococci and vancomycin-susceptible Enterococcus faecalis.
• Off-label use in bone and joint infection and in mycobacterial disease where linezolid toxicity limits therapy.