Linezolid

• Brand names: Zyvox, Zyvoxid
• Route: Oral and intravenous (identical dosing)

Linezolid binds the 23S ribosomal RNA of the 50S subunit and prevents the 70S initiation complex from forming, so protein synthesis never starts.

This binding site is not shared with any other antibiotic class, so cross-resistance is rare.

It is bacteriostatic against staphylococci but suppresses production of Panton-Valentine leukocidin and other toxins, which is one reason it is favoured in necrotising infection.

• 600 mg every 12 hours, orally or intravenously, in adults. Oral bioavailability is close to 100%, so there is no dose change when switching from the drip to tablets.
• Skin and soft-tissue infection is usually treated for 10–14 days; pneumonia for 7–14 days.
• No dose adjustment is needed for kidney or mild liver impairment, but full blood counts should be checked weekly.
• Courses longer than 28 days carry a substantially higher risk of nerve and marrow toxicity and need specialist supervision.

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

The oxazolidinone scaffold was discovered at DuPont in the 1970s as a plant-disease treatment; the early compounds were too toxic for human use.

Pharmacia & Upjohn refined the series in the 1990s, producing linezolid, which reached the market in 2000 as the first genuinely new antibiotic class in 35 years.

It became a mainstay for MRSA once trials showed better clinical cure in hospital-acquired MRSA pneumonia than vancomycin.

• Reversible bone-marrow suppression, especially low platelets, which becomes common beyond two weeks of therapy.
• Peripheral and optic neuropathy with prolonged use; optic neuropathy may not be fully reversible.
• Serotonin syndrome when combined with SSRIs, SNRIs, triptans or MAO inhibitors, because linezolid is a weak monoamine oxidase inhibitor.
• Nausea, diarrhoea, headache, tongue discolouration, and lactic acidosis in rare cases.

• Vancomycin-resistant Enterococcus faecium infection.
• Multidrug-resistant tuberculosis, where it is part of modern all-oral regimens such as BPaL.
• Nocardiosis and some drug-resistant mycobacterial infections.