Part III: Guidelines for Selected Antimicrobial Use

3.2 Linezolid

Linezolid is an oxazolidinone antibiotic, which inhibits bacterial protein synthesis by binding to a site on 23S ribosomal RNA of the 50S subunit.
It is active against antibiotic-resistant Gram-positive bacteria, such as MRSA, VRE, and some mycobacteria. It is not active against aerobic and facultative anaerobic Gram-negative bacteria. Multiple mechanisms of oxazolidinone resistance have been described. [156]
It can be used to treat pneumonia, skin and soft tissue infections caused by susceptible Gram-positive bacteria.
Dosing [157]

Adults with normal kidney function:

Nosocomial pneumonia, community-acquired pneumonia, complicated skin and soft tissue infections, vancomycin-resistant Enterococcus faecium infections: oral or intravenous, 600 mg every 12 hours

Uncomplicated skin and soft tissue infections: oral, 400 mg every 12 hours

Renal impairment

No adjustment is recommended in the manufacturer’s labelling. [157] However, caution and frequent monitoring of complete blood count are advised, and the duration of use should be limited whenever possible. Increased risk of thrombocytopaenia associated with linezolid use in patients with kidney impairment has been observed, with the odds increased up to six-fold in end-stage renal disease. [158–161] Some experts advocated standard dose reduction of 50% after 2 days of standard dosing in patients with estimated glomerular filtration of <60 mL/min/1.73m². [162]

Hepatic impairment

No dosage adjustment in mild to moderate impairment (Child-Pugh class A or B); there are no dosage adjustment provided in the manufacturer’s labelling for severe impairment. [157] However, linezolid concentrations may be increased in patients with cirrhosis leading to increased risk of thrombocytopaenia. [163,164]

Adverse reactions (non-exhaustive)

Myelosuppression including anaemia, leukopaenia, thrombocytopaenia or pancytopaenia

Linezolid-related thrombocytopaenia has been described as dose dependent and generally occurs after two weeks of treatment. [162]

Risk factors associated with thrombocytopaenia include renal insufficiency, liver dysfunction, and prolonged duration of therapy. [161,164,165]

Lactic acidosis [166]

Peripheral neuropathy [167]

Optic neuropathy (recovery of visual function may not be complete) [168]

Serotonin toxicity

Being a weak non-selective monoamine oxidase (MAO) inhibitor, the concomitant administration of linezolid and drugs that increase serotonin concentrations (e.g. fluoxetine, mirtazapine, tramadol) potentially causes the rare but life-threatening serotonin syndrome. [169–171]

Hypoglycaemia [172]

Hyponatraemia and/or syndrome of inappropriate antidiuretic hormone secretion (SIADH) [173]

Please consult a clinical microbiologist or infectious disease physician for the use of linezolid.