Linezolid Flashcards
What is the mechanism of action of linezolid?
Linezolid is an oxazolidinone that binds to the 23S rRNA of the 50S subunit, preventing formation of the 70S initiation complex. This inhibition blocks protein synthesis at the initiation step (bacteriostatic against most staph and enterococci, bactericidal against most streptococci).
Describe the spectrum of activity of linezolid.
Linezolid covers primarily Gram-positive organisms: it’s active against MRSA, vancomycin-resistant Enterococcus (VRE), penicillin-resistant Streptococcus pneumoniae, and other Gram-positive cocci. It has no meaningful activity against Gram-negative organisms.
How do bacteria develop resistance to linezolid?
Resistance is most often due to a point mutation in the 23S rRNA binding site, reducing linezolid binding. Also, a plasmid-borne gene (cfr) encoding an rRNA methyltransferase can modify the binding site and confer linezolid resistance.
Outline key pharmacokinetic features of linezolid.
Linezolid has ~100% oral bioavailability, allowing easy switch from IV to oral. It distributes well into tissues (including lung and CNS). It is metabolized by non-enzymatic oxidation (not a significant CYP substrate), forming two inactive metabolites. Excretion is partly renal (as metabolites) and partly non-renal; no dosage adjustment is needed for mild to moderate renal or hepatic impairment.
What major drug interactions occur with linezolid?
Linezolid is a weak reversible MAO inhibitor, so it can precipitate serotonin syndrome if given with SSRIs, SNRIs, TCAs, or meperidine. It can also cause hypertensive reactions with tyramine-rich foods or sympathomimetics. Otherwise, it has no significant CYP450 interactions.
What are the primary clinical indications for linezolid?
Linezolid is used for serious Gram-positive infections that are resistant to other antibiotics or in patients who cannot receive beta-lactams or vancomycin. Indications include hospital-acquired and skin/soft tissue infections caused by MRSA, VRE infections (e.g., VRE faecium bacteremia), and pneumonia caused by drug-resistant pneumococci or staph. It’s often reserved for multi-drug resistant infections.
What are important contraindications or cautions for linezolid therapy?
Avoid use with other serotonergic drugs due to risk of serotonin syndrome, or ensure careful monitoring and perhaps a washout period (contraindicated with MAOIs or within 2 weeks of taking them). Use with caution in patients with uncontrolled hypertension or hyperthyroidism (because of MAO inhibition effect on catecholamines). No absolute contraindication besides hypersensitivity, but it should be used judiciously to preserve its efficacy.
List major adverse effects and toxicities of linezolid.
Linezolid can cause bone marrow suppression, especially thrombocytopenia (often seen after ~2 weeks of therapy), as well as anemia and neutropenia with longer courses. It may cause peripheral neuropathy and optic neuropathy with prolonged use (due to mitochondrial toxicity). Lactic acidosis is a rare adverse effect. Also watch for serotonin syndrome (symptoms: fever, agitation, hyperreflexia) if combined with serotonergic agents.
Is there a mnemonic to remember key facts about linezolid?
Think “LINEzolid is on the LINE (line) for MRSA & VRE when others fail, but watch your blood LINE (bone marrow suppression) and serotonin line (serotonin syndrome).”
