"How it works" series: Linezolid

Linezolid (Zyvox) is one of only two antibiotics currently on the market in the oxazolidinone class (see what the other one is at the bottom of this article).  The unique structure makes cross resistance to other antibiotics like beta-lactams or vancomycin unlikely.  It works by binding to the 50S subunit of ribosomes in bacteria, preventing it from joining its partner 30S subunit.  In stopping the 50S subunit from binding the 30S subunit, the completed complex (70S) is never formed and therefore cannot begin to
perform its usual function of converting mRNA into proteins within the bacteria (yes, the 50S subunit plus the 30S subunit becomes a full 70S ribosome (not 80S) because the S refers to the sedimentation rate of the ribosome subunit, which is not an additive property).  The image represents how the larger 50S (light green) subunit and smaller 30S (darker green) subunit are normally bound together translating protein in the absence of linezolid.  Linezolid likely binds to the A or P sites and possibly others.

This mechanism makes linezolid bacteriostatic against most bacteria.  It has empiric activity against:

• Gram-positive organisms
• Staphylococcus aureus (methicillin-susceptible and -resistant)
• Coagulase-negative staphylococci
• Enterococcus faecalis (vancomycin-susceptible and -resistant)
• Enterococcus faecium
• Streptococci
• Note that activity is bactericidal against S. pneumoniae and S. pyogenes
• Gram-negative organisms
• Activity is minimal
• Mycobacterium tuberculosis and avium complex

Other notable features:

• Bioavailability = 100% so 600 mg IV = 600 mg po
• No adjustments necessary in renal or hepatic disease
• Causes myelosuppression - duration dependent
• Thrombocytopenia > anemia > neutropenia
• 48% of patients receiving median 12 days of therapy developed thrombocytopenia (but several studies have only single digit rates)
• Inhibits monoamine oxidase - careful for interactions
• Serotonergic agents - causes serotonin syndrome (see more about that interaction here)
• Tyramine foods and adrenergic agents (ie. pseudoephedrine) - increases blood pressure
• The other oxazolidinone antibiotic is tedizolid (Sivextro) which was approved in 2014 for skin and skin structure infections.  Its mechanism is the same as linezolid.

References:

Donowitz GR, Cox HL.  Chapter 33: Linezolid and other oxazolidinones.  In: Mandell GL, Bennett JE, Dolin R, eds.  Principles and practice of infectious diseases. 7th ed. Philadelphia, PA: Elsevier; 2010:471-4.

Orrick JJ, Johns T, Janelle J, et al.  Thrombocytopenia secondary to linezolid administration: What is the risk?  Clin Infect Dis  2002;35(3):348-9.

MacDougall C, Chambers HF.  Protein synthesis inhibitors and miscellaneous antibacterial agents.  In: Brunton LL, Chabner BA, Knollmann BC. eds.  Goodman & Gilman's: The pharmacological basis of therapeutics. 12e.  New York, NY: McGraw-Hill; 2011.