Linezolid (Zyvox)

Indications

Community-Acquired Pneumonia (CAP)

  • Staphylococcus Aureus (see Staphylococcus Aureus, [[Staphylococcus Aureus]])
    • Methicillin-Sensitive Staphylococcus Aureus (MSSA)
    • Methicillin-Resistant Staphylococcus Aureus (MRSA)
  • Streptococcus (see Streptococcus, [[Streptococcus]])
  • xxx (see xxxx, [[xxxx]])
  • xxx (see xxxx, [[xxxx]])
  • xxx (see xxxx, [[xxxx]])
  • xxx (see xxxx, [[xxxx]])
  • xxx (see xxxx, [[xxxx]])
  • xxx (see xxxx, [[xxxx]])

Healthcare-Associated Pneumonia (HAP)

  • xxx (see xxxx, [[xxxx]])
  • xxx (see xxxx, [[xxxx]])
  • xxx (see xxxx, [[xxxx]])
  • xxx (see xxxx, [[xxxx]])
  • xxx (see xxxx, [[xxxx]])

Uncomplicated and Complicated Skin/Skin Structure Infections

  • xxx (see xxxx, [[xxxx]])
  • xxx (see xxxx, [[xxxx]])
  • xxx (see xxxx, [[xxxx]])
  • xxx (see xxxx, [[xxxx]])

FDA-Approved for Treatment of Resistant Gram-Positive Bacterial Infections

  • Vancomycin-Resistant Enterococcus Faecium (VRE) (see Enterococcus Faecium, [[Enterococcus Faecium]])

Pharmacology

  • Oxazolidinone Antibiotic: first commercially available from this class
    • Mechanism: binds to bacterial 50S ribosomal subunit -> inhibition of bacterial protein synthesis
      • Bacteriostatic: against most organisms
      • Inhibits synthesis of Panton-Valentine Leukocidin (PVL), alpha-hemolysin, and toxic shock syndrome toxin-1
    • Impairment of Human Mitochondrial Function: linezolid is believed to interact with human mitochondrial 16S RNA, due to its resemblance to bacterial 23S rRNA
    • MAO Inhibitor Activity In Humans: MAO normally functions to degrades serotonin in the brain
      • FDA Alert (7/26/11): avoid use in conjunction with SSRI’s

Metabolism

  • xx

Administration

  • PO (Community-Acquired Pneumonia, Healthcare-Associated Pneumonia, Uncomplicated or Complicated Skin/Skin Structure Infections, VRE with or without Bacteremia): 600 mg q12 hrs
  • IV (Healthcare-Associated Pneumonia, Complicated Skin/Skin Structure Infections, VRE with or without Bacteremia): 600 mg q12 hrs

Dose Adjustment

  • Hepatic
    • Child-Pugh Class A or B: none
    • Child-Pugh Class C: use has not been evaluated
  • Renal: none

Adverse Effects

Gastrointestinal Adverse Effects

  • Altered Taste: occurs in 1.2% of cases
  • Diarrhea (see xxxx, [[xxxx]]): occurs in 4.3% of cases
  • Nausea (see xxxx, [[xxxx]]): occurs in 3.4% of cases

Hematologic Adverse Effects

  • Myelosuppression: risk is increased with renal failure, baseline cytopenias, and duration of therapy >14 days
    • Thrombocytopenia (see Thrombocytopenia, [[Thrombocytopenia]]): most frequently observed cytopenia with linezolid
      • Case reports describe reversal of thrombocytopenia with administration of pyridoxine

Neurologic Adverse Effects

  • Headache (see xxxx, [[xxxx]]): occurs in 2.2% of cases
  • Peripheral Neuropathy (see Peripheral Neuropathy, [[Peripheral Neuropathy]]): due to impairment of mitochondrial functio

Opthalmologic Adverse Effetcs

  • Optic Neuritis (see Optic Neuritis, [[Optic Neuritis]]): may be due to impairment of mitochondrial function or nutritional deficiency

Renal Adverse Effects

  • Lactic Acidosis (see Lactic Acidosis, [[Lactic Acidosis]]): due to impairment of mitochondrial function

Toxicologic Adverse Effects

  • Serotonin Syndrome (see Serotonin Syndrome, [[Serotonin Syndrome]])
    • FDA Alert (7/26/11): avoid linezolid use in conjunction with SSRI’s

Other Adverse Effects

  • xx
  • xxx
  • xxx

References

  • Linezolid-Induced Lactic Acidosis. NEJM 2003, 348:86-87
  • Does Linezolid Cause Lactic Acidosis by Inhibiting Mitochondrial Protein Synthesis? Clinical Infectious Disease 2005; 40:e113 -6
  • Linezolid and Serotonin Syndrome. Prim Care Companion J Clin Psychiatry. 2009; 11(6): 353–356