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
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
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