Vancomycin-resistant Infection Agents

Question 1

Linezolid

(Oxazolidinone)

Answer 1

• MOA = protein synthesis inhibitor
  
  • **​binds RNA od 50S subunit **
  • **prevents formation of functional 70S initiation complex **
• useful for infections due to Vanc-resistant orgs
• **PO and parenteral **
• hepatic metabolism
• **renal excretion **(no dosage adjustments recommended for renal dysnfunction)
• little activity against G - orgs
• adverse effects =
  
  • **myelosuppression **(incl anemia, leukopenia, thrombocytopenia)
  • hepatic enzyme elevations
  • **peripheral and optic neuropathy **(reversible)
• drug interactions
  
  • **mild inhibitor of monoamine oxidase **(HTN if take w/ foods rich in tyramine)
  • dangerous in pts taking SSRIs
• • no interactions w/ P450s
• rarely cross resistant w/ other PSIs
• resistance = due to **mutation **of ribosomal binding site in RNA

Question 2

Daptomycin

Answer 2

• useful alternative to vanc for MRSA, **G+ ONLY **
  
  • ​should be reserved for VRSA
• MOA = **membrane depolarizer **
  
  • ​requires physiologic concentrations of Ca
  • forms ion conduction pore- allows influx of Na and efflux of K and perhaps other ions
• generally more rapid bacterial cell death than vanc, linezolid, or streptogramins
• **renal excretion **(unchanged)
• **IV **
• adverse effects =
  
  • increases in creatine phosphokinase (high doses)
    
    • muscle weakness, discomfort
    • reversible
    • consider stopping statins and other agents ass w/ rhabdomyolysis