Pharm 101: Vancomycin

Class

Glycopeptide antibiotic

Pharmacodynamics

• Bactericidal antibiotic that inhibits cell wall synthesis by binding to peptidoglycan pentapeptide
  • This inhibitions transglycosylase, preventing further elongation of peptidoglycan and cross-linking
  • Peptidoglycan is weakened, and cell becomes suspcetible to lysis
  • Cell membrane also damaged
• Resistance to vancomycin is due to modification of binding site of peptidoglycan

Pharmacokinetics

• Poor oral absorption
  • Oral administration is only for treatment of C difficile colitis
• Widely distributed, including adipose tissue
  • CSF levels 7-30% of serum concentration in presence of meningeal inflammation
• 90% excreted by glomerular filtration
  • Half-life 6 hours
  • Accumulation occurs in renal dysfunction
  • Half-life extended to 6-10 days in anephric patients

Antimicrobial activity

• Active primarily against Gram-positive bacteria due to large molecular weight and lack of penetration through Gram-negative cell membranes
• Gram positive bacteria:
  • Staph, including MRSA, and those producing B-lactamase and those resistance to nafcillin
  • Enterococci
• Gram positive anaerobes
  • C difficile
• Clinical uses:
  • MRSA bacteraemia
  • Endocarditis caused by MRSA
  • Meningitis caused by penicillin-resistant pneumococcus (in combination with ceftriaxone)
  • C difficile colitis (oral administration)

Adverse effects

• Local irritation at site of injection
• “Red man syndrome”
  • Infusion-related flushing caused by histamine release
• Fever
• Nephrotoxicity
• Ototoxicity is rare, but risk is increased with co-administration of another ototoxic drug such as an aminoglycoside

Precautions/contraindications

• Dose adjustment required in renal impairment, morbid obesity

Further reading

• Buttner R. Pharm 101: Gentamicin. LITFL

References

• Katzung BG. Basic and Clinical Pharmacology. 14e. 2018: 807-809, 812