Gentamicin

CLASS

• aminoglycoside

MECHANISM OF ACTION

• irreversible binding to bacterial ribosomal proteins -> inhibits protein synthesis

INDICATIONS

• Antimicrobial cover: gram negative rods (including Pseudomonas)

PHARMACEUTICS

• 80mg/2mL, clear, colourless (also topical, bone cements, bead)

DOSE

• up to 5mg/kg loading dose, OD (adjust based on renal function), trough level not > 2mcg/mL

PHARMACOKINETICS

• Administration – IV
• Distribution – <10% protein bound, small Vd
• Metabolism – no active metabolites, no metabolism
• Elimination – entirely by glomerular filtration, t1/2 = 2-3 hrs

ADVERSE EFFECTS

• ototoxicity
• renal toxicity
• prolongation of neuromuscular blockade
• rashes
• abnormal LFT’s
• other uncommon reactions

SUMMARY OF PROS AND CONS (from Australian Therapeutic Guidelines)

Advantages

• rapid bactericidal activity associated with rapid control of Gram-negative infections, including Pseudomonas aeruginosa
• generally low rates of resistance among community-associated and healthcare-associated Gram-negative pathogens
• has a ‘post-antibiotic effect’ (bacterial killing continues for many hours after plasma concentration is undetectable) that allows for effective once-daily therapy with reduced rates of toxicity
• synergistic killing when combined with cell-wall–active drugs (eg beta lactams, glycopeptides) for enterococcal and streptococcal infections
• low rate of drug hypersensitivity reactions
• low rate of C. difficile infection
• low cost

Disadvantages

• nephrotoxicity
  • generally reversible; usually associated with prolonged treatment courses (longer than 5 to 7 days) and pre-existing renal impairment
• vestibular and, less commonly, auditory toxicity
  • generally irreversible; mostly associated with prolonged treatment courses
• some recently identified Enterobacteriaceae strains exhibit resistance to multiple drug classes, including to aminoglycosides

References and Links