gentamicin

Brand: Garamycin

⚠ BBW TDM Required Prototype Drug
Drug Class: antibiotic
Drug Family: antibiotic
Subclass: aminoglycoside
Organ Systems: infectious-disease

Mechanism of Action

Irreversibly binds the 30S ribosomal subunit, causing misreading of mRNA and production of aberrant proteins; requires active transport into bacteria requiring oxygen — ineffective against obligate anaerobes; bactericidal and concentration-dependent.

30S ribosomal subunit

Indications

  • serious gram-negative infections (bacteremia, pneumonia, UTI)
  • synergistic therapy for gram-positive endocarditis (with penicillin or ampicillin)
  • gentamicin-susceptible Pseudomonas infections
  • prophylaxis in high-risk cardiac procedures (with ampicillin)

Contraindications

  • severe aminoglycoside hypersensitivity

Adverse Effects

Common

  • nephrotoxicity (reversible, proximal tubular injury)
  • accumulation with multiple doses without monitoring

Serious

  • nephrotoxicity (AKI — especially with concurrent nephrotoxins or pre-existing CKD)
  • ototoxicity — cochlear (hearing loss, tinnitus) and vestibular (vertigo, imbalance) — may be irreversible
  • neuromuscular blockade (high doses, especially with neuromuscular blocking agents)

Pharmacokinetics (ADME)

Absorption IV or IM; not absorbed orally (used topically for ocular/skin infections)
Distribution Protein binding <10%; Vd 0.2–0.35 L/kg (increased in sepsis/burns); does not cross BBB
Metabolism Not metabolized
Excretion Entirely renal; half-life dramatically prolonged in renal failure
Half-life 2–3 hours (normal renal function)
Onset End of infusion
Peak 30–60 minutes post-infusion
Duration q8h (traditional); q24h (extended interval; preferred)
Protein Binding <10%
Vd 0.2–0.35 L/kg

Drug Interactions

Drug / Agent Mechanism Severity
vancomycin additive nephrotoxicity and ototoxicity major
loop diuretics (furosemide) additive ototoxicity; loop diuretics alone are ototoxic major
neuromuscular blocking agents aminoglycosides potentiate neuromuscular blockade major

Nursing Considerations

  1. Extended-interval dosing (extended interval gentamicin: 5–7 mg/kg q24h) is now the preferred approach in most institutions; it exploits concentration-dependent killing and post-antibiotic effect while reducing nephrotoxicity
  2. Therapeutic drug monitoring: for traditional q8h dosing, target peak 5–10 mcg/mL and trough <2 mcg/mL; for extended interval, use Hartford nomogram to assess trough at 6–14h post-infusion
  3. Monitor SCr and BUN every 24–48 hours; assess audiometric function if prolonged therapy (>5 days) or in patients with risk factors; question patients about tinnitus and balance
  4. Do not mix with penicillins in the same IV line — aminoglycosides are inactivated by penicillins in vitro; administer separately

Clinical Pearls

  • Extended-interval aminoglycoside dosing (once-daily dosing) is as effective and less nephrotoxic than traditional dosing for most indications, exploiting concentration-dependent killing and the post-antibiotic effect
  • Ototoxicity from aminoglycosides preferentially affects cochlear outer hair cells and vestibular hair cells — hearing loss may be irreversible and can continue progressing after drug discontinuation due to ongoing cellular damage

Safety Profile

Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Required