gentamicin

Aminoglycoside antibiotic· Brands: Cidomycin, Garamycin, GenticynIMIVTOP

Mechanism of action

Gentamicin binds irreversibly to the 30S ribosomal subunit, inhibiting protein synthesis and causing misreading of mRNA, leading to bacterial cell death. It is bactericidal, particularly against Gram-negative aerobes, and exhibits concentration-dependent killing and a post-antibiotic effect.

Pharmacokinetics

Gentamicin is poorly absorbed orally, so it is given parenterally. It is not metabolised and is excreted unchanged by glomerular filtration. It has a large volume of distribution and distributes poorly into CSF and fat. Its half-life is about 2-3 hours with normal renal function, prolonged in renal impairment.

Indications & dosing

Gram-negative bacteraemia and sepsis

Extended-interval dosing; monitor renal function and serum gentamicin levels.

adult · IV: 5–7 mg/kg once daily · Extended-interval dosing; monitor renal function and serum gentamicin levels.

Complicated urinary tract infection / pyelonephritis

Used when other options are unsuitable; ensure adequate hydration.

adult · IV: 5–7 mg/kg once daily · Used when other options are unsuitable; ensure adequate hydration.

Infective endocarditis (synergy)

In combination with a beta-lactam for enterococcal or staphylococcal endocarditis; monitor serum levels.

adult · IV: 1 mg/kg every 8 hours · In combination with a beta-lactam for enterococcal or staphylococcal endocarditis; monitor serum levels.

Neonatal sepsis

Dose varies with gestational age; monitor levels.

neonatal · IV: 4–5 mg/kg once daily · Dose varies with gestational age; monitor levels.

Febrile neutropenia (in combination)

Used with an antipseudomonal beta-lactam; adjust for renal function.

adult · IV: 5–7 mg/kg once daily · Used with an antipseudomonal beta-lactam; adjust for renal function.

Contraindications & precautions

Hypersensitivity to gentamicin or other aminoglycosides · Cross-sensitivity to other aminoglycosides is possible.
Myasthenia gravis · Aminoglycosides can exacerbate neuromuscular blockade.
Severe renal impairment · Dose adjustment required; monitoring of serum levels essential.
Pregnancy · Risk of fetal ototoxicity; use only if benefit outweighs risk.
Concurrent use of other nephrotoxic or ototoxic drugs · Includes loop diuretics, amphotericin B, other aminoglycosides.
History of hearing disorder · Increased risk of ototoxicity.
Monitor renal function (serum creatinine, urea) before and during therapy.
Monitor serum gentamicin levels (peak and trough) to optimise dosing and reduce toxicity risk.
Ensure adequate hydration throughout treatment.
Avoid co-administration with other nephrotoxic or ototoxic drugs where possible (e.g., loop diuretics, amphotericin B).
Use with caution in patients with pre-existing renal impairment, adjusting dose according to renal function.
Caution in elderly patients and neonates, as they are at increased risk of toxicity.

Adverse effects

Nephrotoxicityserious
Ototoxicity (vestibular and cochlear)serious
Neuromuscular blockadeserious
Hypersensitivity reaction (anaphylaxis)serious
Rash
Fever
Electrolyte disturbances (hypokalemia, hypomagnesemia)

Interactions

furosemidemajorAvoid concurrent use if possible. If unavoidable, ensure adequate hydration, monitor renal function (serum creatinine and urea) and hearing before and during therapy. Adjust gentamicin doses based on renal function and consider alternative diuretics or antibacterial agents when appropriate.
vancomycinmajorAvoid the combination if possible. If co-prescription is necessary, monitor renal function (serum creatinine, urea, electrolytes, urine output) at least daily. Consider therapeutic drug monitoring for both agents, and adjust doses according to renal function. Ensure adequate hydration and consider alternative antibiotics, extended-interval aminoglycoside dosing, or shorter courses of therapy.

Renal & hepatic adjustment

eGFR 80+: No dose adjustment required.
eGFR 50–79: Reduce dose to 75% of normal or extend dosing interval. Monitor drug levels.
eGFR 10–49: Reduce dose to 50% of normal or extend dosing interval significantly. Consider therapeutic drug monitoring.
eGFR 0–9: Avoid use unless benefits outweigh risks. If essential, use with extreme caution and therapeutic drug monitoring. (avoid)

Monitoring, pregnancy & toxicity

Serum creatinine and eGFR · Baseline, then at least every 48-72 hours during therapy
Gentamicin serum levels (trough and peak) · After reaching steady state (usually 2-3 doses), then as clinically indicated
Audiometry · Baseline and at end of therapy, or if symptoms of ototoxicity occur
Urinalysis · Baseline and periodically to detect proteinuria, haematuria, or casts
Vestibular function · Monitor for dizziness, vertigo, or ataxia; refer for audiological assessment if suspected
Pregnancy: Avoid in pregnancy unless there is no safer alternative and benefit outweighs risk. Gentamicin crosses the placenta and may cause fetal nephrotoxicity and ototoxicity. Use only if clearly needed.
Toxicity: Nephrotoxicity (rising creatinine, reduced urine output) · Discontinue gentamicin, maintain hydration, monitor renal function. Consider haemodialysis in severe cases.
Toxicity: Ototoxicity (hearing loss, tinnitus, vestibular dysfunction) · Stop the drug immediately, refer for audiometric assessment. Damage may be irreversible.
Toxicity: Neuromuscular blockade (respiratory paralysis, muscle weakness) · Administer intravenous calcium gluconate, provide ventilatory support, and discontinue the drug.

Clinical notes

It is used for serious Gram-negative infections, often in combination with a beta-lactam for synergy. It has a narrow therapeutic index; therapy is monitored with serum levels and renal function. Ototoxicity and nephrotoxicity are major risks. Dosing is usually once daily in patients with normal renal function, adjusted for renal impairment.

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BNF; local formulary