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Aminoglycoside — Drug-Resistant Gram-Negative / MDR-TB Pregnancy: Avoid — aminoglycosides cross placenta; cochlear toxicity in fetus reported; use only if life-threatening and no alternative

Amikacin

Brand names: Amikin

Adult dose

Dose: Gram-negative sepsis: 15–20 mg/kg IV once daily; TB (MDR): 15–20 mg/kg IV once daily (typically 5 days/week); Neonatal sepsis (specialist): weight-based
Route: Intravenous infusion over 30–60 minutes
Frequency: Once daily (extended-interval dosing preferred)
Max: 1.5 g/day (short-term); guided by TDM
Reserved for MDR gram-negative infections and MDR-TB where gentamicin-resistant organisms present. Aminoglycoside with broadest resistance coverage against gram-negatives — stable against most aminoglycoside-modifying enzymes (except AAC(6')Ib). Requires TDM — target Cmax 20–30 mg/L; trough <5 mg/L (once-daily dosing).

Paediatric dose

Dose: 15–22.5 mg/kg mg/kg
Route: IV
Frequency: Once daily (age and renal function dependent)
Max: 1.5 g/day
BNFc: neonates — complex age/weight-based dosing; always use TDM; check neonatal formulary

Dose adjustments

Renal

Extend dosing interval based on CrCl and TDM; CrCl <30: every 48–72 hours guided by trough levels; contraindicated in severe renal failure unless dialysed

Hepatic

No dose adjustment required

Paediatric weight-based calculator

BNFc: neonates — complex age/weight-based dosing; always use TDM; check neonatal formulary

Clinical pearls

  • Amikacin preferred over gentamicin when gentamicin resistance confirmed or for MDR-TB regimens (WHO group B drug) — broader stability against aminoglycoside-modifying enzymes
  • Ototoxicity risk is cumulative and often irreversible — audiometry monitoring essential in prolonged courses; cochlear damage causes high-frequency hearing loss first (often asymptomatic initially)
  • Once-daily extended-interval dosing (EID): exploits concentration-dependent killing and post-antibiotic effect — same or better efficacy with lower nephrotoxicity than multiple daily dosing
  • Hartford nomogram or Bayesian TDM software used to interpret levels and adjust dosing
  • Inhalation route for lung infections: nebulised amikacin (ALIS — amikacin liposome inhalation suspension) licensed for refractory MAC lung disease

Contraindications

  • Pre-existing deafness or vestibular disorder
  • Myasthenia gravis
  • Hypersensitivity to aminoglycosides

Side effects

  • Nephrotoxicity (acute tubular necrosis)
  • Ototoxicity (cochlear — irreversible high-frequency hearing loss; vestibular)
  • Neuromuscular blockade (high doses)
  • Rash

Interactions

  • Vancomycin — additive nephrotoxicity
  • Loop diuretics — additive ototoxicity
  • Neuromuscular blocking agents — enhanced blockade
  • Ciclosporin — additive nephrotoxicity
  • Amphotericin B — additive nephrotoxicity

Monitoring

  • Serum levels: Cmax (1 hour post-dose target 20–30 mg/L) and trough (pre-dose target <5 mg/L)
  • Renal function daily in acutely ill
  • Audiometry (weekly in prolonged courses)
  • Vestibular symptoms
  • Neuromuscular function

Reference: BNFc; BNF 90; WHO MDR-TB Treatment Guidelines 2022; BSAC Aminoglycoside TDM Guidelines; PHE Antibiotic Guidelines. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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