Amikacin

Amikacin is a semisynthetic aminoglycoside that resists many aminoglycoside-modifying enzymes, so it is active against many gentamicin-resistant Gram-negative bacilli. It is also used for nontuberculous mycobacteria and multidrug-resistant tuberculosis.

Classification. Aminoglycoside.

Mechanism. Binds the 30S ribosomal subunit; bactericidal, concentration-dependent.

Spectrum. Enterobacterales (including many gentamicin-resistant strains), Pseudomonas aeruginosa, Acinetobacter, Nocardia, Mycobacterium tuberculosis, Mycobacterium avium complex and Mycobacterium abscessus. Not active against anaerobes or streptococci.

Pharmacokinetics. IV or IM (inhaled liposomal form for lung disease). Half-life 2 to 3 hours. Eliminated by glomerular filtration. Poor CSF penetration.

Dose by ideal body weight (adjusted weight in obesity). Maximum 1.5 g daily.

Adults. - Extended-interval: 15 mg/kg IV once every 24 hours (up to 20 mg/kg in critical illness with levels). - Conventional: 5 mg/kg every 8 hours or 7.5 mg/kg every 12 hours. - Gram-negative sepsis, febrile neutropenia, complicated urinary tract infection: with a beta-lactam, for 3 to 7 days. - Drug-resistant tuberculosis (reserve use): 15 mg/kg once daily (maximum 1 g), or 25 mg/kg three times weekly, for the intensive phase under specialist direction.

Newer all-oral regimens have largely replaced injectable agents. - Mycobacterium avium complex (injectable phase): 10 to 15 mg/kg three times weekly or daily for the first 2 to 3 months. Refractory lung disease: liposomal inhaled amikacin 590 mg once daily. - Mycobacterium abscessus complex: 10 to 15 mg/kg once daily for the initial intensive phase.

Children. 15 to 20 mg/kg once daily (conventional 5 to 7.5 mg/kg every 8 hours). Neonates: 15 mg/kg once daily in term infants and every 36 to 48 hours in preterm infants.

Alternatives. Gentamicin, tobramycin, meropenem, colistin-based regimens.

Contraindications. Myasthenia gravis; known mitochondrial 12S rRNA mutation (m.1555A>G); hypersensitivity.

Adverse effects. Nephrotoxicity, ototoxicity (cochlear more than vestibular, irreversible), neuromuscular blockade, hypomagnesaemia, hypokalaemia, hypocalcaemia, rash. Inhaled form: cough, dysphonia, bronchospasm.

Interactions. Loop diuretics, vancomycin, amphotericin B, ciclosporin, cisplatin, contrast agents and NSAIDs; neuromuscular blockers; beta-lactams in the same bag (inactivation).

Common prescribing errors. Dosing on actual weight in obesity, no audiometry during tuberculosis therapy, no dose adjustment in renal failure, and unmonitored prolonged courses.

Special groups. - Pregnancy: avoid (foetal eighth nerve damage and deafness). Breastfeeding: compatible. - Older adults: increased risk of hearing loss and renal injury. - Kidney impairment (15 mg/kg regimen): creatinine clearance over 60 mL/min every 24 hours; 40 to 59 mL/min every 36 hours; 20 to 39 mL/min every 48 hours; under 20 mL/min dose by levels. Haemodialysis: 5 to 7.5 mg/kg after each session. - Liver impairment: no adjustment.

Preparation. Dilute 500 mg in 100 to 200 mL of 0.9% sodium chloride or 5% glucose and infuse over 30 to 60 minutes. IM injection into a large muscle is possible.

Baseline and monitoring. - Baseline: creatinine, weight, audiometry in prolonged therapy, electrolytes, medication review. - Levels: extended-interval peak 30 to 60 minutes after the infusion (usual aim 40 to 60 mg/L) and trough under 5 mg/L (under 1 mg/L preferred); conventional peak 20 to 30 mg/L and trough 5 to 10 mg/L. - Creatinine and electrolytes twice weekly; audiometry monthly during tuberculosis treatment.

Stop rules. Stop for creatinine rising by 0.3 mg/dL (26 micromol/L) or more, new tinnitus or hearing loss, vertigo, or neuromuscular weakness.

Referral and escalation. Infectious diseases or respiratory specialist for tuberculosis, nontuberculous mycobacterial infection and all courses over 7 days.