Tobramycin

Tobramycin is an aminoglycoside with the strongest activity against Pseudomonas aeruginosa of the class. It is used systemically for Gram-negative sepsis and Pseudomonas infection and by inhalation for chronic Pseudomonas infection in cystic fibrosis.

Classification. Aminoglycoside.

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

Spectrum. Enterobacterales, Pseudomonas aeruginosa (two to four times more active than gentamicin), Staphylococcus aureus. It is less reliable than gentamicin for enterococcal synergy. Not active against anaerobes or streptococci alone.

Pharmacokinetics. IV or IM; inhaled forms act locally with low systemic absorption. Half-life 2 to 3 hours. Eliminated by glomerular filtration. Clearance is higher in cystic fibrosis.

Dose by ideal body weight (adjusted weight in obesity). Courses of 7 days or less where possible.

Adults, systemic. - Extended-interval: 5 to 7 mg/kg IV once every 24 hours. - Conventional: 1 to 1.7 mg/kg every 8 hours. - Gram-negative sepsis, pyelonephritis, febrile neutropenia: with an antipseudomonal beta-lactam, for 3 to 7 days. - Cystic fibrosis exacerbation with Pseudomonas: 8 to 10 mg/kg IV once daily with an antipseudomonal beta-lactam, for 14 days, with levels.

Adults, inhaled (specialist). Nebulised solution 300 mg every 12 hours for 28 days, then 28 days off; or dry powder 112 mg (four 28 mg capsules) every 12 hours for 28 days on and 28 off.

Children. 7.5 mg/kg IV once daily (conventional 2.5 mg/kg every 8 hours); cystic fibrosis 10 mg/kg once daily. Neonates: 4 to 5 mg/kg once daily in term infants, every 36 hours in preterm infants.

Alternatives. Gentamicin, amikacin, ciprofloxacin, ceftazidime, colistin (inhaled).

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

Adverse effects. Nephrotoxicity, ototoxicity (vestibular and cochlear), neuromuscular blockade, hypomagnesaemia, rash. Inhaled: cough, bronchospasm, dysphonia, tinnitus, taste change.

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

Common prescribing errors. Monotherapy for severe Pseudomonas infection, under-dosing in cystic fibrosis, mixing with beta-lactams, and no level monitoring.

Special groups. - Pregnancy: avoid unless essential (foetal eighth nerve damage). Breastfeeding: compatible (systemic) with caution. - Older adults: reduce by kidney function. - Kidney impairment (5 mg/kg regimen): creatinine clearance 60 mL/min or more 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: 1 to 2 mg/kg after each session. - Liver impairment: no adjustment.

Preparation. Infuse over 30 to 60 minutes in 50 to 100 mL of 0.9% sodium chloride or 5% glucose. Inhaled forms: use the device and storage directions supplied; give bronchodilator first if wheeze.

Baseline and monitoring. - Baseline: creatinine, weight, medication review, hearing history, spirometry for inhaled use. - Levels: extended-interval trough under 1 mg/L; conventional peak 5 to 10 mg/L and trough under 2 mg/L; in cystic fibrosis once-daily peak 20 to 30 mg/L. - Creatinine at least twice weekly; audiometry in prolonged courses; for inhaled use, creatinine and audiology annually.

Stop rules. Stop for creatinine rising by 0.3 mg/dL (26 micromol/L) or more, new hearing loss or vertigo, or neuromuscular weakness; stop inhaled therapy for severe bronchospasm.

Referral and escalation. Respiratory or cystic fibrosis team for inhaled therapy; infectious diseases for resistant Pseudomonas; nephrology for acute kidney injury.