Gentamicin

Gentamicin is a widely available aminoglycoside with rapid concentration-dependent killing of aerobic Gram-negative bacilli. It is used with a beta-lactam in sepsis, pyelonephritis, neonatal sepsis, obstetric infection and endocarditis (for synergy). Nephrotoxicity and ototoxicity limit duration.

Classification. Aminoglycoside.

Mechanism. Binds the 30S ribosomal subunit and causes misreading and premature termination; bactericidal, concentration-dependent with a post-antibiotic effect.

Spectrum. Enterobacterales, Pseudomonas aeruginosa (with an antipseudomonal beta-lactam), Staphylococcus aureus and enterococci (synergy with a cell wall agent), Brucella, Yersinia pestis and Francisella. Not active against anaerobes or streptococci alone; inactive in acidic or anaerobic conditions.

Pharmacokinetics. IV or IM; not absorbed orally. Half-life 2 to 3 hours (up to 50 hours in renal failure). Negligible protein binding. Over 90% excreted unchanged by glomerular filtration. Poor CSF penetration.

Dose by ideal body weight; in obesity (total weight over 120% of ideal) use adjusted weight (ideal weight plus 0.4 times the excess). Maximum duration usually 7 days.

Adults, extended-interval (once daily) dosing. 5 to 7 mg/kg IV once every 24 hours; 5 mg/kg is the usual dose and up to 7 mg/kg is used in critical illness with levels.

• Gram-negative sepsis, pyelonephritis, intra-abdominal infection, febrile neutropenia: with a beta-lactam, for 3 to 5 days empirically and longer only with levels and kidney function monitored.
• Chorioamnionitis and endometritis: 5 mg/kg once daily with ampicillin and clindamycin or metronidazole.
• Brucellosis (alternative): 5 mg/kg once daily for 7 days with doxycycline.
• Plague, tularaemia: 5 mg/kg once daily for 7 to 10 days.

Adults, conventional dosing. 1 to 1.7 mg/kg IV every 8 hours, or 3 mg/kg once daily (for endocarditis synergy). - Endocarditis, synergy with a cell wall agent: 3 mg/kg once daily, or 1 mg/kg every 8 hours. Viridans group streptococci 2 weeks (short course), enterococci and staphylococci 3 to 6 weeks, depending on the drug partner and valve type. - Surgical prophylaxis: single 5 mg/kg dose where used.

Children. 1 month to 11 years 7 mg/kg once daily; 12 to 17 years 6 mg/kg once daily (maximum 480 mg), or 2.5 mg/kg every 8 hours.

Neonates. 4 to 5 mg/kg once daily in term infants; 4 to 5 mg/kg every 36 hours in preterm infants (dose interval by gestation and postnatal age).

Alternatives. Amikacin, tobramycin, ciprofloxacin, ceftriaxone, piperacillin tazobactam.

Contraindications. Myasthenia gravis; known mitochondrial 12S rRNA mutation (m.1555A>G) or family history of aminoglycoside deafness; hypersensitivity.

Adverse effects. Nephrotoxicity (tubular injury, often non-oliguric and usually reversible), ototoxicity (cochlear and vestibular, often irreversible; risk rises with duration, high troughs and renal impairment), neuromuscular blockade, hypomagnesaemia, hypokalaemia, hypocalcaemia, rash.

Interactions. Loop diuretics (ototoxicity), vancomycin, amphotericin B, ciclosporin, tacrolimus, cisplatin, contrast agents and NSAIDs (nephrotoxicity); neuromuscular blockers (prolonged block); do not mix in the same bag or line with beta-lactams (inactivation).

Common prescribing errors. Dosing on actual weight in obesity, not adjusting for renal function, continuing beyond 7 days without levels, using it alone for Pseudomonas, and omitting a creatinine check before the second dose.

Special groups.

• Pregnancy: avoid unless essential (foetal eighth nerve damage); acceptable in chorioamnionitis.
• Breastfeeding: compatible (poor oral absorption).
• Older adults: reduce dose interval by creatinine clearance; ototoxicity risk is higher.
• 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.
• Creatinine clearance under 20 mL/min: give the first dose, then re-dose only when the level is under 1 mg/L.
• Haemodialysis: 1 to 2 mg/kg after each session, set by pre-dialysis levels.
• Liver impairment: no adjustment; hepatorenal risk is higher.
• Region: widely used and inexpensive in East Africa; levels are often unavailable. Use once-daily 5 mg/kg, limit to 3 to 5 days, check creatinine before each repeat dose and avoid other nephrotoxins.

Preparation. Infuse over 30 to 60 minutes in 100 mL of 0.9% sodium chloride or 5% glucose. IM injection is possible. Give separately from beta-lactams.

Baseline and monitoring.

• Baseline: creatinine, weight, medication review, hearing and balance history, pregnancy status.
• Extended-interval: level 6 to 14 hours after the first dose (interpreted on a nomogram) or a trough before the next dose, aiming for a trough under 1 mg/L; repeat levels weekly or when kidney function changes.
• Conventional: peak 5 to 10 mg/L (3 to 5 mg/L for synergy), trough under 2 mg/L (under 1 mg/L for synergy and prolonged courses).
• Creatinine at least twice weekly (daily in unstable patients); audiometry and vestibular review in courses over 7 to 10 days.

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

Referral and escalation. Infectious diseases for endocarditis, prolonged courses and renal impairment; nephrology for acute kidney injury; ENT or audiology for hearing change.