Makindo Medical Notes

Key Toxicity Warning: Gentamicin can damage cochlear hair cells by disrupting mitochondrial protein synthesis, leading to increased oxygen free radical generation (via inducible nitric oxide synthase).
Age-Related Dose Limitation: In patients aged >65 years, the recommended maximum dose is 3 mg/kg per day, regardless of renal function (consult local guidelines).

📖 About

• Aminoglycoside antibiotic used for severe Gram-negative infections.
• Ototoxic (vestibular & auditory) and nephrotoxic.
• Toxicity worsened by loop diuretics and other nephrotoxic drugs.
• Usually given once daily (5–7 mg/kg/day), except in endocarditis (smaller divided doses for synergy).
• Target trough concentration: <1 mg/L to minimise toxicity.

⚙️ Mechanism of Action

• Binds irreversibly to bacterial 30S ribosomal subunit.
• Causes mRNA misreading → defective proteins → bacterial cell death (bactericidal).
• Post-antibiotic effect: continues to suppress bacteria after levels fall.

🎯 Indications

• Severe infections: Septicaemia, pneumonia, biliary tract infection, pyelonephritis.
• Endocarditis: With β-lactams for synergy (streptococcal, enterococcal, HACEK).
• Neonatal sepsis (with amoxicillin/benzylpenicillin).
• Surgical prophylaxis (selected cases, e.g. urology, colorectal).
• Ineffective against anaerobes, fungi, viruses.

💊 Dose & Administration

• Once-daily regimen: 5–7 mg/kg IV (except in endocarditis or severe renal impairment).
• Endocarditis (synergy): 1 mg/kg q8–12h (or once daily if streptococcal).
• Elderly (>65 yrs): Max 3 mg/kg/day (local guidance).
• Give as slow IV infusion (30 mins in 100 mL NaCl 0.9%).
• Use ideal body weight (IBW) in obese patients.

🧮 Dosing by Renal Function (First Dose Guidance)

Always confirm with local policy; check levels to individualise therapy.

🧾 Pocket Card – Monitoring Summary

• Check baseline: U&E, creatinine, weight, consider audiometry if prolonged course.
• Peak (1 h post-dose):
  • Standard infection: 5–10 mg/L
  • Endocarditis (synergy): 3–5 mg/L
  • Cystic fibrosis: 8–12 mg/L
• Trough (pre-dose):
  • Standard: <2 mg/L
  • Endocarditis: <1 mg/L
• Toxic: >12 mg/L (but ototoxicity may occur at lower levels, esp. elderly/renal impairment).
• Check levels: after 3rd–4th dose (multiple-dose regimen) or after 1st–2nd dose (once-daily regimen).

⚠️ Side Effects

• Ototoxicity: Hearing loss, tinnitus, vertigo, nystagmus.
• Nephrotoxicity: Accumulates in renal cortex; reversible if detected early.
• Neuromuscular blockade: May worsen myasthenia gravis.
• GI upset, rash, rare seizures.

🔄 Interactions

• Loop diuretics: Additive nephro/ototoxicity.
• Ciclosporin, cisplatin, cytotoxics: Increase nephrotoxicity.
• β-lactams: Synergy vs Gram-positives (e.g. enterococci), but don’t mix in same line.

🚫 Contraindications & Cautions

• Myasthenia gravis (neuromuscular blockade risk).
• Hypersensitivity to aminoglycosides.
• Severe renal impairment (dose adjust, avoid high-dose once daily if CrCl <20 mL/min).
• Pregnancy: crosses placenta → fetal ototoxicity risk.
• Elderly: more prone to ototoxicity even at lower levels.

📚 References

• Summary of Product Characteristics
• BNF: Gentamicin