Kanamycin
Kanamycin
Generic Name
Kanamycin
Mechanism
- Binding: Kanamycin binds irreversibly to the 30 S ribosomal subunit (specifically the ‑30S rRNA, A-site region).
- Translation inhibition: It prevents initiation and causes misreading of mRNA, leading to truncated, nonfunctional proteins.
- Bactericidal: The damage to cellular machinery rapidly kills susceptible bacteria.
Pharmacokinetics
- Absorption: Oral: negligible. IM: ~50 % bioavailability; IV: complete.
- Distribution: Volume of distribution ≈ 0.2 L/kg (limited penetration into CSF, pleural fluid, and fat).
- Metabolism: Minimal hepatic metabolism; largely excreted unchanged by the kidneys.
- Elimination: Renal clearance depends on CrCl; half‑life ≈ 2–3 h in full‑functioning kidneys.
- Protein binding: < 10 % (unbound drug is pharmacologically active).
Indications
- Severe gram‑negative infections: e.g., *P. aeruginosa* bacteremia, ventilator‑associated pneumonia, septic shock.
- Multidrug‑resistant organisms: when *Pseudomonas*, *Acinetobacter*, or *Enterobacter* spp. show susceptibility.
- Combination therapy: With β‑lactams or glycopeptides for synergistic effect in mixed infections.
Contraindications
- Renal dysfunction: Use with caution; dose adjustment required (CrCl 7 days).
Dosing
| Setting | Dose | Frequency | Notes |
| Adult IV | 15–20 mg/kg (total) | Every 24 h | 1‑dose loading (15–20 mg/kg) → maintenance |
| Adult IM | 10–15 mg/kg (total) | Every 24 h | IM absorption ~50 % |
| Pediatric | 15 mg/kg (total) | Every 24 h | Adjust for weight and renal function |
| Renal Adjustment (CrCl < 30 mL/min) | 5–10 mg/kg | Every 24 h | Monitor troughs < 0.5 µg/mL |
• Titrate based on serum trough trough levels (≤ 0.5 µg/mL) and clinical response.
• Avoid simultaneous use of other nephro‑ or ototoxic drugs (e.g., loop diuretics, cisplatin).
Adverse Effects
- Nephro‑toxic: Acute tubular necrosis – rising BUN/creatinine, oliguria.
- Ototoxic (hearing/vestibular): Sensorineural hearing loss, tinnitus, vertigo.
- Neurogenic (less common): Irreversible neuromuscular blockade, especially with high doses.
- Allergic: Rash, urticaria, anaphylaxis.
- Miscellaneous: Hypotension (rare), thrombocytopenia.
*Serious events* are dose‑dependent; cumulative exposure above 240 mg cumulative dose notably increases risk.
Monitoring
- Renal: Serum creatinine and CrCl at baseline, days 3–5, then every 3–5 days while on therapy.
- Drug Levels: Trough (before next dose) < 0.5 µg/mL; peak 7 days of therapy.
- Neurologic: Monitor for muscle weakness or respiratory compromise when combined with neuromuscular blockers.
Clinical Pearls
- Loading dose key: A single high loading dose (15–20 mg/kg) achieves therapeutic troughs quickly, crucial for life‑threatening sepsis.
- Synergy tip: Pair Kanamycin with a β‑lactam (e.g., piperacillin‑tazobactam) for *Pseudomonas* infections; the combined bactericidal effect allows lower aminoglycoside exposure.
- Renal safety: Use continuous renal‑replacement therapy (CRRT) or modified continuous infusion in patients with severe AKI to maintain therapeutic troughs and mitigate toxicity.
- Avoid poly‑mining: Do not co‑administer multiple aminoglycosides; choose one agent (e.g., Kanamycin or Amikacin) based on susceptibility and risk profile.
- Ototoxicity prevention: Ensure adequate hydration and avoid concurrent use of loop diuretics; switch to an alternative drug if otic symptoms appear.
*Bottom line*: Kanamycin remains a valuable but narrow‑margin antibiotic—use judiciously with close pharmacokinetic and toxicity monitoring to ensure efficacy while preventing irreversible harm.*