Gentamicin

Active Ingredient & Mechanism of Action

• Active Ingredient: Gentamicin sulfate.
• Mechanism:
  1. Binds to the 30S Ribosomal Subunit: Gentamicin irreversibly binds to the 30S subunit of bacterial ribosomes.
  2. Inhibits Protein Synthesis: This binding causes misreading of transfer RNA ($tRNA$), producing nonfunctional proteins and stopping essential bacterial protein synthesis.
  3. Disrupts Cell Wall: Defective proteins incorporate into the bacterial cell membrane, altering its permeability and causing cell lysis and death.

Dosage Forms & Formulations

• Injectable Solutions (IV / IM): Ampoules and vials (e.g., 20 mg/2 mL, 40 mg/2 mL, 80 mg/2 mL) used for systemic intravenous infusion or intramuscular injection in hospital settings.
• Ophthalmic Drops & Ointment (0.3%): Used topically for superficial bacterial eye infections (e.g., conjunctivitis, blepharitis, or corneal ulcers).
• Otic Drops: Formulated for external ear bacterial infections (must only be used if the eardrum is intact).
• Topical Creams & Ointments (0.1%): Applied to localized skin infections like impetigo or infected minor wounds.

Clinical Indications

• Severe Systemic Infections: Reserved for serious Gram-negative infections caused by organisms like Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Proteus, and Enterobacter species.
• Sepsis & Bacteremia: Used in acute inpatient settings for life-threatening blood infections.
• Complicated Urinary Tract Infections (UTIs): Severe pyelonephritis or complicated kidney infections.
• Infective Endocarditis: Combined with a cell-wall synthesis inhibitor (like penicillin or ampicillin) for synergistic bactericidal activity against Enterococcus or Streptococcus species.
• Topical Ocular Infections: Bacterial conjunctivitis, keratitis, and blepharitis.

Key Pharmacokinetics

• Absorption: Poor oral bioavailability; systemic administration requires intravenous (IV) or intramuscular (IM) dosing.
• Distribution: Hydrophilic molecule that distributes primarily into extracellular fluid. Penetrates poorly into the central nervous system (CNS) unless meninges are inflamed.
• Elimination: Excreted almost entirely unchanged by the kidneys via glomerular filtration. Half-life is approximately 2 to 3 hours in adults with normal renal function, but significantly prolonged in patients with kidney impairment.

Critical Boxed Warnings & Safety Concerns

1. Nephrotoxicity (Kidney Damage): Direct damage to renal tubular cells. Dose adjustments and routine monitoring of serum creatinine, blood urea nitrogen (BUN), and peak/trough drug levels are required.
2. Ototoxicity (Ear Damage): Can cause irreversible vestibular toxicity (dizziness, vertigo, loss of balance) and auditory toxicity (tinnitus, high-frequency hearing loss). Risk increases with prolonged therapy or high trough levels.
3. Neuromuscular Blockade: Can cause muscle weakness or respiratory paralysis, especially when co-administered with neuromuscular blocking agents or in patients with myasthenia gravis.

Dosing & Therapeutic Drug Monitoring (TDM)

• Peak & Trough Levels: For IV therapy, blood draws are performed to measure peak levels (ensuring efficacy) and trough levels (ensuring clearance to prevent ototoxicity and nephrotoxicity).
• Once-Daily (Extended-Interval) Dosing: Often preferred in clinical practice to maximize peak concentration (concentration-dependent killing) while allowing serum levels to drop low enough to minimize toxicity.