Gentamicin exerts its bactericidal effect by inhibiting bacterial protein synthesis. According to the Lippincott Textbook of Pharmacology, gentamicin binds to the 30S ribosomal subunit of bacteria, leading to:

• Misreading of the genetic code.
• Inhibition of translocation during protein synthesis.
• Disruption of bacterial cell membrane integrity.

The Lange Basic & Clinical Pharmacology further explains that gentamicin's bactericidal activity is concentration-dependent, meaning higher doses result in more effective bacterial killing. It is also effective against certain Gram-positive bacteria when used in combination with beta-lactam antibiotics, as it enhances their activity.

Gentamicin is indicated for the treatment of severe infections caused by susceptible organisms, including:

1. Severe Gram-Negative Infections:
   • Sepsis.
   • Pneumonia.
   • Intra-abdominal infections.
   • Urinary tract infections (UTIs), particularly pyelonephritis.
2. Bone and Joint Infections: Such as osteomyelitis.
3. Skin and Soft Tissue Infections: Including burns and wound infections.
4. Meningitis: In combination with other antibiotics.
5. Endocarditis: Particularly caused by Enterococcus or Streptococcus species (in combination with a beta-lactam).
6. Ophthalmic Infections: Bacterial conjunctivitis and keratitis (in eye drop form).
7. Topical Infections: Superficial skin infections (in cream or ointment form).

The British National Formulary (BNF) emphasizes that gentamicin should only be used for infections caused by susceptible organisms and is ineffective against viral, fungal, or anaerobic bacterial infections.

The dosage of gentamicin varies depending on the type and severity of the infection, the patient's age, weight, and renal function. Due to its narrow therapeutic index, dosing must be carefully calculated and monitored.

General Dosage Guidelines

• Adults and Children: 3-5 mg/kg/day in divided doses every 8 hours (for conventional dosing).
• Once-Daily Dosing (Extended-Interval Dosing): 5-7 mg/kg once daily, preferred for most infections due to improved efficacy and reduced toxicity.
• Neonates: 4-7 mg/kg once daily, adjusted based on gestational age and renal function.

Renal Impairment

• Dose adjustments are critical for patients with impaired kidney function. For example:
  • Creatinine clearance (CrCl) 40-60 mL/min: Reduce dose by 50%.
  • CrCl 20-40 mL/min: Reduce dose by 75%.
  • CrCl <20 mL/min: Avoid or use with extreme caution.

Monitoring

• Serum Gentamicin Levels: Peak and trough levels should be monitored to ensure therapeutic efficacy and minimize toxicity.
  • Peak Level: Measured 30 minutes after IV infusion (target: 5-10 mg/L for conventional dosing; 15-20 mg/L for once-daily dosing).
  • Trough Level: Measured just before the next dose (target: <2 mg/L for conventional dosing; <1 mg/L for once-daily dosing).

Gentamicin is associated with several potential side effects, particularly with prolonged use or high doses. Common side effects, as listed in the Lippincott Textbook of Pharmacology, include:

• Nephrotoxicity: Kidney damage, indicated by elevated serum creatinine or reduced urine output.
• Ototoxicity: Hearing loss (cochlear toxicity) or balance disturbances (vestibular toxicity).
• Neuromuscular Blockade: Rare but serious, leading to muscle weakness or respiratory paralysis.

Less common side effects may include:

• Hypersensitivity Reactions: Rash, fever, or anaphylaxis.
• Electrolyte Imbalances: Such as hypokalemia or hypomagnesemia.
• Gastrointestinal Issues: Nausea or vomiting (more common with oral or topical use).

Patients experiencing severe side effects should seek medical attention immediately.

Before starting gentamicin, certain precautions should be taken:

1. Renal Impairment: Gentamicin is primarily excreted by the kidneys, so dose adjustments are necessary for patients with reduced kidney function.
2. Hearing or Balance Disorders: Use with caution in patients with pre-existing hearing loss or vestibular dysfunction.
3. Pregnancy and Breastfeeding: Gentamicin should be avoided during pregnancy unless absolutely necessary, as it can cause fetal harm. It is excreted in breast milk, so breastfeeding should be avoided during treatment.
4. Pediatric Use: Use with caution in neonates and infants due to the risk of toxicity.
5. Elderly Patients: Increased risk of nephrotoxicity and ototoxicity.
6. Dehydration: Ensure adequate hydration to reduce the risk of nephrotoxicity.

Gentamicin may interact with other medications, potentially increasing the risk of toxicity or reducing its efficacy. Key interactions highlighted in the BNF and Lange Basic & Clinical Pharmacology include:

• Other Nephrotoxic Drugs: Such as vancomycin, amphotericin B, or non-steroidal anti-inflammatory drugs (NSAIDs), which may increase the risk of kidney damage.
• Ototoxic Drugs: Such as furosemide or ethacrynic acid, which may increase the risk of hearing loss.
• Neuromuscular Blocking Agents: Such as succinylcholine, which may enhance neuromuscular blockade, leading to respiratory depression.
• Penicillins: Physically incompatible when mixed in the same IV solution, leading to inactivation of gentamicin.

Always inform your healthcare provider about all medications, supplements, and herbal products you are taking before starting gentamicin.

Gentamicin is the active ingredient in various brand-name medications. In pharmacies, it may also be available under generic names, including:

• Gentamicin Sulfate
• Gentamicin Injection
• Gentamicin Eye Drops
• Gentamicin Cream/Ointment