Makindo Medical Notes

About: Always check the BNF or equivalent guidelines for up-to-date prescribing advice.

• Gentamicin is a potent, broad-spectrum aminoglycoside antibiotic that inhibits bacterial protein synthesis.

Mode of Action

• Primarily binds to the 30S ribosomal subunit (some aminoglycosides bind the 50S subunit).
• Inhibits the translocation of peptidyl-tRNA from the A-site to the P-site.
• Causes misreading of mRNA, preventing synthesis of vital bacterial proteins.

Indications

• Gentamicin: Effective against aerobic Gram-negative rods and staphylococci.
• Synergy with β-lactams (e.g., penicillins): Especially important in certain streptococcal infections such as endocarditis.
• Highly effective in the management of Gram-negative sepsis.

Contraindications & Cautions

• Renal impairment: Gentamicin is renally eliminated; dose adjustments and frequent monitoring are required to prevent toxicity.
• Myasthenia Gravis: Risk of neuromuscular blockade, especially with rapid IV administration.
• Pregnancy: Crosses the placenta and may cause fetal ototoxicity.

Dosing must follow local guidelines

• Once-Daily/Extended-Interval Dosing:
  • Typical dose: 5–7 mg/kg (actual or adjusted body weight) once daily.
  • Provides maximal bactericidal effect and may reduce nephrotoxicity.
  • Serum level monitoring is usually done at a single time point (e.g., 6–14 hours post-dose) using a nomogram (e.g., Hartford or Birmingham) to guide interval adjustments.
  • Post-antibiotic effect allows once-daily administration without compromising efficacy.
• Multiple-Daily Dosing (Conventional Dosing):
  • Typical dose: 1–2 mg/kg every 8 hours (q8h).
  • Peak (30 minutes after infusion) and trough (immediately before next dose) levels are measured:
    • Trough: Aim for < 1 mg/L (minimizes toxicity).
    • Peak: Varies by indication:
      • Serious infections: ~5–10 mg/L.
      • Synergy (e.g., endocarditis): ~3–5 mg/L.
  • Trough levels > 2 mg/L significantly increase the risk of toxicity.

Single-Dose Gentamicin for UTIs and Catheter Changes

In certain clinical scenarios—such as uncomplicated UTIs or prophylaxis around catheter changes—a single dose of gentamicin may be used. This practice varies by local protocol, so it is crucial to consult your local guidelines. Below are some general considerations:

• Prophylaxis for Catheter Changes:
  • Some guidelines suggest a single low dose (e.g., 80–160 mg IV or IM) of gentamicin immediately before the catheter change.
  • This aims to reduce the risk of bacteriuria or symptomatic UTI associated with instrumentation.
  • Dose adjustments may be necessary in patients with reduced renal function.
• Uncomplicated UTIs:
  • A single dose of gentamicin (e.g., 3–5 mg/kg IV or IM) may occasionally be used for uncomplicated lower urinary tract infections, especially if the local resistance pattern supports its use.
  • However, single-dose gentamicin is not universally recommended and depends on local susceptibility rates and antimicrobial stewardship practices.
• Monitoring and Considerations:
  • Even with a single dose, monitor renal function in patients at higher risk of toxicity (e.g., the elderly, those with pre-existing renal impairment).
  • Avoid or use extreme caution in patients with significant hearing impairment or vestibular disorders, given the risk of ototoxicity.
  • As always, check local guidelines for specific dose recommendations and patient selection criteria.
  • In summary, single-dose gentamicin can be an option for certain UTI or prophylactic indications, but it must be guided by local policy, patient factors (especially renal function), and microbial resistance patterns.
• Other Aminoglycosides:
  • Streptomycin: Has anti-tuberculous activity.
  • Kanamycin, Tobramycin: Similar mechanisms and considerations.
  • Neomycin: Often used orally to reduce colonic bacterial load (e.g., before GI surgery).

Monitoring

• Serum Levels: For once-daily dosing, check a random level (6–14 hours post-dose) and use a nomogram. For multiple-daily dosing, check peak (30 mins after infusion) and trough (immediately before the next dose).
• Renal Function: Monitor U&E/creatinine at baseline and frequently during treatment; dose adjustments may be necessary.
• Hearing: Ask about tinnitus or balance issues. Consider audiometry if clinically indicated.

Side Effects

• Ototoxicity — can affect vestibular or auditory function (Kanamycin is particularly associated with auditory toxicity).
• Nephrotoxicity — may cause proximal tubular damage; reversible if identified early.
• Neuromuscular Blockade — especially in patients with Myasthenia Gravis or those receiving rapid IV doses.