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: Always check the BNF or local protocols for comprehensive prescribing advice.

• Aminoglycoside commonly used for severe infections (especially Gram-negative).
• Known ototoxic (vestibular and/or auditory) and nephrotoxic.
• Toxic effects can be exacerbated by loop diuretics.
• Typically given once daily (5–7 mg/kg/day) except in certain scenarios (e.g., endocarditis: 1 mg/kg q8h).
• Recommended trough level <1 mg/L to minimize toxicity.

Mechanism of Action

• Binds irreversibly to the 30S ribosomal subunit of bacteria.
• Causes misreading of mRNA codons, leading to defective proteins and bacterial cell death (bactericidal).

Clinical Use Highlight: Gentamicin offers broad Gram-negative coverage and remains a top-line choice for Gram-negative sepsis and surgical prophylaxis in certain settings.

Indications

• Severe Infections: Septicaemia, meningitis, biliary tract infections, pneumonia (in hospitalized patients).
• Endocarditis: Often combined with a β-lactam (e.g., penicillin) for synergy (particularly in streptococcal or enterococcal endocarditis).
• Pyelonephritis and neonatal sepsis (commonly combined with penicillin/metronidazole).
• Targets Gram-negative aerobic rods (Pseudomonas, Proteus) and can have anti-staphylococcal activity when used in combination therapy.
• Ineffective against fungi, viruses, and most anaerobes.

Dose & Administration

Any total daily dose >480 mg may require specialist input. Always confirm with local policy.

• Septicaemia, Meningitis, Biliary Tract Infections, Pyelonephritis, Pneumonia, Prostatitis
  • Gentamicin 3–5 mg/kg/day in 3 divided doses (q8h) IV.
  • Or once-daily regimen of 5–7 mg/kg/day IV.
• Endocarditis (Gram-positive or HACEK organisms; in combination with other agents):
  • Enterococcal Endocarditis: 1 mg/kg q8–12h IV.
  • Streptococcal Endocarditis: 3 mg/kg once daily IV.
  • HACEK/Gram-positive Endocarditis: 1 mg/kg q12h IV.
• Acute Pyelonephritis or UTIs (Catheter-associated):
  • Once daily: 5–7 mg/kg IV.
• Patients Over 65 Years:
  • Maximum recommended dose: 3 mg/kg/day (consult local guidelines).
• Give by slow IV infusion (e.g., 30 minutes in 100 mL NaCl 0.9%).

Key Dosing Information

• For obese patients, use ideal body weight (IBW) to calculate dose and monitor gentamicin levels closely.
• In renal impairment, adjust dose/frequency based on creatinine clearance (CrCl). Avoid high-dose (once-daily) regimens if CrCl <20 mL/min.
• Serum gentamicin concentration monitoring is crucial, especially in the elderly or those with renal dysfunction.
• Normal renal function: check gentamicin concentrations after the 3^rd or 4^th dose in a multiple-daily regimen (or after the 1^st or 2^nd dose if once-daily) and whenever doses change.

Dosing Table (First-Dose Guidance by CrCl)

Local protocols may vary; always confirm with up-to-date guidelines.

CrCl (mL/min)	Under 40 kg	40–49 kg	50–59 kg	60–69 kg	70–79 kg	Over 80 kg
<21	2.5 mg/kg (max 180 mg), then measure levels after 24 hrs
21–30	5 mg/kg	180 mg every 48h	200 mg every 48h	240 mg every 48h	240 mg every 48h	260 mg every 48h
31–40	5 mg/kg	200 mg every 48h	240 mg every 48h	280 mg every 48h	300 mg every 48h	320 mg every 48h
41–50	5 mg/kg	240 mg every 48h	280 mg every 48h	320 mg every 48h	360 mg every 48h	400 mg every 48h
51–60	5 mg/kg	200 mg every 24h	240 mg every 24h	280 mg every 24h	300 mg every 24h	320 mg every 24h
>60	5 mg/kg	240 mg every 24h	280 mg every 24h	320 mg every 24h	360 mg every 24h	400 mg every 24h

Serum Concentration Monitoring

• Peak (1 hour post-dose):
  • Standard infections: 5–10 mg/L.
  • Endocarditis: 3–5 mg/L.
  • Cystic fibrosis: 8–12 mg/L.
• Trough (just before next dose):
  • Standard: <2 mg/L.
  • Endocarditis: <1 mg/L.
• Toxic level: >12 mg/L. However, clinical toxicity can occur even at lower levels, especially with prolonged treatment or renal impairment.

Side Effects & Toxicity

• Vestibular & Cochlear Ototoxicity: May manifest as dizziness, tinnitus, vertigo, hearing loss, or nystagmus. Can be idiosyncratic or related to elevated levels/prolonged use.
• Nephrotoxicity: Aminoglycosides accumulate in the renal cortex; risk increases with renal impairment or concurrent nephrotoxic drugs.
• Neuromuscular blockade: May worsen myasthenia gravis or block effects of pyridostigmine/neostigmine.
• Rash, nausea, vomiting, potential for seizures (rare).

Interactions

• Loop diuretics: Increase ototoxic and nephrotoxic risk.
• Ciclosporin, cytotoxics: Can potentiate gentamicin toxicity.
• β-lactams: Often synergistic (especially for Gram-positive coverage), but avoid mixing in the same IV line to prevent inactivation.
• Monitor carefully and consult BNF/Pharmacy when combining with other medications.

Contraindications & Cautions

• Myasthenia gravis: Risk of severe neuromuscular blockade.
• Hypersensitivity to aminoglycosides.
• Severe renal impairment: Dose adjustments and level monitoring are essential. Once-daily high-dose regimens may be contraindicated if CrCl <20 mL/min.
• Pregnancy: Can cross placenta and cause fetal 8th nerve damage.
• Multiple myeloma: Increased risk of nephrotoxicity and ototoxicity.

Key Renal Points

• Excreted primarily via the kidneys; accumulation and higher toxicity risk in renal impairment.
• Once-daily, high-dose regimens are generally avoided if CrCl <20 mL/min.
• If severe renal impairment, extend dosing intervals and/or reduce the dose; closely monitor levels.
• Obtain earlier and more frequent serum gentamicin levels in renal impairment.

References

• Summary of Product Characteristics