Gentamicin 7-Day Protocol
Standard Dosing for Serious Infections
For most serious infections in adults with normal renal function, gentamicin should be dosed at 3 mg/kg/day divided into three equal doses every 8 hours for 7-10 days, with mandatory therapeutic drug monitoring to maintain peak levels of 4-6 μg/mL and trough levels <1 μg/mL. 1
Key Dosing Parameters
- Standard dose: 3 mg/kg/day divided every 8 hours (1 mg/kg per dose) 1
- Life-threatening infections: May increase to 5 mg/kg/day divided every 8 hours (1.7 mg/kg per dose), then reduce to 3 mg/kg/day as soon as clinically indicated 1
- Duration: 7-10 days is standard; longer courses require enhanced monitoring for toxicity 1
Critical Exception: Sepsis Requires Higher Dosing
In septic patients with preserved renal function (CrCl >50 mL/min), use once-daily dosing at 5-7 mg/kg as a single daily dose, NOT the standard 3 mg/kg/day divided dosing. 2 This is because:
- Septic patients have markedly increased volume of distribution from fluid resuscitation, requiring higher loading doses 2
- Aminoglycoside efficacy is concentration-dependent, requiring high peak concentrations for optimal bacterial killing 2
- Once-daily dosing achieves superior clinical efficacy with potentially decreased nephrotoxicity compared to multiple daily dosing 2, 3
Critical Exception: Endocarditis Requires Different Dosing
For endocarditis, gentamicin must be dosed at 3 mg/kg/day divided every 8 hours (NOT once-daily) for synergy with beta-lactams, typically for only 2 weeks of the total treatment course. 4
- Once-daily dosing is explicitly contraindicated in endocarditis and may cause treatment failure 2
- Dosing is 3-6 mg/kg/day divided every 8 hours in children; 3-5 mg/kg/day divided every 8 hours in adults 4
Mandatory Therapeutic Drug Monitoring
Peak Level Monitoring
- Timing: Measure 30-60 minutes after completion of infusion 1
- Target: 4-6 μg/mL for standard dosing 1
- Never exceed: 12 μg/mL 1
Trough Level Monitoring
- Timing: Measure immediately before next dose 1
- Target: <1 μg/mL to minimize nephrotoxicity 4
- Never exceed: 2 μg/mL 1
- European guidelines: Recommend trough <0.1 mg/L for optimal safety 4
Renal Function Monitoring
- Monitor serum creatinine at least weekly during therapy 2
- Nephrotoxicity is defined as serum creatinine rise ≥45 μmol/L (≥0.5 mg/dL) 3
Renal Impairment Adjustments
Mild Impairment (CrCl 20-50 mL/min)
- Give full once-daily equivalent dose but extend interval to 36-72 hours based on drug levels 2
- Alternative: Reduce dose and maintain 8-hour intervals using formula: Normal dose ÷ serum creatinine (mg/dL) 1
- Interval extension formula: Serum creatinine (mg/dL) × 8 = hours between doses 1
Severe Impairment (CrCl <20 mL/min)
- Do NOT use once-daily dosing 2
- Use reduced doses with extended intervals guided by therapeutic drug monitoring 2
- Consider alternative antibiotics 2
Hemodialysis Patients
- Dose 2-8 mg/kg just before dialysis, with dose interval of at least 96 hours (eliminated by two dialysis sessions) 5
- Lower doses (2 mg/kg) for MIC = 1 mg/L; higher doses (8 mg/kg) for MIC = 4 mg/L 5
Common Pitfalls to Avoid
Underdosing in Sepsis
- Using standard 3 mg/kg/day dosing in septic patients leads to subtherapeutic levels due to increased volume of distribution 2, 6
- Septic patients require 5-7 mg/kg once daily 2
Applying Once-Daily Dosing to Endocarditis
- This is explicitly contraindicated and may cause treatment failure 2
- Endocarditis requires divided dosing every 8 hours for synergistic bactericidal activity 4, 2
Inadequate Monitoring Beyond 7 Days
- Toxicity risk increases significantly with treatment >10 days 1, 7
- Ototoxicity incidence increases from 3% to 12% when therapy exceeds 10 days 7
- Enhanced monitoring of renal and auditory function is mandatory for courses >10 days 1
Using Standard Dosing in Renal Impairment
- Gentamicin accumulates rapidly in renal dysfunction, leading to toxicity 2, 1
- Dose adjustment is mandatory when CrCl <50 mL/min 2, 1