What is the recommended dosing of vancomycin in patients with impaired renal function?

Vancomycin Dosing in Renal Impairment

For patients with impaired renal function, vancomycin dosing should be adjusted based on creatinine clearance, with the daily dose calculated as approximately 15 times the glomerular filtration rate in mL/min. 1

Initial Dosing Recommendations

• A weight-based loading dose of 20-25 mg/kg (actual body weight) should be administered regardless of renal function to achieve prompt therapeutic serum concentrations 1, 2
• For maintenance dosing in renal impairment, adjust according to creatinine clearance using this formula 1:
  • Daily dose (mg) = 15 × creatinine clearance (mL/min)
• For functionally anephric patients, an initial dose of 15 mg/kg followed by maintenance doses of 1.9 mg/kg/24 hr is recommended 1
• In marked renal impairment, consider maintenance doses of 250-1,000 mg every several days rather than daily administration 1
• In anuria, a dose of 1,000 mg every 7-10 days has been recommended 1

Monitoring Recommendations

• Trough vancomycin concentrations should be obtained at steady state, prior to the fourth or fifth dose 3
• For serious infections (bacteremia, endocarditis, osteomyelitis, meningitis, pneumonia, severe SSTI), maintain trough concentrations of 15-20 μg/mL 3
• Monitoring is strongly recommended for patients with renal dysfunction, morbid obesity, or fluctuating volumes of distribution 3
• Vancomycin-induced nephrotoxicity should be suspected if multiple (2-3) consecutive high serum creatinine concentrations (increase of 0.5 mg/dL or 150% increase from baseline) occur after several days of therapy 3

Special Considerations by Level of Renal Impairment

• For mild-moderate renal impairment: Use the formula-based approach (daily dose = 15 × CrCl) 1
• For severe renal impairment (CrCl <10 mL/min): Consider extended interval dosing (e.g., 1,000 mg every several days) 1
• For hemodialysis patients: Weight-based loading dose (20-25 mg/kg) followed by maintenance dosing based on pre-dialysis trough levels 2

Risk Factors for Vancomycin-Associated Nephrotoxicity

• Initial vancomycin trough levels ≥15 mg/L increase nephrotoxicity risk (OR 5.2) 4
• Concomitant use of other nephrotoxic agents, particularly aminoglycosides (OR 2.67) 4
• Prolonged duration of vancomycin therapy (12% increased risk per additional treatment day) 4
• Higher daily doses, especially ≥4 g/day 5
• Pre-existing chronic kidney disease 5

Practical Dosing Algorithm

1. Calculate creatinine clearance using Cockcroft-Gault formula:

   • Men: [Weight (kg) × (140 – age)]/[72 × serum creatinine (mg/dL)]
   • Women: 0.85 × above value 1

2. Administer loading dose of 20-25 mg/kg actual body weight 1, 2

3. Calculate maintenance dose:

   • If CrCl >100 mL/min: Standard dosing of 15-20 mg/kg every 8-12 hours 3
   • If CrCl 50-100 mL/min: 15 mg/kg every 12-24 hours 1
   • If CrCl 10-50 mL/min: 15 mg/kg every 24-48 hours 1
   • If CrCl <10 mL/min: 15 mg/kg every 3-7 days 1
   • If anephric: 1,000 mg every 7-10 days 1

4. Monitor trough levels before the 4th dose and adjust as needed to maintain appropriate trough concentrations (15-20 μg/mL for serious infections) 3

Common Pitfalls to Avoid

• Failing to administer an adequate loading dose in patients with renal impairment, which can delay achieving therapeutic concentrations 2
• Using estimated rather than measured creatinine clearance in unstable patients 1
• Overestimating creatinine clearance in patients with shock, heart failure, oliguria, obesity, liver disease, edema, ascites, or malnutrition 1
• Not accounting for residual nonrenal clearance in acute renal failure, which can be substantial early in the course (16.2 ± 7.0 mL/min) but decreases with duration of renal failure 6
• Inadequate monitoring of trough levels in patients with fluctuating renal function 3
• Failing to adjust dosing when concomitant nephrotoxic agents are used 4