Vancomycin Dosing in Renal Impairment
In patients with impaired renal function, vancomycin dosing must be reduced by extending the dosing interval or decreasing the dose based on creatinine clearance, with the initial dose being at least 15 mg/kg regardless of renal function, followed by maintenance dosing adjusted to achieve target trough levels of 15-20 mg/L while avoiding levels >20 mg/L to prevent nephrotoxicity. 1, 2
Initial Dosing Strategy
Always administer a loading dose of 15-20 mg/kg (up to 25-30 mg/kg for serious infections like meningitis) regardless of renal function to rapidly achieve therapeutic concentrations, as the initial dose should be no less than 15 mg/kg even in patients with mild to moderate renal insufficiency 3, 2
For patients with normal renal function (CrCl >50 mL/min), the standard maintenance dose is 15-20 mg/kg every 8-12 hours 2
Dose Adjustment Based on Creatinine Clearance
The fundamental principle is that vancomycin clearance correlates directly with creatinine clearance (r = 0.92), requiring systematic dose reduction as renal function declines 4:
CrCl >50 mL/min: No adjustment needed; standard dosing of 15-20 mg/kg every 8-12 hours 2
CrCl 30-50 mL/min: Extend interval to every 24 hours or reduce dose proportionally 1, 2
CrCl 10-30 mL/min: Extend interval to every 48-72 hours or give 250-1000 mg every several days 2
CrCl <10 mL/min or anuria: Give 1000 mg every 7-10 days after initial 15 mg/kg loading dose 2
Hemodialysis patients: Vancomycin clearance averages only 0.086 mL/min/kg; dosing should be 1000 mg every 7-10 days, administered after dialysis 2, 4
Target Trough Monitoring
Target trough levels of 15-20 mg/L for serious infections (bacteremia, endocarditis, osteomyelitis, meningitis, hospital-acquired pneumonia) to achieve AUC/MIC ratio >400 1, 3:
Measure trough levels before the fourth dose (at steady state), obtained 30 minutes before the next scheduled dose 3
Monitor trough levels before each dose adjustment and at least twice weekly throughout therapy 1
If trough exceeds 20 mg/L, immediately hold the next dose and recheck trough before administering subsequent doses 1
Once trough decreases to 15-20 mg/L, resume at reduced dose or extended interval 1
Critical Nephrotoxicity Prevention
Sustained trough concentrations >20 μg/mL exponentially increase nephrotoxicity risk without improving efficacy 5, 1:
Monitor serum creatinine at least twice weekly for nephrotoxicity, defined as ≥2-3 consecutive increases of ≥0.5 mg/dL or 150% increase from baseline 5, 1
Never combine vancomycin with aminoglycosides without compelling indication, as this combination dramatically increases nephrotoxicity and ototoxicity risk through additive tubular injury mechanisms 5
Concurrent nephrotoxic medications (loop diuretics, NSAIDs, contrast agents) amplify nephrotoxicity risk and warrant more frequent monitoring 5, 3
Special Populations Requiring Adjustment
Augmented renal clearance (CrCl >130 mL/min): Standard dosing results in subtherapeutic levels in 53.6% of patients; increase frequency to every 8 hours (15 mg/kg) to achieve AUC/MIC >400 in 82% of patients versus 46% with every 12-hour dosing 6
Critically ill patients: Continuous infusion protocols achieve target concentrations more rapidly in patients with kidney dysfunction compared to intermittent dosing, though 28% still develop supratherapeutic levels regardless of renal function 7
Elderly patients: Greater dosage reductions than expected may be necessary due to decreased renal function beyond what creatinine clearance estimates suggest 2
Common Pitfalls to Avoid
Never use standard nomograms in patients with renal impairment, as these were not designed to achieve current therapeutic targets (AUC/MIC >400) and will result in overdosing 1
Never continue the same dose when trough exceeds 20 mg/L, as this dramatically increases nephrotoxicity risk without clinical benefit 1
Never monitor peak levels, as this provides no clinical value and is not recommended by current guidelines 1
Never rely solely on serum creatinine in patients with changing renal function, shock, severe heart failure, oliguria, obesity, liver disease, edema, ascites, debilitation, or malnutrition, as calculated creatinine clearance overestimates actual clearance in these conditions 2
Alternative Therapy Considerations
When vancomycin MIC ≥2 mg/L, consider alternative therapies (linezolid, daptomycin, ceftaroline), as target AUC/MIC ratios of ≥400 are not achievable with conventional dosing in renal impairment without unacceptable nephrotoxicity risk 1, 3
Infusion Rate Requirements
Each dose should be administered over at least 60 minutes, or at a rate no faster than 10 mg/min, whichever is longer, to minimize infusion-related reactions 2. For doses exceeding 1 g, extend infusion time to 1.5-2 hours 3.