Evaluation of Vancomycin Bolus/Standard and Continuous Infusion on Nephrotoxicity in a Rat Model

Vancomycin continuous infusion (CI) has been associated with lower nephrotoxicity. This study compared a 3-minute bolus/standard infusion comparator (SI) with 24-hour CI in a validated rat model. Male Sprague-Dawley rats (n=14) received a target total dose of 150 mg/kg as a 3-minute intravenous bolus followed by a 24-hour saline infusion (SI, n=7) or as an initial loading administration followed by continuous infusion to 24 hours (CI, n=7). Urine and serial plasma samples were collected, and terminal whole-kidney homogenates were assayed for vancomycin. Day 1 urine output increased from baseline in SI animals (19.4 vs 8.9 mL/24 h; p<0.001) but not in CI animals (12.4 vs 10.1 mL/24 h; p=0.446). Urinary KIM-1 and clusterin excretion increased on Day 1 in SI compared with baseline and CI (both p<0.001). Median AUC_0-24h was 354.1 mg·h/L (IQR, 277.1-427.0) with SI and 379.9 mg·h/L (IQR, 337.7-500.9) with CI (exact Wilcoxon W=28; p=0.710). Whole-kidney vancomycin concentrations were numerically higher with SI (88.02 ± 85.12 vs 27.97 ± 18.74 µg/g; p=0.11). Urinary KIM-1 showed a four-parameter sigmoidal relationship with whole-kidney vancomycin concentration (R²=0.62). Continuous infusion was associated with lower biomarker-defined renal tubular stress and lower whole-kidney drug accumulation without a detectable difference in total systemic AUC_0-24h.