NEPHROTOXICITY OF GENTAMICIN AND VANCOMYCIN GIVEN ALONE AND IN COMBINATION AS DETERMINED BY ENZYMURIA AND CORTICAL ANTIBIOTIC LEVELS IN RATS

The purpose of this study was to compare the nephrotoxicity of gentami cin and vancomycin alone and in combination. Thirty-two male Sprague-D awley rats were randomized into 4 groups of 8 animals. Each group rece ived 200 mg/kg gentamicin (G) i.m., or 300 mg/kg vancomycin (V) i.v., or an association of 200 mg/kg gentamicin + 300 mg/kg vancomycin (i.m. and i.v., respectively), or 0.9% NaCl solution i.m. and i.v. (control s). To determine AAP, GGT, and NAG enzyme excretions, urine samples we re taken over 24-h periods before and after the start of the experimen t. A single renal cortical sample was obtained at necropsy far quantit ation of antibiotic levels. No significant modifications of urinary ex cretions of creatinine and enzymuria were noted during the 24-h period before each drug administration or in controls. AAP, GGT, and NAG exc retions were significantly increased after G and G + V injections (p < 0.001), whereas only AAP and GGT were statistically higher in rats re ceiving V (p < 0.05). NAG elimination (mean +/- SD) was higher in G V (16.0 +/- 0.2 IU/mmol creatinine/24 h; p < 0.001) than G (8.8 +/- 0. 6) or V (1.7 +/- 0.2). Surprisingly, mean vancomycin cortical levels d ecreased in the combination (827 +/- 131 cs. 1964 +/- 23 mu g/g for V alone; p < 0.001), whereas gentamicin concentration was unchanged (826 +/- 66 vs. 839 +/- 28 mu g/g for G alone). Determination of enzymuria allowed the nephrotoxicity of the antibiotics to be graded in the fol lowing order: vancomycin + gentamicin > gentamicin > vancomycin.