The influence of cephem antibiotics on gentamicin nephrotoxicity in normal, acidotic, dehydrated, and unilaterally nephrectomized rats.

Normal, acidotic, dehydrated, or unilaterally nephrectomized rats (Sprague-Dawley) were injected with gentamicin (80 mg/kg/day) alone or in combination with cefoxitin (2 g/kg/day), cephalothin (2 g/kg/day), or cephaloridine (1 g/kg/day) once daily for 10 consecutive days. Serum creatinine levels and renal cortical concentrations of gentamicin were determined and histopathological examination of the kidneys was made. Gentamicin caused marked renal damage in all the groups of rats. In normal rats, all the cephem antibiotics significantly reduced both gentamicin nephrotoxicity and renal gentamicin levels. In acidotic, dehydrated, and unilaterally nephrectomized rats, cefoxitin still significantly reduced gentamicin nephrotoxicity without affecting renal gentamicin concentration, whereas cephalothin and cephaloridine did not show any significant reduction of nephrotoxicity or gentamicin concentration, but rather caused general deterioration of the animals. Hence, the intrinsic nephrotoxic potential of cefoxitin, cephalothin, and cephaloridine may contribute to the difference in the combined effect rather than the concentration of gentamicin in the kidney.