Nephrotoxicity of newer cephalosporins and aminoglycosides alone and in combination in a rat model

Abstract

Aminoglycosides were administered subcutaneously twice daily for 10 days to Fischer 344 rats. The rank order of nephrotoxicity of the drugs, as judged by histologic change and the development of azotemia, was gentamicin > tobramycin > netilmicin. Amikacin, given in twice the dosage, caused damage which was intermediate between that of tobramycin and netilmicin. When cephalothin, cefamandole, or cefazolin was given concomitantly, the combination of cephalo-sporin plus aminoglycoside generally produced significantly less nephrotoxicity than the aminoglycoside alone. Cefazolin was the least protective cephalosporin. There was a marked correspondence between the reduction of nephrotoxicity and diminished cortical concentrations of aminoglycoside in animals given concomitant cephalosporins.