Nephrotoxicity of cephalosporin antibiotics in experimental animals.

Abstract

To delineate the site and morphology of renal lesions produced by cephalosporin antibiotics, rabbits and rats were treated with various doses of either cephalothin, cephaloridine, or cefazolin. In rabbits, a single 200 mg/kg injection of cephaloridine, administered in a previous study conducted in our laboratory, resulted in renal tubular necrosis in each of six animals treated, whereas in the present study, 500 mg of cefazolin/kg caused less extensive lesions and not in all rabbits. In rats treated with 250 mg of cephaloridine/kg per day for 28 days, two of 40 developed tubular injury, whereas no lesions were observed by light microscopy in rats treated with cephalothin or cefazolin. A daily dosage of 1,100 mg of cephalothin/kg administered to rats for 28 days produced no renal lesions; abnormalities were observed in the tubules after treatment with cephaloridine and cefazolin. When 2,200 mg of cephaloridine/kg was administered daily to rats for only five days, all developed massive tubular necrosis, whereas treatment with cephalothin and cefazolin resulted in only subtle abnormalities. These data demonstrate that cephaloridine produces a dose-dependent lesion of the proximal renal tubule in the rabbit and rat. The lesions produced by cefazolin are less marked, and only subtle changes are observed with cephalothin. The use of cephalosporin antibiotics in clinical practice has been purported to carry with it the hazard of nephrotoxicity. Several authors have reported acute tubular necrosis following the use of cephaloridine [1-3], and cephalothin also has been incriminated to a lesser extent in the production of injury to renal tubules [4, 5]. The present study compares the potential for nephrotoxicity of three cephalosporin antibiotics, cephalothin, cephaloridine and cefazolin, in experiments involving both short- and long-term therapy. In a previous report from this laboratory [6], fixation of renal tissue by intravascular perfusion was employed to define early and subtle changes in renal tubules caused by cephaloridine. The same technique, utilized in the present series of experiments, permitted detailed examination of renal tubules and avoided the artifacts produced during fixation by immersion procedures. This