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Antimicrob Agents Chemother. 1975 August; 8(2): 209-215
Copyright © 1975 American Society for Microbiology. All Rights Reserved.

Gentamicin Nephrotoxicity: Failure of Three Cephalosporins to Potentiate Injury in Rats

William O. Harrison, Fredric J. Silverblatt1 and Marvin Turck

Veterans Administration Hospital, Seattle, Washington, 98108
Department of Medicine, University of Washington School of Medicine, Seattle, Washington, 98195

ABSTRACT

The possibility that gentamicin and cephalosporin antibiotics may act synergistically to produce nephrotoxicity was evaluated in an experimental model. Necrosis of the proximal tubules occurred when rats were treated with 60 to 120 mg/kg of gentamicin for 5 days but not when 15 to 20 mg/kg per day was given for up to 4 weeks. In all gentamicin-treated animals lysosomes of proximal tubules were increased in size and number and the lumens of many tubules contained a granular deposit. Examination by electron microscopy revealed that the abnormal lysosomes contained membranous whorls. The luminal deposits consisted of similar material; identical bodies were also present in the urinary sediment. To determine whether concurrent administration of a cephalosporin would augment the nephrotoxic potential of gentamicin, additional rats were treated for 4 weeks with daily injections of gentamicin (20 mg/kg) and either cephaloridine, cephalothin, or cefazolin (500 mg/kg). None of the combination regimens produced any more injury than did gentamicin alone.

FOOTNOTES

1 Present address: Department of Medicine, University of Tennessee, Center for the Health Sciences, Memphis, Tenn. 38163.

Antimicrob Agents Chemother. 1975 August; 8(2): 209-215
Copyright © 1975 American Society for Microbiology. All Rights Reserved.





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Copyright © 1975 by the American Society for Microbiology. All rights reserved.