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. 1977 Oct;12(4):465–469. doi: 10.1128/aac.12.4.465

Effect of Cefamandole Nafate on the Toxicity of Tobramycin

J S Wold 1, S A Turnipseed 1, W D Broddle 1, N V Owen 1
PMCID: PMC429947  PMID: 921240

Abstract

Because of the potential for an interaction between cephalosporins and aminoglycosides leading to renal injury, an evaluation of the effect of a new cephalosporin, cefamandole nafate, on the toxicity of the aminoglycoside tobramycin was performed in laboratory animals. High doses of cefamandole nafate did not increase the acute toxicity (lethality) of tobramycin in rats or mice. In a subacute experiment in rats, dose-related tobramycin nephrotoxicity, as evidenced by blood urea nitrogen changes, increased kidney weights, and histologically determined tubular nephrosis and necrosis, was observed. Concomitant treatment with cefamandole nafate, 500 mg/kg, did not increase tobramycin nephrotoxicity, but protected against the aminoglycoside-induced renal injury. Determination of tissue radioactivity after administration of [14C]tobramycin indicated that cefamandole nafate treatment resulted in uniformly lower tobramycin tissue concentrations compared with the control, suggesting that the protective effect was produced by enhanced excretion of tobramycin after cefamandole nafate treatment.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bennett W. M., Hartnett M. N., Gilbert D., Houghton D., Porter G. A. Effect of sodium intake on gentamicin nephrotoxicity in the rat. Proc Soc Exp Biol Med. 1976 Apr;151(4):736–738. doi: 10.3181/00379727-151-39296. [DOI] [PubMed] [Google Scholar]
  2. Bobrow S. N., Jaffe E., Young R. C. Anuria and acute tubular necrosis associated with gentamicin and cephalothin. JAMA. 1972 Dec 18;222(12):1546–1547. [PubMed] [Google Scholar]
  3. Cabanillas F., Burgos R. C., Rodríguez C., Baldizón C. Nephrotoxicity of combined cephalothin-gentamicin regimen. Arch Intern Med. 1975 Jun;135(6):850–852. [PubMed] [Google Scholar]
  4. Dellinger P., Murphy T., Barza M., Pinn V., Weinstein L. Effect of cephalothin on renal cortical concentrations of gentamicin in rats. Antimicrob Agents Chemother. 1976 Apr;9(4):587–588. doi: 10.1128/aac.9.4.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dellinger P., Murphy T., Pinn V., Barza M., Weinstein L. Protective effect of cephalothin against gentamincin-induced nephrotoxicity in rats. Antimicrob Agents Chemother. 1976 Jan;9(1):172–178. doi: 10.1128/aac.9.1.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fanning W. L., Gump D., Jick H. Gentamicin- and cephalothin-associated rises in blood urea nitrogen. Antimicrob Agents Chemother. 1976 Jul;10(1):80–82. doi: 10.1128/aac.10.1.80. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fillastre J. P., Laumonier R., Humbert G., Dubois D., Metayer J., Delpech A., Leroy J., Robert M. Acute renal failure associated with combined gentamicin and cephalothin therapy. Br Med J. 1973 May 19;2(5863):396–397. doi: 10.1136/bmj.2.5863.396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Harrison W. O., Silverblatt F. J., Turck M. Gentamicin nephrotoxicity: failure of three cephalosporins to potentiate injury in rats. Antimicrob Agents Chemother. 1975 Aug;8(2):209–215. doi: 10.1128/aac.8.2.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Indelicato J. M., Wilham W. L., Cerimele B. J. Conversion of cefamandole nafate to cefamandole sodium. J Pharm Sci. 1976 Aug;65(8):1175–1178. doi: 10.1002/jps.2600650811. [DOI] [PubMed] [Google Scholar]
  10. Kleinknecht D., Ganeval D., Droz D. Acute renal failure after high doses of gentamicin and cephalothin. Lancet. 1973 May 19;1(7812):1129–1129. doi: 10.1016/s0140-6736(73)90447-9. [DOI] [PubMed] [Google Scholar]
  11. Luft F. C., Patel V., Yum M. N., Kleit S. A. Nephrotoxicity of cephalosporin-gentamicin combinations in rats. Antimicrob Agents Chemother. 1976 May;9(5):831–839. doi: 10.1128/aac.9.5.831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. MARSH W. H., FINGERHUT B., MILLER H. AUTOMATED AND MANUAL DIRECT METHODS FOR THE DETERMINATION OF BLOOD UREA. Clin Chem. 1965 Jun;11:624–627. [PubMed] [Google Scholar]
  13. Opitz A., Herrmann I., van Herrath D., Schaefer K. Akute Niereninsuffizienz nach Gentamycin-Cephalosporin-Kombinationstherapie. Med Welt. 1971 Mar 13;11:434–438. [PubMed] [Google Scholar]
  14. Plager J. E. Association of renal injury with combined cephalothin-gentamicin therapy among patients severely ill with malignant disease. Cancer. 1976 Apr;37(4):1937–1943. doi: 10.1002/1097-0142(197604)37:4<1937::aid-cncr2820370445>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  15. Welles J. S., Emmerson J. L., Gibson W. R., Nickander R., Owen N. V., Anderson R. C. Preclinical toxicology studies with tobramycin. Toxicol Appl Pharmacol. 1973 Jul;25(3):398–409. doi: 10.1016/0041-008x(73)90313-x. [DOI] [PubMed] [Google Scholar]
  16. Wick W. E., Preston D. A. Biological properties of three 3-heterocyclic-thiomethyl cephalosporin antibiotics. Antimicrob Agents Chemother. 1972 Mar;1(3):221–234. doi: 10.1128/aac.1.3.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Wilhelm J., Sack K. Tierexperimentelle Studie zur Frage der Nephrotoxizität von Cephalotin und Cephalotin-Aminoglykosid-Kombinationen. Infection. 1975;3(2):89–95. doi: 10.1007/BF01641048. [DOI] [PubMed] [Google Scholar]

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