Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1986 Jul;30(1):20–24. doi: 10.1128/aac.30.1.20

Vancomycin enhancement of experimental tobramycin nephrotoxicity.

C A Wood, S J Kohlhepp, P W Kohnen, D C Houghton, D N Gilbert
PMCID: PMC176427  PMID: 3752981

Abstract

The influence of vancomycin on tobramycin nephrotoxicity was assessed in male Fischer rats. Treatment groups included controls receiving diluent and groups receiving vancomycin alone at a dosage of 200 mg/kg (body weight) per day, tobramycin alone at a dosage of 80 mg/kg per day, and a combination of vancomycin and tobramycin at the above dosages. All regimens were injected on a twice-a-day schedule. The animals were sacrificed on days 1, 3, 10, 14, 17, and 21. When compared with controls, animals receiving vancomycin alone exhibited no detectable renal toxicity. Compared with the case with controls, tobramycin alone was toxic, as manifested by lower mean animal weights, increased blood urea nitrogen concentrations on days 14 and 17 (P less than 0.005), increased serum creatinine concentrations on days 17 and 21 (P less than 0.005), and the presence of renal cortical tubular necrosis and regeneration. When compared with tobramycin alone, the combination of vancomycin and tobramycin caused earlier and more severe toxicity. By day 10, the magnitude of weight loss, the rise in blood urea nitrogen, and the increase in serum creatinine concentration were all greater in the rats given the combination of vancomycin plus tobramycin than in the animals given tobramycin alone (P less than 0.005). In addition, there was more proximal tubular necrosis and regeneration in rats given vancomycin plus tobramycin compared with those given tobramycin alone. In this animal model, vancomycin alone caused no detectable renal injury, tobramycin alone produced minimal proximal tubular damage, and the combination of vancomycin and tobramycin resulted in a greater degree of kidney injury than observed with tobramycin alone.

Full text

PDF
20

Selected References

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

  1. Appel G. B., Neu H. C. The nephrotoxicity of antimicrobial agents (second of three parts). N Engl J Med. 1977 Mar 31;296(13):722–728. doi: 10.1056/NEJM197703312961305. [DOI] [PubMed] [Google Scholar]
  2. Aronoff G. R., Sloan R. S., Dinwiddie C. B., Jr, Glant M. D., Fineberg N. S., Luft F. C. Effects of vancomycin on renal function in rats. Antimicrob Agents Chemother. 1981 Feb;19(2):306–308. doi: 10.1128/aac.19.2.306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Farber B. F., Moellering R. C., Jr Retrospective study of the toxicity of preparations of vancomycin from 1974 to 1981. Antimicrob Agents Chemother. 1983 Jan;23(1):138–141. doi: 10.1128/aac.23.1.138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Geraci J. E., Hermans P. E. Vancomycin. Mayo Clin Proc. 1983 Feb;58(2):88–91. [PubMed] [Google Scholar]
  5. Gilbert D. N., Plamp C., Starr P., Bennet W. M., Houghton D. C., Porter G. Comparative nephrotoxicity of gentamicin and tobramycin in rats. Antimicrob Agents Chemother. 1978 Jan;13(1):34–40. doi: 10.1128/aac.13.1.34. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Griffith R. S. Vancomycin use--an historical review. J Antimicrob Chemother. 1984 Dec;14 (Suppl 500):1–5. doi: 10.1093/jac/14.suppl_d.1. [DOI] [PubMed] [Google Scholar]
  7. Herzstein J., Ryan J. L., Mangi R. J., Greco T. P., Andriole V. T. Optimal therapy for enterococcal endocarditis. Am J Med. 1984 Feb;76(2):186–191. doi: 10.1016/0002-9343(84)90772-1. [DOI] [PubMed] [Google Scholar]
  8. Karchmer A. W., Archer G. L., Dismukes W. E. Staphylococcus epidermidis causing prosthetic valve endocarditis: microbiologic and clinical observations as guides to therapy. Ann Intern Med. 1983 Apr;98(4):447–455. doi: 10.7326/0003-4819-98-4-447. [DOI] [PubMed] [Google Scholar]
  9. Levine D. P., Cushing R. D., Jui J., Brown W. J. Community-acquired methicillin-resistant Staphylococcus aureus endocarditis in the Detroit Medical Center. Ann Intern Med. 1982 Sep;97(3):330–338. doi: 10.7326/0003-4819-97-3-330. [DOI] [PubMed] [Google Scholar]
  10. Marre R., Schulz E., Anders T., Sack K. Renal tolerance and pharmacokinetics of vancomycin in rats. J Antimicrob Chemother. 1984 Sep;14(3):253–260. doi: 10.1093/jac/14.3.253. [DOI] [PubMed] [Google Scholar]
  11. Mellor J. A., Kingdom J., Cafferkey M., Keane C. T. Vancomycin toxicity: a prospective study. J Antimicrob Chemother. 1985 Jun;15(6):773–780. doi: 10.1093/jac/15.6.773. [DOI] [PubMed] [Google Scholar]
  12. Sorrell T. C., Collignon P. J. A prospective study of adverse reactions associated with vancomycin therapy. J Antimicrob Chemother. 1985 Aug;16(2):235–241. doi: 10.1093/jac/16.2.235. [DOI] [PubMed] [Google Scholar]
  13. WOODLEY D. W., HALL W. H. The treatment of severe staphylococcal infections with vancomycin. Ann Intern Med. 1961 Aug;55:235–249. doi: 10.7326/0003-4819-55-2-235. [DOI] [PubMed] [Google Scholar]
  14. Wilkowske C. J. Enterococcal endocarditis. Mayo Clin Proc. 1982 Feb;57(2):101–105. [PubMed] [Google Scholar]
  15. Wold J. S., Turnipseed S. A. Toxicology of vancomycin in laboratory animals. Rev Infect Dis. 1981 Nov-Dec;3 Suppl:S224–S229. [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES