Abstract
A rat model was utilized to compare the nephrotoxic potential of gentamicin and tobramycin. Gentamicin, 40 mg/kg per day, predictably produced renal failure and morphological evidence of proximal tubular necrosis over 14 days of treatment. An identical dosage of tobramycin was associated with only minimal morphological changes and normal concentrations of serum creatinine and blood urea nitrogen. Similar results were obtained even after the tobramycin dosage was tripled to 120 mg/kg per day. A decrease in urine osmolality, mechanism unknown, was observed in all aminoglycoside-treated rats, but the lowest osmolalities were found in the gentamicin-treated rats. According to both histological criteria and renal function measurements, gentamicin was more nephrotoxic than tobramycin in this animal model.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Briedis D. J., Robson H. G. Comparative activity of netilmicin, gentamicin, amikacin, and tobramycin against Pseudomonas aeruginosa and Enterobacteriaceae. Antimicrob Agents Chemother. 1976 Oct;10(4):592–597. doi: 10.1128/aac.10.4.592. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brummett R. E., Himes D., Saine B., Vernon J. A comparative study of the ototoxicity of tobramycin and gentamicin. Arch Otolaryngol. 1972 Dec;96(6):505–512. doi: 10.1001/archotol.1972.00770090783003. [DOI] [PubMed] [Google Scholar]
- Cohen L., Lapkin R., Kaloyanides G. J. Effect of gentamicin on renal function in the rat. J Pharmacol Exp Ther. 1975 Apr;193(1):264–273. [PubMed] [Google Scholar]
- Davis S. D. Activity of gentamicin, tobramycin, polymyxin B, and colistimethate in mouse protection tests with Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1975 Jul;8(1):50–53. doi: 10.1128/aac.8.1.50. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HAUGEN H. N. The determination of endogenous creatinine in plasma and urine. Scand J Clin Lab Invest. 1953;5(1):48–57. doi: 10.3109/00365515309093511. [DOI] [PubMed] [Google Scholar]
- Houghton D. C., Hartnett M., Campbell-Boswell M., Porter G., Bennett W. A light and electron microscopic analysis of gentamicin nephrotoxicity in rats. Am J Pathol. 1976 Mar;82(3):589–612. [PMC free article] [PubMed] [Google Scholar]
- Israel K. S., Welles J. S., Black H. R. Aspects of the pharmacology and toxicology of tobramycin in animals and humans. J Infect Dis. 1976 Aug;134 (Suppl):S97–103. doi: 10.1093/infdis/134.supplement_1.s97. [DOI] [PubMed] [Google Scholar]
- Kosek J. C., Mazze R. I., Cousins M. J. Nephrotoxicity of gentamicin. Lab Invest. 1974 Jan;30(1):48–57. [PubMed] [Google Scholar]
- LUFT J. H. Improvements in epoxy resin embedding methods. J Biophys Biochem Cytol. 1961 Feb;9:409–414. doi: 10.1083/jcb.9.2.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Levison M. E., Kaye D. In vitro comparison of four aminoglycoside antibiotics: sisomicin, gentamicin, tobramycin, and BB-K8. Antimicrob Agents Chemother. 1974 Jun;5(6):667–669. doi: 10.1128/aac.5.6.667. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Luft F. C., Kleit S. A. Renal parenchymal accumulation of aminoglycoside antibiotics in rats. J Infect Dis. 1974 Dec;130(6):656–659. doi: 10.1093/infdis/130.6.656. [DOI] [PubMed] [Google Scholar]
- 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]
- Luft F. C., Patel V., Yum M. N., Patel B., Kleit S. A. Experimental aminoglycoside nephrotoxicity. J Lab Clin Med. 1975 Aug;86(2):213–220. [PubMed] [Google Scholar]
- Luft F. C., Yum M. N., Kleit S. A. Comparative nephrotoxicities of netilmicin and gentamicin in rats. Antimicrob Agents Chemother. 1976 Nov;10(5):845–849. doi: 10.1128/aac.10.5.845. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neu H. C. Tobramycin: an overview. J Infect Dis. 1976 Aug;134 (Suppl):S3–19. doi: 10.1093/infdis/134.supplement_1.s3. [DOI] [PubMed] [Google Scholar]
- Patel V., Luft F. C., Yum M. N., Patel B., Zeman W., Kleit S. A. Enzymuria in gentamicin-induced kidney damage. Antimicrob Agents Chemother. 1975 Mar;7(3):364–369. doi: 10.1128/aac.7.3.364. [DOI] [PMC free article] [PubMed] [Google Scholar]
- REYNOLDS E. S. The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol. 1963 Apr;17:208–212. doi: 10.1083/jcb.17.1.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Regamey C., Gordon R. C., Kirby W. M. Comparative pharmacokinetics of tobramycin and gentamicin. Clin Pharmacol Ther. 1973 May-Jun;14(3):396–403. doi: 10.1002/cpt1973143396. [DOI] [PubMed] [Google Scholar]
- Smith A. L., Smith D. H. Gentamicin:adenine mononucleotide transferase: partial purification, characterization, and use in the clinical quantitation of gentamicin. J Infect Dis. 1974 Apr;129(4):391–401. doi: 10.1093/infdis/129.4.391. [DOI] [PubMed] [Google Scholar]
- Smith C. R., Baughman K. L., Edwards C. Q., Rogers J. F., Lietman P. S. Controlled comparison of amikacin and gentamicin. N Engl J Med. 1977 Feb 17;296(7):349–353. doi: 10.1056/NEJM197702172960701. [DOI] [PubMed] [Google Scholar]
- Stevens P., Young L. S., Hewitt W. L. Radioimmunoassay, acetylating radio-enzymatic assay, and microbioassay of gentamicin: a comparative study. J Lab Clin Med. 1975 Aug;86(2):349–359. [PubMed] [Google Scholar]
- Szwed J. J., Luft F. C., Black H. R., Elliott R. A., Kleit S. A. Comparison of the distribution of tobramycin and gentamicin in body fluids of dogs. Antimicrob Agents Chemother. 1974 May;5(5):444–446. doi: 10.1128/aac.5.5.444. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vera-Roman J., Krishnakantha T. P., Cuppage F. E. Gentamicin nephrotoxicity in rats. I. Acute biochemical and ultrastructural effects. Lab Invest. 1975 Oct;33(4):412–417. [PubMed] [Google Scholar]
- Waitz J. A., Moss E. L., Jr, Drube C. G., Weinstein M. J. Comparative activity of sisomicin, gentamicin, kanamycin, and tobramycin. Antimicrob Agents Chemother. 1972 Dec;2(6):431–437. doi: 10.1128/aac.2.6.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Watanakunakorn C. Comparative in vitro activity of Sch 20656, netilmicin, gentamicin, and tobramycin. Antimicrob Agents Chemother. 1976 Aug;10(2):382–383. doi: 10.1128/aac.10.2.382. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wellwood J. M., Lovell D., Thompson A. E., Tighe J. R. Renal damage caused by gentamicin: a study of the effects on renal morphology and urinary enzyme excretion. J Pathol. 1976 Mar;118(3):171–182. doi: 10.1002/path.1711180307. [DOI] [PubMed] [Google Scholar]