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Risk factors for toxicity in elderly patients given aminoglycosides once daily

Journal of General Internal Medicine volume 13, pages 735–739 (1998)Cite this article

Abstract

OBJECTIVE: To determine the risk factors for aminoglycoside toxicity in the elderly.

DESIGN: Prospective observational study.

SETTING: Acute care teaching hospital serving predominantly veterans.

PARTICIPANTS: Consecutive patients aged 70 years and over receiving aminoglycosides.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Thirteen (15%) of 88 patients developed aminoglycoside-related nephrotoxicity and 3 (3.4%) developed otovestibular toxicity. Multivariate analysis showed that increasing duration of aminoglycoside therapy was the only factor significantly associated with development of toxicity. Elevated baseline serum creatinine level (p=.02) and use of allopurinol (p=.03) were risk factors specifically for nephrotoxicity. Only 2 (3.9%) of 51 patients receiving aminoglycosides 7 or fewer days developed nephrotoxicity, as compared with 11 (30%) of 37 receiving the drugs for 8 to 14 days and 4 (50%) of 8 treated for more than 14 days.

CONCLUSIONS: Although toxicity is common in elderly patients treated with aminoglycosides, limiting the duration of aminoglycoside therapy to less than a week can substantially reduce risk of toxicity.

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References

  1. Freeman CD, Nicolau DP, Belliveau PP, Nightingale CH. Oncedaily dosing of aminoglycosides: review and recommendations for clinical practice. J Antimicrob Chemother. 1997;39:677–86.

    PubMed  Article  CAS  Google Scholar 

  2. Cronin RE. Aminoglycoside nephrotoxicity: pathogenesis and prevention. Clin Nephrol. 1979;11:251–6.

    PubMed  CAS  Google Scholar 

  3. Moellering RC. Factors influencing the clinical use of antimicrobial agents in elderly patients. Geriatrics. 1978;33:83–91.

    PubMed  Google Scholar 

  4. Hilf M, Yu VL, Sharp J, Zuravleff JJ, Korvick JA, Muder RR. Antibiotic therapy for Pseudomonas aeruginosa bacteremia: outcome correlations in a prospective study of 200 patients. Am J Med. 1989;87:540–6.

    PubMed  CAS  Article  Google Scholar 

  5. Korvick JA, Bryan CS, Farber B, et al. Prospective observational study of Klebsiella bacteremia in 230 patients: outcome for antibiotic combinations versus monotherapy. Antimicrob Agents Chemother. 1992;36:2639–44.

    PubMed  CAS  Google Scholar 

  6. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31–41.

    PubMed  CAS  Article  Google Scholar 

  7. Koo J, Tight R, Rajkumar V, Hawa Z. Comparison of once-daily versus pharmacokinetic dosing of aminoglycosides in elderly patients. Am J Med. 1996;101:177–83.

    PubMed  Article  CAS  Google Scholar 

  8. Brummett RE, Fox KE. Aminoglycoside-induced hearing loss in humans. Antimicrob Agents Chemother. 1989;33:797–800.

    PubMed  CAS  Google Scholar 

  9. Turnidge J, Bell J, Mascaro L. The peak-AUC method for aminoglycoside dosage adjustment. Presented at the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, La, September 1996. Abstract A102.

  10. Marre R, Tarara N, Louton T, Sack K. Age-dependent nephrotoxicity and the pharmacokinetics of gentamicin in rats. Eur J Pediatr. 1980;133:25–9.

    PubMed  Article  CAS  Google Scholar 

  11. McMartin DN, Engel SG. Effect of aging on gentamicin nephrotoxicity and pharmacokinetics in rats. Res Commun Chem Pathol Pharmacol. 1982;38:193–207.

    PubMed  CAS  Google Scholar 

  12. Rowe JW. Clinical research on aging: strategies and directions. N Engl J Med. 1977;297:1332–6.

    PubMed  Article  Google Scholar 

  13. Cuppage FE, Setter K, Sullivan LP, Reitzes E, Melnykovych A. Gentamicin nephrotoxicity. Physiological, biochemical and morphological effects of prolonged administration to rats. Virchows Arch B Cell Pathol. 1977;234:121–38.

    Google Scholar 

  14. Houghton DC, English J, Bennett WM. Chronic tubulointerstitial nephritis and renal insufficiency associated with long-term “subtherapeutic” gentamicin. J Lab Clin Med. 1988;112:694–703.

    PubMed  CAS  Google Scholar 

  15. Ter Braak EW, DeVries PJ, Bouter KP, Van Der Vegt SG, Dorrestein GC, Nortier JW. Once-daily dosing regimen for aminoglycosides plus beta-lactam combination therapy of serious bacterial infections: comparative trial with netilmicin plus ceftriaxone. Am J Med. 1990;89:58–66.

    PubMed  Article  Google Scholar 

  16. Moore RD, Smith CR, Lipsky JJ, Mellits ED, Lietman PS. Risk factors for nephrotoxicity in patients treated with aminoglycosides. Ann Intern Med. 1984;100:352–7.

    PubMed  CAS  Google Scholar 

  17. Nicolau DP, Freeman CD, Belliveau PP, Nightingale CH, Ross JW, Quintiliani R. Experience with a once-daily aminoglycoside program administered to 2184 adult patients. Antimicrob Agents Chemother. 1995;39:650–5.

    PubMed  CAS  Google Scholar 

  18. Prins JM, Weverling GJ, De Blok K, Van Ketel R, Speelman P. Validation and nephrotoxicity of a simplified once-daily aminoglycoside dosing schedule and guidelines for monitoring therapy. Antimicrob Agents Chemother. 1996;40:2494–9.

    PubMed  CAS  Google Scholar 

  19. Giuliano RA, Verpooten GA, DeBroe ME. The effect of dosing strategy on kidney cortical accumulation of aminoglycosides in rats. Am J Kidney Dis. 1986;8:297–303.

    PubMed  CAS  Google Scholar 

  20. Lane AZ, Wright GE, Blair DC. Ototoxicity and nephrotoxicity of amikacin: an overview of phase II and phase III experience in the United States. Am J Med. 1977;62:911–8.

    PubMed  Article  CAS  Google Scholar 

  21. Schimpf SC, Gaya H, Klastersky J, Zinner SH. Three antibiotic regimens in the treatment of infection in febrile granulocytopenic patients with cancer. The EORTC International Antimicrobial Therapy Project Group. J Infect Dis. 1978;137:14–29.

    Google Scholar 

  22. Bertino JS, Booker LA, Franck PA, et al. Incidence of and significant risk factors for aminoglycoside-associated nephrotoxicity in patients dosed by using individualized pharmacokinetic monitoring. J Infect Dis. 1993;167:173–9.

    PubMed  Google Scholar 

  23. Farber BF, Moellering RC. Retrospective study of the toxicity of preparations of vancomycin from 1974–1981. Antimicrob Agents Chemother. 1983;23:138–41.

    PubMed  CAS  Google Scholar 

  24. Rybak MJ, Albrecht LM, Boike SC, et al. Nephrotoxicity of vancomycin alone and with an aminoglycoside. J Antimicrob Chemother. 1990;25:679–87.

    PubMed  Article  CAS  Google Scholar 

  25. Emmerson BT. The management of gout. N Engl J Med. 1996;334:445–51.

    PubMed  Article  CAS  Google Scholar 

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Authors and Affiliations

  1. the Infectious Disease Section, VA Medical Center, University Dr. C, 15240, Pittsburgh, PA

    David L. Paterson MBBS, FRACP & Marilyn M. Wagener MPH

  2. Drs. J.J. Sullivan, N.J. Nicolaides, and Partners, Taringa, Brisbane, Australia

    Jennifer M. B. Robson MBBS, FRACP, FRCPA

Authors
  1. David L. Paterson MBBS, FRACP
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  2. Jennifer M. B. Robson MBBS, FRACP, FRCPA
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  3. Marilyn M. Wagener MPH
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Paterson, D.L., Robson, J.M.B. & Wagener, M.M. Risk factors for toxicity in elderly patients given aminoglycosides once daily. J GEN INTERN MED 13, 735–739 (1998). https://doi.org/10.1046/j.1525-1497.1998.00224.x

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  • DOI: https://doi.org/10.1046/j.1525-1497.1998.00224.x

Key words

  • aminoglycosides
  • gentamicin
  • nephrotoxicity
  • elderly