Skip to main content
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1995 Jun;39(6):597–603.

Aminoglycosides--50 years on.

E J Begg 1, M L Barclay 1
PMCID: PMC1365070  PMID: 7654476

Abstract

1. The aminoglycoside antibiotics are 50 years old. Their success and continuing use can be attributed to various factors including rapid concentration-dependent bactericidal effect, synergism with beta-lactam antibiotics, clinical effectiveness, a low rate of true resistance and low cost. 2. The aminoglycosides remain drugs of choice in many circumstances including septicaemia, other serious infections due to Gram negative bacilli, and bacterial endocarditis. 3. Nephrotoxicity and ototoxicity have been the main drawbacks clinically for the aminoglycosides. 4. There has been an evolution in dosing strategies largely aimed at reducing toxicity. Therapeutic drug monitoring has been used extensively to assist dosing, and target concentrations have been advocated, such as peak concentrations of between 6 and 10 mg l-1 and through concentrations of < 2 mg l-1 for gentamicin, tobramycin and netilmicin. 5. Recently there has been a minor revolution in the approach to aminoglycoside dosing, with a change to larger doses, given less frequently. In its most convenient form this is 'Once-daily aminoglycoside dosing'. It offers the hope of better efficacy, less toxicity, and easier administration and monitoring. 6. This article summarises the background of aminoglycoside usage, leading up to the recent changes in dosing strategy.

Full text

PDF
603

Selected References

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

  1. Anderson R. J., Linas S. L., Berns A. S., Henrich W. L., Miller T. R., Gabow P. A., Schrier R. W. Nonoliguric acute renal failure. N Engl J Med. 1977 May 19;296(20):1134–1138. doi: 10.1056/NEJM197705192962002. [DOI] [PubMed] [Google Scholar]
  2. Appel G. B. Aminoglycoside nephrotoxicity. Am J Med. 1990 Mar 23;88(3C):16S–42S. doi: 10.1016/0002-9343(90)90082-o. [DOI] [PubMed] [Google Scholar]
  3. Barclay M. L., Begg E. J. Aminoglycoside toxicity and relation to dose regimen. Adverse Drug React Toxicol Rev. 1994 Winter;13(4):207–234. [PubMed] [Google Scholar]
  4. Barclay M. L., Begg E. J., Chambers S. T. Adaptive resistance following single doses of gentamicin in a dynamic in vitro model. Antimicrob Agents Chemother. 1992 Sep;36(9):1951–1957. doi: 10.1128/aac.36.9.1951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barclay M. L., Begg E. J., Hickling K. G. What is the evidence for once-daily aminoglycoside therapy? Clin Pharmacokinet. 1994 Jul;27(1):32–48. doi: 10.2165/00003088-199427010-00004. [DOI] [PubMed] [Google Scholar]
  6. Barza M., Brown R. B., Shen D., Gibaldi M., Weinstein L. Predictability of blood levels of gentamicin in man. J Infect Dis. 1975 Aug;132(2):165–174. doi: 10.1093/infdis/132.2.165. [DOI] [PubMed] [Google Scholar]
  7. Beaubien A. R., Desjardins S., Ormsby E., Bayne A., Carrier K., Cauchy M. J., Henri R., Hodgen M., Salley J., St Pierre A. Incidence of amikacin ototoxicity: a sigmoid function of total drug exposure independent of plasma levels. Am J Otolaryngol. 1989 Jul-Aug;10(4):234–243. doi: 10.1016/0196-0709(89)90002-1. [DOI] [PubMed] [Google Scholar]
  8. Beckhouse M. J., Whyte I. M., Byth P. L., Napier J. C., Smith A. J. Altered aminoglycoside pharmacokinetics in the critically ill. Anaesth Intensive Care. 1988 Nov;16(4):418–422. doi: 10.1177/0310057X8801600406. [DOI] [PubMed] [Google Scholar]
  9. Begg E. J., Atkinson H. C., Jeffery G. M., Taylor N. W. Individualised aminoglycoside dosage based on pharmacokinetic analysis is superior to dosage based on physician intuition at achieving target plasma drug concentrations. Br J Clin Pharmacol. 1989 Aug;28(2):137–141. doi: 10.1111/j.1365-2125.1989.tb05405.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Begg E. J., Peddie B. A., Chambers S. T., Boswell D. R. Comparison of gentamicin dosing regimens using an in-vitro model. J Antimicrob Chemother. 1992 Apr;29(4):427–433. doi: 10.1093/jac/29.4.427. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Bertino J. S., Jr, Booker L. A., Franck P. A., Jenkins P. L., Franck K. R., Nafziger A. N. Incidence of and significant risk factors for aminoglycoside-associated nephrotoxicity in patients dosed by using individualized pharmacokinetic monitoring. J Infect Dis. 1993 Jan;167(1):173–179. doi: 10.1093/infdis/167.1.173. [DOI] [PubMed] [Google Scholar]
  13. Blaser J. Efficacy of once- and thrice-daily dosing of aminoglycosides in in-vitro models of infection. J Antimicrob Chemother. 1991 May;27 (Suppl 100):21–28. doi: 10.1093/jac/27.suppl_c.21. [DOI] [PubMed] [Google Scholar]
  14. Bleich H. L., Boro E. S., Rowe J. W. Clinical research on aging: strategies and directions. N Engl J Med. 1977 Dec 15;297(24):1332–1336. doi: 10.1056/NEJM197712152972406. [DOI] [PubMed] [Google Scholar]
  15. Brummett R. E., Fox K. E. Aminoglycoside-induced hearing loss in humans. Antimicrob Agents Chemother. 1989 Jun;33(6):797–800. doi: 10.1128/aac.33.6.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Bryan L. E. General mechanisms of resistance to antibiotics. J Antimicrob Chemother. 1988 Jul;22 (Suppl A):1–15. doi: 10.1093/jac/22.supplement_a.1. [DOI] [PubMed] [Google Scholar]
  17. Bryan L. E., Van den Elzen H. M. Streptomycin accumulation in susceptible and resistant strains of Escherichia coli and Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1976 Jun;9(6):928–938. doi: 10.1128/aac.9.6.928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Burton M. E., Brater D. C., Chen P. S., Day R. B., Huber P. J., Vasko M. R. A Bayesian feedback method of aminoglycoside dosing. Clin Pharmacol Ther. 1985 Mar;37(3):349–357. doi: 10.1038/clpt.1985.51. [DOI] [PubMed] [Google Scholar]
  19. Burton M. E., Vasko M. R., Brater D. C. Comparison of drug dosing methods. Clin Pharmacokinet. 1985 Jan-Feb;10(1):1–37. doi: 10.2165/00003088-198510010-00001. [DOI] [PubMed] [Google Scholar]
  20. Counts G. W., Blair A. D., Wagner K. F., Turck M. Gentamicin and tobramycin Kinetics. Clin Pharmacol Ther. 1982 May;31(5):662–668. doi: 10.1038/clpt.1982.92. [DOI] [PubMed] [Google Scholar]
  21. Craig W. A., Redington J., Ebert S. C. Pharmacodynamics of amikacin in vitro and in mouse thigh and lung infections. J Antimicrob Chemother. 1991 May;27 (Suppl 100):29–40. doi: 10.1093/jac/27.suppl_c.29. [DOI] [PubMed] [Google Scholar]
  22. Dahlgren J. G., Anderson E. T., Hewitt W. L. Gentamicin blood levels: a guide to nephrotoxicity. Antimicrob Agents Chemother. 1975 Jul;8(1):58–62. doi: 10.1128/aac.8.1.58. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Daikos G. L., Jackson G. G., Lolans V. T., Livermore D. M. Adaptive resistance to aminoglycoside antibiotics from first-exposure down-regulation. J Infect Dis. 1990 Aug;162(2):414–420. doi: 10.1093/infdis/162.2.414. [DOI] [PubMed] [Google Scholar]
  24. Daikos G. L., Lolans V. T., Jackson G. G. First-exposure adaptive resistance to aminoglycoside antibiotics in vivo with meaning for optimal clinical use. Antimicrob Agents Chemother. 1991 Jan;35(1):117–123. doi: 10.1128/aac.35.1.117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Dasta J. F., Armstrong D. K. Variability in aminoglycoside pharmacokinetics in critically ill surgical patients. Crit Care Med. 1988 Apr;16(4):327–330. doi: 10.1097/00003246-198804000-00004. [DOI] [PubMed] [Google Scholar]
  26. Denaro C. P., Ravenscroft P. J. Comparison of Sawchuk-Zaske and Bayesian forecasting for aminoglycosides in seriously ill patients. Br J Clin Pharmacol. 1989 Jul;28(1):37–44. doi: 10.1111/j.1365-2125.1989.tb03503.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Dudley M. N., Zinner S. H. Single daily dosing of amikacin in an in-vitro model. J Antimicrob Chemother. 1991 May;27 (Suppl 100):15–19. doi: 10.1093/jac/27.suppl_c.15. [DOI] [PubMed] [Google Scholar]
  28. Efficacy and toxicity of single daily doses of amikacin and ceftriaxone versus multiple daily doses of amikacin and ceftazidime for infection in patients with cancer and granulocytopenia. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer. Ann Intern Med. 1993 Oct 1;119(7 Pt 1):584–593. doi: 10.7326/0003-4819-119-7_Part_1-199310010-00006. [DOI] [PubMed] [Google Scholar]
  29. Fee W. E., Jr Aminoglycoside ototoxicity in the human. Laryngoscope. 1980 Oct;90(10 Pt 2 Suppl 24):1–19. doi: 10.1288/00005537-198010001-00001. [DOI] [PubMed] [Google Scholar]
  30. Fischel-Ghodsian N., Prezant T. R., Bu X., Oztas S. Mitochondrial ribosomal RNA gene mutation in a patient with sporadic aminoglycoside ototoxicity. Am J Otolaryngol. 1993 Nov-Dec;14(6):399–403. doi: 10.1016/0196-0709(93)90113-l. [DOI] [PubMed] [Google Scholar]
  31. Ganesan M. G., Weiner N. D., Schacht J. Effects of calcium and neomycin on phase behavior of phospholipid bilayers. J Pharm Sci. 1983 Dec;72(12):1465–1467. doi: 10.1002/jps.2600721224. [DOI] [PubMed] [Google Scholar]
  32. Gilleland L. B., Gilleland H. E., Gibson J. A., Champlin F. R. Adaptive resistance to aminoglycoside antibiotics in Pseudomonas aeruginosa. J Med Microbiol. 1989 May;29(1):41–50. doi: 10.1099/00222615-29-1-41. [DOI] [PubMed] [Google Scholar]
  33. Gingell J. C., Chisholm G. D., Calnan J. S., Waterworth P. M. The dose, distribution, and excretion of gentamicin with speical reference to renal failure. J Infect Dis. 1969 Apr-May;119(4):396–401. doi: 10.1093/infdis/119.4-5.396. [DOI] [PubMed] [Google Scholar]
  34. Giuliano R. A., Verpooten G. A., Verbist L., Wedeen R. P., De Broe M. E. In vivo uptake kinetics of aminoglycosides in the kidney cortex of rats. J Pharmacol Exp Ther. 1986 Feb;236(2):470–475. [PubMed] [Google Scholar]
  35. Govaerts P. J., Claes J., van de Heyning P. H., Jorens P. G., Marquet J., De Broe M. E. Aminoglycoside-induced ototoxicity. Toxicol Lett. 1990 Aug;52(3):227–251. doi: 10.1016/0378-4274(90)90033-i. [DOI] [PubMed] [Google Scholar]
  36. Hickling K. G., Begg E. J., Perry R. E., Atkinson H. C., Sharman J. R. Serum aminoglycoside clearance is predicted as poorly by renal aminoglycoside clearance as by creatinine clearance in critically ill patients. Crit Care Med. 1991 Aug;19(8):1041–1047. doi: 10.1097/00003246-199108000-00012. [DOI] [PubMed] [Google Scholar]
  37. Hickling K., Begg E., Moore M. L. A prospective randomised trial comparing individualised pharmacokinetic dosage prediction for aminoglycosides with prediction based on estimated creatinine clearance in critically ill patients. Intensive Care Med. 1989;15(4):233–237. doi: 10.1007/BF00271057. [DOI] [PubMed] [Google Scholar]
  38. Higgins C. E., Kastner R. E. Nebramycin, a new broad-spectrum antibiotic complex. II. Description of Streptomyces tenebrarius. Antimicrob Agents Chemother (Bethesda) 1967;7:324–331. [PubMed] [Google Scholar]
  39. Hoffa D. E. Serial pharmacokinetic dosing of aminoglycosides: a community hospital experience. Ther Drug Monit. 1989 Sep;11(5):574–579. [PubMed] [Google Scholar]
  40. Hu D. N., Qui W. Q., Wu B. T., Fang L. Z., Zhou F., Gu Y. P., Zhang Q. H., Yan J. H., Ding Y. Q., Wong H. Genetic aspects of antibiotic induced deafness: mitochondrial inheritance. J Med Genet. 1991 Feb;28(2):79–83. doi: 10.1136/jmg.28.2.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Ibrahim S., Derde M. P., Kaufman L., Clerckx-Braun F., Jacqmin P., Brulein V., Donnez J., Tulkens P. M. Safety, pharmacokinetics and efficacy of once-a-day netilmicin and amikacin versus their conventional schedules in patients suffering from pelvic inflammatory disease. Ren Fail. 1990;12(3):199–203. doi: 10.3109/08860229009065564. [DOI] [PubMed] [Google Scholar]
  42. Jackson G. G., Arcieri G. Ototoxicity of gentamicin in man: a survey and controlled analysis of clinical experience in the United States. J Infect Dis. 1971 Dec;124 (Suppl):S130–S137. doi: 10.1093/infdis/124.supplement_1.s130. [DOI] [PubMed] [Google Scholar]
  43. Josepovitz C., Levine R., Farruggella T., Kaloyanides G. J. Comparative effects of aminoglycosides on renal cortical and urinary phospholipids in the rat. Proc Soc Exp Biol Med. 1986 May;182(1):1–5. doi: 10.3181/00379727-182-42300. [DOI] [PubMed] [Google Scholar]
  44. Kabins S. A., Nathan C., Cohen S. In vitro comparison of netilmicin, a semisynthetic derivative of sisomicin, and four other aminoglycoside antibiotics. Antimicrob Agents Chemother. 1976 Jul;10(1):139–145. doi: 10.1128/aac.10.1.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Kadurugamuwa J. L., Clarke A. J., Beveridge T. J. Surface action of gentamicin on Pseudomonas aeruginosa. J Bacteriol. 1993 Sep;175(18):5798–5805. doi: 10.1128/jb.175.18.5798-5805.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Kapusnik J. E., Hackbarth C. J., Chambers H. F., Carpenter T., Sande M. A. Single, large, daily dosing versus intermittent dosing of tobramycin for treating experimental pseudomonas pneumonia. J Infect Dis. 1988 Jul;158(1):7–12. doi: 10.1093/infdis/158.1.7. [DOI] [PubMed] [Google Scholar]
  47. Kawaguchi H., Naito T., Nakagawa S., Fujisawa K. I. BB-K 8, a new semisynthetic aminoglycoside antibiotic. J Antibiot (Tokyo) 1972 Dec;25(12):695–708. doi: 10.7164/antibiotics.25.695. [DOI] [PubMed] [Google Scholar]
  48. Kloth D. D., Tegtmeier B. R., Kong C., Akahoshi M. P., Leach S. H., Beatty J. D., Zaia J. A. Altered gentamicin pharmacokinetics during the perioperative period. Clin Pharm. 1985 Mar-Apr;4(2):182–185. [PubMed] [Google Scholar]
  49. Koup J. R., Killen T., Bauer L. A. Multiple-dose non-linear regression analysis program. Aminoglycoside dose prediction. Clin Pharmacokinet. 1983 Sep-Oct;8(5):456–462. doi: 10.2165/00003088-198308050-00006. [DOI] [PubMed] [Google Scholar]
  50. Lerner A. M., Reyes M. P., Cone L. A., Blair D. C., Jansen W., Wright G. E., Lorber R. R. Randomised, controlled trial of the comparative efficacy, auditory toxicity, and nephrotoxicity of tobramycin and netilmicin. Lancet. 1983 May 21;1(8334):1123–1126. doi: 10.1016/s0140-6736(83)92864-7. [DOI] [PubMed] [Google Scholar]
  51. Lodhi S., Weiner N. D., Schacht J. Interactions of neomycin with monomolecular films of polyphosphoinositides and other lipids. Biochim Biophys Acta. 1979 Oct 19;557(1):1–8. doi: 10.1016/0005-2736(79)90084-1. [DOI] [PubMed] [Google Scholar]
  52. Luft F. C., Bloch R., Sloan R. S., Yum M. N., Costello R., Maxwell D. R. Comparative nephrotoxicity of aminoglycoside antibiotics in rats. J Infect Dis. 1978 Oct;138(4):541–545. doi: 10.1093/infdis/138.4.541. [DOI] [PubMed] [Google Scholar]
  53. Luft F. C. Clinical significance of renal changes engendered by aminoglycosides in man. J Antimicrob Chemother. 1984 Jan;13 (Suppl A):23–30. doi: 10.1093/jac/13.suppl_a.23. [DOI] [PubMed] [Google Scholar]
  54. Mattie H., Craig W. A., Pechère J. C. Determinants of efficacy and toxicity of aminoglycosides. J Antimicrob Chemother. 1989 Sep;24(3):281–293. doi: 10.1093/jac/24.3.281. [DOI] [PubMed] [Google Scholar]
  55. Matz G. J. Aminoglycoside cochlear ototoxicity. Otolaryngol Clin North Am. 1993 Oct;26(5):705–712. [PubMed] [Google Scholar]
  56. Moore R. D., Smith C. R., Lietman P. S. Association of aminoglycoside plasma levels with therapeutic outcome in gram-negative pneumonia. Am J Med. 1984 Oct;77(4):657–662. doi: 10.1016/0002-9343(84)90358-9. [DOI] [PubMed] [Google Scholar]
  57. Moore R. D., Smith C. R., Lietman P. S. The association of aminoglycoside plasma levels with mortality in patients with gram-negative bacteremia. J Infect Dis. 1984 Mar;149(3):443–448. doi: 10.1093/infdis/149.3.443. [DOI] [PubMed] [Google Scholar]
  58. Moore R. D., Smith C. R., Lipsky J. J., Mellits E. D., Lietman P. S. Risk factors for nephrotoxicity in patients treated with aminoglycosides. Ann Intern Med. 1984 Mar;100(3):352–357. doi: 10.7326/0003-4819-100-3-352. [DOI] [PubMed] [Google Scholar]
  59. Noone P., Parsons T. M., Pattison J. R., Slack R. C., Garfield-Davies D., Hughes K. Experience in monitoring gentamicin therapy during treatment of serious gram-negative sepsis. Br Med J. 1974 Mar 16;1(5906):477–481. doi: 10.1136/bmj.1.5906.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Perkins M. W. Failure of a nomogram to achieve target aminoglycoside concentrations. Br J Clin Pharmacol. 1990 Apr;29(4):495–496. doi: 10.1111/j.1365-2125.1990.tb03670.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Prins J. M., Büller H. R., Kuijper E. J., Tange R. A., Speelman P. Once versus thrice daily gentamicin in patients with serious infections. Lancet. 1993 Feb 6;341(8841):335–339. doi: 10.1016/0140-6736(93)90137-6. [DOI] [PubMed] [Google Scholar]
  62. Reed R. L., 2nd, Wu A. H., Miller-Crotchett P., Crotchett J., Fischer R. P. Pharmacokinetic monitoring of nephrotoxic antibiotics in surgical intensive care patients. J Trauma. 1989 Nov;29(11):1462–1470. doi: 10.1097/00005373-198911000-00002. [DOI] [PubMed] [Google Scholar]
  63. Rescott D. L., Nix D. E., Holden P., Schentag J. J. Comparison of two methods for determining in vitro postantibiotic effects of three antibiotics on Escherichia coli. Antimicrob Agents Chemother. 1988 Apr;32(4):450–453. doi: 10.1128/aac.32.4.450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Rodvold K. A., Blum R. A. Predictive performance of Sawchuk-Zaske and Bayesian dosing methods for tobramycin. J Clin Pharmacol. 1987 May-Jun;27(5):419–424. doi: 10.1002/j.1552-4604.1987.tb03042.x. [DOI] [PubMed] [Google Scholar]
  65. Rodvold K. A., Pryka R. D., Kuehl P. G., Blum R. A., Donahue P. Bayesian forecasting of serum gentamicin concentrations in intensive care patients. Clin Pharmacokinet. 1990 May;18(5):409–418. doi: 10.2165/00003088-199018050-00005. [DOI] [PubMed] [Google Scholar]
  66. Sawchuk R. J., Zaske D. E., Cipolle R. J., Wargin W. A., Strate R. G. Kinetic model for gentamicin dosing with the use of individual patient parameters. Clin Pharmacol Ther. 1977 Mar;21(3):362–369. doi: 10.1002/cpt1977213362. [DOI] [PubMed] [Google Scholar]
  67. Schacht J. Biochemical basis of aminoglycoside ototoxicity. Otolaryngol Clin North Am. 1993 Oct;26(5):845–856. [PubMed] [Google Scholar]
  68. Schentag J. J., Jusko W. J., Vance J. W., Cumbo T. J., Abrutyn E., DeLattre M., Gerbracht L. M. Gentamicin disposition and tissue accumulation on multiple dosing. J Pharmacokinet Biopharm. 1977 Dec;5(6):559–577. doi: 10.1007/BF01059684. [DOI] [PubMed] [Google Scholar]
  69. Schwartz J. H., Schein P. Fanconi syndrome associated with cephalothin and gentamicin therapy. Cancer. 1978 Feb;41(2):769–772. doi: 10.1002/1097-0142(197802)41:2<769::aid-cncr2820410251>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
  70. Sheiner L. B., Beal S. L. Bayesian individualization of pharmacokinetics: simple implementation and comparison with non-Bayesian methods. J Pharm Sci. 1982 Dec;71(12):1344–1348. doi: 10.1002/jps.2600711209. [DOI] [PubMed] [Google Scholar]
  71. Sheiner L. B., Beal S., Rosenberg B., Marathe V. V. Forecasting individual pharmacokinetics. Clin Pharmacol Ther. 1979 Sep;26(3):294–305. doi: 10.1002/cpt1979263294. [DOI] [PubMed] [Google Scholar]
  72. Simon A., d'Aubrac C. A., Safran C., Carbon C. Cefotaxime optimal dosage in adult patients. A reappraisal. Drugs. 1988;35 (Suppl 2):221–230. doi: 10.2165/00003495-198800352-00049. [DOI] [PubMed] [Google Scholar]
  73. 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]
  74. Smith C. R., Lipsky J. J., Laskin O. L., Hellmann D. B., Mellits E. D., Longstreth J., Lietman P. S. Double-blind comparison of the nephrotoxicity and auditory toxicity of gentamicin and tobramycin. N Engl J Med. 1980 May 15;302(20):1106–1109. doi: 10.1056/NEJM198005153022002. [DOI] [PubMed] [Google Scholar]
  75. Summer W. R., Michael J. R., Lipsky J. J. Initial aminoglycoside levels in the critically ill. Crit Care Med. 1983 Dec;11(12):948–950. doi: 10.1097/00003246-198312000-00011. [DOI] [PubMed] [Google Scholar]
  76. Takada A., Schacht J. Calcium antagonism and reversibility of gentamicin-induced loss of cochlear microphonics in the guinea pig. Hear Res. 1982 Oct;8(2):179–186. doi: 10.1016/0378-5955(82)90073-9. [DOI] [PubMed] [Google Scholar]
  77. Tofte R. W., Canafax D. M., Simmons R. L., Peterson P. K. Aminoglycoside dosing in renal transplant patients. Comparison of nomogram and individualized pharmacokinetic methods in patients with shifting renal function. Ann Surg. 1982 Mar;195(3):287–293. doi: 10.1097/00000658-198203000-00008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Townsend P. L., Fink M. P., Stein K. L., Murphy S. G. Aminoglycoside pharmacokinetics: dosage requirements and nephrotoxicity in trauma patients. Crit Care Med. 1989 Feb;17(2):154–157. [PubMed] [Google Scholar]
  79. Tran Ba Huy P., Bernard P., Schacht J. Kinetics of gentamicin uptake and release in the rat. Comparison of inner ear tissues and fluids with other organs. J Clin Invest. 1986 May;77(5):1492–1500. doi: 10.1172/JCI112463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Triginer C., Izquierdo I., Fernández R., Rello J., Torrent J., Benito S., Net A. Gentamicin volume of distribution in critically ill septic patients. Intensive Care Med. 1990;16(5):303–306. doi: 10.1007/BF01706354. [DOI] [PubMed] [Google Scholar]
  81. UMEZAWA H., UEDA M., MAEDA K., YAGISHITA K., KONDO S., OKAMI Y., UTAHARA R., OSATO Y., NITTA K., TAKEUCHI T. Production and isolation of a new antibiotic: kanamycin. J Antibiot (Tokyo) 1957 Sep;10(5):181–188. [PubMed] [Google Scholar]
  82. Van der Auwera P., Meunier F., Ibrahim S., Kaufman L., Derde M. P., Tulkens P. M. Pharmacodynamic parameters and toxicity of netilmicin (6 milligrams/kilogram/day) given once daily or in three divided doses to cancer patients with urinary tract infection. Antimicrob Agents Chemother. 1991 Apr;35(4):640–647. doi: 10.1128/aac.35.4.640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Vogelman B., Craig W. A. Kinetics of antimicrobial activity. J Pediatr. 1986 May;108(5 Pt 2):835–840. doi: 10.1016/s0022-3476(86)80754-5. [DOI] [PubMed] [Google Scholar]
  84. Vogelman B., Gudmundsson S., Turnidge J., Leggett J., Craig W. A. In vivo postantibiotic effect in a thigh infection in neutropenic mice. J Infect Dis. 1988 Feb;157(2):287–298. doi: 10.1093/infdis/157.2.287. [DOI] [PubMed] [Google Scholar]
  85. WEINSTEIN M. J., LUEDEMANN G. M., ODEN E. M., WAGMAN G. H., ROSSELET J. P., MARQUEZ J. A., CONIGLIO C. T., CHARNEY W., HERZOG H. L., BLACK J. GENTAMICIN, A NEW ANTIBIOTIC COMPLEX FROM MICROMONOSPORA. J Med Chem. 1963 Jul;6:463–464. doi: 10.1021/jm00340a034. [DOI] [PubMed] [Google Scholar]
  86. Waksman S. A., Lechevalier H. A. Neomycin, a New Antibiotic Active against Streptomycin-Resistant Bacteria, including Tuberculosis Organisms. Science. 1949 Mar 25;109(2830):305–307. doi: 10.1126/science.109.2830.305. [DOI] [PubMed] [Google Scholar]
  87. Wilkinson P. M., Gorst D. W., Tooth J. A., Delamore I. W. The management of fever in blood dyscrasias: results of a prospective controlled trial of a prescribing aid for gentamicin. J Antimicrob Chemother. 1977 Jul;3(4):297–303. doi: 10.1093/jac/3.4.297. [DOI] [PubMed] [Google Scholar]
  88. Williams P. D., Bennett D. B., Gleason C. R., Hottendorf G. H. Correlation between renal membrane binding and nephrotoxicity of aminoglycosides. Antimicrob Agents Chemother. 1987 Apr;31(4):570–574. doi: 10.1128/aac.31.4.570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Zaske D. E., Cipolle R. J., Rotschafer J. C., Solem L. D., Mosier N. R., Strate R. G. Gentamicin pharmacokinetics in 1,640 patients: method for control of serum concentrations. Antimicrob Agents Chemother. 1982 Mar;21(3):407–411. doi: 10.1128/aac.21.3.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. ter Braak E. W., de Vries P. J., Bouter K. P., van der Vegt S. G., Dorrestein G. C., Nortier J. W., van Dijk A., Verkooyen R. P., Verbrugh H. A. Once-daily dosing regimen for aminoglycoside plus beta-lactam combination therapy of serious bacterial infections: comparative trial with netilmicin plus ceftriaxone. Am J Med. 1990 Jul;89(1):58–66. doi: 10.1016/0002-9343(90)90099-y. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES