Clinical Pharmacokinetics

, Volume 27, Issue 1, pp 32–48 | Cite as

What is the Evidence for Once-Daily Aminoglycoside Therapy?

  • Murray L. Barclay
  • Evan J. Begg
  • Keith G. Hickling
Review Article Drug Disposition


Aminoglycosides are important antibacterial agents for the treatment of serious infection. Evidence suggests that high peak plasma concentrations must be achieved early in the course of treatment if these agents are to be effective, but prolonged high concentrations may cause ototoxicity and nephrotoxicity. Peak plasma concentrations of 6 to 10 mg/L and trough concentrations of less than 2 mg/L for gentamicin and tobramycin have been traditional goals of therapy. Extensive recent evidence from in vitro, animal and human studies suggests that these target concentrations need revision.

Aminoglycosides display concentration-dependent bacterial killing, have a long postantibiotic effect, and induce adaptive resistance in Gram-negative bacteria. All of these factors support the use of larger doses of aminoglycosides that are given less frequently than conventional therapy. Studies in vitro support this approach, showing greater activity when aminoglycosides are given less frequently. Animal studies comparing different dosage intervals have shown varying results, with only a slight bias favouring the longer dosage interval. However, the short elimination half-lives for the drugs in animals limit the applicability of these models to humans. Importantly, there is convincing evidence in animal studies that nephrotoxicity and ototoxicity are both reduced when the same total daily dose is administered in less frequent doses.

There have been at least 29 clinical trials comparing once-daily administration of aminoglycosides with conventional administration 2 to 4 times daily. In general, efficacy has not been shown to be different between regimens, although one trial showed an advantage for once-daily administration compared with administration 3 times daily. A small number of trials have shown less nephrotoxicity and ototoxicity with once-daily administration, leading several authors to suggest that there is sufficient evidence to warrant a change to once-daily administration of aminoglycosides. However, once-daily administration has not been well studied in the paediatric population, or in patients with renal failure or endocarditis, and cannot be recommended in these patients as yet.

The choice of a 24-hour dosage interval is somewhat arbitrary, and the optimal interval may not necessarily be 24 hours. No studies have included dosage adjustment based on pharmacokinetic modelling methods, and the effect of this on treatment outcome needs to be assessed. The best method of administering aminoglycosides once daily is yet to be determined.


Adis International Limited Gentamicin Aminoglycoside Amikacin Tobramycin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Jackson GG, Arcieri G. Ototoxicity of gentamicin in man: A survey and controlled analysis of clinical experience in the United States. J Infect Dis 1971; 124 Suppl.: S130–7PubMedCrossRefGoogle Scholar
  2. 2.
    Waitz JA, Moss EL, Weinstein MJ. Aspect of the chronic toxicity of gentamicin sulphate in cats. J Infect Dis 1971; 124 Suppl.: S125–9PubMedCrossRefGoogle Scholar
  3. 3.
    Black RE, Lau WK, Weinstein RJ, et al. Ototoxicity of amikacin. Antimicrob Agents Chemother 1976; 9: 956–61PubMedCrossRefGoogle Scholar
  4. 4.
    Goodman EL, Van Gelder J, Holmes R. Prospective comparative study of variable dosage and variable frequency regimens. Antimicrob Agents Chemother 1975; 8: 434–8PubMedCrossRefGoogle Scholar
  5. 5.
    Sawyers CL, Moore RD, Lerner SA, et al. A model for predicting nephrotoxicity in patients treated with aminoglycosides. J Infect Dis 1986; 153: 1062–8PubMedCrossRefGoogle Scholar
  6. 6.
    Barza M, Brown RB, Shen D, et al. Predictability of blood levels of gentamicin in man. J Infect Dis 1975; 132: 165–74PubMedCrossRefGoogle Scholar
  7. 7.
    Dahlgren JG, Anderson ET, Hewitt WL. Gentamicin blood levels: A guide to nephrotoxicity. Antimicrob Agents Chemother 1975; 8: 58–62PubMedCrossRefGoogle Scholar
  8. 8.
    Hewitt WL. Gentamicin toxicity in perspective. Post Grad Med J 1974; 50S: 55–9Google Scholar
  9. 9.
    Wenk W, Vozeh S, Follath F. Serum level monitoring of antibacterial drugs: a review. Clin Pharmacokinet 1984; 9: 475–92PubMedCrossRefGoogle Scholar
  10. 10.
    Moore RD, Smith CR, Lipsky JJ, et al. Risk factors for nephrotoxicity in patients treated with aminoglycosides. Ann Intern Med 1984; 100: 352–7PubMedGoogle Scholar
  11. 11.
    Moore RD, Smith CR, Lietman PS. The association of plasma levels with therapeutic outcome in gram negative pneumonia. Am J Med 1984; 77: 657–62PubMedCrossRefGoogle Scholar
  12. 12.
    Noone P, Parsons TMC, Pattison JR, et al. Experience in monitoring gentamicin therapy during treatment of serious gram negative sepsis. BMJ 1974; 1: 477–81PubMedCrossRefGoogle Scholar
  13. 13.
    Moore RD, Smith CR, Lietman PS. The association of aminoglycoside plasma levels with mortality in patients with Gram-negative bacteremia. J Infect Dis 1984; 149: 443–8PubMedCrossRefGoogle Scholar
  14. 14.
    Neu HC. Chemotherapy of infections. In: Braunwalde et al. (Eds) Harrisons Principles of Internal Medicine. 11th Ed. New York: McGraw-Hill, 1987: 485–502Google Scholar
  15. 15.
    Lietman PS. Aminoglycosides and spectinomycin: aminocyclitols. In: Mandell et al. (Eds) Principles and Practice of Infectious Diseases. Edinburgh: Churchill Livingstone, 1990: 269–84Google Scholar
  16. 16.
    Burton ME, Vasko MR, Brater DC. Comparison of drug dosing methods. Clin Pharmacokinet 1985; 10: 1–37PubMedCrossRefGoogle Scholar
  17. 17.
    Sawchuk RJ, Zaske DE, Cipolle RJ, et al. Kinetic model for gentamicin with the use of individual patient parameters. Clin Pharmacol Ther 1977; 21: 362–9PubMedGoogle Scholar
  18. 18.
    Begg EJ, Atkinson HC, Jeffery M, et al. Individualised aminoglycoside dosing based on pharmacokinetic analysis is superior to dosage based on physician intuition at achieving target plasma drug concentrations. Br J Clin Pharmacol 1989; 28: 137–41PubMedCrossRefGoogle Scholar
  19. 19.
    Erdman SM, Rodvold KA, Pryka RD. An updated comparison of drug dosing methods. Part III: aminoglycoside antibiotics. Clin Pharmacokinet 1991; 20: 374–88PubMedCrossRefGoogle Scholar
  20. 20.
    Vogelman BS, Craig WA. Kinetics of antimicrobial activity. J Pediatr 1986; 108: 835–40PubMedCrossRefGoogle Scholar
  21. 21.
    Dudley MN, Zinner SH. Single daily dosing of amikacin in an in-vitro model. J Antimicrob Chemother 1991; 27 Suppl. C: 15–9PubMedGoogle Scholar
  22. 22.
    Kapusnik JE, Hackbarth CJ, Chambers HF, et al. Single, large, daily dosing versus intermittent dosing of tobramycin for treating experimental Pseudomonas pneumonia. J Infect Dis 1988; 158: 7–12PubMedCrossRefGoogle Scholar
  23. 23.
    Ericsson CD, Fischer RP, Rowlands BJ, et al. Prophylactic antibiotics in trauma: The hazards of underdosing. J Trauma 1989; 29: 1356–61PubMedCrossRefGoogle Scholar
  24. 24.
    Mattie H, Craig WA, Pechere PC. Determinants of efficacy and toxicity of aminoglycosides. J Antimicrob Chemother 1989; 24: 281–93PubMedCrossRefGoogle Scholar
  25. 25.
    Rescott DL, Nix DE, Holden P, et al. Comparison of two methods for determining in vitro postantibiotic effects of three antibiotics on Escherichia coli. Antimicrob Agents Chemother 1988; 32: 450–3PubMedCrossRefGoogle Scholar
  26. 26.
    Vogelman B, Gudmundsson S, Turnidge J, et al. In vivo postantibiotic effect in a thigh infection in neutropenic mice. J Infect Dis 1988; 157: 287–98PubMedCrossRefGoogle Scholar
  27. 27.
    Craig WA, Redington J, Ebert SC. Pharmacodynamics of amikacin in vitro and in mouse thigh and lung infections. J Antimicrob Chemother 1991; 27 Suppl. C: 29–40PubMedGoogle Scholar
  28. 28.
    Blaser J. Efficacy of once- and thrice-daily dosing of aminoglycosides in in-vitro models of infection. J Antimicrob Chemother 1991; 27 Suppl. C: 21–8PubMedGoogle Scholar
  29. 29.
    Begg EJ, Peddie BA, Chambers ST, et al. Comparison of gentamicin dosing regimens using an in-vitro model. J Antimicrob Chemother 1992; 29: 427–33PubMedCrossRefGoogle Scholar
  30. 30.
    Daikos GL, Jackson GG, Lolans VT, et al. Adaptive resistance to aminoglycoside antibiotics from first-exposure down-regulation. J Infect Dis 1990; 162: 414–20PubMedCrossRefGoogle Scholar
  31. 31.
    Daikos GL, Lolans VT, Jackson GG. First-exposure adaptive resistance to aminoglycosides in vivo with meaning for optimal clinical use. Antimicrob Agents and Chemother 1991; 35: 117–23CrossRefGoogle Scholar
  32. 32.
    Barclay ML, Begg EJ, Chambers ST. Adaptive resistance following single doses of gentamicin in a dynamic in vitro model. Antimicrob Agents Chemother 1992; 36: 1951–7PubMedCrossRefGoogle Scholar
  33. 33.
    Gilleland LB, Gilleland HE, Gibson JA, et al. Adaptive resistance to aminoglycoside antibiotics in Pseudomonas aeruginosa. J Med Microbiol 1989; 29(1): 41–50PubMedCrossRefGoogle Scholar
  34. 34.
    Blaser J, Stone BB, Zinner SH. Efficacy of intermittent versus continuous administration of netilmicin in a two-compartment in vitro model. Antimicrob Agents Chemother 1985; 27: 343–9PubMedCrossRefGoogle Scholar
  35. 35.
    Blaser J, Stone BB, Groner MC, et al. Impact of netilmicin regimens on the activities of ceftazidime-netilmicin combinations against Pseudomonas aeruginosa in an in vitro pharmacokinetic model. Antimicrob Agents Chemother 1985; 28: 64–68PubMedCrossRefGoogle Scholar
  36. 36.
    Powell S, Thompson W, Luthe M, et al. Once-daily vs continuous aminoglycoside dosing: Efficacy and toxicity in animal and clinical studies of gentamicin, netilmicin and tobramycin. J Infect Dis 1983; 147(5): 918–32PubMedCrossRefGoogle Scholar
  37. 37.
    Gerber AU, Craig WA, Brugger HP, et al. Impact of dosing intervals on activity of gentamicin and ticarcillin against Pseudomonas aeruginosa in granulocytopenic mice. J Infect Dis 1983; 147: 910–7PubMedCrossRefGoogle Scholar
  38. 38.
    Mordend JJ, Quintiliani R, Nightingale CH. Combination antibiotic therapy: Comparison of constant infusion and intermittent bolus dosing in an experimental animal model. J Antimicrob Chemother 1985; 15 Suppl A: 313–21Google Scholar
  39. 39.
    Kapusnik JE, Sande MA. Novel approaches for the use of aminoglycosides: The value of experimental models. J Antimicrob Chemother 1986; 17 Suppl A: 7–10PubMedGoogle Scholar
  40. 40.
    Pechere M, Letarte R, Pechere J-C. Efficacy of different dosing schedules of tobramycin for treating a murine Klebsiella pneumoniae bronchopneumonia. J Antimicrob Chemother 1987; 19: 487–91PubMedCrossRefGoogle Scholar
  41. 41.
    Herscovici L, Grise G, Thauvin C, et al. Efficacy and safety of once daily versus intermittent dosing of tobramycin in rabbits with acute pyelonephritis. Scand J Infect Dis 1988; 20: 205–12PubMedCrossRefGoogle Scholar
  42. 42.
    Wood CA, Norton DR, Kohlhepp SJ, et al. The influence of tobramycin dosing regimens on nephrotoxicity, ototoxicity, and antibacterial efficacy in a rat model of subcutaneous abscess. J Infect Dis 1988; 158: 13–22PubMedCrossRefGoogle Scholar
  43. 43.
    Weber M, Voirot P, Dopff C, et al. In vivo bactericidal activity of an oxacillin-netilmicin combination against Staphylococcus aureus. Influence of the rhythm of netilmicin administration. Pathol Biol 1988; 36: 389–93PubMedGoogle Scholar
  44. 44.
    Gerber AU. Comparison of once-daily versus thrice-daily human equivalent dosing of aminoglycosides: Basic considerations and experimental approach. J Drug Dev 1988; 1 Suppl. 3: 17–23Google Scholar
  45. 45.
    Gerber AU, Kozak S, Segessenmann C, et al. Once-daily versus thrice-daily administration of netilmicin in combination therapy of Pseudomonas aeruginosa infection in a man-adapted neutropenic animal model. Eur J Clin Microbiol Infect Dis 1989; 8(3): 233–7PubMedCrossRefGoogle Scholar
  46. 46.
    Gerber AU, Stritzko T, Segessenmann C, et al. Simulation of human pharmacokinetic profiles in mice, and impact on antimicrobial efficacy of netilmicin, ticarcillin and ceftazidime in the peritonitis-septicaemia model. Scand J Infect Dis 1990; 74: 195–203Google Scholar
  47. 47.
    Fantin B, Carbon C. Importance of the aminoglycoside dosing regimen in the penicillin-netilmicin combination for treatment of Enterococcus faecalis-induced experimental endocarditis. Antimicrob Agents Chemother 1990; 34: 2387–91PubMedCrossRefGoogle Scholar
  48. 48.
    Potel G, Caillon J, Fantin B, et al. Impact of dosage schedule on the efficacy of gentamicin, tobramycin, or amikacin in an experimental model of Serratia marcescens endocarditis: In vitro-in vivo correlation. Antimicrob Agents Chemother 1991; 35: 111–6PubMedCrossRefGoogle Scholar
  49. 49.
    Saleh-Mghir A, Cremieux A, Vallois J, et al. Optimal aminoglycoside dosing regimen for penicillin-tobramycin synergism in experimental Streptococcus adjacens endocarditis. Antimicrob Agents Chemother 1992; 36: 2403–7PubMedCrossRefGoogle Scholar
  50. 50.
    Craig WA, Leggett J, Totsuka K, et al. Key pharmacokinetic parameters of antibiotic efficacy in experimental animal infections. J Drug Dev 1988; 1 Suppl. 3: 7–15Google Scholar
  51. 51.
    Hottendorf GH, Gordon LL. Comparative low-dose nephrotoxicities of gentamicin, tobramycin, and amikacin. Antimicrob Agents Chemother 1980; 18: 176–81PubMedCrossRefGoogle Scholar
  52. 52.
    Luft FC. The nephrotoxic potential of netilmicin as determined in a rat model. Scand J Infect Dis 1980; 12 Suppl. 23: 82–90Google Scholar
  53. 53.
    Olier B, Viotte G, Morin JP, et al. Influence of dosage regimen on experimental tobramycin nephrotoxicity. Chemotherapy 1983; 29: 385–94PubMedCrossRefGoogle Scholar
  54. 54.
    Luft FC, Bloch R, Sloan RS, et al. Comparative nephrotoxicity of aminoglycoside antibiotics in rats. J Infect Dis 1978; 138: 541–5PubMedCrossRefGoogle Scholar
  55. 55.
    Giuliano RA, Verpooten GA, Verbist L, et al. In vivo uptake kinetics of aminoglycosides in the kidney cortex of rats. J Pharmacol Exp Ther 1986; 236: 470–5PubMedGoogle Scholar
  56. 56.
    Frame PT, Phair JP, Watanakunakorn C, et al. Pharmacologic factors associated with gentamicin nephrotoxicity in rabbits. J Infect Dis 1977; 135: 952–6PubMedCrossRefGoogle Scholar
  57. 57.
    Reiner NE, Bloxham DD, Thompson WL. Nephrotoxicity of gentamicin and tobramycin given once daily or continuously in dogs. J Antimicrob Chemother 1978; 4 Suppl. A: 85–101PubMedGoogle Scholar
  58. 58.
    Bennett WA, Plamp CE, Gilbert DN, et al. The influence of dosage regimen on experimental gentamicin nephrotoxicity: Dissociation of peak serum levels from renal failure. J Infect Dis 1979; 140: 576–80PubMedCrossRefGoogle Scholar
  59. 59.
    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: 297–303PubMedGoogle Scholar
  60. 60.
    Davis RR, Brummett RE, Bendrick TW, et al. Dissociation of maximum concentration of kanamycin in plasma and perilymph from ototoxic effect. J Antimicrob Chemother 1984; 14: 291–302PubMedCrossRefGoogle Scholar
  61. 61.
    Bamonte F, Dionisotti S, Gambia M, et al. Relation of dosing regimen to aminoglycoside ototoxicity: Evaluation of auditory damage in the guinea pig. Chemotherapy 1990; 36: 41–50PubMedCrossRefGoogle Scholar
  62. 62.
    Takumida M, Nishida I, Nikaido M, et al. Effect of dosing schedule on aminoglycoside ototoxicity: Comparative cochlear ototoxicity of amikacin and isepamicin. ORL; J Otorhinolaryngology and Its Related Specialities 1990; 52: 341–9CrossRefGoogle Scholar
  63. 63.
    Brownell WE, Bader CR, Bertrand D, et al. Evoked mechanical responses of isolated cochlear outer hair cells. Science 1985; 1227: 194–6CrossRefGoogle Scholar
  64. 64.
    Zenner HP, Zimmermann U, Schmitt U. Reversible contraction of isolated mammalian cochlear hair cells. Hear Res 1985; 18: 127–33PubMedCrossRefGoogle Scholar
  65. 65.
    Dulon D, Hayashida T, Hiel H, et al. Uptake of gentamicin and modifications to function of the sensory cochlear hair cells in vitro and in vivo. In vitro methods of pharmaco-toxicology, Paris 3–4 March 1988. Cytotechnology 1988; Suppl. (June) 39Google Scholar
  66. 66.
    Hayashida T, Nomura Y, Iwamori M, et al. Distribution of gentamicin by immunofluorescence in the guinea pig inner ear. Arch Otorhinolaryngology 1985; 242: 257–64CrossRefGoogle Scholar
  67. 67.
    Aran JM, Dulon D, Erre JP, et al. Evidence that gentamicin acts directly on the hair cells of the cochlea. Aphysiopathological, immunohistochemical and radioautographic study in the guinea pig. J Physiol 1988; 406, 58Google Scholar
  68. 68.
    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; 77: 1492–500PubMedCrossRefGoogle Scholar
  69. 69.
    Dulon D, Aran JM, Zajic G, et al. Comparative uptake of gentamicin, netilmicin, and amikacin in the guinea pig cochlea and vestibule. Antimicrob Agents Chemother 1986; 30: 96–100PubMedCrossRefGoogle Scholar
  70. 70.
    Brummett RE, Fox KE, Bendrick TW, et al. Ototoxicity of tobramycin, gentamicin, amikacin, and sisomicin in the guinea pig. J Antimicrob Chemother 1978; 4 Suppl. A: 73–84PubMedGoogle Scholar
  71. 71.
    Aran JM, Erre JP, Guilhaume A, et al. The comparative ototoxicities of gentamicin, tobramycin and dibekacin in the guinea pig. A functional and morphological cochlear and vestibular study. Acta Otolaryngol 1982; 390 (Suppl): 1–30CrossRefGoogle Scholar
  72. 72.
    De Broe ME, Verbist L, Verpooten GA. Influence of dosage schedule on renal cortical accumulation of amikacin and tobramycin in man. J Antimicrob Chemother 1991; 27 (Suppl. C): 41–7PubMedGoogle Scholar
  73. 73.
    Verpooten GA, Giuliano RA, Verbist L, et al. Once-daily dosing decreases renal accumulation of gentamicin and netilmicin. Clin Pharmacol Ther 1989; 45: 22–7PubMedCrossRefGoogle Scholar
  74. 74.
    Giacoia GP, Schentag JJ. Pharmacokinetics and nephrotoxicity of continuous intravenous infusion of gentamicin in low birth weight infants. J Pediatr 1986; 109: 715–9PubMedCrossRefGoogle Scholar
  75. 75.
    Proctor L, Petty B, Thakor R, et al. A study of the potential vestibulotoxic effects of once daily versus thrice daily administration of tobramycin. Laryngoscope 1987; 97: 1443–9PubMedGoogle Scholar
  76. 76.
    Labovitz E, Levison ME, Kaye D. Single dose daily gentamicin therapy in urinary tract infections. Antimicrob Agents Chemother 1974; 6: 465–70PubMedCrossRefGoogle Scholar
  77. 77.
    Angelov A, Barrientos G, Gutensohn G, et al. Die tagliche Einmaldosis von Gentamicin bei der Behandlung von Harnwegsinfektionen. Munch Med Woch 1980; 122: 212–4Google Scholar
  78. 78.
    Cohen B, Saginur R, Clecner B, et al. Double-blind comparative trial of once-daily versus twice-daily netilmicin therapy in severe acute urinary tract infections. Curr Ther Res 1985; 38: 880–4Google Scholar
  79. 79.
    Van der Auwera P, Meunier F, Ibrahim S, et al. 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; 35: 640–7PubMedCrossRefGoogle Scholar
  80. 80.
    Vigano A, Principi N, Brivio L, et al. Comparison of 5 milligrams of netilmicin per kilogram of body weight once daily versus 2 milligrams per kilogram thrice daily for treatment of gram negative pyelonephritis in children. Antimicrob Agents Chemother 1992; 36: 1499–503PubMedCrossRefGoogle Scholar
  81. 81.
    Heininger U, Bowing B, Stehr K, et al. Aminoglycosides in patients with mucoviscidosis and pulmonary exacerbation. Comparison of once or three times daily administration. Klin Padiatr 1993; 205: 18–22PubMedCrossRefGoogle Scholar
  82. 82.
    Vannier J-P, Gardembas-Pain M, Blaysat G, et al. Comparison of two versus three daily infusions of cefotaxime plus amikacin in granulocytopenic children. Drugs 1988; 35 Suppl. 2: 231PubMedCrossRefGoogle Scholar
  83. 83.
    Ibrahim S, Derde MP, Kaufman L, et al. 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): 199–203PubMedCrossRefGoogle Scholar
  84. 84.
    Tulkens PM, Clerkx-Braun F, Donnez J, et al. Safety and efficacy of aminoglycosides once-a-day: Experimental data and randomized, controlled evaluation in patients suffering from pelvic inflammatory disease. J Drug Dev 1988; 1 Suppl. 3: 71–82Google Scholar
  85. 85.
    Sturm AW. Netilmicin in the treatment of gram-negative bacteraemia: Single dose versus multiple daily dosage. J Infect Dis 1989; 159: 931–7PubMedCrossRefGoogle Scholar
  86. 86.
    Fan ST, Lau WY, Teoh-Chan CH, et al. Once daily administration of netilmicin compared with thrice daily, both in combination with metronidazole, in gangrenous and perforated appendicitis. J Antimicrob Chemother 1988; 22: 69–74PubMedCrossRefGoogle Scholar
  87. 87.
    Hollender LF, Bahnini J, De Manzini N, et al. A multicentric study of netilmicin once daily versus thrice daily in patients with appendicitis and other intra-abdominal infections. J Antimicrob Chemother 1989; 23: 773–83PubMedCrossRefGoogle Scholar
  88. 88.
    De Vries PJ, Verkooyen RP, Leguit P, et al. Prospective randomised study of once-daily versus thrice-daily netilmicin regimens in patients with intraabdominal infections. Eur J Clin Microbiol Infect Dis 1990; 9: 161–8PubMedCrossRefGoogle Scholar
  89. 89.
    Ter Braak EW, De Vries PJ, Bouter KP, et al. Once-daily dosing regimen for aminoglycoside plus β-lactam combination therapy of serious bacterial infections: Comparative trial with netilmicin plus ceftriaxone. Am J Med 1990; 89: 58–86PubMedCrossRefGoogle Scholar
  90. 90.
    Giamarellou H, Yiallouros K, Petrikkos G, et al. Comparative kinetics and efficacy of amikacin administered once or twice daily in the treatment of systemic gram-negative infections. J Antimicrob Chemother 1991; 27 Suppl. C: 73–9PubMedGoogle Scholar
  91. 91.
    Mauracher EH, Lau W, Kartowisastro H, et al. Comparison of once-daily and thrice-daily netilmicin regimens in serious systemic infections: A multicenter study in six Asian countries. Clin Ther 1989; 11: 604–13PubMedGoogle Scholar
  92. 92.
    Nordström L, Ringberg H, Cronberg S, et al. Does administration of an aminoglycoside in a single daily dose affect its efficacy and toxicity? J Antimicrob Chemother 1990; 25: 159–73PubMedCrossRefGoogle Scholar
  93. 93.
    Maller R, Ahrne H, Holmen C, et al. Once-versus twice-daily amikacin regimen: efficacy and safety in systemic Gram-negative infections. Scandanavian Amikacin Once Daily Study Group. J Antimicrobial Chemother 1993; 31: 939–48CrossRefGoogle Scholar
  94. 94.
    Prins JM, Büller HR, Kuijper EJ, et al. Once versus thrice daily gentamicin in patients with serious infections. Lancet 1993; 341: 335–9PubMedCrossRefGoogle Scholar
  95. 95.
    Frass M, Traindl O, Podolsky A, et al. Comparison of netilmicin administration once or three times daily in intensive care patients. Wien Klin Wochenschr 1991; 103: 101–4PubMedGoogle Scholar
  96. 96.
    Mendes da Costa P, Kaufman L. Amikacin once daily plus metronidazole versus amikacin twice daily plus metronidazole in colorectal surgery. Hepatogastroenterology 1992; 39: 350–4PubMedGoogle Scholar
  97. 97.
    Leoni F, Ciolli S, Pascarella A, et al. Ceftriaxone plus conventional or single-daily dose amikacin versus ceftazidime/amikacin as empiric therapy in febrile neutropenic patients. Chemotherapy 1993; 39: 147–52PubMedCrossRefGoogle Scholar
  98. 98.
    EORTC International Antimicrobial Therapy Cooperative Group. 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. Ann Intern Med 1993; 119: 584–93Google Scholar
  99. 99.
    Feld R, Rachlis A, Tuffnell P, et al. Empiric therapy for infections in patients with granulocytopenia: Continuous vs. interrupted infusion of tobramycin plus cefamandole. Arch Intern Med 1984; 144: 1005–10PubMedCrossRefGoogle Scholar
  100. 100.
    Gibson J, Johnson L, Snowdon L, et al. Single daily ceftriaxone and tobramycin in the empirical management of febrile neutropenic patients: a randomised trial. Int J Hematol 1993; 58: 63–72PubMedGoogle Scholar
  101. 101.
    Rozdzinski E, Kern WV, Reichle A, et al. Once-daily versus thrice-daily dosing of netilmicin in combination with beta-lactam antibiotics as empirical therapy for febrile neutropenic patients. J Antimicrob Chemother 1993; 34: 585–98CrossRefGoogle Scholar
  102. 102.
    Hansen M, Achen F, Carstensen C, et al. Once versus thrice daily dosing of netilmicin in febrile immunocompromised patients: A randomized, controlled study of efficacy and safety. J Drug Dev 1988; 1: 119–24Google Scholar
  103. 103.
    Vanhaeverbeek M, Siska G, Douchamps J, et al. Comparison of the efficacy and safety of amikacin once or twice-a-day in the treatment of severe gram-negative infections in the elderly. Int J Clin Pharmacol Ther Toxicol 1993; 31(3): 153–6PubMedGoogle Scholar
  104. 104.
    Maller R, Isaksson B, Nilsson L, et al. A study of amikacin given once versus twice daily in serious infections. J Antimicrob Chemother 1988; 22: 75–9PubMedCrossRefGoogle Scholar
  105. 105.
    Brummett RE, Fox KE. Aminoglycoside-induced hearing loss in humans. Antimicrob Agents Chemother 1989; 33: 797–800PubMedCrossRefGoogle Scholar
  106. 106.
    Davey PG, Jabeen FJ, Harpur ES, et al. A controlled study of the reliability of pure tone audiometry for the detection of gentamicin auditory toxicity. J Laryngol Otolaryngol 1983; 97: 27–36Google Scholar
  107. 107.
    Yourassowsky E, Van der Linden MP, Crokaert F. One shot of high-dose amikacin: A working hypothesis. Chemotherapy 1990; 36: 1–7PubMedCrossRefGoogle Scholar
  108. 108.
    Hustinx WNM, Hoepelman IM. Aminoglycoside dosage regimens: is once a day enough? Clin Pharmacokinet 1993; 25: 427–32PubMedCrossRefGoogle Scholar
  109. 109.
    Konrad F, Wagner R, Neumeister B, et al. Studies on drug monitoring in thrice and once daily treatment with aminoglycosides. Intensive Care Med 1993; 19: 215–20PubMedCrossRefGoogle Scholar
  110. 110.
    Parker SE, Davey PG. Practicalities of once daily dosing. J Antimicrob Chemother 1993; 31: 4–8PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1994

Authors and Affiliations

  • Murray L. Barclay
    • 1
  • Evan J. Begg
    • 1
  • Keith G. Hickling
    • 2
  1. 1.Department of Clinical PharmacologyChristchurch HospitalChristchurchNew Zealand
  2. 2.Department of Intensive CareChristchurch HospitalChristchurchNew Zealand

Personalised recommendations