Pharmaceutisch Weekblad

, Volume 12, Issue 3, pp 81–90 | Cite as

Aminoglycoside therapy

Current use and future prospects
  • R. Janknegt
Review Articles


The microbiological, pharmacokinetic, toxicological and clinical aspects of aminoglycosides are reviewed. Aminoglycosides still have an important place in serious infections in neutropenic patients, endocarditis andPseudomonas aeruginosa infections, all in combination with beta-lactams. Monotherapy (with streptomycin) is indicated in less common diseases like tularaemia and bubonic plague. Several experimental studies support a oncedaily dosing regimen for aminoglycosides (comparable or better efficacy with less ototoxicity and nephrotoxicity). Only a very limited number of prospective comparative studies have been performed, and much more data on efficacy, development of resistance and toxicity is needed before once-daily administration can be recommended. The choice of an aminoglycoside should be based primarily on the local sensitivity patterns and cost. Differences in ototoxicity and nephrotoxicity are usually minor. If the acquisition costs of amikacin decline, it is to be expected that amikacin will be the aminoglycoside of choice.


Amikacin Aminoglycosides Drug administration schedule Gentamicins Netilmicin Pharmacokinetics Tobramycin Toxicology 


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  1. 1.
    Edson RS, Terrell CL. The aminoglycosides: streptomycin, kanamycin, gentamicin, tobramycin, amikacin, netilmicin and sisomicin. Mayo Clin Proc 1987;62:916–20.PubMedGoogle Scholar
  2. 2.
    Davis BD. The lethal action of aminoglycosides. J Antimicrob Chemother 1988;22:1–3.Google Scholar
  3. 3.
    Humbert G, Carbon C, Collatz E. Aminoglycosides (aminocyclitols). In: Peterson PK, Verhoef J, eds. Antimicrobial agents annual 3. Amsterdam: Elsevier Science Publishers, 1988:1–14.Google Scholar
  4. 4.
    Cunha BA. Aminoglycosides: current role in antimicrobial therapy. Pharmacotherapy 1988;8:334–50.PubMedGoogle Scholar
  5. 5.
    Pancoast SJ. Aminoglycosides antibiotics in clinical use. Med Clin N Am 1988;72:581–612.PubMedGoogle Scholar
  6. 6.
    Hoffner SE, Källenius G. Susceptibility of streptomycin-resistantM. tuberculosis to amikacin. Eur J Clin Microbiol Infect Dis 1988;7:188–90.PubMedGoogle Scholar
  7. 7.
    Gangaradham PR, Kesavalu L, Rao PN, et al. Activity of amikacin againstM. avium complex under simulatedin vivo conditions. Antimicrob Agents Chemother 1988;32:886–9.PubMedGoogle Scholar
  8. 8.
    Gangaradham PR, Perumal VK, Rao PN, Kesavula L, Iseman MD.In vivo activity of amikacin alone or in combination with clofazimine or rifabutin or both against acute experimentalM. avium complex infections in beige mice. Antimicrob Agents Chemother 1988;32:1400–3.PubMedGoogle Scholar
  9. 9.
    Wallace RJ, Steele LC, Sumter G, Smith JM. Antimicrobial susceptibility patterns ofN. asteroides. Antimicrob Agents Chemother 1988;32:1776–9.PubMedGoogle Scholar
  10. 10.
    Siegenthaler WE, Bonetti A, Lüthy R. Aminoglycosides antibiotics in infectious diseases. Am J Med 1986;80(Suppl 6B):2–14.CrossRefGoogle Scholar
  11. 11.
    Anonymous. The choice of antimicrobial drugs. Med Lett Drugs Ther 1988;30:33–40.Google Scholar
  12. 12.
    Blaser J, Lüthy R. Comparative study on antagonistic effects of low pH and cation supplementation oninvitro activity of quinolones and aminoglycosides againstP. aeruginosa. J Antimicrob Chemother 1988;22:15–22.PubMedGoogle Scholar
  13. 13.
    Bakker-Woudenberg IA, Roosendaal R. Impact of dosage regimens on the efficacy of antibiotics in the immuno-compromised host. J Antimicrob Chemother 1988;21:145–7.PubMedGoogle Scholar
  14. 14.
    Isaksson B, Nilsson L, Maller R, Sörén L. Post-antibiotic effect of aminoglycosides on Gram-negative bacteria evaluated by a new method. J Antimicrob Chemother 1988;22:22–33.Google Scholar
  15. 15.
    Van der Auwera P. Bactericidal activity, killing rate and post-antibiotic effect in the serum of patients with urinary tract infection receiving netilmicin 6 mg/kg once daily in comparison with 2 mg/kg t.i.d. J Drug Dev 1988;1(Suppl 3):25–33.Google Scholar
  16. 16.
    Ristuccia AM, Cunha BA. An overview of amikacin. Ther Drug Monitor 1985;7:12–25.Google Scholar
  17. 17.
    Giamarellou H. Aminoglycosides plus beta-lactams against Gram-negative organisms. Am J Med 1986;80(Suppl 6B):126–37.CrossRefGoogle Scholar
  18. 18.
    Michéa-Hamzepour M, Pechère JC, Marchou B, Auckenthaler R. Combination therapy: a way to limit emergence of resistance. Am J Med 1986;80(Suppl 6B):138–42.CrossRefPubMedGoogle Scholar
  19. 19.
    Dejace P, Klastersky J. Comparative review of combination therapy: two beta-lactams versus beta-lactam plus aminoglycoside. Am J Med 1986;80(Suppl 6B):29–38.CrossRefGoogle Scholar
  20. 20.
    Bingen E, Lambert-Zechovsky N, Auyard Y, et al. Early synergistic killing activity at concentrations attainable in CSF of amoxicillin or cefotaxime and aminoglycosides againstH. influenzae. Infection 1988;16:121–5.CrossRefPubMedGoogle Scholar
  21. 21.
    Mouton Y, Beuscart C, Leroy O, et al. Prospective randomized controlled study of ceftazidime plus pefloxacin versus ceftazidime plus amikacin in nosocomial bacteremia or pneumonia of intensive care patients. 28th Interscience conference on antimicrobial agents and chemotherapy. Los Angeles, 1988. Washington: American Society for Microbiology, 1988: abstract 938.Google Scholar
  22. 22.
    European Study Group.In vitro susceptibility to aminoglycoside antibiotics in blood and urine isolates consecutively collected in 29 European laboratories. Eur J Clin Microbiol 1987;6:378–85.Google Scholar
  23. 23.
    Staehr Johansen K, Storgaard M, Carstensen N, Frank U, Daschner F. An international study on the occurrence of multiresistant bacteria and aminoglycoside consumption pattern. Infection 1988;16:313–22.CrossRefPubMedGoogle Scholar
  24. 24.
    Saavedra S, Vera D, Ramirez Ronda CH. Susceptibility of aerobic Gram-negative bacilli to aminoglycosides. Am J Med 1986;80(Suppl 6B):65–70.CrossRefGoogle Scholar
  25. 25.
    Ruiz-Palacios GM, Ponce de Leon S, Sifuentes J, et al. Control of emergence of multi-resistant Gram-negative bacilli by exclusive use of amikacin. Am J Med 1986;80(Suppl 6B):71–5.CrossRefGoogle Scholar
  26. 26.
    Gerding DN, Larson TA. Resistance surveillance programs and the incidence of Gram-negative bacillary resistance to amikacin from 1967 to 1985. Am J Med 1986;80(Suppl 6B):22–6.CrossRefGoogle Scholar
  27. 27.
    Steenhoek A. Pharmacokinetics of aminoglycosides. Ziekenhuisfarmacie 1987;3:5–7.Google Scholar
  28. 28.
    Lameire N. Using aminoglycosides in patients with chronic renal failure and hemodialysis or peritoneal dialysis. Ziekenhuisfarmacie 1987;3:17–22.Google Scholar
  29. 29.
    Segal JL, Brunneman SR, Gray DR. Gentamicin bioavailability and single-dose pharmacokinetics in spinal cord injury. Drug Intell Clin Pharm 1988;22:461–5.PubMedGoogle Scholar
  30. 30.
    Tointon MM, Job ML, Pettier TT, Murphy JE, Ward ES. Alterations in aminoglycosides volume of distribution in patients below ideal body weight. Clin Pharm 1987;6:160–2.PubMedGoogle Scholar
  31. 31.
    Delage G, Desautels L, Legault S, et al. Individualized aminoglycoside dosage regimens in patients with cystic fibrosis. Drug Intell Clin Pharm 1988;22:386–9.PubMedGoogle Scholar
  32. 32.
    Fuhs DW, Mann HJ, Kubajde CA, Cerra FB. Intrapatient variation of aminoglycoside pharmacokinetics in critically ill surgery patients. Clin Pharm 1988;7:207–13.PubMedGoogle Scholar
  33. 33.
    Mann HJ, Fuhs DW, Awang R, et al. Altered aminoglycoside pharmacokinetics in critically ill patients with sepsis. Clin Pharm 1987;6:148–53.PubMedGoogle Scholar
  34. 34.
    Zaske DE, Cipolle RJ. Gentamicin pharmacokinetics in 1640 patients: method for control of serum concentrations. Antimicrob Agents Chemother 1982;21:407–11.PubMedGoogle Scholar
  35. 35.
    Moore RD, Lietman PS, Smith GR. Clinical response to aminoglycoside therapy; importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis 1987;155:93–9.PubMedGoogle Scholar
  36. 36.
    Barrière SL. Aminoglycosides. A reassessment of their therapeutic role. Clin Pharm 1988;7:385–90.PubMedGoogle Scholar
  37. 37.
    Kunzendorf U, Keller F, Walz G. Multivariate analysis of amino-glycosides levels in hemodialysis patients. Chemotherapy 1989;35:1–6.Google Scholar
  38. 38.
    Tulkens PM, Clerckx-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):71–82.Google Scholar
  39. 39.
    Humes HD. Aminoglycosides nephrotoxicity. Kidney Int 1988;33:900–11.PubMedGoogle Scholar
  40. 40.
    Tulkens PM. Experimental studies on nephrotoxicity of aminoglycosides at low doses. Am J Med 1986;80S:105–14.CrossRefGoogle Scholar
  41. 41.
    Beauchamp D, Pettigrew M. Influence of hydrocortisone on gentamicin-induced nephrotoxicity in rats. Antimicrob Agents Chemother 1988;32:992–6.PubMedGoogle Scholar
  42. 42.
    Hayaski T, Wanabe Y, Kumanio K, et al. Protective effect of piperacillin against nephrotoxicity of cephaloridine and gentamicin in animals. Antimicrob Agents Chemother 1988;32:912–8.PubMedGoogle Scholar
  43. 43.
    Joly V, Bergeron MG, Friedlander G, et al. Endotoxin and tobramycin exhibit potentiated toxicity on renal proximal tubular cells. 28th Interscience conference on antimicrobial agents and chemotherapy. Los Angeles, 1988. Washington: American Society for Microbiology, 1988:abstract 291.Google Scholar
  44. 44.
    Ngeleka M, Beauchamp D, Bergeron MG. Gentamicinvancomycin associated nephrotoxicity in endotoxemic rats. 28th Interscience conference on antimicrobial agents and chemotherapy. Los Angeles, 1988. Washington: American Society for Microbiology, 1988:abstract 292.Google Scholar
  45. 45.
    Desai TK, Tsang TK. Aminoglycoside nephrotoxicity in obstructive jaundice. Am J Med 1988;85:47–50.CrossRefPubMedGoogle Scholar
  46. 46.
    Corcoran GB, Salazar DE, Schentag JJ. Excessive aminoglycoside nephrotoxicity in obese patients. Am J Med 1988;85:279.CrossRefPubMedGoogle Scholar
  47. 47.
    DeBroe ME, Guiliano RA, Verpooten GA. Choice of drug and dosage regimen. Am J Med 1986;80(Suppl 6B):115–8.CrossRefPubMedGoogle Scholar
  48. 48.
    DeBroe ME, Giuliano RA, Verpooten GA. Insights into the renal handling of aminoglycosides: a guideline for prevention of nephrotoxicity. J Drug Dev 1988;1(Suppl 3):83–92.Google Scholar
  49. 49.
    Meyer RD. Risk factors and comparisons of clinical nephrotoxicity of aminoglycosides. Am J Med 1986;80(Suppl 6B):119–25.CrossRefGoogle Scholar
  50. 50.
    Tange RA. Ototoxicity of aminoglycosides. Ziekenhuisfarmacie 1987;3:15–7.Google Scholar
  51. 51.
    Tran ba Huy P, Deffrennes D. Aminoglycosides binding sites in the inner ear of guinea pigs. Antimicrob Agents Chemother 1988;32:467–72.PubMedGoogle Scholar
  52. 52.
    Gatell JM, Ferran F, Aranjo V, et al. Univariate and multivariate analysis of risk factors predisposing to auditory toxicity in patients receiving aminoglycosides. Antimicrob Agents Chemother 1987;31:1383–7.PubMedGoogle Scholar
  53. 53.
    Guag DR. Netilmicin. Drug Intell Clin Pharm 1983;17:83–91.PubMedGoogle Scholar
  54. 54.
    Giala M, Crassaris L, Papadakis E, et al. Interactions of aminoglycoside antibiotics with steroid non-depolarizing muscle relaxant agents. 15th International congress on chemotherapy. Instanbul, 1987:abstract 255.Google Scholar
  55. 55.
    Crassaris L, Mironidou M, Salpigidis G, et al. Interaction of aminoglycoside antibiotics with calcium channel blockers at the neuromuscular junctions. 15th International congress on chemotherapy. Istanbul, 1987:abstract 256.Google Scholar
  56. 56.
    Graig WA, Leggett J, Totsuka K, Vogelman B. Key pharmacokinetic parameters of antibiotic efficacy in experimental animal infections. J Drug Dev 1988;1(Suppl 3):7–15.Google Scholar
  57. 57.
    Jackson GG, Daikos GL, Lolans VT. First exposure effect of netilmicin on bacterial susceptibility as a basis for modifying the dosage regimen of aminoglycoside antibiotics. J Drug Dev 1988;1(Suppl 3):49–54.Google Scholar
  58. 58.
    Herscovici L, Grise G, Thauvin C, Lemeland JF, Fillastre JP. Efficacy and safety of once daily versus intermittent dosing of tobramycin in rabbits with acute pyelonephritis. Scand J Infect Dis 1988;20:205–12.PubMedGoogle Scholar
  59. 59.
    Verpooten GA, Giuliano RA, Verbist L, Eestermans G, DeBroe MC. Once daily dosing decreases renal accumulation of gentamicin and netilmicin. Clin Pharmacol Ther 1989;45:22–7.PubMedGoogle Scholar
  60. 60.
    Tran ba Huy P. Aminoglycoside ototoxicity; influence of dosage regimen on drug uptake, correlation between membrane binding and clinical features. J Drug Dev 1988;1(Suppl 3):93–5.Google Scholar
  61. 61.
    Fan ST, Lau WY, Teoh-Chan CH, Lau KF, Mauracher EM. Once daily administration of netilmicin compared with thrice daily, both in combination with metronidazole, in gangrenous and perforated appendicitis. J Antimicrob Chemother 1988;22:69–74.Google Scholar
  62. 62.
    Hollender LF, Bahnini J, De Manzini N, et al. A multi centric study of netilmicin once daily versus thrice daily in patients with appendicitis and other intraabdominal infections. J Antimicrob Chemother 1989;23:773–83.PubMedGoogle Scholar
  63. 63.
    Hansen M, Achen F, Castersen C, et al. Onceversus thrice-daily dosing of netilmicin in febrile immunocompromized patients: a randomized controlled study of efficacy and safety. J Drug Dev 1988;1(Suppl 3):119–24.Google Scholar
  64. 64.
    Sturm AW. Netilmicin in the treatment of Gramnegative septicemia: single daily versus thrice daily dosage. J Drug Dev 1988;1(Suppl 3):125–8.Google Scholar
  65. 65.
    Muysken MA, Vreede RW, Van Dijk WC, Haverkorn MJ, Kaufman L, Derde MP. A randomized clinical study of efficacy and safety of once daily versus conventional dosing of netilmicin in patients with severe infection. J Drug Dev 1988;1(Suppl 3):145–6.Google Scholar
  66. 66.
    Ter Braak EM, De Vries PJ, Bouter KP, et al. Once daily dosing of netilmicin and ceftriaxone in patients with severe bacterial infections. 28th Interscience conference on antimicrobial agents and chemotherapy. Los Angeles, 1988. Washington: American Society for Microbiology, 1988:abstract 558.Google Scholar
  67. 67.
    De Vries PJ, Verkooyen RP, Leguit P, Verbrugh HA. Efficacy and safety of once daily netilmicin in patients with intraabdominal infections. 28th Interscience conference on antimicrobial agents and chemotherapy. Los Angeles, 1988. Washington: American Society for Microbiology, 1988:abstract 1373.Google Scholar
  68. 68.
    Maller R, Isaksson B, Nilsson L, Sörén L. A study of amikacin given once versus twice daily in serious infections. J Antimicrob Chemother 1988;22:75–9.PubMedGoogle Scholar
  69. 69.
    Brulein V, Jacqmin P, Ibrahim S, et al. Tolerance and efficacy of amikacin once a day versus twice a day: A prospective, controlled study in 40 women suffering from pelvic inflammatory disease. 4th European congress on clinical microbiology. Nice, 1989:abstract 73.Google Scholar
  70. 70.
    Gladen HC. Cost-effective aminoglycoside therapy in surgical patients. Am J Med 1986;80(Suppl 6B):228–33.CrossRefPubMedGoogle Scholar

Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1990

Authors and Affiliations

  • R. Janknegt
    • 1
  1. 1.Department of Clinical PharmacyMaasland HospitalMB SittardThe Netherlands

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