Skip to main content
SpringerLink
Log in

Therapeutic drug monitoring of aminoglycoside antibiotics

Serumspiegelüberwachung von Aminoglykosid-Antibiotika

  • Published:
Infection Aims and scope Submit manuscript

Summary

Aminoglycosides are widely used antibacterial agents, particularly for serious infections. They have a narrow therapeutic margin of efficacy over toxicity relative to many other agents, a disadvantage which can be obviated to some extent by precise dosing regulated by blood concentration monitoring. The relationships of efficacy and toxicity to concentrations are discussed, as are the practical aspects of clinical indications for monitoring and specimen collection. Dosing by predictive methods is useful but not always of sufficient precision. A large number of methods for assay are now available. With care, microbiological plate assays can give results of adequate accuracy and selectivity, and with sufficient speed. Immunoassays give more accurate, specific and rapid answers; EMIT, in particular, seems the best method available at the present time. Whichever method is used, control of its accuracy is essential.

Zusammenfassung

Aminoglykoside sind breit angewandte antibakterielle Agentien, insbesondere für ernste Infektionen. Sie haben eine geringe therapeutische Breite, verglichen mit anderen Substanzen, und dieser Nachteil kann bis zu einem gewissen Grad durch präzise Dosierung unter Überwachung der Blutspiegel ausgeglichen werden. Das Verhältnis zwischen Wirksamkeit und Toxizität zu den Konzentrationen sowie die praktischen Aspekte der klinischen Indikation für die Spiegelüberwachung und die Probengewinnung werden diskutiert. Die Dosierung durch Vorausberechnung ist nützlich, aber in der Regel nicht genügend präzise. Derzeit ist eine große Anzahl von Tests für die Spiegelbestimmung verfügbar. Bei sorgfältiger Durchführung können die mikrobiologischen Plattentests angemessen exakte und selektive Ergebnisse genügend schnell erbringen. Die Bestimmung mit Immunoassays ist präziser, spezifischer und rascher; EMIT insbesondere scheint die beste derzeit verfügbare Methode zu sein. Unabhängig davon, welche Methode angewandt wird, ist die Prüfung ihrer Präzision wesentlich.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Literature

  1. Jackson, G. G., Riff, L. Pseudomonas bacteraemia: Pharmacologic and other bases for failure of treatment with gentamicin. J. Infect. Dis. 124 Suppl. (1971) S 130-S 137.

    Article  Google Scholar 

  2. Noone, P., Parsons, T. M. C., Pathison, J. R., Slack, R. C. S., Garfield-Davies, D., Hughes, K. Experience in monitoring gentamicin therapy during treatment of serious gram-negative sepsis. Br. Med. J. I (1974) 477–481.

    Article  Google Scholar 

  3. Noone, P., Rogers, B. T. Pneumonia caused by coli-forms andPseudomonas aeruginosa. J. Clin. Pathol. 29 (1976) 652–656.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Anderton, J. L., Hanson, E., Raeburn, J. A.: The use of gentamicin in patients with impaired renal function. In:Williams, J. D., Geddes, A. M. (ed.): Chemotherapy (Volume 4). Plenum, London, pp. 121–125.

  5. Wilkinson, P. M., Delamore, I. W., Gorst, D., Tooth, J. A.: Experience with gentamicin and clindamycin in the management of febrile patients with blood dyscrasias. In:Williams, J. D., Geddes, A. M. (ed): Chemotherapy (Volume 1). Plenum, London, pp. 129–135.

  6. Bodey, G. P., Rodriguez, V., Valdivieso, M., Feld, R. Amikacin for treatment of infections in patients with malignant diseases. J. Infect. Dis. 134 Suppl. (1976 S 421-S 427.

    Article  Google Scholar 

  7. 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. 124 Suppl. (1971) S130-S137.

    Article  PubMed  Google Scholar 

  8. Barza, M., Scheife, R. J. Antimicrobial spectrum, pharmacology and therapeutic use of antibiotics-part 4: Aminoglycosides. Am. J. Hosp. Pharm. 34 (1977) 723–737.

    PubMed  CAS  Google Scholar 

  9. Smith, C. R., Baughman, K. L., Edwards, C. Q., Rogers, J. F., Leitman, P. S. Controlled comparison of amikacin and gentamicin. N. Engl. J. Med. 296 (1977) 349–353.

    Article  CAS  PubMed  Google Scholar 

  10. Banck, G., Belfrage, S., Juhlin, I., Nordstrom, L., Tjernstrom, O., Toremalen, N. G. Retrospective study of the ototoxicity of gentamicin. Acta Pathol. Microbiol. Scand. B81 Suppl. 241 (1973) 54–57.

    Google Scholar 

  11. Nordstrom, L., Banck, G., Belfrage, S., Juhlin, I., Tjernstrom, O., Toremalen, N. G. Prospective study of the ototoxicity of gentamicin. Acta Pathol. Microbiol. Scand. B81 Suppl. 241 (1973) 58–61.

    Google Scholar 

  12. Wilson, P., Ramsden, R. T. Immediate effects of tobramycin on human cochlea and correlation with serum tobramycin levels. Br. Med. J. 1 (1977) 259–261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Federspil, P., Schatzle, W., Tiesler, W. Pharmacokinetics and ototoxicity of gentamicin, tobramycin and amikacin. J. Infect. Dis. 134 Suppl. (1976) S200-S205.

    Article  CAS  PubMed  Google Scholar 

  14. Waitz, G. A., Moss, E. L., Weinstein, M. J. Aspects of the chronic toxicity of gentamicin sulfate in cats. J. Infect. Dis. 124 Suppl. (1971) S125-S129.

    Article  CAS  PubMed  Google Scholar 

  15. Line, D. H., Poole, G. W., Waterworth, P. M. Streptomycin levels and dizziness. Tubercle (London) 51 (1970) 76–81.

    Article  CAS  PubMed  Google Scholar 

  16. Mawer, G. E., Ahmad, R., Dobbs, S. M., McGough, J. G., Lucas, C. B., Tooth, J. A. Prescribing aids for gentamicin. Br. J. Clin. Pharmacol. 1 (1974) 45–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Black, R. E., Lau, W. K., Weinstein, R. J., Young, L. S., Hewitt, W. L. Ototoxicity of amikacin. Antimicrob. Agents Chemother. 9 (1975) 956–961.

    Article  Google Scholar 

  18. Dahlgren, J. G., Anderson, E. T., Hewitt, W. L. Gentamicin blood levels: A guide to nephrotoxicity. Antimicrob. Agents Chemother. 8 (1975) 58–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Goodman, E. L., Van Gelder, J., Holmes, R., Hull, A. R., Sanford, J. P. Prospective comparative study of variable dosage and variable frequency regimens for administration of gentamicin. Antimicrob. Agents Chemother. 8 (1975) 434–438.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hewitt, W. L. Gentamicin toxicity in perspective. Postgrad. Med. J. 50 Suppl. 7 (1974) 55–59.

    PubMed  Google Scholar 

  21. Schentag, J. J., Jusko, W. J. Gentamicin persistence in the body. Lancet I (1977) 486.

    Article  Google Scholar 

  22. Siber, G. R., Echeverria, P., Smith, A. L., Paisley, J. W., Smith, D. H. Pharmacokinetics of gentamicin in children and adults. J. Infect. Dis. 132 (1975) 637–651.

    Article  CAS  PubMed  Google Scholar 

  23. Winters, R. E., Chow, A. W., Hecht, R. H., Hewitt, R. L. Combined use of gentamicin and carbenicillin. Ann. Intern. Med. 75 (1971) 925–927.

    Article  CAS  PubMed  Google Scholar 

  24. Kaye, D., Levison, M. E., Labovitz, E. D. The unpredictability of serum concentrations of gentamicin: Pharmacokinetics of gentamicin in patients with normal and abnormal renal function. J. Infect. Dis. 130 (1974) 150–154.

    Article  CAS  PubMed  Google Scholar 

  25. Burza, M., Brown, R. B., Shen, D., Gibaldi, M., Weinstein, L. Predictability of blood levels of gentamicin in man. J. Infect. Dis. 132 (1975) 165–174.

    Article  Google Scholar 

  26. Sawchuk, R. J., Zaske, D. E. Pharmacokinetics of dosing regimens which utilize multiple intravenous infusions: Gentamicin in burn patients. J. Pharmacokinet. Biopharm. 4 (1976) 183–195.

    Article  CAS  PubMed  Google Scholar 

  27. Reeves, D. S., Bywater, M. J., Wise, R., Whitmarsh, V. B. Availability of three antibiotics after intramuscular injection into thigh and buttock. Lancet II (1974) 1421–1422.

    Article  Google Scholar 

  28. Winters, R. E., Litwack, K. D., Hewitt, W. L. Relation between dose and levels of gentamicin in blood. J. Infect. Dis. 124 Suppl. (1971) S90-S95.

    Article  CAS  PubMed  Google Scholar 

  29. Hull, J. H., Sarubbi, F. A. Gentamicin serum concentration: Pharmacokinetic prediction. Ann. Intern. Med. 85 (1976) 183–189.

    Article  CAS  PubMed  Google Scholar 

  30. Schwartz, S. N., Pazin, G. J., Lyon, J. A., Ho, M., Pasculle, A. W. A controlled investigation of the pharmacokinetics of gentamicin and tobramycin in obese subjects. J. Infect. Dis. 138 (1978) 499–505.

    Article  CAS  PubMed  Google Scholar 

  31. Hallynck, T. H., Soep, H. H., Thomis, J. A., Boelaert, J., Doneels, R., Rubinstein, E., Reeves, D. S., Fillastre, J. P. Lean body mass and amikacin dosage. J. Antimicrob. Chemother. 6 (1980) 286–288.

    Article  CAS  PubMed  Google Scholar 

  32. James, W. P. T. Research on obesity. Her Majesty's Stationery Office, London, 1976.

    Google Scholar 

  33. Brøchner-Mortensen, J., Rødbro, P., Tougaard, L. Measurements of glomerular filtration rate. N. Engl. J. Med. 295 (1976) 513.

    PubMed  Google Scholar 

  34. Pijck, J., Hallynck, T. H., Soep, H., Baert, L., Daneels, R., Boelaert, J. J. Pharmakokinetics of amikacin in patients with renal insufficiency: Relation of half-life and creatinine clearance. J. Infect. Dis. 34 (1976) 5. 331–341.

    Article  Google Scholar 

  35. Halprem, B. A., Axline, S. G., Coplar, N. S., Brown, D. M. Clearance of gentamicin during haemodialysis: Comparison of four artificial kidneys. J. Infect. Dis. 133 (1976) 627–636.

    Article  Google Scholar 

  36. Paisley, J. W., Smith, A. L., Smith, D. H. Gentamicin in newborn infants. Am. J. Dis. Child. 126 (1973) 473–477.

    Article  CAS  PubMed  Google Scholar 

  37. Flynn, T. W., Pevonka, M. P., Yost, R. L., Weber, C. E., Stewart, R. B. Use of serum gentamicin levels in hospitalized patients. Am. J. Hosp. Pharm. 35 (1978) 806–808.

    PubMed  CAS  Google Scholar 

  38. Reeves, D. S., Bywater, M. J. Quality control of serum gentamicin assays — experience of national surveys. J. Antimicrob. Chemother. 1 (1975) 103–116.

    Article  CAS  PubMed  Google Scholar 

  39. Reeves, D. S., Bywater, M. J.: Assay of antimicrobial agents. In:de Louvois, J. (ed.): Selected topics in clinical bacteriology. Bailliere Tindall, London, pp. 21–78.

  40. Shanson, D. C., Hince, C. Serum gentamicin assays of 100 clinical serum samples by a rapid 40 °CKlebsiella method compared with overnight plate diffusion and acetyltransferase assays. J. Clin. Pathol. 30 (1977) 521–525.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Broughall, M. J.: Aminoglycosides. In:Reeves, D. S., Phillips, I., Williams, J. D., Wise, R. (ed.): Laboratory methods in antimicrobial chemotherapy. Churchill Livingstone, Edinburgh. pp. 195–207.

  42. Reeves, D. S., Holt, H. A. Resolution of antibiotic mixtures in serum samples by high-voltage electrophoresis. J. Clin. Pathol. 28 (1975) 435–442.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Mahon, W. A., Ezer, J., Wilson, T. W. Radioimmunoassay for measurements of gentamicin in blood. Antimicrob. Agents Chemother. 3 (1973) 585–589.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Minshaw, B. H., Holmes, R. K., Baxter, C. R. Comparison of a radioimmunoassay with an enzymic assay for gentamicin. Antimicrob. Agents Chemother. 7 (1975) 107–109.

    Article  Google Scholar 

  45. Broughton, A., Strong, J. E. Radioimmunoassay of iodinated gentamicin. Clin. Chim. Acta 66 (1976) 125–129.

    Article  CAS  PubMed  Google Scholar 

  46. Broughton, A., Strong, J. E., Pickering, L. K., Bodey, G. P. Radioimmunoassay of iodinated tobramycin. Antimicrob. Agents Chemother. 10 (1976) 652–656.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Broughton, A., Strong, J. E., Bodey, G. P. Radioimmunoassay of sisomicin. Antimicrob. Agents Chemother. 9 (1976) 247–250.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Lewis, J. E., Nelson, J. C., Elder, H. A. Amikacin: A rapid and sensitive radioimmunoassay. Antimicrob. Agents Chemother. 7 (1975) 42–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Stevens, P., Young, L. S., Hewitt, W. L. 125I radioimmunoassay of netilmicin. Antimicrob. Agents Chemother. 11 (1977) 768–770.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Shaw, E. J., Watson, R. A. A., Landon, J., Smith, D. S. Estimation of serum gentamicin by quenching fluoroimmunoassay. J. Clin. Pathol. 30 (1977) 526–531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. White, L. O., Scammell, L. M., Reeves, D. S. An evaluation of a gentamicin fluoroimmunoassay kit: Correlation with radioimmunoassay, acetyltransferase, and microbiological assay. J. Antimicrob. Chemother. 6 (1980) 267–273.

    Article  CAS  PubMed  Google Scholar 

  52. Watson, R. A. A., Landon, J., Shaw, E. J., Smith, D. S. Polarisation fluoroimmunoassay of gentamicin. Clin. Chim. Acta 73 (1976) 51–55.

    Article  CAS  PubMed  Google Scholar 

  53. Wills, P. J., Wise, R. Rapid, simple enzyme immunoassay for gentamicin. Antimicrob. Agents Chemother. 16 (1979) 40–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Mahon, W. A., Feldman, R. I., Scherr, G. H. Haemagglutination inhibition assay for gentamicin. Antimicrob. Agents Chemother. 11 (1979) 359–361.

    Article  Google Scholar 

  55. Broughall, J. M., Reeves, D. S. The acetyl transferase method for the assay of serum gentamicin concentrations and a comparison with other methods. J. Clin. Pathol. 28 (1975) 140–145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Shannon, K. P., Phillips, I. The use of aminoglycoside 2′-N-acetyl transferase for the assay of gentamicin in serum, plasma and urine. J. Antimicrob. Chemother. 3 (1977) 25–33.

    Article  CAS  PubMed  Google Scholar 

  57. Peng, G. W., Jackson, G. G., Chion, W. L. High pressure liquid chromatographic assay of netilmicin in plasma. Antimicrob. Agents Chemother. 12 (1976) 707–709.

    Article  Google Scholar 

  58. Anhalt, J. P. Assay of gentamicin in serum by high pressure liquid chromatography. Antimicrob. Agents Chemother. 11 (1977) 651–655.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Microbiology, Southmead Hospital, Bristol, UK

    D. S. Reeves

Authors
  1. D. S. Reeves
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reeves, D.S. Therapeutic drug monitoring of aminoglycoside antibiotics. Infection 8 (Suppl 3), S313–S320 (1980). https://doi.org/10.1007/BF01639603

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01639603

Keywords

Search

Navigation