Skip to main content
Log in

Pharmacokinetics of antibiotics in critically ill patients

  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Differences in pharmacokinetic data of aminoglycosides, ceftazidime and ceftriaxone between intensive care patients and volunteers or patients who are less severely ill, are described. Similar differences are observed for midazolam. In severely ill patients with normal renal function a wide interpatient variability of aminoglycoside half-life (t1/2) and increased distribution volume (Vd) are observed. This results in inadequate serum levels. A pharmacokinetic approach of drug dosing, based on serum concentrations in individual patients, is advised. For ceftazidime and ceftriaxone similar changes of t1/2 and Vd are observed. Since protein binding is frequently reduced in severely ill patients, the influence of altered binding of highly bound drugs on Vd and drug clearance is discussed. As both may be increased by reduced protein binding, the change of t1/2 to be expected is unpredictable. Dosing regimens should be based on pharmacokinetic data derived from patients whose severity of disease is comparable to that of the patients to be treated.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Byatt CM, Lewis LD, Dawling S, Cochrane GM (1984) Accumulation of midazolam after repeated dosage in patients receiving mechanical ventilation in an intensive care unit. Br Med J 289:799–800

    Google Scholar 

  2. Summer WR, Michael JR, Lipsky JJ (1983) Initial aminoglycoside levels in the critically ill. Crit Care Med 11:948–950

    Google Scholar 

  3. Niemiec PW, Allo MD, Miller CF (1987) Effect of altered volume of distribution on aminoglycoside levels in patients in surgical intensive care. Arch Surg 122:207–212

    Google Scholar 

  4. Driscoll DF, McMahon M, Blackburn GL, Bistrian BR (1988) Phenytoin toxicity in a critically ill, hypoalbuminemic patient with normal serum drug concentrations. Crit Care Med 16:1248–1249

    Google Scholar 

  5. Joos B, Luethy R, Muehlen E, Siegenthaler W (1984) Variability of ceftriaxone pharmacokinetics in hospitalized patients with severe infections. Am J Med [Suppl 4C] 77:59–62

    Google Scholar 

  6. Kaye D, Levison ME, Labovitz ED (1974) The unpredictability of serum concentrations of gentamicin: pharmacokinetics of gentamicin in patients with normal and abnormal renal function. J Infect Dis 130:150–154

    Google Scholar 

  7. Zaske DE, Cipolle RJ, Strate RG (1980) Genetamicin dosage requirements: wide interpatient variations in 242 surgery patients with normal renal function. Surgery 87:164–169

    Google Scholar 

  8. Zaske DE, Cipolle RJ, Strate RG, Dickes WF (1981) Increased gentamicin dosage requirements: rapid elimination in 249 gynecology patients. Am J Obstet Gynecol 139:896–900

    Google Scholar 

  9. Dasta JF, Armstrong DK (1988) Variability in aminoglycoside pharmacokinetics in critically ill surgical patients. Crit Care Med 16:327–330

    Google Scholar 

  10. Van Dalen R, Vree TB, Baars AM, Termond E (1986) Dosage adjustment for ceftazidime in patients with impaired renal function. Eur J Clin Pharmacol 30:597–605

    Google Scholar 

  11. Harding SM, Monro AJ, Thornton JE, Ayrton J, Hogg MIJ (1981) The comparative pharmacokinetics of ceftazidime and cefotaxime in healthy volunteers. J Antimicrob Chemother [Suppl B] 8:263–272

    Google Scholar 

  12. Sommers D, Walters L, van Wyk M, Harding SM, Paton AM, Ayrton J (1983) Pharmacokinetics of ceftazidime in male and female volunteers. Antimicrob Agents Chemother 23:892–896

    Google Scholar 

  13. Van Dalen R, Vree TB, Baars AM (1987) Influence of protein binding and severity of illness on renal elimination of four cephalosporin drugs in intensive care patients. Pharm Weekbl (Sci) 9:98–103

    Google Scholar 

  14. Patel IH, Chen S, Parsonnet M et al. (1981) Pharmacokinetics of ceftriaxone in humans. Antimicrob Agents Chemother 20:634–641

    Google Scholar 

  15. Patel IH, Kaplan SA (1984) Pharmacokinetic profile of ceftriaxone in man. Am J Med [Suppl 4C] 77:17–25

    Google Scholar 

  16. Dundee JW, Collier PS, Carlisle RJT, Harper KW (1986) Prolonged midazolam elimination half-life. Br J Clin Pharmacol 21:425–429

    Google Scholar 

  17. Dirksen MSC, Vree TB, Driessen JJ (1987) Clinical pharmacokinetics of long-term infusion of midazolam in critically ill patients—Preliminary results. Anaesth Intensive Care 15:440–444

    Google Scholar 

  18. Shelly MP, Mendel L, Park GR (1987) Failure of critically ill patients to metabolise midazolam. Anaesthesia 42:619–626

    Google Scholar 

  19. Townsend PL, Fink MP, Stein KL, Murphy SG (1989) Aminoglycoside pharmacokinetics: dosage requirements and nephrotoxicity in trauma patients. Crit Care Med 17:154–157

    Google Scholar 

  20. Vree TB, Shimoda M, Driessen JJ et al. (1989) Decreased plasma albumin concentration results in increased volume of distribution and decreased elimination of midazolam in intensive care patients. Clin Pharmacol Ther 46:537–544

    Google Scholar 

  21. Rowland M (1984) Protein binding and drug clearance. Clin Pharmacokinet [Suppl 1] 9:10–17

    Google Scholar 

  22. Wise R (1986) The clinical relevance of protein binding and tissue concentrations in antimicrobial therapy. Clin Pharmacokinet 11:470–482

    Google Scholar 

  23. Craig WA, Welling PG (1977) Protein binding of antimicrobials: clinical pharmacokinetic and therapeutic implications. Clin Pharmacokinet 2:252–268

    Google Scholar 

  24. Tillement JP, Lhoste F, Giudicelli JF (1978) Diseases and drug protein binding. Clin Pharmacokinet 3:144–154

    Google Scholar 

  25. Wedlund PJ, Branch RA (1983) Adjustment of medications in liver failure. In: Chernow B, Lake CR (eds) The pharmacologic approach to the critically ill patient. Williams and Wilkins, Baltimore, pp 84–114

    Google Scholar 

  26. Wilkins RG, Faragher EB (1983) Acute renal failure in an intensive care unit: incidence, prediction and outcome. Anaesthesia 38:628–634

    Google Scholar 

  27. Menashe PI, Ross SA, Gottlieb JE (1988) Acquired renal insufficiency in critically ill patients. Crit Care Med 16:1106–1109

    Google Scholar 

  28. Maher JF (1983) Adjustment of medications in renal failure. In: Chernow B, Lake CR (eds) The pharmacologic approach to the critically ill patient. Williams and Wilkins, Baltimore, pp 65–83

    Google Scholar 

  29. Chelluri L, Jastremski MS (1987) Inadequacy of standard aminoglycoside loading doses in acutely ill patients. Crit Care Med 15:1143–1145

    Google Scholar 

  30. Moore RD, Lietman PS, Smith CR (1987) Clinical response to aminoglycoside therapy: Importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis 155:93–99

    Google Scholar 

  31. Moore RD, Smith CR, Lietman PS (1984) The association of aminoglycoside plasma levels with mortality in patients with gramnegative bacteremia. J Infect Dis 149:443–448

    Google Scholar 

  32. Franson TR, Quebbeman EJ, Whipple J et al. (1988) Prospective comparison of traditional and pharmacokinetic aminoglycoside dosing methods. Crit Care Med 16:840–843

    Google Scholar 

  33. Hickling K, Begg E, Moore ML (1989) 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 15:233–237

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

van Dalen, R., Vree, T.B. Pharmacokinetics of antibiotics in critically ill patients. Intensive Care Med 16 (Suppl 3), S235–S238 (1990). https://doi.org/10.1007/BF01709707

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01709707

Key words

Navigation