Antibiotics by Continuous Infusion: Time for Re-evaluation?

  • D. L. A. Wyncoll
  • R. Bowry
  • L. J. Giles


Severe sepsis and septic shock account for 15–20% of intensive care unit (ICU) admissions and when associated with multi-organ dysfunction there is a 55% mortality [1]. Surgical evacuation of any focus of infection should be undertaken where possible, however, the mainstay of treatment is antibiotic therapy. In recent years there have been considerable advances in the support of these patients with emphasis being placed on early, adequate volume resuscitation [2], administration of stress-dose corticosteroids [3], immunonutrition [4], and, more recently, manipulation of coagulation pathways [5]. However, the way in which antibiotics are administered has remained largely unchanged since the 1940s. At a time when many standard therapies are being re-evaluated we should ask the question ‘Are we using antibiotics to their greatest potential?’


Severe Sepsis Continuous Infusion Antimicrob Agent Intermittent Infusion Intermittent Bolus 
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.
    Brun-Buisson C, Doyon F, Carlet J, et al (1995) Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. A multicenter prospective study in intensive care units. French ICU Group for Severe Sepsis. JAMA 274: 968–974Google Scholar
  2. 2.
    Rivers E, Nguyen B, Haystad S, et al (2001) Early goal directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345: 1368–1377PubMedCrossRefGoogle Scholar
  3. 3.
    Bollaert P-E, Charpentier C, Levy B, et al (1998) Reversal of late septic shock with supra-physiological doses of hydrocortisone. Crit Care Med 26: 645–650PubMedCrossRefGoogle Scholar
  4. 4.
    Wyncoll D, Beale R (2001) Immunologically enhanced enteral nutrition: current status. Curr Opin Crit Care 7: 128–132PubMedCrossRefGoogle Scholar
  5. 5.
    Bernard GR, Vincent JL, Laterre PF, et al (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344: 699–709PubMedCrossRefGoogle Scholar
  6. 6.
    de Man P, Verhoeven B, Verbrugh H, Vos M, van den Anker J (2000) An antibiotic policy to prevent emergence of resistant bacilli. Lancet 355: 973–978PubMedCrossRefGoogle Scholar
  7. 7.
    Carbon C (1992) Single-dose antibiotic therapy: what has the past taught us? J Clin Pharmacol 32: 686–691PubMedCrossRefGoogle Scholar
  8. 8.
    Rotschafer JC, Zabinski RA, Walker KJ, Vance-Bryan K (1992) Pharmacotherapy and pharmacodynamics in the management of bacterial infection. J Clin Pharmacol 32: 1083–1088PubMedGoogle Scholar
  9. 9.
    Drusano GL (1988) Role of pharmacokinetics in the outcome of infections. Antimicrob Agents Chemother 32: 289–297PubMedCrossRefGoogle Scholar
  10. 10.
    Craig WA (1995) Antibiotic selection factors and description of a hospital-based outpatient antibiotic therapy program in the USA. Eur J Clin Microbiol Infect Dis 14: 636–642PubMedCrossRefGoogle Scholar
  11. 11.
    MacGowan AP, Bowker KE (1998) Continuous infusion of ß-lactam antibiotics. Clin Pharmacokinet 35: 391–402PubMedCrossRefGoogle Scholar
  12. 12.
    MacGowan AP, Bowker KE (1997) Pharmacodynamics of antimicrobial agents and rationale for their dosing. J Chemotherapy 9: 64–73Google Scholar
  13. 13.
    Young RJ, Lipman J, Gin T, Gomersall CD, Joynt GM, Oh TE (1997) Intermittent bolus dosing of ceftazidime in critically ill patients. J Antimicrob Chemother 40: 269–273PubMedCrossRefGoogle Scholar
  14. 14.
    Lipman J, Gomersall CD, Gin T, Joynt GM, Young RJ (1999) Continuous infusion ceftazidime in intensive care: a randomised controlled trial. J Antimicrob Chemother 43: 309–311PubMedCrossRefGoogle Scholar
  15. 15.
    Gould IM (1997) Pharmacodynamics and the relationship between in vitro and in vivo activity of antimicrobial agents. J Chemother 9: 73–83Google Scholar
  16. 16.
    Thalhammer F, Traunmüller F, Menyawi IE, et al (1999) Continuous infusion versus intermittent administration of meropenem in critically ill patients. J Antimicrob Chemother 43: 523–527PubMedCrossRefGoogle Scholar
  17. 17.
    Massias L, Dubois C, de Lentdecker P, et al (1992) Penetration of vancomycin in uninfected sternal bone. Antimicrob Agents Chemother 36: 2539–2541PubMedCrossRefGoogle Scholar
  18. 18.
    Cruciani M, Gatti G, Lazzarini L, et al (1996) Penetration of vancomycin into human lung tissue. J Antimicrob Chemother 38: 865–869PubMedCrossRefGoogle Scholar
  19. 19.
    Georges H, Leroy O, Alfandari S, et al (1997) Pulmonary disposition of vancomycin in critically ill patients. Eur J Clin Microbiol Infect Dis 16: 385–388PubMedCrossRefGoogle Scholar
  20. 20.
    Ellner PD, Neu HC (1981) The inhibitory quotient. A method for interpreting minimum inhibitory concentration data. JAMA 246: 1575–1578Google Scholar
  21. 21.
    Levine DP, Fromm BS, Reddy BR (1991) Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis. Ann Intern Med 115: 674–680PubMedCrossRefGoogle Scholar
  22. 22.
    James JK, Palmer SM, Levine DP, Rybak MJ (1966) Comparison of conventional dosing versus continuous-infusion vancomycin therapy for patients with suspected or documented gram-positive infections. Antimicrob Agents Chemother 40: 696–700Google Scholar
  23. 23.
    Wysocki M, Delatour F, Faurisson F, et al (2001) Continuous versus intermittent infusion of vancomycin in severe Staphylococcal infections: prospective multicenter randomised study. Antimicrob Agents Chemother 45: 2460–2467PubMedCrossRefGoogle Scholar
  24. 24.
    NcNabb JJ, Nightingale CH, Quintiliani R, Nicolau DP (2001) Cost-effectiveness of ceftazidime by continuous infusion versus intermittent infusion for nosocomial pneumonia. Pharmacotherapy 21: 549–555CrossRefGoogle Scholar
  25. 25.
    Saunders NJ (1994) Why monitor peak vancomycin concentrations. Lancet 344: 1748–1750PubMedCrossRefGoogle Scholar
  26. 26.
    Eagle HR, Fleischman R, Musselman (1950) Effect of schedule of administration on the therapeutic efficacy of penicillin: importance of the aggregate time penicillin remains at effectively bactericidal levels. Am J Med 9: 280–299PubMedCrossRefGoogle Scholar
  27. 27.
    Servaais H, Tulkens PM (2001) Stability and compatibility of ceftazidime administered by continuous infusion to intensive care patients. Antimicrob Agents Chemother 45: 2643–2647CrossRefGoogle Scholar
  28. 28.
    Trissel LA (1998) Handbook on Injectable Drugs, 10th ed. American Society of Health System Pharmacists, BethesdaGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • D. L. A. Wyncoll
  • R. Bowry
  • L. J. Giles

There are no affiliations available

Personalised recommendations