Skip to main content
SpringerLink
Log in

Impact of the duration of infection on the activity of ceftazidime, gentamicin and ciprofloxacin inKlebsiella pneumoniae pneumonia and septicemia in leukopenic rats

  • Article
  • Published:
European Journal of Clinical Microbiology and Infectious Diseases Aims and scope Submit manuscript

Abstract

An experimentalKlebsiella pneumoniae pneumonia and septicemia in leukopenic rats was used to study the impact of the duration of infection on the bactericidal activity of ceftazidime, gentamicin and ciprofloxacin. It appeared that the number of bacteria persisting after a single intravenous injection progressively increased with delay of antibiotic administration up to 3 h after bacterial inoculation with each of the drugs tested. This effect was most pronounced for ciprofloxacin. An inoculum effect could not explain this decrease in bacterial killing. It was also observed that a single injection with a particular dose of each of the respective drugs did not kill all theKlebsiella pneumoniae organisms in the lung. Persisting bacteria did not represent a preexisting less susceptible subpopulation selected after antibiotic administration. In further experiments the impact of delay of the start of treatment on the efficacy of ceftazidime or ciprofloxacin after administration for a period of four days with intramuscular injections at 6 h intervals was investigated. Treatment was started at 5, 12 or 24 h after bacterial inoculation. The therapeutic efficacy of both drugs decreased with the increase of duration of infection, which may be at least in part due to the progressive number of bacteria persisting after antibiotic administration. These data underline the need to start antimicrobial treatment as soon as possible.

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

References

  1. Wade JC, Schimpff SC Antibiotic therapy for febrile granulocytopenic patients. In: Klastersky J, Staquet MJ (ed): Combination antibiotic therapy in the compromised host. Raven Press, New York, 1982, p. 125–146.

    Google Scholar 

  2. Klastersky J, Glauser MP, Schimpff SC, Zinner SH, Gaya H The European Organization for Research on Treatment of Cancer Antimicrobial Therapy Project Group: Prospective randomized comparison of three antibiotic regimens for empirical therapy of suspected bacteremic infection in febrile granulocytopenic patients. Antimicrobial Agents and Chemotherapy 1986, 29: 263–270.

    PubMed  Google Scholar 

  3. Sculier JP, Weerts D, Klastersky J Causes of death in febrile granulocytopenic cancer patients receiving empiric antibiotic therapy. European Journal of Cancer and Clinical Oncology 1984, 20: 55–60.

    Google Scholar 

  4. Bakker-Woudenberg IAJM, van den Berg JC, Michel MF Therapeutic activities of cefazolin, cefotaxime, and ceftazidime against experimentally inducedKlebsiella pneumoniae pneumonia in rats. Antimicrobial Agents and Chemotherapy 1982, 22: 1042–1050.

    PubMed  Google Scholar 

  5. Roosendaal R, Bakker-Woudenberg IAJM, van den Berghe-van Raffe M, Michel MF Continuous versus intermittent administration of ceftazidime in experimental pneumonia in normal and leukopenic rats. Antimicrobial Agents and Chemotherapy 1986, 30: 403–408.

    PubMed  Google Scholar 

  6. Roosendaal R, Bakker-Woudenberg IAJM, van den Berghe-van Raffe M, Vink-van den Berg JC, Michel MF Impact of the dosage schedule on the efficacy of ceftazidime, gentamicin and ciprofloxacin inKlebsiella pneumoniae pneumonia and septicemia in leukopenic rats. European Journal of Clinical Microbiology and Infectious Diseases 1989, 8: 787–887.

    Google Scholar 

  7. Sachs L Evaluation of biologically active substances based on dosage-dichotomous effect curves. In: Sachs L (ed): Applied statistics. A handbook of techniques. Springer Verlag, New York, 1982, p. 224–228.

    Google Scholar 

  8. Leggett JE, Fantin B, Ebert S, Totsuka K, Vogelman B, Calame W, Mattie H, Craig WA Comparative doseeffect relations at several dosing intervals in murine pneumonitis and thigh-infection models. Journal of Infectious Diseases 1989, 159: 281–292.

    PubMed  Google Scholar 

  9. Davey PG, Barza M, Stuart M Dose response of experimental pseudomonas endophthalmitis to ciprofloxacin, gentamicin, and imipenem: evidence for resistance to “late” treatment of infections. Journal of Infectious Diseases 1987, 155: 518–523.

    PubMed  Google Scholar 

  10. Davey PG, Barza M, Stuart M Tolerance ofPseudomonas aeruginosa to killing by ciprofloxacin, gentamicin and imipenem in vitro and in vivo. Journal of Antimicrobial Chemotherapy 1988, 22: 395–404.

    PubMed  Google Scholar 

  11. Greenwood D Phenotypic resistance to antimicrobial agents. Journal of Antimicrobial Chemotherapy 1985, 15: 653–658.

    PubMed  Google Scholar 

  12. Brown MRW Nutrient depletion and antibiotic susceptibility. Journal of Antimicrobial Chemotherapy 1977, 3: 198–201.

    PubMed  Google Scholar 

  13. Gerber AU, Craig WA Aminoglycoside-selected subpopulations ofPseudomonas aeruginosa. Characterization and virulence in normal and leukopenic mice. Journal of Laboratory and Clinical Medicine 1982, 100: 671–681.

    PubMed  Google Scholar 

  14. Gerber AU, Vastola AP, Brandel J, Craig WA Selection of aminoglycoside-resistant variants ofPseudomonas aeruginosa in an in vivo model. Journal of Infectious Diseases 1982, 146: 691–697.

    PubMed  Google Scholar 

  15. Musher DM, Baughn RE, Merrell GL Selection of small-colony variants ofEnterobacteriaceae by in vitro exposure of aminoglycosides: pathogenicity for experimental animals. Journal of Infectious Diseases 1979, 140: 209–214.

    PubMed  Google Scholar 

  16. Roosendaal R, Bakker-Woudenberg IAJM, van den Berghe-van Raffe M, Vink-van den Berg JC, Michel MF Comparative activities of ciprofloxacin and ceftazidime againstKlebsiella pneumoniae in vitro and in experimental pneumonia in leukopenic rats. Antimicrobial Agents and Chemotherapy 1987, 31: 1809–1815.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Microbiology, Academic Hospital Free University, PO Box 7057, 1007 MB, Amsterdam, The Netherlands

    R. Roosendaal

  2. Department of Clinical Microbiology and Antimicrobial Therapy, Erasmus University Rotterdam, PO Box 1738, 3000 DR, Rotterdam, The Netherlands

    I. A. J. M. Bakker-Woudenberg, M. van den Berghe-van Raffe, J. C. Vink-van den Berg & M. F. Michel

Authors
  1. R. Roosendaal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. A. J. M. Bakker-Woudenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. van den Berghe-van Raffe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. C. Vink-van den Berg
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. F. Michel
    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

Roosendaal, R., Bakker-Woudenberg, I.A.J.M., van den Berghe-van Raffe, M. et al. Impact of the duration of infection on the activity of ceftazidime, gentamicin and ciprofloxacin inKlebsiella pneumoniae pneumonia and septicemia in leukopenic rats. Eur. J. Clin. Microbiol. Infect. Dis. 10, 1019–1025 (1991). https://doi.org/10.1007/BF01984923

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01984923

Keywords

Search

Navigation