Original article
Influence of cytostatic agents on the pulmonary defence of mice infected with Klebsiella pneumoniae and on the efficacy of treatment with ceftriaxone

https://doi.org/10.1016/S0163-4453(94)95087-3Get rights and content

Summary

The effect of cytostatic treatment on the cellular defence and the efficacy of treatment with ceftriaxone in Klebsiella pneumoniae pneumonia was studied. Mice, made monocytopenic and granulocytopenic by cyclophosphamide or monocytopenic by etoposide, were infected intratracheally with K. pneumoniae (approximately 104 CFU) and then treated with ceftriaxone. At various intervals, the numbers of bacteria in the broncho-alveolar lavage (BAL) fluid and in lungs homogenised after lavage were determined. Cyclophosphamide reduced the numbers of granulocytes in the BAL fluid significantly but reduced only slightly the number of alveolar macrophages at the time of inoculation, 12 and 15 h later. The number of CFU in cyclophosphamide-treated mice was higher than that in controls, being significant in the homogenised lungs at 15 h after infection. In etoposide-treated mice, the numbers of alveolar phagocytes in BAL did not differ from those in control mice, whereas the number of bacteria was lower (only significantly in BAL fluid at 15 h after infection) than that in the controls. In this short experimental infection cytostatic treatment did not affect the outgrowth of Klebsiella pneumoniae substantially or the efficacy of treatment with ceftriaxone.

References (41)

  • GurneyH

    The problem of neutropenia resulting from cancer therapy

    Clinician

    (1989)
  • CalameW et al.

    Influence of etoposide and cyclophosphamide on the efficacy of cloxacillin and erythromycin in an experimental staphylococcal infection

    Antimicrob Agents Chemother

    (1989)
  • JakabGJ et al.

    Lung defenses against viral and bacterial challenges during immunosuppression with cyclophosphamide in mice

    Am Rev Respir Dis

    (1981)
  • MayerP et al.

    Studies of lung infections caused by Pseudomonas aeruginosa in mice treated with cyclophosphamide

    Infection

    (1983)
  • HoogeterpJJ et al.

    Quantitative effect of granulocytes on antibiotic treatment of experimental Staphylococcal infection

    Antimicrob Agents Chemother

    (1987)
  • van der VoetGB et al.

    Quantitative determination of the effect of granulocytes on the course of experimental infections during antibiotic treatment

    Infection

    (1984)
  • MeddensMJM et al.

    Role of granulocytes and monocytes in experimental Staphylococcus epidermidis endocarditis

    Infect Immun

    (1983)
  • Van't WoutJW et al.

    Effect of irradiation, cyclophosphamide and etoposide (VP-16) on the number of peripheral blood and peritoneal leucocytes in mice under normal conditions and during an acute inflammatory reaction

    Inflammation

    (1988)
  • RosenstreichDL

    The macrophage

  • Blussé van Oud AlblasA et al.

    Origin, kinetics and characteristics of pulmonary macrophages in the normal steady state

    J Exp Med

    (1983)
  • Cited by (21)

    • Apoptosis in rheumatoid arthritis: Friend or foe

      2004, Rheumatic Disease Clinics of North America
    • Inflammatogenic properties of bacterial DNA following cutaneous exposure

      2003, Journal of Investigative Dermatology
      Citation Excerpt :

      A volume of 120 μL, which corresponded to 12.5 mg per kg body weight of etoposide, was injected subcutaneously (s.c.) in BALB/C mice on 2 consecutive days before, and on 5 consecutive days after, intradermal injection of the phosphorothioate ogliodeoxynucleotide. The dose of etoposide was chosen according to that established in earlier studies (Calame et al, 1994). Fluorescence-activated cell sorter analysis of peripheral blood was performed to assess the effect of macrophage depletion, as previously described in detail (Verdrengh and Tarkowski, 2000), and showed that etoposide depleted the monocyte population by 80%.

    View all citing articles on Scopus
    View full text