Effect of cytostatic agents on the number of alveolar phagocytes and the efficacy of ceftriaxone in an experimental murine lung infection.
Mice made monocytopenic and granulocytopenic by cyclophosphamide or monocytopenic by etoposide were infected by exposure to an aerosol containing Klebsiella pneumoniae. Eighteen hours later ceftriaxone was administered and three hours after that the experiment was ended. At the time of infection and at 18 and 21 h the numbers of alveolar macrophages and granulocytes in bronchoalveolar lavage (BAL) fluid were significantly lower in the cyclophosphamide-pretreated animals than in the controls. Furthermore, outgrowth of K. pneumoniae in the lungs was significantly stronger in cyclophosphamide-pretreated mice and a fourfold higher dose of ceftriaxone was needed to obtain the same antibacterial effect as in the controls. In the etoposide-pretreated mice the number of alveolar macrophages in BAL was not significantly lower than that in the controls, but the number of granulocytes was. Compared with the controls, there was no significant difference in the number of K. pneumoniae in the lungs, and the efficacy of ceftriaxone did not differ either.
Calame
W
W
Dept of Infectious Diseases, University Hospital, Leiden, The Netherlands.
Mattie
H
H
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002443:Ceftriaxone / Q000008:administration & dosage / Q000627:therapeutic use*; D002452:Cell Count; D003520:Cyclophosphamide / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000627:therapeutic use; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000473:pathology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000254:growth & development; D008171:Lung Diseases / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D010586:Phagocytes / Q000187:drug effects*; D011650:Pulmonary Alveoli / Q000473:pathology*
D005047:Etoposide; D002443:Ceftriaxone; D003520:Cyclophosphamide