Contribution of alveolar phagocytes to antibiotic efficacy in an experimental lung infection with Streptococcus pneumoniae.
OBJECTIVE
The effect of cyclophosphamide-induced leukocytopenia on the cellular defence and on the efficacy of penicillin treatment in a Streptococcus pneumoniae pneumonia model in mice was studied.


METHODS
The number of alveolar phagocytes was determined in broncho-alveolar lavage (BAL) fluid as well as the number of bacteria in both BAL fluid and homogenized lung tissue.


RESULTS
Eighteen and 21 h after infection, leukocytopenic animals had significantly lower numbers of alveolar phagocytes than controls, while the numbers of bacteria in both BAL fluid and lungs were significantly higher. The number of bacteria was inversely related to the dose of penicillin and the number of alveolar macrophages. The number of alveolar granulocytes was inversely related to the dose of penicillin.


CONCLUSIONS
Leukocytopenia due to cyclophosphamide impairs the cellular defence in the lung against Streptococcus pneumoniae and the dose of penicillin must be increased to compensate for the higher outgrowth of bacteria in these leukocytopenic mice, compared to normal animals.
Calame
W
W
Department of Infectious Diseases, University Hospital, Bldg 1, C5-P, 2300 RC Leiden, The Netherlands. calame@mgz.fgg.eur.nl
Douwes-Idema
A E
AE
van den Barselaar
M T
MT
Mattie
H
H
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D003520:Cyclophosphamide / Q000009:adverse effects*; D004195:Disease Models, Animal; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007970:Leukopenia / Q000139:chemically induced*; D051379:Mice; D010406:Penicillins / Q000008:administration & dosage / Q000494:pharmacology*; D010586:Phagocytes / Q000187:drug effects*; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D010406:Penicillins; D003520:Cyclophosphamide