Therapeutic efficacy of granulocyte colony-stimulating factor alone and in combination with antibiotics against Pseudomonas aeruginosa infections in mice.
The therapeutic efficacy of granulocyte colony-stimulating factor (G-CSF) against an experimental intramuscular infection induced by Pseudomonas aeruginosa in mice was confirmed. Bacterial growth in the infected thigh muscle was suppressed by G-CSF treatment. The change in the number of peripheral blood polymorphonuclear leukocytes (PMN) after bacterial challenge was investigated. The results showed that G-CSF could stimulate stronger defense mechanisms after stimulation by bacterial challenge. In the G-CSF-treated group, more clusters of matured PMN were observed in the infected thigh muscle 6 h after bacterial challenge. Next, the correlation between the number of PMN in the blood at the time of infection and the therapeutic efficacy of antibiotics was investigated. The therapeutic efficacy of ceftazidime, a beta-lactam antibiotic, was affected by the number of blood PMN at the time of infection. In particular, a decrease of peripheral blood PMN at the time of infection resulted in a dramatic decrease in the efficacy of ceftazidime. The reduction in leukopenia by G-CSF remarkably strengthened the therapeutic effect of antibiotics in mice.
Yasuda
H
H
Biological Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Ajiki
Y
Y
Shimozato
T
T
Kasahara
M
M
Kawada
H
H
Iwata
M
M
Shimizu
K
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002442:Ceftazidime / Q000627:therapeutic use; D015169:Colony Count, Microbial; D003115:Colony-Stimulating Factors / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D016179:Granulocyte Colony-Stimulating Factor; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009132:Muscles / Q000382:microbiology / Q000473:pathology; D009135:Muscular Diseases / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D009428:Netilmicin / Q000627:therapeutic use; D009504:Neutrophils; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000473:pathology
D000900:Anti-Bacterial Agents; D003115:Colony-Stimulating Factors; D016179:Granulocyte Colony-Stimulating Factor; D009428:Netilmicin; D003520:Cyclophosphamide; D002442:Ceftazidime