KW-2228, a mutationally modified recombinant human
granulocyte colony-stimulating factor (rhG-CSF), possesses some excellent properties such as high specific activity in stimulating granulocyte colony-formation in vitro, great
biological stability in plasma, good pharmacokinetic profile and high potency in granulopoiesis in normal mice in vivo. Recently, the application of
G-CSF against
infectious diseases has been considered, and some animal experiments have been carried out to support such an application on human
infectious diseases. In this paper, we examined combination effect of
KW-2228 with various chemotherapeutic drugs in experimental infectious in mice. A combination effect of
KW-2228 with
ceftazidime (CAZ) was evaluated in a systemic
infection with Pseudomonas aeruginosa in normal mice. Combination effects of
KW-2228 with CAZ,
astromicin and
amphotericin B were also evaluated in experimental systemic
infections caused by P. aeruginosa, Serratia marcescens and Candida albicans in immunosuppressed mice treated with
cyclophosphamide. Synergistic effects were generally observed at
KW-2228 doses from 1 to 5 micrograms per mouse with all combinations. We concluded that combination
therapies of
KW-2228 with various chemotherapeutic drugs in experimental
infections in mice showed that it should be effective in normal and immunosuppressed host. These results of our laboratory studies suggest that
KW-2228 in combination with
antibiotics would be useful in the clinical treatment of microbial
infections. Recently, clinical efficacy studies of
KW-2228 have been initiated in Japan.