A modified recombinant human
granulocyte colony-stimulating factor (rhG-CSF),
KW-2228, has 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 its clinical applications. In this paper, we investigated protective effects of
KW-2228 against systemic
infections caused by Klebsiella pneumoniae in mice with
leukopenia induced by the administration of
cyclophosphamide.
KW-2228 (1 microgram/mouse) was administered (s.c.) once a day for 4 days following
cyclophosphamide administration, then mice were challenged with K. pneumoniae (i.p.) 4 hours after the last administration of
KW-2228. An
antibiotic was administered (s.c., p.o.) 2 hours after the bacterial challenge. Combination effects of
KW-2228 with cefazoline,
cefmetazole,
ceftazidime or
cefaclor were evaluated in the systemic
infection with K. pneumoniae. Each combination
therapy using
KW-2228 with each of the cephems exhibited an excellent protective effect in comparison to the
therapy with a cephem alone. These results show the possibility that
KW-2228 could be of use in treating obstinate
infections not successfully treated with an
antimicrobial agent alone.