[Combination effect of KW-2228 and cephem antibiotics in a systemic infection model in neutropenic mice].
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.
Yoshino
T
T
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.
Sato
K
K
D000818:Animals; D002511:Cephalosporins / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000009:adverse effects; D004359:Drug Therapy, Combination; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D007710:Klebsiella Infections / Q000188:drug therapy*; D007711:Klebsiella pneumoniae; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications*; D011994:Recombinant Proteins / Q000008:administration & dosage
D002511:Cephalosporins; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; C072115:nartograstim