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[Combination effect of KW-2228 and cephem antibiotics in a systemic infection model in neutropenic mice].

Abstract
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.
AuthorsT Yoshino, K Sato
JournalThe Japanese journal of antibiotics (Jpn J Antibiot) Vol. 45 Issue 1 Pg. 106-11 (Jan 1992) ISSN: 0368-2781 [Print] Japan
PMID1379649 (Publication Type: Journal Article)
Chemical References
  • Cephalosporins
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Cyclophosphamide
  • nartograstim
Topics
  • Animals
  • Cephalosporins (administration & dosage)
  • Cyclophosphamide (adverse effects)
  • Drug Therapy, Combination
  • Granulocyte Colony-Stimulating Factor (administration & dosage)
  • Klebsiella Infections (drug therapy)
  • Klebsiella pneumoniae
  • Male
  • Mice
  • Mice, Inbred Strains
  • Neutropenia (chemically induced, complications)
  • Recombinant Proteins (administration & dosage)

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