Abstract
1. Cefixime (CFIX) exhibited a marked in vitro antibacterial activity against clinical isolates of gram-negative bacteria including indole-positive Proteus spp., E. cloacae, E. aerogenes, C. freundii and S. marcescens which are not susceptible to cefaclor or cephalexin.
2. CFIX was highly stable to various types of β-lactamases produced by organisms other than B. fragilis.
3. The therapeutic effect of CFIX orally given in normal and immunosuppressed mice infected with S. pyogenes, S. pneumoniae, E. coli, K. pneumoniae, P. vulgaris or P. mirabilis was by far superior to that of cefaclor and cephalexin.
4. The therapeutic effect of CFIX in mice infected with K. pneumoniae by inhalation was about 20 times higher than that of cefaclor. The remaining bacterial counts in the lung and blood after dosing with 5mg/kg of CFIX was lower than that after dosing with 80mg/kg of cefaclor. The inhibition of bacterial growth in the lung and blood of the infected mice was stronger in repeated doses than in a single dose. CFIX at 20mg/kg maintained 3 and 60 times the MIC level respectively in the lung and serum 6 hrs after dosing.
In contrast, cefaclor at 80mg/kg maintained only 2 times the MIC level in the lung1 hr after dosing 3 times the MIC level in the serum 4 hrs after dosing. The most effective dosage schedule of CFIX in this model infection was started from 4 hrs after infection. Synergism of neutrophils and both drugs was obtained in the in vitro phagocytic killing of K. pneumoniae. The killing activity of CFIX at 0.02μg/ml was almost thesame as that of cefaclor at 0.2μg/ml in the presence of neutrophils.
