Abstract
The combined effects of cefasolin and gentamicin on the fatal murine pneumonia due to Klebsiella pneumoniae have been studied, utilizing the method for quantitating both intrapulmonary viable bacteria and drug concentrations, and revealed the synergistic action small dose of gentamicin with cefazolin.
Before the in vivo experiments, in vitro synergistic effect of cefazolin and gentamicin on the growth curve of Klebsiella pneumoniae B-54 (MIC of cefasolin 1.56 μg/ml; gentamicin 0.39 μg/ml) was examined, using Biophotorecorder TN-112 D [Toyo Kagaku Co.]. This study revealed that 1/50 MIC (0.008 μg/ml) of gentamicin clearly strengthened the suppressing effect of cefazolin on the bacterial growth.
As reported in our previous papers [Chemotherapy 27: 109-115 & 801-806, 1979], in each experment, 150 mice infected with 500 LD50 of Kiebsiella pneumoniae B-54 (LD50; 9.7×10 C. F. U./lung) were treated by subcutaneous injections of cefazolin and/or gentamicin, begun at 12 hours after infection. The curative action of repeated injections of cefazolin 50mg/kg plus either gentamicin 1mg/kg, 0.1mg/kg or 0.01mg/kg was superior to that of cefazolin alone. Furthermore, even the injections of 0.01 mg/kg of gentamicin q. 6h. clearly increased the curative effect of the injections of cefazolin 50 mg/kg q. 1 1/2h. The single injection of cefazolin 50mg/kg plus gentamicin 0.01mg/kg suppressed the bacterial growth in the murine lung during more than 3 hours, while the single injection of cefazolin 50 mg/kg alone suppressed during only one hour.
