Comparative activities of ciprofloxacin and ceftazidime against Klebsiella pneumoniae in vitro and in experimental pneumonia in leukopenic rats

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Abstract
The antibacterial activities of ciprofloxacin and ceftazidime against Klebsiella pneumoniae in vitro and in vivo were compared. Although there was only a minor difference between the MBCs of both drugs, the bacterial killing rate of ciprofloxacin in vitro was very fast in comparison with that of ceftazidime. Similarly, the intravenous administration of ciprofloxacin at 1 h after bacterial inoculation resulted in effective bacterial killing in the lungs of leukopenic rats. This killing was dose dependent, in contrast to the dose-independent bactericidal effect of ceftazidime. The high antibacterial activity of ciprofloxacin in the lungs as compared with that of ceftazidime was also reflected in its therapeutic efficacy in K. pneumoniae pneumonia and septicemia in leukopenic rats when these infections were treated at 6-h intervals over 4 days, starting at 5 h after bacterial inoculation. Concentrations of ciprofloxacin and ceftazidime in lung tissue were not significantly different. Regarding the antibacterial activity of both drugs against K. pneumoniae in relation to the bacterial growth rate in vitro and in the lungs of leukopenic rats, ciprofloxacin killed K. pneumoniae organisms that were not actively growing, whereas ceftazidime did not. In addition, it was demonstrated that when the intravenous administration of antibiotic was delayed from 1 h up to 24 h after bacterial inoculation, ceftazidime lost its antibacterial activity in the lungs and blood of leukopenic rats, whereas ciprofloxacin was still very effective. These data suggest that the capacity of an antibiotic to kill bacteria at a slow growth rate may be relevant for its therapeutic effect in established infections, in which slowly growing bacteria form a substantial part of the total bacterial population.

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