Evaluation of ceftazidime in experimental Klebsiella pneumoniae pneumonia: comparison with other antibiotics and measurement of its penetration into respiratory tissues and secretions

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Abstract
The activity of ceftazidime was examined in a murine model of Klebsiella pneumoniae pneumonia in which the antibiotic was administered subcutaneously 6 h after intra-nasal infection and then twice daily for the next three days (i.e. seven doses). In a series of experiments using this test, the dose of ceftazidime giving 50% survival relative to controls (SD50) ranged from 1.0–9.0 mg/kg/dose while the dose required to reduce the log10 cfu/lung by 50% (CD50) ranged from 24–64 mg/kg/dose. Ceftazidime was considerably more effective than cefotiam, amoxycillin-clavulanic acid or kanamycin in the test. Pharmacokinetic studies with ceftazidime showed that no differences in respiratory tract penetration existed between uninfected mice and mice infected for 48 h with K. pneumoniae. The percentage penetration of ceftazidime from serum was 73% for pleural fluid, 44% for tracheal fluid, 27% for tracheal wall tissue and 17% for whole lung tissue after a subcutaneous injection of 100 mg/kg. At this dose, ceftazidime remained at supra-MIC concentrations for 2–3 h in all compartments examined.