Evaluation of ceftazidime in experimental Klebsiella pneumoniae pneumonia: comparison with other antibiotics and measurement of its penetration into respiratory tissues and secretions.
The activity of ceftazidime was examined in a murine model of Klebsiella pneumoniae pneumonia in which the antibiotic was administered subcutaneously 6 h after intranasal 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.
D000658:Amoxicillin / Q000627:therapeutic use; D000818:Animals; D001826:Body Fluids / Q000032:analysis; D002439:Cefotaxime / Q000031:analogs & derivatives / Q000627:therapeutic use; D015310:Cefotiam; D002442:Ceftazidime / Q000032:analysis / Q000378:metabolism / Q000627:therapeutic use*; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D007612:Kanamycin / Q000627:therapeutic use; D007710:Klebsiella Infections / Q000188:drug therapy*; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008168:Lung / Q000032:analysis; D051379:Mice; D010994:Pleura / Q000032:analysis; D011014:Pneumonia / Q000188:drug therapy*; D014018:Tissue Distribution; D014132:Trachea / Q000032:analysis
D002969:Clavulanic Acids; D004338:Drug Combinations; D019818:Clavulanic Acid; D007612:Kanamycin; D000658:Amoxicillin; D015310:Cefotiam; D002442:Ceftazidime; D002439:Cefotaxime