Penetration of beta-lactam antibiotics into cardiac vegetations, aorta and heart muscle in experimental Staphylococcus aureus endocarditis: comparison of ceftazidime, cefuroxime and methicillin.
The penetration of ceftazidime, cefuroxime and methicillin into cardiac vegetations, normal aorta wall tissue, heart muscle and heart muscle tissue fluid was measured in rabbits with Staphylococcus aureus (853E) endocarditis. After a 100 mg/kg intramuscular injection, ceftazidime attained significantly higher peak concentrations than cefuroxime and methicillin in all compartments with the exception of aorta where no difference was observed between ceftazidime and methicillin. The half life of ceftazidime in each compartment (50-65 min) was approximately twice that of cefuroxime and methicillin. The area under the concentration/time curve for ceftazidime in vegetations over a post dosing 6 h period was approximately five times greater than that for cefuroxime and three times that for methicillin. Ceftazidime remained for a longer time period in all compartments, however cefuroxime persisted the longest at supra-MIC concentrations in all compartments except serum. Compared to cefuroxime and methicillin where vegetation and aorta tissue levels were similar, ceftazidime attained peak levels in vegetations which were more than double those found in aorta tissue. Analysis of the percentage penetration from serum into vegetation, suggested that the higher concentrations of ceftazidime in vegetation tissue were probably not a function of increased fluid content relative to undamaged aorta but were more likely caused by an intrinsically better penetrating capacity for vegetation tissue.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000627:therapeutic use; D001826:Body Fluids / Q000378:metabolism; D002442:Ceftazidime / Q000378:metabolism; D002444:Cefuroxime / Q000378:metabolism; D004697:Endocarditis, Bacterial / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D008712:Methicillin / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D002442:Ceftazidime; D002444:Cefuroxime; D008712:Methicillin