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Query: UMLS:C0014118 (endocarditis)
 15,629 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Penetration of beta-lactam antibiotics into cardiac vegetations, aorta and heart muscle in experimental Staphylococcus aureus endocarditis: comparison of ceftazidime, cefuroxime and methicillin. 390 61

Ceftazidime and amikacin were administered in a Pseudomonas aeruginosa rabbit endocarditis model using computer-controlled intravenous (iv) infusion pumps to simulate human serum concentrations for the following regimens: continuous (constant rate) infusion of 4, 6 or 8 g of ceftazidime over 24 h or intermittent dosing of 2 g every 8 h either alone or in combination with amikacin (15 mg/kg once daily). The in vivo activities of these regimens were tested on four Pseudomonas aeruginosa strains. Animals were killed 24 h after the beginning of treatment. Efficacy was assessed by comparing the effects of the different groups on bacterial counts in vegetations for each strain tested. For a susceptible reference strain (ATCC 27853; MICs of ceftazidime and amikacin 1 and 2 mg/L, respectively), continuous infusion of 4 g alone or with amikacin was as effective as intermittent dosing with amikacin. For a clinical isolate producing an oxacillinase (MICs of ceftazidime and amikacin 8 and 32 mg/L, respectively), continuous infusion of 6 g was equivalent to intermittent dosing. For a clinical isolate producing a TEM-2 penicillinase (MIC of ceftazidime and amikacin 4 mg/L), continuous infusion of 6 g, but not intermittent dosing, had a significant in vivo effect. For a clinical isolate producing an inducible, chromosomally encoded cephalosporinase (MIC of ceftazidime and amikacin 8 and 4 mg/L, respectively), neither continuous infusion nor intermittent dosing proved effective. Determination of ceftazidime concentrations in vegetations showed that continuous infusion produced tissue concentrations at the infection site far greater than the MIC throughout the treatment. It is concluded that continuous infusion of the same total daily dose provides significant activity as compared with fractionated infusion. This study confirms that a concentration of 4-5 x MIC is a reasonable therapeutic target in most clinical settings of severe P. aeruginosa infection.
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PMID:In vivo efficacy of continuous infusion versus intermittent dosing of ceftazidime alone or in combination with amikacin relative to human kinetic profiles in a Pseudomonas aeruginosa rabbit endocarditis model. 1132 73