EXPERIMENTAL PNEUMOCOCCUS INFECTION IN MICE: COMPARATIVE IN VITRO AND IN VIVO EFFECT OF CEFUROXIME, CEFOTAXIME AND CEFTRIAXONE

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Abstract
In a mouse model using intraperitoneal inoculation of Streptococcus pneumoniae type 3, the 50% effective dose, ED50, after single doses one hour post-inoculation was considerably lower for ceftriaxone (CRO) than for cefuroxime (CXM) and cefotaxime (CTX), in spite of the same minimal inhibitory concentration, MIC, of 0.02 mcg/ml against the pneumococcus for all 3 drugs. The bactericidal activity as meaasured by time-kill curves was similar for the 3 drugs, as was the post-antibiotic effect in vitro. Protein binding in mouse serum was consideably higher for CRO (87%) than for both CTX (35%) and CXM (15%), respectively. Of pharmacokinetic parameters investigated on doses equal to the ED50s, the time the serum antibiotic concentration remained above the MIC (.DELTA.T(MIC)) was the factor that varied the least among 3 drugs. Therefore, the superior in vivo effect for CRO is not due to higher intrinsic activity against the pathogen but to the long serum-elimination half-ife resulting in an extended .DELTA.T(MIC), probably related to the high serum protein binding.