Experimental pneumococcus infection in mice: comparative in vitro and in vivo effect of cefuroxime, cefotaxime and ceftriaxone.
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 measured by time-kill curves was similar for the 3 drugs, as was the post-antibiotic effect in vitro. Protein binding in mouse serum was considerably 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-life resulting in an extended delta T(MIC), probably related to the high serum protein binding.
Frimodt-Møller
N
N
Department of Antibiotics, Statens Seruminstitut, Copenhagen, Denmark.
Bentzon
M W
MW
Thomsen
V F
VF
D000818:Animals; D002439:Cefotaxime / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002443:Ceftriaxone / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002444:Cefuroxime / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002511:Cephalosporins / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008826:Microbial Sensitivity Tests; D011008:Pneumococcal Infections / Q000188:drug therapy*; D011485:Protein Binding; D013296:Streptococcus pneumoniae / Q000187:drug effects*
D002511:Cephalosporins; D002443:Ceftriaxone; D002439:Cefotaxime; D002444:Cefuroxime