title: Pharmacodynamics of simulated total versus free-drug serum concentrations of a low versus a high protein bound third-generation oral cephalosporin (Cefpodoxime versus cefditoren) against Streptococcus pneumoniae.
abstract: Pharmacodynamic parameters and bactericidal activity against Streptococcus pneumoniae were investigated by simulating total and free serum concentrations of cefpodoxime versus cefditoren. Total drug T>MIC against the penicillin-intermediate (PISP) and resistant (PRSP) strains were 70.6% and 42.9% for cefpodoxime, and 89.6% and 62.5% for cefditoren, respectively. Comparing activity of free versus total cefpodoxime, there were reductions of 8.5% and 19.1% in T>MIC, related to bactericidal activity reductions from approximately 4.5 to 3 log(10), and from 3 to 2.5 log(10 )against PISP and PRSP, respectively, at 10-12h. For cefditoren, reductions of 45.4% and 100% in T>MIC, were related to bactericidal activity reductions from approximately 5.5 to 2-2.5 log(10 )and from approximately 2.5 to 1.5 log(10 )against PISP and PRSP, respectively, at 10-12h. Higher differences in activity were found against the less resistant strains when comparing total versus free-drug profile.
authors.affiliation: Microbiology Department, School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: O
authors.initials: O
authors.lastname: Echeverria
authors.forename: L
authors.initials: L
authors.lastname: Alou
authors.forename: D
authors.initials: D
authors.lastname: Sevillano
authors.forename: N
authors.initials: N
authors.lastname: Gonzalez
authors.forename: M L
authors.initials: ML
authors.lastname: Gomez-Lus
authors.forename: L
authors.initials: L
authors.lastname: Aguilar
authors.forename: J
authors.initials: J
authors.lastname: Prieto
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001798:Blood Proteins / Q000378:metabolism*; D015296:Ceftizoxime / Q000031:analogs & derivatives* / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology*; D003198:Computer Simulation; D024881:Drug Resistance, Bacterial; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D011485:Protein Binding; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D000097623:Cefpodoxime
chemical_list: D000900:Anti-Bacterial Agents; D001798:Blood Proteins; D015296:Ceftizoxime; D002511:Cephalosporins; D000097623:Cefpodoxime; C073460:cefditoren