title: [In vitro and in vivo activities of cefpodoxime proxetil against penicillin-resistant Streptococcus pneumoniae].
abstract: We evaluated in vitro and in vivo activities of cefpodoxime proxetil (CPDX-PR) in comparison with other oral beta-lactams, cefdinir (CFDN), cefditoren pivoxil (CDTR-PI), and faropenem (FRPM), against penicillin-susceptible and -resistant Streptococcus pneumoniae. In vitro activities (MICs) of CPDX, CFDN, CDTR, and FRPM against clinical isolates, penicillin-susceptible S. pneumoniae (PSSP: MIC of penicillin G, < or = 0.063 microgram/ml), penicillin-intermediate S. pneumoniae (PISP: MIC of penicillin G, 0.125-1 microgram/ml), and penicillin-resistant S. pneumoniae (PRSP: MIC of penicillin G, > or = 2 micrograms/ml), were tested by an agar dilution method. The MIC80s of CPDX against 27 PSSP strains, 23 PISP strains, and 23 PRSP strains were 0.032, 1, and 8 micrograms/ml, respectively, which were superior to or equal to those of CFDN (0.063, 4, and 8 micrograms/ml) and were inferior to those of CDTR (0.016, 0.5, and 1 microgram/ml) and FRPM (< or = 0.008, 0.25, and 1 microgram/ml). Infection was induced in mice by inoculating with a PRSP clinical isolate, 9605 or 9601 (serotype 6), or 10692 (serotype 19), through the nares of male ddY mice into the lungs. The mice were treated with drugs with doses of 2-50 mg/kg at 18, 26, 42, and 50 hours after the infection. Viable cell numbers in the lungs and blood were assayed at 66 hours after the infection. The efficacy of each drug was dose-dependent. CPDX-PR showed the most potent in vivo efficacy among the drugs tested against the infections caused by the PRSP strains. MICs of the drugs against PRSP 9605, 9601, and 10692 were as follows: CPDX, 4, 4 and 2 micrograms/ml; CFDN, 16, 16, and 4 micrograms/ml; CDTR, 1, 1, and 0.5 microgram/ml; and FRPM, 1, 0.5, and 0.5 microgram/ml, respectively. Thus, CPDX-PR showed a stronger in vivo activity than that expected from the MICs of CPDX. This was probably caused by the pharmacokinetic advantage of CPDX over the other drugs used in this study.
authors.affiliation: Biological Research Laboratories, SANKYO CO., LTD.
authors.forename: H
authors.initials: H
authors.lastname: Kawada
authors.forename: A
authors.initials: A
authors.lastname: Kitayama
authors.forename: T
authors.initials: T
authors.lastname: Fukuoka
authors.forename: C
authors.initials: C
authors.lastname: Ishii
authors.forename: T
authors.initials: T
authors.lastname: Abe
authors.forename: M
authors.initials: M
authors.lastname: Kakuta
authors.forename: H
authors.initials: H
authors.lastname: Domon
authors.forename: S
authors.initials: S
authors.lastname: Ohya
authors.forename: Y
authors.initials: Y
authors.lastname: Utsui
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000077525:Cefdinir; D015296:Ceftizoxime / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002511:Cephalosporins / Q000494:pharmacology; D007769:Lactams; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy*; D011355:Prodrugs / Q000494:pharmacology / Q000627:therapeutic use; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D047090:beta-Lactams; D000097627:Cefpodoxime Proxetil
chemical_list: D000900:Anti-Bacterial Agents; D000077525:Cefdinir; D015296:Ceftizoxime; D002511:Cephalosporins; D007769:Lactams; D011355:Prodrugs; D047090:beta-Lactams; D000097627:Cefpodoxime Proxetil; C057710:cefditoren pivoxil; C107057:fropenem