We evaluated
in vitro and
in vivo activities of cefpodoxime proxetil (CPDX-PR) in comparison with otheroral β-lactams, cefdinir (CFDN), cefditoren pivoxil (CDTR-PI), and faropenem (FRPM), against penicillin-susceptibleand -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, ≤0.063μg/ml), penicillin-intermediate
S. pneumoniae(PISP: MIC of penicillin G, 0.125-1μg/ml), and penicillin-resistant
S. pneumoniae(PRSP: MIC of penicillin G, ≥2μg/ml), were tested by an agar dilution method. The MIC
80s of CPDX against 27 PSSP strains, 23 PISP strains, and 23 PRSP strains were 0.032, 1, and 8μg/ml, respectively, which were superior to or equal to those of CFDN (0.063, 4, and 8μg/ml) and were inferior to those of CDTR (0.016, 0.5, and 1μg/ml) and FRPM (≤0.008, 0.25, and 1μg/ml).
Infection was induced in mice by inoculating with a PRSP clinical isolate, 9605 or 9601 (serotype 6), or10692 (serotype 19), through the nares of male ddY mice into the lungs. The mice were treated with drugs withdoses of 2-50 mg/kg at 18, 26, 42, and 50 hours after the infection. Viable cell numbers in the lungs and bloodwere assayed at 66 hours after the infection. The efficacy of each drug was dose-dependent. CPDX-PR showedthe most potent in vivo efficacy among the drugs tested against the infections caused by the PRSP strains. MICsof the drugs against PRSP 9605, 9601, and 10692 were as follows: CPDX, 4, 4 and 2μg/ml; CFDN, 16, 16, and4μg/ml; CDTR, 1, 1, and 0.5μg/ml; and FRPM, 1, 0.5, and 0.5μg/ml, respectively. Thus, CPDX-PR showed astronger 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.
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