Open AccessIn Vitro and In Vivo Activities of a New Cephalosporin, FR264205, against Pseudomonas aeruginosa
Author(s) -
Shinobu Takeda,
Toru Nakai,
Yoshimi Wakai,
Fumiaki Ikeda,
Kazuo Hatano
Publication year - 2007
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00860-06
Subject(s) - pseudomonas aeruginosa , ceftazidime , microbiology and biotechnology , cephalosporin , ciprofloxacin , efflux , in vivo , imipenem , in vitro , antibiotics , antibacterial agent , biology , pseudomonadales , chemistry , bacteria , antibiotic resistance , biochemistry , genetics
FR264205 is a novel parenteral 3′-aminopyrazolium cephalosporin. This study evaluated the in vitro and in vivo activities of FR264205 againstPseudomonas aeruginosa . The MIC of FR264205 at which 90% of 193 clinical isolates ofP. aeruginosa were inhibited was 1 μg/ml, 8- to 16-fold lower than those of ceftazidime (CAZ), imipenem (IPM), and ciprofloxacin (CIP). FR264205 also exhibited this level of activity against CAZ-, IPM-, and CIP-resistantP. aeruginosa . The reduction in the susceptibility of FR264205 by AmpC β-lactamase was lower than that of CAZ, indicating a relatively high stability of FR264205 against AmpC β-lactamase, the main resistance mechanism for cephalosporins. Neither expression of efflux pumps nor deficiency of OprD decreased the activity of FR264205. No spontaneous resistance mutants were selected in the presence of FR264205, and the reduction in susceptibility to FR264205 was lower than that to CAZ, IPM, and CIP after serial passage, suggesting that FR264205 has a low propensity for selecting resistance. In murine pulmonary, urinary tract, and burn wound models of infection caused byP. aeruginosa , the efficacy of FR264205 was superior or comparable to those of CAZ and IPM. These results indicate that FR264205 should have good potential as an antibacterial agent forP. aeruginosa .