Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 51 (3), 826-30

In Vitro and in Vivo Activities of a New Cephalosporin, FR264205, Against Pseudomonas Aeruginosa

Affiliations

In Vitro and in Vivo Activities of a New Cephalosporin, FR264205, Against Pseudomonas Aeruginosa

Shinobu Takeda et al. Antimicrob Agents Chemother.

Abstract

FR264205 is a novel parenteral 3'-aminopyrazolium cephalosporin. This study evaluated the in vitro and in vivo activities of FR264205 against Pseudomonas aeruginosa. The MIC of FR264205 at which 90% of 193 clinical isolates of P. aeruginosa were inhibited was 1 microg/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-resistant P. aeruginosa. The reduction in the susceptibility of FR264205 by AmpC beta-lactamase was lower than that of CAZ, indicating a relatively high stability of FR264205 against AmpC beta-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 by P. 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 for P. aeruginosa.

Figures

FIG. 1.
FIG. 1.
Chemical structure of FR264205.
FIG. 2.
FIG. 2.
Development of resistance in P. aeruginosa PAO1 after serial passage. P. aeruginosa PAO1 was cultured in medium containing FR264205 (•), CAZ (○), IPM (▵), and CIP (□).
FIG. 3.
FIG. 3.
Therapeutic activity of FR264205 in pulmonary infection (A), urinary tract infection (B), and burn wound infection (C) caused by P. aeruginosa 93. Gray and filled columns indicate 2-mg/kg and 10-mg/kg doses, respectively (A), 0.5-mg/kg and 2-mg/kg doses, respectively (B), and 10-mg/kg and 50-mg/kg doses, respectively (C).

Similar articles

See all similar articles

Cited by 29 PubMed Central articles

See all "Cited by" articles

MeSH terms

LinkOut - more resources

Feedback