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Antimicrobial Agents and Chemotherapy, March 2007, p. 826-830, Vol. 51, No. 3
0066-4804/07/$08.00+0     doi:10.1128/AAC.00860-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

In Vitro and In Vivo Activities of a New Cephalosporin, FR264205, against Pseudomonas aeruginosa{triangledown}

Shinobu Takeda,* Toru Nakai, Yoshimi Wakai, Fumiaki Ikeda, and Kazuo Hatano

Pharmacology Research Labs, Astellas Pharma, Inc., 1-6, 2-Chome Kashima, Yodogawa-ku, Osaka 532-8514, Japan

Received 14 July 2006/ Returned for modification 5 October 2006/ Accepted 22 November 2006

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 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-resistant P. aeruginosa. The reduction in the susceptibility of FR264205 by AmpC ß-lactamase was lower than that of CAZ, indicating a relatively high stability of FR264205 against AmpC ß-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.

* Corresponding author. Mailing address: Infectious Diseases, Pharmacology Research Labs, Drug Discovery Research, Astellas Pharma, Inc., 1-6, Kashima 2-Chome, Yodogawa-ku, Osaka 532-8514, Japan. Phone: 81-6-6390-1146. Fax: 81-6-6304-5367. E-mail: shinobu.takeda{at}jp.astellas.com.

{triangledown} Published ahead of print on 4 December 2006.

Antimicrobial Agents and Chemotherapy, March 2007, p. 826-830, Vol. 51, No. 3
0066-4804/07/$08.00+0     doi:10.1128/AAC.00860-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Livermore, D. M. (2009). Has the era of untreatable infections arrived?. J Antimicrob Chemother 64: i29-i36 [Abstract] [Full Text]  
  • Giske, C. G., Ge, J., Nordmann, P. (2009). Activity of cephalosporin CXA-101 (FR264205) and comparators against extended-spectrum-{beta}-lactamase-producing Pseudomonas aeruginosa. J Antimicrob Chemother 64: 430-431 [Full Text]  


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