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Antimicrobial Agents and Chemotherapy, August 2008, p. 2849-2854, Vol. 52, No. 8
0066-4804/08/$08.00+0     doi:10.1128/AAC.00413-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Potent In Vitro Activity of Tomopenem (CS-023) against Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa{triangledown}

Tetsufumi Koga,* Nobuhisa Masuda, Masayo Kakuta, Eiko Namba, Chika Sugihara, and Takashi Fukuoka

Biological Research Laboratories IV, Daiichi Sankyo Co., Ltd., 16-13, 1-Chome Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan

Received 26 March 2008/ Returned for modification 24 April 2008/ Accepted 28 May 2008

Tomopenem (formerly CS-023) is a novel 1β-methylcarbapenem with broad-spectrum coverage of gram-positive and gram-negative pathogens. Its antibacterial activity against European clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa was compared with those of imipenem and meropenem. The MICs of tomopenem against MRSA and P. aeruginosa at which 90% of the isolates tested were inhibited were 8 and 4 µg/ml, respectively, and were equal to or more than fourfold lower than those of imipenem and meropenem. The antibacterial activity of tomopenem against MRSA was correlated with a higher affinity for the penicillin-binding protein (PBP) 2a. Its activity against laboratory mutants of P. aeruginosa with (i) overproduction of chromosomally coded AmpC β-lactamase; (ii) overproduction of the multidrug efflux pumps MexAB-OprM, MexCD-OprJ, and MexEF-OprN; (iii) deficiency in OprD; and (iv) various combinations of AmpC overproduction, MexAB-OprM overproduction, and OprD deficiency were tested. The increases in the MIC of tomopenem against each single mutant compared with that against its parent strain were within a fourfold range. Tomopenem exhibited antibacterial activity against all mutants, with an observed MIC range of 0.5 to 8 µg/ml. These results suggest that the antibacterial activity of tomopenem against the clinical isolates of MRSA and P. aeruginosa should be ascribed to its high affinity for PBP 2a and its activity against the mutants of P. aeruginosa, respectively.

* Corresponding author. Mailing address: Biological Research Laboratories IV, Daiichi Sankyo Co., Ltd., 16-13, 1-Chome Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan. Phone: 81-3-5696-3915. Fax: 81-3-5696-4264. E-mail: koga.tetsufumi.zj{at}daiichisankyo.co.jp

{triangledown} Published ahead of print on 2 June 2008.

Antimicrobial Agents and Chemotherapy, August 2008, p. 2849-2854, Vol. 52, No. 8
0066-4804/08/$08.00+0     doi:10.1128/AAC.00413-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • El Solh, A. A., Alhajhusain, A. (2009). Update on the treatment of Pseudomonas aeruginosa pneumonia. J Antimicrob Chemother 64: 229-238 [Abstract] [Full Text]  
  • Koga, T., Sugihara, C., Kakuta, M., Masuda, N., Namba, E., Fukuoka, T. (2009). Affinity of Tomopenem (CS-023) for Penicillin-Binding Proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 53: 1238-1241 [Abstract] [Full Text]  


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