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Antimicrobial Agents and Chemotherapy, August 2008, p. 2709-2717, Vol. 52, No. 8
0066-4804/08/$08.00+0     doi:10.1128/AAC.00266-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Comparative Study of the Susceptibilities of Major Epidemic Clones of Methicillin-Resistant Staphylococcus aureus to Oxacillin and to the New Broad-Spectrum Cephalosporin Ceftobiprole{triangledown}

Marilyn Chung, Aude Antignac, Choonkeun Kim, and Alexander Tomasz*

Laboratory of Microbiology, The Rockefeller University, New York, New York

Received 26 February 2008/ Returned for modification 7 May 2008/ Accepted 20 May 2008

Multidrug-resistant strains of Staphylococcus aureus continue to increase in frequency worldwide, both in hospitals and in the community, raising serious problems for the chemotherapy of staphylococcal disease. Ceftobiprole (BPR; BAL9141), the active constituent of the prodrug ceftobiprole medocaril (BAL5788), is a new cephalosporin which was already shown to have powerful activity against a number of bacterial pathogens, including S. aureus. In an effort to test possible limits to the antibacterial spectrum and efficacy of BPR, we examined the susceptibilities of the relatively few pandemic methicillin-resistant S. aureus (MRSA) clones that are responsible for the great majority of cases of staphylococcal disease worldwide. We also included in the tests the highly oxacillin-resistant subpopulations that are present with low frequencies in the cultures of these clones. Such subpopulations may represent a natural reservoir from which MRSA strains with decreased susceptibility to BPR may emerge in the future. We also tested the efficacy of BPR against MRSA strains with reduced susceptibility to vancomycin and against MRSA strains carrying the enterococcal vancomycin resistance gene complex. BPR was shown to be uniformly effective against all these resistant MRSA strains, and the mechanism of superb antimicrobial activity correlated with the strikingly increased affinity of the cephalosporin against penicillin-binding protein 2A, the protein product of the antibiotic resistance determinant mecA.

* Corresponding author. Mailing address: The Rockefeller University, 1230 York Avenue, New York, NY 10065. Phone: (212) 327-8277. Fax: (212) 327-8688. E-mail: tomasz{at}rockefeller.edu

{triangledown} Published ahead of print on 27 May 2008.

Antimicrobial Agents and Chemotherapy, August 2008, p. 2709-2717, Vol. 52, No. 8
0066-4804/08/$08.00+0     doi:10.1128/AAC.00266-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Llarrull, L. I., Fisher, J. F., Mobashery, S. (2009). Molecular Basis and Phenotype of Methicillin Resistance in Staphylococcus aureus and Insights into New {beta}-Lactams That Meet the Challenge. Antimicrob. Agents Chemother. 53: 4051-4063 [Full Text]  


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