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Antimicrobial Agents and Chemotherapy, September 2007, p. 3089-3095, Vol. 51, No. 9
0066-4804/07/$08.00+0     doi:10.1128/AAC.00218-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Interactions of Ceftobiprole with ß-Lactamases from Molecular Classes A to D{triangledown}

Anne Marie Queenan,1* Wenchi Shang,1 Malgosia Kania,2 Malcolm G. P. Page,2 and Karen Bush1

Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 1000 Route 202 South, Raritan, New Jersey 08869,1 Basilea Pharmaceutica Ltd., Grenzacherstrasse 487, P.O. Box, CH-4005 Basel, Switzerland2

Received 13 February 2007/ Returned for modification 5 April 2007/ Accepted 14 June 2007

The interactions of ceftobiprole with purified ß-lactamases from molecular classes A, B, C, and D were determined and compared with those of benzylpenicillin, cephaloridine, cefepime, and ceftazidime. Enzymes were selected from functional groups 1, 2a, 2b, 2be, 2d, 2e, and 3 to represent ß-lactamases from organisms within the antibacterial spectrum of ceftobiprole. Ceftobiprole was refractory to hydrolysis by the common staphylococcal PC1 ß-lactamase, the class A TEM-1 ß-lactamase, and the class C AmpC ß-lactamase but was labile to hydrolysis by class B, class D, and class A extended-spectrum ß-lactamases. Cefepime and ceftazidime followed similar patterns. In most cases, the hydrolytic stability of a substrate correlated with the MIC for the producing organism. Ceftobiprole and cefepime generally had lower MICs than ceftazidime for AmpC-producing organisms, particularly AmpC-overexpressing Enterobacter cloacae organisms. However, all three cephalosporins were hydrolyzed very slowly by AmpC cephalosporinases, suggesting that factors other than ß-lactamase stability contribute to lower ceftobiprole and cefepime MICs against many members of the family Enterobacteriaceae.

* Corresponding author. Mailing address: Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 1000 Route 202 South, Raritan, NJ 08869. Phone: (908) 704-5515. Fax: (908) 707-3501. E-mail: aqueenan{at}prdus.jnj.com

{triangledown} Published ahead of print on 25 June 2007.

Antimicrobial Agents and Chemotherapy, September 2007, p. 3089-3095, Vol. 51, No. 9
0066-4804/07/$08.00+0     doi:10.1128/AAC.00218-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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