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Antimicrob. Agents Chemother. doi:10.1128/AAC.00218-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Interactions of Ceftobiprole with -Lactamases from Molecular Classes A to D

Johnson & Johnson Pharmaceutical Research and Development, L.L.C. 1000 Route 202 South, Raritan NJ 08869; Basilea Pharmaceutica Ltd, Grenzacherstrasse 487, PO Box, CH-4005 Basel, Switzerland

^* To whom correspondence should be addressed. Email: aqueenan{at}prdus.jnj.com.

	Abstract

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

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