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Cefcapene inactivates chromosome-encoded class C β-lactamases

Abstract

The stability of cefcapene and cefpodoxime, oral antibacterial cephalosporins, toward different classes of β-lactamases was evaluated. For the class A β-lactamases, TEM-1, SHV-1, and NMC-A, only the steady-state kinetic parameter (k cat /Km) values were calculated (3100 − 1.1 × 107 M−1·s−1), because these enzymes have very high Km values for cefpodoxime and cefotaxime. As for class B β-lactamases L1, IMP-1, and CcrA, in general, similar k cat /Km values were obtained. However, regarding class C β-lactamases from Enterobacter cloacae, Escherichia coli, Pseudomonas aeruginosa, and Citrobacter freundii, we found major differences in stability between the two compounds. Cefpodoxime acted as a good substrate for the class C β-lactamases, except for the enzyme from E. cloacae; its k cat and Km values were successfully calculated (k cat /Km, 1.8 × 105 − 1.2 × 107 M−1·s−1). On the other hand, cefcapene acted as a poor substrate or an inactivator for class C β-lactamases; its k 2/K value was successfully calculated (8.7 × 105 − 7.0 × 106 M−1·s−1). In addition, k 3 values were determined for β-lactamases from P. aeruginosa (2.3 × 10−2·s−1) and C. freundii (2.1 × 10−1·s−1). Even though these values could be calculated, transient inactivation as an enzyme reactivation reaction for all these enzymes was observed. These findings suggest the potential of cephem compounds as inhibitors of class C β-lactamases.

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Received: January 24, 2002 / Accepted: March 27, 2002

Acknowledgments This study was supported in part by a grant from the Ministry of Health, Labour and Welfare of Japan during 2000–2001 (Scientific Research Foundation on Drug Resistant Bacteria), by a grant from the Japan Health Sciences Foundation, by a grant from Shionogi and Co., Ltd., and by Project Research Grants 12-20 and 13-12 from the Toho University School of Medicine. J. Alba was supported by a scholarship from the Japanese Ministry of Education, Culture, Sports, Science and Technology. We are grateful to Professor A. Iwamoto, University of Tokyo, for his useful advice.

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Alba, J., Ishii, Y., Galleni, M. et al. Cefcapene inactivates chromosome-encoded class C β-lactamases. J Infect Chemother 8, 207–210 (2002). https://doi.org/10.1007/s10156-002-0177-7

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  • DOI: https://doi.org/10.1007/s10156-002-0177-7

  • Key words β-Lactamase
  • Cefcapene
  • Inactivation of class C β-lactamase