Journal Article

Post-antibiotic and post-β-lactamase inhibitor effects of ceftazidime plus sulbactam on extended-spectrum β-lactamase-producing Gram-negative bacteria

Jean-Philippe Lavigne, Richard Bonnet, Sylvie Michaux-Charachon, Jacques Jourdan, Jocelyne Caillon and Albert Sotto

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 53, issue 4, pages 616-619
Published in print April 2004 | ISSN: 0305-7453
Published online April 2004 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkh140
Post-antibiotic and post-β-lactamase inhibitor effects of ceftazidime plus sulbactam on extended-spectrum β-lactamase-producing  Gram-negative bacteria

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Objectives: To measure the in vitro post-antibiotic effect (PAE) and post-β-lactamase inhibitor effect (PLIE) of a ceftazidime–sulbactam combination on bacteria producing extended-spectrum β-lactamases (ESBLs).

Methods: PAE and PLIE were studied for ESBL-producing strains of Escherichia coli and Klebsiella pneumoniae. Two ATCC β-lactamase-negative strains of E. coli and K. pneumoniae were used as controls. The MICs of a ceftazidime–sulbactam combination were determined with a fixed concentration of sulbactam (8 mg/L). The organisms were exposed to the antibiotics at twice the MIC for 2 h before removal of the antibiotics by filtration of the culture. Bacteria on the filter were resuspended in drug-free medium to determine the PAE and in medium containing ceftazidime, at the same concentration as originally present, to determine the PLIE.

Results: The PAE of ceftazidime was similar for bacteria producing the same ESBL except for E. coli producing CTX-M-1. PLIE values varied according to the type of β-lactamase but similar results were observed for the strains producing the same ESBLs. PLIEs were longer than PAEs and were longer when the MICs of ceftazidime were lower.

Conclusions: To the best of our knowledge, we describe here for the first time an in vitro PLIE for a ceftazidime–sulbactam combination on different bacteria producing different ESBLs. These findings indicate that suicide inhibitors may be used in combination with third-generation cephalosporins.

Keywords: Keywords: ESBLs, PAE, PLIE, ceftazidime–sulbactam, cephalosporins, suicide inhibitors

Journal Article.  2826 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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