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JAC Advance Access originally published online on February 25, 2004
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Journal of Antimicrobial Chemotherapy (2004) 53, 616-619
© 2004 The British Society for Antimicrobial Chemotherapy

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

Jean-Philippe Lavigne1,3, Richard Bonnet2, Sylvie Michaux-Charachon1,3, Jacques Jourdan3, Jocelyne Caillon4 and Albert Sotto3,*

1 Laboratoire de Bactériologie-Virologie, Centre Hospitalo—Universitaire de Nîmes, Groupe Hospitalo—Universitaire de Carémeau, Place du Professeur Robert Debré, 30029 Nîmes Cedex 09; 2 Laboratoire de Bactériologie, Faculté de Médecine, 28 Place Henri Dunant, 63001 Clermont-Ferrand Cedex; 3 Laboratoire Universitaire d’Antibiologie, Faculté de Médecine, Avenue Kennedy, 30900 Nîmes; 4 Laboratoire d’Antibiologie, Faculté de Médecine, 1 rue Gaston Veil, 44035 Nantes, France

Received 7 October 2003; returned 3 December 2003; revised 13 January 2004; accepted 13 January 2004

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

Methods: PAE and PLIE were studied for ESBL-producing strains of Escherichia coli and Klebsiella pneumoniae. Two ATCC ß-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 ß-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: ESBLs, PAE, PLIE, ceftazidime–sulbactam, cephalosporins, suicide inhibitors

* Corresponding author. Tel: +33-4-66-68-32-31; Fax: +33-4-66-68-38-24; E-mail: albert.sotto{at}chu-nimes.fr


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