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JAC Advance Access published online on February 25, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh140
© 2004 by The British Society for Antimicrobial Chemotherapy
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© 2004 The British Society for Antimicrobial Chemotherapy

Original articles

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

Jean-Philippe Lavigne 1 , Richard Bonnet 2 , Sylvie Michaux-Charachon 1 , Jacques Jourdan 3 , Jocelyne Caillon 4 , and Albert Sotto 3 *

1 Laboratoire de Bactériologie-Virologie, Centre Hospitalo--Universitaire de Nîmes, Groupe Hospitalo--Universitaire de Carémeau, Place du Professeur Robert Debré, 30029 Nîmes Cedex 09; Laboratoire Universitaire d’Antibiologie, Faculté de Médecine, Avenue Kennedy, 30900 Nîmes;
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

* Corresponding author. E-mail: albert.sotto{at}chu-nimes.fr.

Received 7 October 2003 ; revised 13 January 2004 ; accepted 13 January 2004

Abstract

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

Methods: PAE and PLIE were studied for ESBL-producing strains of Escherichia coli and Klebsiella pneumoniae. Two ATCC {beta}-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 {beta}-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
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