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

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.