Post-antibiotic and post-beta-lactamase inhibitor effects of ceftazidime plus sulbactam on extended-spectrum beta-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.