Avibactam, a non-β-
lactam β-lactamase inhibitor with activity against extended-spectrum β-lactamases (ESBLs), KPC, AmpC, and some OXA
enzymes, extends the antibacterial activity of
ceftazidime against most
ceftazidime-resistant organisms producing these
enzymes. In this study, the bactericidal activity of
ceftazidime-avibactam against 18 Pseudomonas aeruginosa isolates and 15 Enterobacteriaceae isolates, including wild-type isolates and ESBL, KPC, and/or AmpC producers, was evaluated.
Ceftazidime-avibactam MICs (0.016 to 32 μg/ml) were lower than those for
ceftazidime alone (0.06 to ≥256 μg/ml) against all isolates except for 2 P. aeruginosa isolates (1 blaVIM-positive isolate and 1 blaOXA-23-positive isolate). The minimum bactericidal concentration/MIC ratios of
ceftazidime-avibactam were ≤4 for all isolates, indicating bactericidal activity. Human serum and
human serum albumin had a minimal effect on
ceftazidime-avibactam MICs.
Ceftazidime-avibactam time-kill kinetics were evaluated at low MIC multiples and showed time-dependent reductions in the number of CFU/ml from 0 to 6 h for all strains tested. A ≥3-log10 decrease in the number of CFU/ml was observed at 6 h for all Enterobacteriaceae, and a 2-log10 reduction in the number of CFU/ml was observed at 6 h for 3 of the 6 P. aeruginosa isolates. Regrowth was noted at 24 h for some of the isolates tested in time-kill assays. These data demonstrate the potent bactericidal activity of
ceftazidime-avibactam and support the continued clinical development of
ceftazidime-avibactam as a new treatment option for
infections caused by Enterobacteriaceae and P. aeruginosa, including isolates resistant to
ceftazidime by mechanisms dependent on
avibactam-sensitive β-lactamases.