The in vitro activity of ceftazidime-avibactam was evaluated against 34,062 isolates of Enterobacteriaceae from patients with intra-abdominal, urinary tract, skin and soft-tissue, lower respiratory tract, and blood infections collected in the INFORM (International Network For Optimal Resistance Monitoring) global surveillance study (176 medical center laboratories in 39 countries) in 2012 to 2014. Overall, 99.5% of Enterobacteriaceae isolates were susceptible to ceftazidime-avibactam using FDA approved breakpoints (susceptible MIC of ≤8 μg/ml; resistant MIC of ≥16 μg/ml). For individual species of the Enterobacteriaceae, the ceftazidime-avibactam MIC inhibiting ≥90% of isolates (MIC90) ranged from 0.06 μg/ml for Proteus species to 1 μg/ml for Enterobacter spp. and Klebsiella pneumoniae Carbapenem-susceptible isolates of Escherichia coli, K. pneumoniae, Klebsiella oxytoca, and Proteus mirabilis with a confirmed extended-spectrum β-lactamase (ESBL) phenotype, or a ceftazidime MIC of ≥16 μg/ml if the ESBL phenotype was not confirmed by clavulanic acid inhibition, were characterized further to identify the presence of specific ESBL- and plasmid-mediated AmpC β-lactamase genes using a microarray-based assay and additional PCR assays. Ceftazidime-avibactam demonstrated potent activity against molecularly confirmed ESBL-producing (n = 5,354; MIC90, 0.5 μg/ml; 99.9% susceptible), plasmid-mediated AmpC-producing (n = 246; MIC90, 0.5 μg/ml; 100% susceptible), and ESBL- and AmpC-producing (n = 152; MIC90, 1 μg/ml; 100% susceptible) isolates of E. coli, K. pneumoniae, K. oxytoca, and P. mirabilis We conclude that ceftazidime-avibactam demonstrates potent in vitro activity against globally collected clinical isolates of Enterobacteriaceae, including isolates producing ESBLs and AmpC β-lactamases.