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Thein vitro activity of ceftazidime-avibactam was evaluated against 34,062 isolates ofEnterobacteriaceae 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% ofEnterobacteriaceae 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 theEnterobacteriaceae , the ceftazidime-avibactam MIC inhibiting ≥90% of isolates (MIC90 ) ranged from 0.06 μg/ml forProteus species to 1 μg/ml forEnterobacter spp. andKlebsiella pneumoniae . Carbapenem-susceptible isolates ofEscherichia coli ,K. pneumoniae ,Klebsiella oxytoca , andProteus 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 ofE. coli ,K. pneumoniae ,K. oxytoca , andP. mirabilis . We conclude that ceftazidime-avibactam demonstrates potentin vitro activity against globally collected clinical isolates ofEnterobacteriaceae , including isolates producing ESBLs and AmpC β-lactamases.

antimicrobial agents and chemotherapy

Activity of Ceftazidime-Avibactam against Extended-Spectrum- and AmpC β-Lactamase-Producing Enterobacteriaceae Collected in the INFORM Global Surveillance Study from 2012 to 2014