Longitudinal analysis of the in vitro activity of ceftazidime/avibactam versus Enterobacteriaceae, 2012-2016

Abstract

Objectives: The in vitro activities of ceftazidime/avibactam and comparator antimicrobial agents were analysed against 59 828 Enterobacteriaceae isolates collected by 190 centres from all global regions except North America from 2012-2016 as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance programme.

Methods: Antimicrobial susceptibility testing was performed using Clinical and Laboratory Standards Institute broth microdilution panels at a central reference laboratory, except for isolates collected in China that were tested using frozen, dehydrated broth microdilution panels at a central laboratory in China. The presence of extended-spectrum β-lactamases (ESBLs) was confirmed by multiplex PCR assays.

Results: Ceftazidime/avibactam was the most active agent against all Enterobacteriaceae (MIC₉₀, ≤1mg/L, ≥98.4% susceptibility). High rates of susceptibility (>88%) were observed amongst Citrobacter freundii, Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella pneumoniae and Klebsiella oxytoca to colistin, meropenem, amikacin and tigecycline. Ceftazidime/avibactam showed consistent in vitro activity against ESBL-positive isolates of E. coli (n=5674; MIC₉₀, 0.5mg/L, 99.5% susceptible), K. pneumoniae (n=7097; MIC₉₀, 2mg/L, 97.0% susceptible) and K. oxytoca (n = 565; MIC₉₀, 1mg/L, 96.8% susceptible). Isolates identified as metallo-β-lactamase-positive (n=242) were not susceptible to ceftazidime/avibactam but were susceptible to tigecycline (76.9%) and colistin (n=194 isolates tested; 92.8%).

Conclusions: Clinical Enterobacteriaceae isolates, including ESBL-positive phenotypes, collected globally (excluding North America) from 2012-2016 were highly susceptible to ceftazidime/avibactam, suggesting it is a useful agent for serious infections caused by multidrug-resistant organisms belonging to the family Enterobacteriaceae when therapeutic options are limited.

Keywords: Ceftazidime/avibactam; ESBL; Enterobacteriaceae; Global; INFORM; Surveillance.