Avibactam reverts the ceftazidime MIC90 of European Gram-negative bacterial clinical isolates to the epidemiological cut-off value

Objectives: Ceftazidime-avibactam consists of the beta-lactam ceftazidime and the novel non-beta-lactam beta-lactamase inhibitor avibactam. The effect of avibactam on the ceftazidime MIC frequency distribution of Gram-negative European clinical isolates was observed and compared to European Committee for Antimicrobial Susceptibility Testing (EUCAST) MIC frequency distributions and epidemiological cut-off values (ECOFFs) listed for ceftazidime. Methods: Ceftazidime and ceftazidime-avibactam MICs were determined using Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution methods for Pseudomonas aeruginosa, Escherichia coli, Klebsiella spp., Serratia spp., Enterobacter spp., and Proteus mirabilis isolates collected from medical centres in Europe during 2009. Results: The MIC90 values for ceftazidime and ceftazidime-avibactam against P. aeruginosa isolates from a 2009 European surveillance programme were >32 and 8 mg/l, respectively. That is, the presence of avibactam reverted the ceftazidime MIC90 for P. aeruginosa to the ECOFF. Similarly, the MIC90 values for ceftazidime against E. coli, Klebsiella spp., Serratia spp., and P. mirabilis were also reduced to the ECOFF by the presence of avibactam. Avibactam reduced the ceftazidime MIC90 value against collected Enterobacter spp. to 1 mg/l (>32-fold reduction). No ECOFF has been defined for Enterobacter spp. however, it is 1 mg/l for Enterobacter aerogenes and Enterobacter cloacae. Conclusions: The presence of avibactam reverted the ceftazidime MIC90 for Gram-negative bacteria to the ECOFF.