Ceftazidime-avibactam and ceftolozane-tazobactam susceptibility of multidrug resistant Pseudomonas aeruginosa strains in Hungary

Our objective was to compare the activity ceftazidime-avibactam (C/A) and ceftolozane-tazobactam (C/T) against multidrug (including carbapenem) resistant Pseudomonas aeruginosa clinical isolates collected from six diagnostic centers in Hungary and to reveal the genetic background of their carbapenem resistance. Two hundred and fifty consecutive, non-duplicate, carbapenem-resistant multidrug resistant (MDR) P. aeruginosa isolates were collected in 2017. Minimal inhibitory concentration values of ceftazidime, cefepime, piperacillin/tazobactam, C/A and C/T were determined by broth microdilution method and gradient diffusion test. Carbapenem inactivation method (CIM) test was performed on all isolates. Carbapenemase-encoding bla(VIM), bla(IMP), bla(KPC), bla(OXA 48 like )and bla(NDM) genes were identified by multiplex PCR. Of the isolates tested, 33.6% and 32.4% showed resistance to C/A and C/T, respectively. According to the CIM test results, 26% of the isolates were classified as carbapenemase producers. The susceptibility of P. aeruginosa isolates to C/A and C/T without carbapenemase production was 89% and 91%, respectively. Of the CIM-positive isolates, 80% were positive for bla(VIM) and 11% for bla(NDM). The prevalence of Verona integron-encoded metallo-beta-lactamase (VIM)-type carbapenemase was 20.8%. NDM was present in 2.8% of the isolates. Although the rate of carbapenemase-producing P. aeruginosa strains is high, a negative CIM result indicates that either C/A or C/T could be effective even if carbapenem resistance has been observed.