LAUSR

OBJECTIVE This study aims to investigate the prevalence of ceftazidime-avibactam (CZA) resistance among carbapenemase-producing Enterobacterales (CPE) blood culture (BC) isolates and the performance of the main carbapenemase phenotypic detection methods to identify KPC variants associated with resistance to CZA. METHODS Non-duplicate CPE strains isolated from BCs during 2018-2020 were tested for antimicrobial susceptibility. Molecular testing was used to identify carbapenemase producers. Strains harbouring blaKPC and expressing CZA MIC ≥ 8 mg/L were investigated by sequencing; subsequentially, five phenotypic carbapenemase detection methods were evaluated on these strains: mCIM, Rapidec Carba NP, Disc Diffusion Synergy test, NG-Test CARBA 5 and RESIST-5 O.O.K.N.V. RESULTS Overall, CZA resistance rate was high (13.7%) and remained relevant (5.9%) excluding metallo-β-lactamases-producers. All isolates harboring blaKPC mutants (n = 8) were associated with reduced carbapenems MICs and negative results by all the methods based on revelation of enzyme activity. Lateral flow immunoassays failed to detect KPC-31 (n = 4) and KPC-33 (n = 2) but correctly identified KPC-14 (n = 2). Conversely, isolates harboring wild-type KPC genes (n = 3) were associated with high level of CZA resistance, carbapenems resistance and tested positive by all the evaluated methods. CONCLUSION In the CZA-based therapies era, molecular blaKPC identification followed by a carbapenem-hydrolysis-based phenotypic assay could be the most reasonable diagnostic algorithm to detect all KPC-producers and identify mutants associated with impaired carbapenemase activity and CZA resistance.