Genetic diversity and in vitro activity of ceftazidime/avibactam and aztreonam/avibactam against imipenem-resistant Enterobacteriaceae isolates in Southwest China: a single-centre study.

Abstract Objectives This study aims to investigate the molecular mechanisms of imipenem-resistant Enterobacteriaceae and assess the antimicrobial activities of ceftazidime/avibactam (CAZ/AVI) and aztreonam/avibactam (ATM/AVI) against the imipenem-resistant isolates in a tertiary hospital in China. Methods A total of 91 imipenem-resistant Enterobacteriaceae were collected and genes encoding carbapenemases, ESBLs, AmpCs, and porins were detected using PCR. MICs and susceptibility were determined using in-house-prepared broth microdilution panels and interpreted with CLSI breakpoints. Results Imipenem-resistant isolates comprising of 54 Klebsiella pneumoniae, 18 Escherichia coli, eight Enterobacter cloacae, six Serratia marcescens, three Klebsiella oxytoca, and two Klebsiella aerogenes were collected independently. Five different carbapenemase genes were identified namely, blaKPC-2 (n = 60), blaNDM-5 (n = 14), blaNDM-1 (n = 11), blaKPC-3 (n = 4), and blaIMP-4 (n = 1). Among the 91 carbapenem-resistant Enterobacteriaceae (CRE) isolates, 85 isolates harboured at least one ESBL and/or ampC gene, including five strains without carbapenemase-encoding genes. Thirty-one K. pneumoniae isolates carried ompK35 and/or ompK36 mutations. MLST results showed that 54 K. pneumoniae belonged to 12 different STs, with ST11 being predominant (29/54, 53.7%). Overall, 17.6%, 25.3%, 41.8%, 65.9%, and 100% of 91 CRE strains were susceptible to amikacin, trimethoprim/sulfamethoxazole, tetracycline, CAZ/AVI, and ATM/AVI, respectively. Conclusions Our study revealed that CRE isolates differ significantly in their species, STs, porin genes, and carbapenemase genes, in a single Chinese hospital. ATM/AVI exhibited potent activity against CRE isolates, even for the most notorious double-carbapenemase producers with porin defects, whereas CAZ/AVI is active against all the non-metallo-β-lactamase-producing isolates.