Genetic Diversity and in vitro Activity of Aztreonam/Avibactam and Ceftazidime/Avibactam Against Carbapenem-Resistant Enterobacterales: A Multi-Center Study in Southwest China

Purpose: This study aimed to understand the distribution characteristics of carbapenemase genes and assess the antimicrobial activities of aztreonam/avibactam (ATM/AVI) and ceftazidime/avibactam (CAZ/AVI) against carbapenem-resistant Enterobacterales (CRE) isolates in Chongqing, Southwest China. Methods: CRE isolates and their clinical information were collected from 22 hospitals covering all the five regions across Chongqing between January 1, 2016 and December 31, 2017. PCR was used to screen for common carbapenemase genes. And minimum inhibitory concentrations (MICs) were determined by broth microdilution method. Results: A total of 312 unduplicated CRE isolates (eg, 206 Klebsiella pneumoniae, 43 Escherichia coli, and 42 Enterobacter cloacae) were collected during the two-year study period. Among these CRE isolates, 92.3% carried carbapenemase genes, with a majority of isolates carrying single bla(KPC-2) (47.1%) or single bla(NDM/IPM) (36.2%) and 8.9% of isolates carrying two or three carbapenemase genes. Notably, 95.6% (197/206) K. pneumoniae, 86.0% (37/43) E. coli and 88.1% (37/42) E. cloacae harbored carbapenemase genes. In addition, bla(KPC-2) was prevalent in K. pneumoniae (70.4%), while bla(NDM) was predominant in E. coli (83.7%) and E. cloacae (78.6%). Besides, only metallo-beta-lactamase (MBL) genes were detected in the CRE isolates from children. Overall, 0.0%, 48.1%, 59.0%, 61.5% and 63.1% of the CRE isolates were resistant to ATM/AVI, CAZ/AVI, nitrofurantoin, amikacin and trimethoprim/sulfamethoxazole, respectively. 99.7% of the total 312 isolates could be killed by ATM/AVI with the MIC 1 mu g/mL, whereas CAZ/AVI showed good antibacterial activity (98.0% susceptible) against the bla(KPC-2)-carriers with the MIC50/90 values of 1/4 mu g/mL. Conclusion: The distribution features of carbapenemase genes in Chongqing were comprehensively illustrated in terms of species and sources of CRE for the first time in this multi-center study that covered all the geographical locations across Chongqing. ATM/AVI showed superior activity against all CRE isolates regardless of their genotype, whereas CAZ/AVI was active against almost all KPC-producers.