<p>In vitro Activity of Ceftazidime-Avibactam and Aztreonam-Avibactam Against Carbapenem-resistant <em>Enterobacteriaceae</em> Isolates Collected from Three Secondary Hospitals in Southwest China Between 2018 and 2019</p>

Abstract

Purpose: To assess the antimicrobial activities of ceftazidime/avibactam (CAZ/AVI) and aztreonam/avibactam (ATM/AVI) against carbapenem-resistant Enterobacteriaceae (CRE) isolates collected from three secondary hospitals in Southwest China between 2018 and 2019. Materials and Methods: A total of 120 unique CRE clinical isolates were collected and carbapenemase genes were detected using PCR. Antimicrobial susceptibility was determined using standard broth microdilution method and the results were interpreted according to CLSI breakpoints. Results: The 120 carbapenem-resistant strains included 92 Klebsiella pneumoniae , 10 Escherichia coli , 10 Enterobacter cloacae , five Klebsiella aerogenes , and three Klebsiella oxytoca isolates. Seventy-four percent of these 120 CRE isolates were collected from patients located in non-ICUs; 65.0% of these CRE isolates were collected from male patients; and 34.2% of these isolates were isolated from respiratory tracts. Four different carbapenemase genes were identified among 103 carbapenemase-producing Enterobacteriaceae (CPE) isolates, including bla KPC-2 (n=77), bla NDM-1 (n=16), bla NDM-5 (n=12) and bla IMP-4 (n=2). Overall, 21.7%, 37.5%, 40.8%, 75.0%, and 100% of the CRE strains were susceptible to levofloxacin, trimethoprim/sulfamethoxazole, amikacin, CAZ/AVI, and ATM/AVI, respectively. In addition, antimicrobial susceptibility testing showed that 96.7% isolates (n=116) were resistant to aztreonam, and the addition of avibactam (4 mg/L) significantly reduced the MICs of those aztreonam-resistant isolates by more than 128-fold (range: ≤ 0.125– 4 mg/L), and 90.0% (n=108) of total 120 isolates were inhibited at ATM/AVI concentration ≤ 1 mg/L. Conclusion: Our study revealed significant antimicrobial resistance among the CRE isolates against some commonly used antibiotics in three secondary Chinese hospitals. ATM/AVI exhibited potent activity against CRE isolates, including double carbapenemase-producing isolates, whereas CAZ/AVI was active against all KPC producers. Keywords: carbapenem-resistant Enterobacteriaceae , carbapenemase-producing Enterobacteriaceae , ceftazidime/avibactam, aztreonam/avibactam