In Vitro Activity Comparison of Ceftazidime-Avibactam and Aztreonam-Avibactam Against Bloodstream Infections With Carbapenem-Resistant Organisms in China.

Wei Yu,Yunbo Chen,Luying Xiong,Zhiying Liu,Qixia Luo,Jinru Ji,Chaoqun Ying,Yonghong Xiao

doi:10.3389/fcimb.2021.780365

Abstract

ObjectivesThe aim of this work was to investigate the activity of ceftazidime–avibactam (CZA) and aztreonam–avibactam (AZA) against bloodstream infections caused by carbapenem-resistant organisms (CROs).MethodsNon-duplicate CROs, including 56 carbapenem-resistant Escherichia coli (CR-Eco), 318 carbapenem-resistant Klebsiella pneumoniae (CR-Kpn), and 65 carbapenem-resistant Pseudomonas aeruginosa (CR-Pae), were collected using the Blood Bacterial Resistant Investigation Collaborative System (BRICS) program in China. The minimum inhibitory concentrations (MICs) of 24 antibiotics were tested. Carbapenemase genes were amplified for CZA-resistant CROs by PCR. The MICs of CZA and AZA were further determined with avibactam at 8 and 16 mg/L, respectively.ResultsThe resistance rate of polymyxin B against CROs was less than 5%. Only one CR-Kpn was resistant to tigecycline. The resistance rates of CZA against CR-Eco, CR-Kpn, and CR-Pae were 75.0%, 12.6%, and 18.5%, respectively. The MIC90 values of AZA against CR-Eco, CR-Kpn, and CR-Pae were 2/4, 1/4, and 64/4 mg/L, respectively. Among the CZA-resistant CROs, 42 (100%) CR-Eco, 24 (60%) CR-Kpn, and 1 (8.3%) CR-Pae isolates harbored metallo-β-lactamase genes. The increase of avibactam concentration enhanced the susceptibility of CZA and AZA against CROs, especially for CR-Eco and CR-Kpn.ConclusionsThe in vitro activity of AZA was superior to that of CZA against CR-Eco and CR-Kpn, whereas CZA showed better effect against CR-Pae.

Highlights

Carbapenem-resistant organisms (CROs) have become a global epidemic problem for many years
The increase of avibactam concentration enhanced the susceptibility of CZA and aztreonam– avibactam (AZA) against CROs, especially for carbapenem-resistant E. coli (CR-Eco) and carbapenem-resistant Klebsiella pneumoniae (CR-Kpn)
Most strains were isolated from East China (EC) and Central China (CC) due to the majority of the involved hospitals located in these areas

Summary

Introduction

Carbapenem-resistant organisms (CROs) have become a global epidemic problem for many years. Current evidence revealed that carbapenemase and b-lactamases combined with mutations that decrease permeability were associated with carbapenem resistance (Queenan and Bush, 2007). Several novel b-lactam/blactamase inhibitor combinations have been developed against various CROs, such as ceftazidime–avibactam (CZA), aztreonam– avibactam (AZA), meropenem–vaborbactam, and imipenem/ cilastatin–relebactam (Papp-Wallace, 2019). As a bridged diazabicyclo[3.2.1]octanone (DBO) non-b-lactam inhibitor, provides excellent inhibition of class A, class C, and some of the class D b-lactamases (Bush and Bradford, 2019). CZA represented an important advance in the treatment of infections caused by CR-Pae and carbapenem-resistant Enterobacteriaceae (CRE) (Onorato et al, 2019). This study aimed to compare the in vitro activity of these two avibactam combinations (CZA and AZA) against BSIs-CROs

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