A Simple Disk Stacking Plus Micro-Elution Method for Rapid Detection of the Synergistic Effect of Aztreonam and Ceftazidime/Avibactam Against Metallo-β-Lactamase Producing Enterobacterales

Zhou Liu; Xiubing Hang; Tao Yan; Wenwen Chu; Zhen Gong; Yanyan Liu; Yuanyuan Dai; Min Yang; Jiabin Li; Qiang Zhou

doi:10.2147/IDR.S402275

A Simple Disk Stacking Plus Micro-Elution Method for Rapid Detection of the Synergistic Effect of Aztreonam and Ceftazidime/Avibactam Against Metallo-β-Lactamase Producing Enterobacterales

Infect Drug Resist. 2023 Mar 15:16:1537-1543. doi: 10.2147/IDR.S402275. eCollection 2023.

Authors

Zhou Liu^#¹, Xiubing Hang^#¹, Tao Yan¹, Wenwen Chu¹, Zhen Gong¹, Yanyan Liu^{2

3

4}, Yuanyuan Dai⁵, Min Yang⁶, Jiabin Li^{2

3

4}, Qiang Zhou¹

Affiliations

¹ Department of Laboratory Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.
² Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.
³ Anhui Center for Surveillance of Bacterial Resistance, Hefei, Anhui, People's Republic of China.
⁴ Institute of Bacterial Resistance, Anhui Medical University, Hefei, Anhui, People's Republic of China.
⁵ Department of Laboratory Medicine, Anhui Provincial Hospital, Hefei, Anhui, People's Republic of China.
⁶ Department of Intensive Care, The Second Affiliated Hospital of Anhui Medical University , Hefei, Anhui, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: To establish and evaluate a simple disk stacking plus micro-elution (DSE) method that can be routinely performed to rapidly detect the synergistic effect between aztreonam (ATM) and ceftazidime/avibactam (CZA) against metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE).

Methods: The DSE method was established, and a total of 32 MBL-producing CRE isolates collected from multiple centers were tested for ATM-CZA synergy. The results obtained after 8 h of incubation were compared with those obtained by a reference checkerboard assay (CBA) after 18~24 h. Reproducibility experiments were completed on three separate days.

Results: The reproducibility study showed that the results of the DSE method were precise. Compared with CBA, the DSE method exhibited excellent performance, with 92.8% sensitivity, 100.0% specificity 93.8% categorical agreement, 0.0% very major error, 0.0% major error, and 6.2% minor error over three days of testing.

Conclusion: The DSE method is a simple, rapid and practical method for ATM-CZA combination testing. Further evaluation should be completed to improve its clinical application.

Keywords: Enterobacterales; antimicrobial combinations; aztreonam; ceftazidime/avibactam; clinical method; metallo-β-lactamases.

Grants and funding

This study was supported by the Anhui Province University Natural Science Research Major Project of China (No. KJ2021ZD0029), Anhui Translational Medicine Research Fund Project (No. 2021zhyx-C47), and Scientific Research Fund of Anhui Medical University (No.2022xkj172).