DOT-MGA for rapid determination of susceptibility to the combination of Ceftazidime-avibactam and Aztreonam among Enterobacterales

DOT-MGA 用于快速测定肠杆菌科细菌对头孢他啶-阿维巴坦和氨曲南联合用药的敏感性

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Abstract

The clinical management of severe infections caused by Enterobacterales co-producing KPC and metallo-beta-lactamases is challenging. In these situations, the use of aztreonam-avibactam (AZA), or the association of aztreonam (ATM) with ceftazidime-avibactam (CZA), in scenarios where AZA is not available, has demonstrated clinical efficacy. However, the time to obtain results of in vitro antimicrobial susceptibility test may be a concern. We aimed to evaluate DOT-MGA (Direct-on-target microdroplet growth assay) as a tool for the rapid determination of susceptibility to AZA, as well as CZA plus ATM, to improve patient’s outcome and reinforce antimicrobial stewardship policies. A total of 161 Enterobacterales, harboring or not (n = 8) a variety of resistance genes (54 bla(KPC), 70 bla(NDM), 26 bla(KPC) + bla(NDM), 2 bla(NDM) + bla(OXA−48−like), and 1 bla(OXA−48−like)), were evaluated for 4 different antibiotics/combination (CZA, ATM, ATM-CZA and AZA). According to broth microdilution (BMD), 61.5% isolates were resistant to CZA and 64.6% to ATM. All isolates were susceptible to ATM-CZA and AZA. DOT-MGA presented categorical agreement of 99.2% for CZA, ATM and ATM-CZA, and 98.4% for AZA compared to BMD. Only 2 VME and 3 ME were observed. DOT-MGA demonstrated excellent performance, with a considerably reduced turnaround time to results (approximately 4 h, instead of 16–20 h of the gold standard broth microdilution), demonstrating a potential to improve treatment of patients with infections caused by MDR bacteria. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42770-025-01833-4.

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