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

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 blaKPC, 70 blaNDM, 26 blaKPC + blaNDM, 2 blaNDM + blaOXA−48−like, and 1 blaOXA−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.