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<p>The clinical management of severe infections caused by <i>Enterobacterales</i> 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 <i>Enterobacterales</i>, harboring or not (<i>n</i> = 8) a variety of resistance genes (54 <i>bla</i><sub>KPC</sub>, 70 <i>bla</i><sub>NDM</sub>, 26 <i>bla</i><sub>KPC</sub> + <i>bla</i><sub>NDM</sub>, 2 <i>bla</i><sub>NDM</sub> + <i>bla</i><sub>OXA−48−like</sub>, and 1 <i>bla</i><sub><i>OXA−48−like</i></sub>), 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&#xa0;h, instead of 16–20&#xa0;h of the gold standard broth microdilution), demonstrating a potential to improve treatment of patients with infections caused by MDR bacteria.</p>

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

  • 期刊论文

  • 发表日期：

    2025年12月17日

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  • Natália Kehl Moreira,
  • Gabriela da Silva Collar,
  • Julia Becker,
  • Mariana Preussler Mott,
  • Patricia Orlandi Barth,
  • Clara Gubert Rodrigues,
  • Afonso Luís Barth,
  • Juliana Caireão

摘要

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.