High <i>in vitro</i> activity of aztreonam/avibactam against NDM-producing Enterobacterales with emerging resistance in <i>Escherichia coli</i> in the United States Mid-Atlantic region

The approval of aztreonam/avibactam provides a critical therapeutic option for treating infections caused by metallo-β-lactamase-producing Enterobacterales, including NDM-positive strains that are resistant to nearly all other β-lactams. However, emerging resistance due to PBP3 (<i>ftsI</i>) insertions and AmpC co-production threatens its efficacy. This study demonstrates that while aztreonam/avibactam remains highly active against most NDM-producing Enterobacterales, resistance is already emerging in diverse <i>Escherichia coli</i> lineages carrying specific <i>ftsI</i> insertions. By correlating phenotypic susceptibility with genomic determinants, our findings underscore the need for laboratories to implement standardized testing for aztreonam/avibactam and for continued genomic surveillance to detect evolving resistance. This work provides critical regional data supporting stewardship and diagnostic preparedness as clinical use of aztreonam/avibactam expands.