{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:59:35Z","timestamp":1792004375959,"version":"4.4.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100020365","name":"Centers for Disease Control and Prevention Foundation","doi-asserted-by":"publisher","award":["CK19-1904, CK24-0002"],"award-info":[{"award-number":["CK19-1904, CK24-0002"]}],"id":[{"id":"10.13039\/100020365","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      New Delhi metallo-\u03b2-lactamase (NDM)-producing Enterobacterales represent a critical antimicrobial resistance threat with limited therapeutic options. Aztreonam\/avibactam, which combines the stability of aztreonam against metallo-\u03b2-lactamases with the inhibition of serine \u03b2-lactamases by avibactam, is a promising therapeutic candidate. However, emerging resistance associated with\n                      <jats:italic toggle=\"yes\">ftsI<\/jats:italic>\n                      (penicillin-binding protein 3 [PBP3]) insertions and expression of AmpC \u03b2-lactamases has been described. We evaluated 95 NDM-producing Enterobacterales isolates submitted to the Maryland Department of Health Laboratories Administration through the AR Lab Network between 2020 and 2025. Susceptibility testing for aztreonam, ceftazidime\/avibactam, and aztreonam\/avibactam was performed by broth microdilution. Whole-genome sequencing was used to identify sequence types, resistance genes, and\n                      <jats:italic toggle=\"yes\">ftsI<\/jats:italic>\n                      alterations. The isolates included\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 40),\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 32),\n                      <jats:italic toggle=\"yes\">Enterobacter cloacae<\/jats:italic>\n                      complex (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 8), and other Enterobacterales (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 15). All isolates carried NDM; 12 harbored OXA-48-like, and 3 harbored KPC carbapenemases. All isolates were resistant to ceftazidime\/avibactam, and 83% were non-susceptible to aztreonam alone. In contrast, 86% (82\/95) were susceptible to aztreonam\/avibactam, 7% intermediate, and 6% resistant. Non-susceptibility was concentrated in\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      (30%, 12\/40) and related to four\u2013amino acid\n                      <jats:italic toggle=\"yes\">ftsI<\/jats:italic>\n                      insertions (YRIN, KYRI), particularly when combined with CMY-type AmpC \u03b2-lactamases. Non-susceptible\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      was genetically diverse and distributed across multiple jurisdictions with no evidence of clonal spread. Aztreonam\/avibactam demonstrated high\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      activity against NDM-producing Enterobacterales, but resistance is emerging, predominantly in\n                      <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                      with PBP3 alterations and AmpC co-production. These findings underscore the importance of susceptibility testing and genomic surveillance to preserve the clinical utility of aztreonam\/avibactam as its clinical use expands.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      The approval of aztreonam\/avibactam provides a critical therapeutic option for treating infections caused by metallo-\u03b2-lactamase-producing Enterobacterales, including NDM-positive strains that are resistant to nearly all other \u03b2-lactams. However, emerging resistance due to PBP3 (\n                      <jats:italic toggle=\"yes\">ftsI<\/jats:italic>\n                      ) 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\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      lineages carrying specific\n                      <jats:italic toggle=\"yes\">ftsI<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.03971-25","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T14:00:47Z","timestamp":1770732047000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["High\n                    <i>in vitro<\/i>\n                    activity of aztreonam\/avibactam against NDM-producing Enterobacterales with emerging resistance in\n                    <i>Escherichia coli<\/i>\n                    in the United States Mid-Atlantic region"],"prefix":"10.1128","volume":"14","author":[{"given":"Eetu","family":"Eklund","sequence":"first","affiliation":[{"name":"Maryland Department of Health Laboratories Administration","place":["Baltimore, 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