{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:59:27Z","timestamp":1792004367745,"version":"4.4.0"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":5,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004169","name":"Meiji Seika Pharma Co., Ltd","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004169","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We assessed the in vitro activity of aztreonam\u2013nacubactam and cefepime\u2013nacubactam against a 2021\u20132023 global collection of clinical isolates of Gram-negative bacilli (12\u200a613 Enterobacterales, 3748 Pseudomonas aeruginosa and 601 Acinetobacter baumannii). Nacubactam is a novel diazabicyclooctane \u03b2-lactamase inhibitor that also possesses intrinsic antimicrobial (PBP2 inhibition) and \u03b2-lactam enhancer (for \u03b2-lactams that bind PBP3 and other non-PBP2 PBPs) activities against Enterobacterales. Aztreonam\u2013nacubactam and cefepime\u2013nacubactam are in clinical development for the treatment of complicated urinary tract infections, acute uncomplicated pyelonephritis and various infections caused by carbapenem-resistant Enterobacterales (CRE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MICs were determined for aztreonam\u2013nacubactam (1:1 ratio), cefepime\u2013nacubactam (1:1 ratio) and 13 comparators using the CLSI broth microdilution method.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>For all Enterobacterales isolates, the MIC90s of aztreonam\u2013nacubactam and cefepime\u2013nacubactam were 1 and 0.5\u2005mg\/L, respectively; 99.8% of all Enterobacterales isolates and 99.8% of CRE isolates (n\u200a=\u200a917) were inhibited by aztreonam\u2013nacubactam at 4\u2005mg\/L and by cefepime\u2013nacubactam at 8\u2005mg\/L. Both aztreonam-resistant and cefepime-resistant isolate MICs demonstrated a modal decrease of 64-fold by the addition of nacubactam at a 1:1 ratio. Aztreonam\u2013nacubactam and cefepime\u2013nacubactam were active against the majority of Enterobacterales isolates that were resistant to aztreonam\u2013avibactam, ceftazidime\u2013avibactam, imipenem\u2013relebactam, meropenem\u2013vaborbactam and cefiderocol. The MIC90s for aztreonam\u2013nacubactam and cefepime\u2013nacubactam were 16 and 8\u2005mg\/L for P. aeruginosa and &amp;gt;64 and 64\u2005mg\/L for A. baumannii.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The results of this study support the continued development of aztreonam\u2013nacubactam and cefepime\u2013nacubactam as potential therapies for infections caused by CRE where resistance or potential toxicity to marketed antimicrobial agents excludes their use.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jacamr\/dlag061","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T11:50:25Z","timestamp":1775735425000},"source":"Crossref","is-referenced-by-count":2,"title":["<i>In vitro<\/i>\n                    activity of aztreonam\u2013nacubactam and cefepime\u2013nacubactam against a global collection of clinically important Gram-negative Bacilli collected in 2021\u20132023"],"prefix":"10.1093","volume":"8","author":[{"given":"James A","family":"Karlowsky","sequence":"first","affiliation":[{"name":"IHMA , Schaumburg, IL 60173 ,","place":["USA"]},{"name":"Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba , Winnipeg, MB R3E 0J9 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3941-6589","authenticated-orcid":false,"given":"Mark","family":"Estabrook","sequence":"additional","affiliation":[{"name":"IHMA , Schaumburg, IL 60173 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eisuke","family":"Suzuki","sequence":"additional","affiliation":[{"name":"R&D Division, Meiji Seika Pharma Co. 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