{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T01:46:00Z","timestamp":1789004760291,"version":"build-2803163510"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,9,26]],"date-time":"2021-09-26T00:00:00Z","timestamp":1632614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Aztreonam\/avibactam is being developed for its broad activity against carbapenemase-producing Enterobacterales, including those with metallo-\u03b2-lactamases (MBLs). Its potential to select resistance in target pathogens was explored. Findings are compared with previous data for ceftazidime\/avibactam and ceftaroline\/avibactam.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Single-step mutants were sought from 52 Enterobacterales with AmpC, ESBL, KPC, MBL and OXA-48-like enzymes. Mutation frequencies were calculated. MICs were determined by CLSI agar dilution. Genomes were sequenced using Illumina methodology.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Irrespective of \u03b2-lactamase type and of whether avibactam was used at 1 or 4\u2009mg\/L, mutants could rarely be obtained at &amp;gt;4\u00d7 the starting MIC, and most MIC rises were correspondingly small. Putative resistance (MIC &amp;gt;8\u2009+\u20094\u2009mg\/L) associated with changes to \u03b2-lactamases was seen only for mutants of AmpC, where it was associated with Asn346Tyr and Tyr150Cys substitutions. Asn346Tyr led to broad resistance to avibactam combinations; Tyr150Cys significantly affected only aztreonam\/avibactam. MIC rises up to 4\u2009+\u20094\u2009mg\/L were seen for producers of mutant KPC-2 or -3 enzymes, and were associated with Trp105Arg, Ser106Pro and Ser109Pro substitutions, which all reduced the MICs of other \u03b2-lactams. For producers of other \u03b2-lactamase types, we largely found mutants with lesions in baeRS or envZ, putatively affecting drug accumulation. Single mutants had lesions in ampD, affecting AmpC expression or ftsI, encoding PBP3.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The risk of mutational resistance to aztreonam\/avibactam appears smaller than for ceftazidime\/avibactam, where Asp179Tyr arises readily in KPC enzymes, conferring frank resistance. Asn346 substitutions in AmpC enzymes may remain a risk, having been repeatedly selected with multiple avibactam combinations in vitro.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkab346","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T11:16:51Z","timestamp":1631099811000},"page":"98-111","source":"Crossref","is-referenced-by-count":24,"title":["Selection and characterization of mutational resistance to aztreonam\/avibactam in \u03b2-lactamase-producing Enterobacterales"],"prefix":"10.1093","volume":"77","author":[{"given":"Shazad","family":"Mushtaq","sequence":"first","affiliation":[{"name":"Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Public Health England National Infection Service, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Vickers","sequence":"additional","affiliation":[{"name":"Antimicrobial Resistance and Healthcare Associated Infections 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