{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:09:41Z","timestamp":1790644181555,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,8,16]],"date-time":"2019-08-16T00:00:00Z","timestamp":1565913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["FP7\/2007\u20132013"],"award-info":[{"award-number":["FP7\/2007\u20132013"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013322","name":"European Federation of Pharmaceutical Industries and Associations","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:p>Aztreonam\u2010avibactam (<jats:styled-content style=\"fixed-case\">ATM<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">AVI<\/jats:styled-content>) is a promising combination to treat serious infections caused by multidrug\u2010resistant (<jats:styled-content style=\"fixed-case\">MDR<\/jats:styled-content>) pathogens. Three distinct mechanisms of action have been previously characterized for <jats:styled-content style=\"fixed-case\">AVI<\/jats:styled-content>: inhibition of <jats:styled-content style=\"fixed-case\">ATM<\/jats:styled-content> degradation by \u03b2\u2010lactamases, proper bactericidal effect, and enhancement of <jats:styled-content style=\"fixed-case\">ATM<\/jats:styled-content> bactericidal activity. The aim of this study was to quantify the individual contribution of each of the three <jats:styled-content style=\"fixed-case\">AVI<\/jats:styled-content> effects. <jats:italic>In vitro<\/jats:italic> static time\u2010kill studies were performed on four <jats:styled-content style=\"fixed-case\">MDR<\/jats:styled-content> <jats:italic>Enterobacteriaceae<\/jats:italic> with different \u03b2\u2010lactamase profiles. \u03b2\u2010Lactamase activity was characterized by measuring <jats:styled-content style=\"fixed-case\">ATM<\/jats:styled-content> concentrations over 27\u00a0hours. Data were analyzed by a semimechanistic pharmacodynamics modeling approach. Surprisingly, even though <jats:styled-content style=\"fixed-case\">AVI<\/jats:styled-content> prevented <jats:styled-content style=\"fixed-case\">ATM<\/jats:styled-content> degradation, the combined bactericidal activity was mostly explained by the enhancement of <jats:styled-content style=\"fixed-case\">ATM<\/jats:styled-content> effect within clinical range of <jats:styled-content style=\"fixed-case\">ATM<\/jats:styled-content> (5\u2013125\u00a0mg\/L) and <jats:styled-content style=\"fixed-case\">AVI<\/jats:styled-content> concentrations (0.9\u201322.5\u00a0mg\/L). Therefore, when selecting a \u03b2\u2010lactamase inhibitor for combination with a \u03b2\u2010lactam, its capability to enhance the \u03b2\u2010lactam activity should be considered in addition to the spectrum of \u03b2\u2010lactamases inhibited.<\/jats:p>","DOI":"10.1002\/psp4.12452","type":"journal-article","created":{"date-parts":[[2019,8,17]],"date-time":"2019-08-17T06:34:33Z","timestamp":1566023673000},"page":"815-824","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Semimechanistic Pharmacodynamic Modeling of Aztreonam\u2010Avibactam Combination to Understand Its Antimicrobial Activity Against Multidrug\u2010Resistant Gram\u2010Negative Bacteria"],"prefix":"10.1002","volume":"8","author":[{"given":"Alexia","family":"Chauzy","sequence":"first","affiliation":[{"name":"INSERM U1070 P\u00f4le Biologie Sant\u00e9 Poitiers Cedex 9 France"},{"name":"Universit\u00e9 de Poitiers UFR de M\u00e9decine Pharmacie Poitiers 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