{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T18:50:20Z","timestamp":1776883820131,"version":"3.51.2"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004334","name":"Merck & Co., Inc.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Few treatment options exist for serious infections caused by metallo-\u03b2-lactamase (MBL)-producing Pseudomonas aeruginosa. This study evaluated imipenem\/relebactam (I\/R) plus aztreonam (ATM) against Pseudomonas-derived cephalosporinase (PDC)- and MBL-producing P. aeruginosa in a hollow fiber infection model, with ceftazidime\/avibactam (CZA) plus ATM as a comparator.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two isogenic PDC- and MBL-producing P. aeruginosa isolates (MB10480: IMP-1; MB10620: VIM-1) were studied at a starting inoculum of \u223c8 log10 CFU\/mL over 96\u2005hours. Humanized I\/R exposures were evaluated alone and with extended-infusion ATM (1.5\u2005g every 6\u2005hours [q6h], 2\u2005g q8h, and 2\u2005g q6h), with CZA plus ATM (2\u2005g q6h) as a comparator. Combinations were tested in triplicate, and ATM\/relebactam or ATM\/avibactam minimum inhibitory concentrations (MICs) were assessed at 96\u2005hours.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>For both MB10480 (ATM\/relebactam MIC: 8\/4\u2005mg\/L) and MB10620 (4\/4\u2005mg\/L), monotherapy arms mirrored the growth control. Both I\/R plus ATM and CZA plus ATM produced early synergy (\u22652 log10 CFU\/mL reduction relative to the most active monotherapy) with &amp;gt;1 log10 CFU\/mL killing relative to the starting inoculum at 24\u2005hours, followed by regrowth, with bacteriostasis observed at 96\u2005hours across regimens. However, bacterial counts at 96\u2005hours were lowest with I\/R plus ATM 2\u2005g q6h. Two colony morphologies were recovered, and retested MICs were occasionally, but not consistently, elevated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Both I\/R plus ATM and CZA plus ATM showed early synergy against PDC- and MBL-producing P. aeruginosa, but regrowth occurred with all regimens. Higher-dose ATM with I\/R provided more durable suppression, though persistence remained common, underscoring the need to better define dosing and mechanisms of regrowth.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ofid\/ofag172","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T12:36:39Z","timestamp":1774355799000},"source":"Crossref","is-referenced-by-count":0,"title":["Determining the Activity of Imipenem\/Relebactam Plus Aztreonam Against Constitutive\n                    <i>Pseudomonas<\/i>\n                    -Derived Cephalosporinase- and Metallo-\u03b2-Lactamase-Producing\n                    <i>Pseudomonas aeruginosa<\/i>\n                    in a Hollow Fiber Infection Model"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5184-1385","authenticated-orcid":false,"given":"J Nicholas","family":"O\u2019Donnell","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences , Albany, New York ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly E","family":"Moolick","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences , Albany, New York ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avery I","family":"Nahorniak","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences , Albany, New York ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxwell J","family":"Gifford","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences , Albany, New York ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Vaccines, Merck & Co., Inc. , Rahway, New Jersey ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas P","family":"Lodise","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences , Albany, New York ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"2026042214112190500_ofag172-B1","volume-title":"WHO Bacterial Priority Pathogens List, 2024: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance","author":"World Health 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