{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:59:31Z","timestamp":1792004371152,"version":"4.4.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Translational Medicine Faculty Starter"},{"DOI":"10.13039\/100001797","name":"PhRMA Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001797","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Stenotrophomonas maltophilia complex infections are difficult to treat because of intrinsic resistance mediated by the L1 metallo-\u03b2-lactamase and L2 serine \u03b2-lactamase. Although aztreonam\/avibactam is clinically available, aztreonam combined with ceftazidime\/avibactam remains an alternative, but comparative pharmacodynamic data under clinically relevant exposures are limited. We compared aztreonam\/avibactam and aztreonam + ceftazidime\/avibactam under prolonged human-simulated dosing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Three clinical S. maltophilia complex isolates (17061, 17639 and 16852) were studied in 96-h hollow fibre infection models. Human-simulated aztreonam\/avibactam and aztreonam + ceftazidime\/avibactam regimens were administered as 3-h extended or continuous infusions at total daily aztreonam doses of 6\u2005g or 8\u2005g. blaL1 and blaL2 expression was quantified by RT-qPCR, and population pharmacokinetic modelling with Monte Carlo simulation (n\u200a=\u200a1000) verified target exposures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At 6\u2005g\/day of aztreonam, neither aztreonam\/avibactam nor aztreonam + ceftazidime\/avibactam achieved sustained bactericidal activity; extended infusions failed to produce killing, and continuous infusion produced only transient bactericidal effects followed by regrowth. In contrast, continuous-infusion aztreonam\/avibactam at 8\u2005g\/day produced rapid and durable bactericidal activity across all isolates through 96\u2005h with stable minimum inhibitory concentrations (MICs), whereas aztreonam + ceftazidime\/avibactam at the same dose achieved early killing followed by regrowth. Transcriptionally, aztreonam\/avibactam limited or uncoupled blaL1 and blaL2 induction even at intensified dosing, while aztreonam + ceftazidime\/avibactam more consistently promoted blaL1 up-regulation and greater \u03b2-lactamase variability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Under human-simulated conditions, only continuous-infusion aztreonam\/avibactam with intensified aztreonam exposure (8\u2005g\/day) achieved durable bactericidal activity against S. maltophilia complex, whereas adding ceftazidime did not improve pharmacodynamic outcomes and was associated with greater \u03b2-lactamase induction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag177","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T11:39:38Z","timestamp":1778067578000},"source":"Crossref","is-referenced-by-count":1,"title":["Durability and mechanistic performance of aztreonam\/avibactam versus aztreonam plus ceftazidime\/avibactam against\n                    <i>Stenotrophomonas maltophilia<\/i>\n                    complex"],"prefix":"10.1093","volume":"81","author":[{"given":"Ashlan J","family":"Kunz Coyne","sequence":"first","affiliation":[{"name":"University of Kentucky College of Pharmacy Department of Pharmacy Practice and Science, , Lexington, KY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3740-2525","authenticated-orcid":false,"given":"Rachel","family":"Gray","sequence":"additional","affiliation":[{"name":"University of Kentucky College of Pharmacy Department of Pharmacy Practice and Science, , Lexington, KY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavani","family":"Gonnabathula","sequence":"additional","affiliation":[{"name":"University of Kentucky College of Pharmacy Department of Pharmacy Practice and Science, , Lexington, KY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth S","family":"May","sequence":"additional","affiliation":[{"name":"University of Kentucky College of Pharmacy Department of Pharmacy Practice and Science, , Lexington, KY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Puccio","sequence":"additional","affiliation":[{"name":"University of Kentucky HealthCare Department of Pharmacy, , Lexington, KY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Wu","sequence":"additional","affiliation":[{"name":"University of Kentucky HealthCare Department of Pharmacy, , Lexington, KY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"2026052202043852200_dkag177-B1","doi-asserted-by":"publisher","DOI":"10.1093\/jacamr\/dlac040","article-title":"Clinical challenges treating Stenotrophomonas maltophilia infections: an update","volume":"4","author":"Mojica","year":"2022","journal-title":"JAC Antimicrob Resist"},{"key":"2026052202043852200_dkag177-B2","doi-asserted-by":"publisher","first-page":"162","DOI":"10.3390\/medicina60010162","article-title":"Hemorrhagic pneumonia caused by Stenotrophomonas maltophilia in patients with hematologic malignancies-A systematic review and meta-analysis","volume":"60","author":"Huang","year":"2024","journal-title":"Med Kaunas Lith"},{"key":"2026052202043852200_dkag177-B3","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1002\/phar.2828","article-title":"Steno-sphere: navigating the enigmatic world of emerging multidrug-resistant Stenotrophomonas maltophilia","volume":"43","author":"Kunz Coyne","year":"2023","journal-title":"Pharmacother"},{"key":"2026052202043852200_dkag177-B4","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1186\/s12879-024-10293-4","article-title":"Evaluation of clinical outcomes and risk factors associated with mortality in patients with Stenotrophomonas maltophilia bloodstream infection: a multicenter study","volume":"24","author":"Gezer","year":"2024","journal-title":"BMC Infect Dis"},{"key":"2026052202043852200_dkag177-B5","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1007\/s15010-019-01369-4","article-title":"The clinical impact of Stenotrophomonas maltophilia bacteremia on the 30-day mortality rate in patients with hematologic disorders: a single-institution experience","volume":"48","author":"Bao","year":"2020","journal-title":"Infection"},{"key":"2026052202043852200_dkag177-B6","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1186\/s12931-023-02544-w","article-title":"Mortality and exacerbations associated with Stenotrophomonas maltophilia in chronic obstructive pulmonary disease. 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