{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T05:54:20Z","timestamp":1761630860600,"version":"3.37.3"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,5,14]],"date-time":"2019-05-14T00:00:00Z","timestamp":1557792000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100009947","name":"Merck Sharp & Dohme Corp.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009947","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Merck & Co., Inc., Kenilworth"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Relebactam is a diazabicyclooctane non-\u03b2-lactam inhibitor of Ambler class A and C \u03b2-lactamases that is in clinical development in combination with imipenem\/cilastatin. The current study evaluated the in vitro activity of imipenem\/relebactam against 5447 isolates of Pseudomonas aeruginosa submitted to the SMART global surveillance programme in 2015\u201317 by 67 clinical laboratories in 22 European countries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MICs were determined using the CLSI broth microdilution reference method (Eleventh Edition: M07, 2018). Relebactam was tested at a fixed concentration of 4\u2009mg\/L in combination with doubling dilutions of imipenem. MICs were interpreted using EUCAST clinical breakpoints (version 8.1); imipenem breakpoints were applied to imipenem\/relebactam.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Rates of susceptibility to imipenem and imipenem\/relebactam (MIC \u22644\u2009mg\/L) were 69.4% and 92.4%, respectively, for all isolates of P. aeruginosa. Over one-third of all isolates (34.9%, 1902\/5447) were MDR; lower respiratory tract isolates (38.3%, 1327\/3461) were more frequently MDR than were intraabdominal (28.5%, 355\/1245) or urinary tract (29.7%, 212\/714) isolates. Of all MDR isolates, 78.2% were susceptible to imipenem\/relebactam, a rate that was 50\u201377 percentage points higher than the rate of susceptibility to imipenem or any other \u03b2-lactam tested; rates of susceptibility to imipenem\/relebactam were similar for MDR isolates from lower respiratory tract (77.8% susceptible), intraabdominal (80.3%) and urinary tract (76.4%) infections. Overall, relebactam restored imipenem susceptibility to 75.2% (1254\/1668) of imipenem-non-susceptible isolates of P. aeruginosa and to 69.6% (947\/1361) of imipenem-non-susceptible isolates with an MDR phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Relebactam restored in vitro susceptibility to imipenem for most imipenem-non-susceptible and MDR clinical isolates of P. aeruginosa from European patients.<\/jats:p><\/jats:sec>","DOI":"10.1093\/jac\/dkz191","type":"journal-article","created":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T19:12:33Z","timestamp":1556219553000},"page":"2284-2288","source":"Crossref","is-referenced-by-count":39,"title":["Activity of imipenem\/relebactam against MDR Pseudomonas aeruginosa in Europe: SMART 2015\u201317"],"prefix":"10.1093","volume":"74","author":[{"given":"Sibylle H","family":"Lob","sequence":"first","affiliation":[{"name":"International Health Management Associates (IHMA), Inc., Schaumburg, IL 60173, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James A","family":"Karlowsky","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Young","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc., Kenilworth, NJ 07033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary R","family":"Motyl","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc., Kenilworth, NJ 07033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Hawser","sequence":"additional","affiliation":[{"name":"IHMA Europe S\u00e0rl, Monthey\/VS, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nimmi D","family":"Kothari","sequence":"additional","affiliation":[{"name":"IHMA Europe S\u00e0rl, Monthey\/VS, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melinda E","family":"Gueny","sequence":"additional","affiliation":[{"name":"IHMA Europe S\u00e0rl, Monthey\/VS, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel F","family":"Sahm","sequence":"additional","affiliation":[{"name":"International Health Management Associates (IHMA), Inc., Schaumburg, IL 60173, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,5,13]]},"reference":[{"key":"2019071909303011500_dkz191-B1","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1093\/jac\/dku048","article-title":"Epidemiology and carbapenem resistance mechanisms of carbapenem-non-susceptible Pseudomonas aeruginosa collected during 2009-11 in 14 European and Mediterranean countries","volume":"69","author":"Castanheira","year":"2014","journal-title":"J Antimicrob 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