{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T17:42:53Z","timestamp":1781890973696,"version":"3.54.5"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100006342","name":"Vaincre la Mucoviscidose","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006342","id-type":"DOI","asserted-by":"publisher"}]},{"name":"l\u2019Association Gr\u00e9gory Lemarchal","award":["RF20220503036"],"award-info":[{"award-number":["RF20220503036"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Mycobacterium abscessus is the most frequent of the rapidly growing mycobacteria responsible for lung infections in patients suffering from cystic fibrosis and COPD. Imipenem is currently recommended in the treatment of these infections in spite of \u03b2-lactamase production. Since the targets of \u03b2-lactams include transpeptidases of both the l,d and d,d specificities, we tested, in vitro, intracellularly and in vivo, a combination of two \u03b2-lactams active on these enzymes, amoxicillin and imipenem, alone or in combination with the \u03b2-lactamase inhibitor relebactam.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Drug combinations were evaluated against M. abscessus CIP 104536T and clinical isolates (n\u200a=\u200a35) by determining MICs, FIC indices and time\u2013killing. Drug combinations were also evaluated in macrophages and in mice.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In the presence of relebactam, synergy between amoxicillin and imipenem was observed against both M. abscessus CIP 104536T and the clinical isolates. Against M. abscessus CIP 104536T, the addition of 1\u2005mg\/L imipenem and 4\u2005mg\/L relebactam led to a decrease in the MIC of amoxicillin from 64 to 1\u2005mg\/L. The triple combination was active in vitro and intracellularly (a 4.30 decrease in the log10\u2005cfu\/mL and 82% killing, respectively). The triple combination was effective in reducing log10\u2005cfu in mouse organs and mouse spleen weights, and in preventing losses in mouse weights.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The amoxicillin\/imipenem\/relebactam combination was synergistic in vitro and effective in vivo against M. abscessus. Since these drugs are clinically available, the triple combination should be considered by clinicians and further evaluated based on the reporting of the patient outcomes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaf101","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T04:21:18Z","timestamp":1742271678000},"page":"1560-1567","source":"Crossref","is-referenced-by-count":3,"title":["<i>In vitro,<\/i> intracellular and <i>in vivo s<\/i>ynergy between amoxicillin, imipenem and relebactam against <i>Mycobacterium abscessus<\/i>"],"prefix":"10.1093","volume":"80","author":[{"given":"Maria","family":"Bitar","sequence":"first","affiliation":[{"name":"INSERM ERL 1336, UMRS 8228, Sorbonne Universit\u00e9-ENS-PSL-CNRS , Paris F-75006 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Le Moigne","sequence":"additional","affiliation":[{"name":"Inserm, Universit\u00e9 Paris-Saclay, UVSQ, Infection et inflammation , Montigny-Le-Bretonneux F-78180 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Louis","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Inserm, Universit\u00e9 Paris-Saclay, UVSQ, Infection et inflammation , Montigny-Le-Bretonneux F-78180 ,","place":["France"]},{"name":"Assistance Publique-H\u00f4pitaux de Paris, GHU Paris-Saclay, Service de Microbiologie, H\u00f4pital Raymond Poincar\u00e9 , Garches F-92380 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1007-636X","authenticated-orcid":false,"given":"Michel","family":"Arthur","sequence":"additional","affiliation":[{"name":"INSERM ERL 1336, UMRS 8228, Sorbonne Universit\u00e9-ENS-PSL-CNRS , Paris F-75006 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Luc","family":"Mainardi","sequence":"additional","affiliation":[{"name":"INSERM ERL 1336, UMRS 8228, Sorbonne Universit\u00e9-ENS-PSL-CNRS , Paris F-75006 ,","place":["France"]},{"name":"Assistance Publique-H\u00f4pitaux de Paris, Centre-Universit\u00e9 de Paris, Universit\u00e9 Paris Cit\u00e9, Service de Microbiologie, H\u00f4pital Europ\u00e9en Georges Pompidou , Paris F-75015 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"2025060219523852800_dkaf101-B1","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.ijid.2022.10.013","article-title":"Global trends of pulmonary infections with nontuberculous mycobacteria: a systematic review","volume":"125","author":"Dahl","year":"2022","journal-title":"Int J Infect Dis"},{"key":"2025060219523852800_dkaf101-B2","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1055\/s-0038-1660864","article-title":"Geographic distribution of nontuberculous mycobacteria isolated from clinical specimens: a 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