{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T20:02:57Z","timestamp":1771272177582,"version":"3.50.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T00:00:00Z","timestamp":1597276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100009820","name":"Assistance Publique-H\u00f4pitaux de Paris","doi-asserted-by":"publisher","award":["2018-10-14"],"award-info":[{"award-number":["2018-10-14"]}],"id":[{"id":"10.13039\/501100009820","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Soci\u00e9t\u00e9 de Pathologie Infectieuse de Langue Fran\u00e7aise"},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["DEQ20161136698"],"award-info":[{"award-number":["DEQ20161136698"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Carbapenemase-producing Enterobacterales represent a major therapeutic challenge. MBLs, requiring zinc at their catalytic site, could be inhibited by meso-dimercaptosuccinic acid (DMSA), a heavy metal chelator already widely used for treating lead intoxication.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To evaluate the activity of carbapenems alone or combined with DMSA against MBL-producing Escherichia coli in a severe murine peritonitis model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Isogenic strains of wild-type E. coli CFT073 producing the MBLs NDM-1, VIM-2 and IMP-1, and the control serine carbapenemases OXA-48 and KPC-3 were constructed. MIC determinations and time\u2013kill assays were performed for imipenem, meropenem and ertapenem alone or in combination with DMSA. Infected mice were treated intraperitoneally for 24\u2009h with imipenem, DMSA or their combination. Bacterial counts in peritoneal fluid and spleen were assessed at 24\u2009h.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>DMSA in combination with each carbapenem caused a significant decrease in the MICs for all MBL-producing strains, in a concentration-dependent manner, but did not provide benefit against non-MBL strains. In mice infected with the NDM-1-producing strain, the combination of imipenem and DMSA significantly reduced bacterial counts in peritoneal fluid (P\u2009=\u20090.0006) and spleen (P\u2009&amp;lt;\u20090.0001), as compared with imipenem alone, with no benefit against the KPC-3-producing and CFT073 strains. DMSA concentrations in plasma of mice were comparable to those obtained in humans with a standard oral dose.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>DMSA restores the activity of carbapenems against MBL-producing strains, and its combination with carbapenems appears to be a promising strategy for the treatment of NDM-producing E. coli infections.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaa347","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T19:29:14Z","timestamp":1596569354000},"page":"3593-3600","source":"Crossref","is-referenced-by-count":12,"title":["Dimercaptosuccinic acid in combination with carbapenems against isogenic strains of <i>Escherichia coli<\/i> producing or not producing a metallo-\u03b2-lactamase <i>in vitro<\/i> and in murine peritonitis"],"prefix":"10.1093","volume":"75","author":[{"given":"G","family":"Cheminet","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Paris, IAME, UMR 1137 INSERM, F-75018 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V","family":"de Lastours","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, IAME, UMR 1137 INSERM, F-75018 Paris, France"},{"name":"M\u00e9decine interne, H\u00f4pital Beaujon, AP-HP Nord, Universit\u00e9 de Paris, F-92110 Clichy, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Poirel","sequence":"additional","affiliation":[{"name":"IAME, UMR 1137 Laboratoire Europ\u00e9en Associ\u00e9 INSERM, Universit\u00e9 de Fribourg, Fribourg, Switzerland"},{"name":"Microbiologie M\u00e9dicale et Mol\u00e9culaire, D\u00e9partement de M\u00e9decine, Facult\u00e9 des Sciences et de M\u00e9decine, Centre de R\u00e9f\u00e9rence des R\u00e9sistances Emergentes aux Antibiotiques (NARA), Universit\u00e9 de Fribourg, Fribourg, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Chau","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, IAME, UMR 1137 INSERM, F-75018 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Peoc\u2019h","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, CRI, UMR 1149 INSERM, F-75018 Paris, France"},{"name":"Laboratoire de biochimie, H\u00f4pital Beaujon, AP-HP Nord, F-92110 Clichy, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Massias","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, IAME, UMR 1137 INSERM, F-75018 Paris, France"},{"name":"Laboratoire de pharmacologie et toxicologie, AP-HP Nord, H\u00f4pital Bichat-Claude Bernard, F-75018 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7904-9402","authenticated-orcid":false,"given":"B","family":"Fantin","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, IAME, UMR 1137 INSERM, F-75018 Paris, France"},{"name":"M\u00e9decine interne, H\u00f4pital Beaujon, AP-HP Nord, Universit\u00e9 de Paris, F-92110 Clichy, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Nordmann","sequence":"additional","affiliation":[{"name":"IAME, UMR 1137 Laboratoire Europ\u00e9en Associ\u00e9 INSERM, Universit\u00e9 de Fribourg, Fribourg, Switzerland"},{"name":"Microbiologie M\u00e9dicale et Mol\u00e9culaire, D\u00e9partement de M\u00e9decine, Facult\u00e9 des Sciences et de M\u00e9decine, Centre de R\u00e9f\u00e9rence des R\u00e9sistances Emergentes aux Antibiotiques (NARA), Universit\u00e9 de Fribourg, Fribourg, 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