{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T20:45:13Z","timestamp":1778964313254,"version":"3.51.4"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T00:00:00Z","timestamp":1710806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"IAME"},{"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"}]},{"DOI":"10.13039\/501100002738","name":"Assistance-Publique H\u00f4pitaux de Paris","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Temocillin is a narrow spectrum \u03b2-lactam active against MDR Enterobacterales. Mechanisms of acquired resistance to temocillin are poorly understood. We analysed resistance mechanisms in clinical isolates of Escherichia coli and evaluated their impact on temocillin efficacy in vitro and in a murine peritonitis model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Two sets of isogenic clinical E. coli strains were studied: a susceptible isolate (MLTEM16S) and its resistant derivative, MLTEM16R (mutation in nmpC porin gene); and temocillin-resistant derivatives of E. coli CFT073: CFT-\u0394nmpC (nmpC deletion), CFTbaeS-TP and CFTbaeS-AP (two different mutations in the baeS efflux-pump gene).<\/jats:p>\n                  <jats:p>Fitness cost, time\u2013kill curves and phenotypic expression of resistance were determined. Temocillin efficacy was assessed in a murine peritonitis model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>MICs of temocillin were 16 and 64 mg\/L for MLTEM16S and MLTEM16R, respectively, and 8, 128, 256 and 256 mg\/L for E. coli-CFT073, CFT-\u0394nmpC, CFTbaeS-TP and CFTbaeS-AP, respectively. No fitness cost of resistance was evidenced. All resistant strains showed heteroresistant profiles, except for CFTbaeS-AP, which displayed a homogeneous pattern. In vitro, temocillin was bactericidal against MLTEM16R, CFT-\u0394nmpC, CFTbaeS-TP and CFTbaeS-AP at 128, 256, 512 and 512 mg\/L, respectively.<\/jats:p>\n                  <jats:p>In vivo, temocillin was as effective as cefotaxime against MLTEM16R, CFT-\u0394nmpC and CFTbaeS-TP, but inefficient against CFTbaeS-AP (100% mortality).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Heteroresistant NmpC porin alteration and active efflux modification do not influence temocillin efficacy despite high MIC values, unfavourable pharmacokinetic\/pharmacodynamic conditions and the absence of fitness cost, whereas homogeneously expressed BaeS efflux pump alteration yielding similar MICs leads to temocillin inefficacy. MIC as sole predictor of temocillin efficacy should be used with caution.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae072","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T12:57:43Z","timestamp":1710853063000},"page":"1051-1059","source":"Crossref","is-referenced-by-count":5,"title":["Impact of the phenotypic expression of temocillin resistance in <i>Escherichia coli<\/i> on temocillin efficacy in a murine peritonitis model"],"prefix":"10.1093","volume":"79","author":[{"given":"Elise","family":"Mallart","sequence":"first","affiliation":[{"name":"IAME Research Group, UMR1137 INSERM and Uiversit\u00e9 Paris Cit\u00e9 , F-75018 Paris , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6821-3131","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Guerin","sequence":"additional","affiliation":[{"name":"UMR1230, INSERM and Universit\u00e9 Rennes 1 , F-35043 Rennes , 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France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Fantin","sequence":"additional","affiliation":[{"name":"IAME Research Group, UMR1137 INSERM and Uiversit\u00e9 Paris Cit\u00e9 , F-75018 Paris , France"},{"name":"Service de M\u00e9decine Interne, H\u00f4pital Beaujon, AP-HP, Universit\u00e9 Paris Cit\u00e9 , F-92210 Clichy , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4026-9912","authenticated-orcid":false,"given":"Vincent","family":"Cattoir","sequence":"additional","affiliation":[{"name":"UMR1230, INSERM and Universit\u00e9 Rennes 1 , F-35043 Rennes , France"},{"name":"Service de Bact\u00e9riologie-Hygi\u00e8ne Hospitali\u00e8re & CNR de la R\u00e9sistance aux Antibiotiques (laboratoire associ\u00e9 \u2018Ent\u00e9rocoques\u2019), CHU Pontchaillou , F-35033 Rennes , 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