{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T09:27:37Z","timestamp":1763458057770,"version":"3.37.3"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T00:00:00Z","timestamp":1635465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"IAME"},{"name":"Fondation pour la Recherche M\u00e9dicale\u2019 (Equipe FRM 2016","award":["DEQ20161136698"],"award-info":[{"award-number":["DEQ20161136698"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Alternative treatments are needed against NDM-1-producing Escherichia coli. Colistin (COL) and fosfomycin (FOS) often remain active in vitro but selection of resistant mutants is frequent if used separately. We determined whether the combination of colistin and fosfomycin may be useful to treat infections with NDM-1-producing E. coli with varying levels of resistance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Isogenic derivatives of E. coli CFT073 with blaNDM-1 and variable levels of resistance to colistin and fosfomycin (CFT073-NDM1, CFT073-NDM1-COL and CFT073-NDM1-FOS, respectively) were used. The combination (colistin + fosfomycin) was tested in vitro and in a fatal peritonitis murine model. Mortality and bacterial loads were determined and resistant mutants detected.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Colistin MICs were 0.5, 16 and 0.5\u2009mg\/L and fosfomycin MICs were 1, 1 and 32\u2009mg\/L against CFT073-NDM1, CFT073-NDM1-COL and CFT073-NDM1-FOS, respectively. In time\u2013kill curves, combining colistin with fosfomycin was synergistic and bactericidal against CFT073-NDM1 and CFT073-NDM1-FOS, with concentrations of 4\u00d7 MIC (for both drugs), but not against CFT073-NDM1-COL (concentrations of colistin\u2009=\u20090.5\u00d7 MIC), due to regrowth with fosfomycin-resistant mutants. Mice died less and bacterial counts were lower in spleen with the combination compared with monotherapy against all strains; the combination prevented selection of resistant mutants except for CFT073-NDM1-COL where fosfomycin-resistant mutants were found in all mice.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Combining colistin and fosfomycin was beneficial in vitro and in vivo against NDM-1-producing E. coli, even with strains less susceptible to colistin and fosfomycin. However, the combination failed to prevent the emergence of fosfomycin-resistant mutants against colistin-resistant strains. Combining colistin and fosfomycin constitutes an alternative for treatment of NDM-1 E. coli, except against colistin-resistant strains.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkab378","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:42:12Z","timestamp":1633567332000},"page":"155-163","source":"Crossref","is-referenced-by-count":7,"title":["Activity of the combination of colistin and fosfomycin against NDM-1-producing <i>Escherichia coli<\/i> with variable levels of susceptibility to colistin and fosfomycin in a murine model of peritonitis"],"prefix":"10.1093","volume":"77","author":[{"given":"Alice","family":"Le Menestrel","sequence":"first","affiliation":[{"name":"IAME Research Group, UMR-1137, Universit\u00e9 de Paris and INSERM, 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":"CHU de Rennes, Service de Bact\u00e9riologie-Hygi\u00e8ne Hospitali\u00e8re & CNR de la R\u00e9sistance aux Antibiotiques (Laboratoire Associ\u00e9 \u2018Ent\u00e9rocoques\u2019), Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7oise","family":"Chau","sequence":"additional","affiliation":[{"name":"IAME Research Group, UMR-1137, Universit\u00e9 de Paris and INSERM, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent","family":"Massias","sequence":"additional","affiliation":[{"name":"IAME Research Group, UMR-1137, Universit\u00e9 de Paris and INSERM, Paris, France"},{"name":"Service de Pharmacologie, H\u00f4pital Bichat, Assistance-Publique H\u00f4pitaux de Paris, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Benchetrit","sequence":"additional","affiliation":[{"name":"IAME Research Group, UMR-1137, Universit\u00e9 de Paris and INSERM, Paris, 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":"CHU de Rennes, Service de Bact\u00e9riologie-Hygi\u00e8ne Hospitali\u00e8re & CNR de la R\u00e9sistance aux Antibiotiques (Laboratoire Associ\u00e9 \u2018Ent\u00e9rocoques\u2019), Rennes, France"},{"name":"Universit\u00e9 de Rennes 1, Unit\u00e9 Inserm U1230, Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7904-9402","authenticated-orcid":false,"given":"Bruno","family":"Fantin","sequence":"additional","affiliation":[{"name":"IAME Research Group, UMR-1137, Universit\u00e9 de Paris and INSERM, Paris, France"},{"name":"Service de M\u00e9decine Interne, H\u00f4pital Beaujon, Assistance-Publique H\u00f4pitaux de Paris, Clichy, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1160-2069","authenticated-orcid":false,"given":"Victoire","family":"de Lastours","sequence":"additional","affiliation":[{"name":"IAME Research Group, UMR-1137, Universit\u00e9 de Paris and INSERM, Paris, France"},{"name":"Service de M\u00e9decine Interne, H\u00f4pital Beaujon, Assistance-Publique H\u00f4pitaux de Paris, Clichy, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,10,29]]},"reference":[{"key":"2022010520153244100_dkab378-B1","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.3201\/eid1710.110655","article-title":"Global Spread of Carbapenemase-producing Enterobacteriaceae","volume":"17","author":"Nordmann","year":"2011","journal-title":"Emerg Infect 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