{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T18:31:13Z","timestamp":1776796273646,"version":"3.51.2"},"reference-count":54,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T00:00:00Z","timestamp":1713916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/01453"],"award-info":[{"award-number":["PI19\/01453"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["RD16\/0016\/0009"],"award-info":[{"award-number":["RD16\/0016\/0009"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Subdirecci\u00f3n General de Redes y Centros de Investigaci\u00f3n Cooperativa, Ministerio de Econom\u00eda, Industria y Competitividad","award":["PI19\/01453"],"award-info":[{"award-number":["PI19\/01453"]}]},{"name":"Subdirecci\u00f3n General de Redes y Centros de Investigaci\u00f3n Cooperativa, Ministerio de Econom\u00eda, Industria y Competitividad","award":["RD16\/0016\/0009"],"award-info":[{"award-number":["RD16\/0016\/0009"]}]},{"name":"Spanish Network for Research in Infectious Diseases","award":["PI19\/01453"],"award-info":[{"award-number":["PI19\/01453"]}]},{"name":"Spanish Network for Research in Infectious Diseases","award":["RD16\/0016\/0009"],"award-info":[{"award-number":["RD16\/0016\/0009"]}]},{"name":"European Union","award":["PI19\/01453"],"award-info":[{"award-number":["PI19\/01453"]}]},{"name":"European Union","award":["RD16\/0016\/0009"],"award-info":[{"award-number":["RD16\/0016\/0009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>This study aimed to evaluate the potential of tamoxifen and N-desmethyltamoxifen metabolites as therapeutic agents against multidrug-resistant Escherichia coli and Acinetobacter baumannii, using a repurposing approach to shorten the time required to obtain a new effective treatment against multidrug-resistant bacterial infections. Characterisation and virulence studies were conducted on E. coli (colistin-susceptible C1-7-LE and colistin-resistant MCR-1+) and A. baumannii (tigecycline-susceptible Ab#9 and tigecycline-resistant Ab#186) strains. The efficacy of the metabolite mix (33.3% each) and N-desmethyltamoxifen in combination with colistimethate sodium (CMS) or tigecycline was evaluated in experimental models in mice. In the pneumonia model, N-desmethyltamoxifen exhibited significant efficacy against Ab#9 and both E. coli strains, especially E. coli MCR-1+ (\u22122.86 log10 CFU\/g lungs, \u22125.88 log10 CFU\/mL blood, and \u221250% mortality), and against the Ab#186 strain when combined with CMS (\u22122.27 log10 CFU\/g lungs, \u22122.73 log10 CFU\/mL blood, and \u221240% mortality) or tigecycline (\u22123.27 log10 CFU\/g lungs, \u22124.95 log10 CFU\/mL blood, and \u221250% mortality). Moreover, the metabolite mix in combination with both antibiotics decreased the bacterial concentrations in the lungs and blood for both A. baumannii strains. In the sepsis model, the significant efficacy of the metabolite mix was restricted to the colistin-susceptible E. coli C1-7-LE strain (\u22123.32 log10 CFU\/g lung, \u22126.06 log10 CFU\/mL blood, and \u221279% mortality). N-desmethyltamoxifen could be a new therapeutic option in combination with CMS or tigecycline for combating multidrug-resistant GNB, specifically A. baumannii.<\/jats:p>","DOI":"10.3390\/antibiotics13050386","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T10:18:36Z","timestamp":1713953916000},"page":"386","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Efficacy of Tamoxifen Metabolites in Combination with Colistin and Tigecycline in Experimental Murine Models of Escherichia coli and Acinetobacter baumannii"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8019-0905","authenticated-orcid":false,"given":"Soraya","family":"Herrera-Espejo","sequence":"first","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas, Microbiolog\u00eda y Parasitolog\u00eda, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, 41013 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Vila-Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas, Microbiolog\u00eda y Parasitolog\u00eda, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, 41013 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8221-0965","authenticated-orcid":false,"given":"Tania","family":"Cebrero-Cangueiro","sequence":"additional","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas, Microbiolog\u00eda y Parasitolog\u00eda, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, 41013 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9302-8384","authenticated-orcid":false,"given":"Younes","family":"Smani","sequence":"additional","affiliation":[{"name":"Centro Andaluz de Biolog\u00eda del Desarrollo, Universidad Pablo de Olavide\/Consejo Superior de Investigaciones Cient\u00edficas\/Junta de Andaluc\u00eda, 41013 Sevilla, Spain"},{"name":"Departamento de Biolog\u00eda Molecular e Ingenier\u00eda Bioqu\u00edmica, Universidad Pablo de Olavide, 41013 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8166-5308","authenticated-orcid":false,"given":"Jer\u00f3nimo","family":"Pach\u00f3n","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, 41013 Sevilla, Spain"},{"name":"Departamento de Medicina, Facultad de Medicina, Universidad de Sevilla, 41009 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5331-6648","authenticated-orcid":false,"given":"Manuel E.","family":"Jim\u00e9nez-Mej\u00edas","sequence":"additional","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas, Microbiolog\u00eda y Parasitolog\u00eda, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, 41013 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7969-8162","authenticated-orcid":false,"given":"Mar\u00eda E.","family":"Pach\u00f3n-Ib\u00e1\u00f1ez","sequence":"additional","affiliation":[{"name":"Unidad Cl\u00ednica de Enfermedades Infecciosas, Microbiolog\u00eda y Parasitolog\u00eda, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, 41013 Sevilla, Spain"},{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28220 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,24]]},"reference":[{"key":"ref_1","unstructured":"WHO (World Health Organization) (2023). 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