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dc.contributor.authorTirado-Velez, José M 
dc.contributor.authorCarreño, David 
dc.contributor.authorSevillano, David
dc.contributor.authorAlou, Luis
dc.contributor.authorYuste, Jose Enrique 
dc.contributor.authorde la Campa, Adela G 
dc.contributor.authorde la Campa
dc.date.accessioned2022-03-29T07:45:51Z
dc.date.available2022-03-29T07:45:51Z
dc.date.issued2021-05-13
dc.identifier.citationAntibiotics (Basel). 2021 May 13;10(5):573.es_ES
dc.identifier.issn2079-6382es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/13871
dc.description.abstractAntibiotic resistance in Streptococcus pneumoniae has increased worldwide, making fluoroquinolones an alternative therapeutic option. Fluoroquinolones inhibit the type II DNA topoisomerases (topoisomerase IV and gyrase). In this study we have evaluated the in vivo activity of seconeolitsine, an inhibitor of topoisomerase I. Levofloxacin (12.5 to 50 mg/kg) or seconeolitsine (5 to 40 mg/kg) were administered every 12 h during two days in mice infected with a serotype 8-resistant strain. At 48 h, a 70% protection was obtained with seconeolitsine (40 mg/kg; p < 0.001). However, survival with levofloxacin was 20%, regardless of the dose. In addition, seconeolitsine decreased bacteremia efficiently. Levofloxacin had higher levels in serum than seconeolitsine (Cmax of 14.7 vs. 1.6; p < 0.01) and higher values of area under the serum concentration-time curve (AUC0-12h of 17.3 vs. 5; p < 0.01). However, seconeolitsine showed higher levels of time to peak concentration and elimination half-life. This is consistent with the higher binding of seconeolitsine to plasma proteins (40% and 80% when used at 1 µg/mL and 50 µg/mL, respectively) in comparison to levofloxacin (12% at 5 µg/mL and 33% at 50 µg/mL). Our results suggest that seconeolitsine would be a promising therapeutic alternative against pneumococcal isolates with high fluoroquinolone resistance levels.es_ES
dc.description.sponsorshipThis research was funded by Ministerio de Economía, Industria y Competitividad (grants BIO2017-82951-R to A.G.d.l.C. and SAF2017-83388 to J.Y.). CIBER de Enfermedades Respiratorias (CIBERES) is an initiative of ISCIII.es_ES
dc.language.isoenges_ES
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI) es_ES
dc.relation.isversionofPreprintes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectDNA topoisomerase I inhibitores_ES
dc.subjectStreptococcus pneumoniaees_ES
dc.subjectInvasive pneumococcal diseasees_ES
dc.subjectResistancees_ES
dc.subjectSeconeolitsinees_ES
dc.titleSeconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strainses_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID34068007es_ES
dc.format.volume10es_ES
dc.format.number5es_ES
dc.identifier.doi10.3390/antibiotics10050573es_ES
dc.contributor.funderMinisterio de Economía, Industria y Competitividad (España) es_ES
dc.contributor.funderInstituto de Salud Carlos III es_ES
dc.description.peerreviewedNoes_ES
dc.relation.publisherversionhttps://doi.org/10.3390/antibiotics10050573es_ES
dc.identifier.journalAntibiotics (Basel, Switzerland)es_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/BIO2017-82951-Res_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/SAF2017-83388es_ES


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