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dc.creatorCebrero Cangueiro, Taniaes
dc.creatorLabrador Herrera, Gemaes
dc.creatorPascual Hernández, Álvaroes
dc.creatorDíaz, Caridades
dc.creatorRodríguez-Baño, Jesúses
dc.creatorPachón Díaz, Jerónimoes
dc.creatorPalacio, José P. deles
dc.creatorPachón Ibáñez, María Eugeniaes
dc.creatorConejo Gonzalo, Mª Carmenes
dc.date.accessioned2022-07-12T11:21:13Z
dc.date.available2022-07-12T11:21:13Z
dc.date.issued2021
dc.identifier.citationCebrero Cangueiro, T., Labrador Herrera, G., Pascual Hernández, Á., Díaz, C., Rodríguez-Baño, J., Pachón Díaz, J.,...,Conejo Gonzalo, M.C. (2021). Efficacy of Fosfomycin and Its Combination With Aminoglycosides in an Experimental Sepsis Model by Carbapenemase-Producing Klebsiella pneumoniae Clinical Strains. Frontiers in Medicine, 8, 615540.
dc.identifier.issn2296-858Xes
dc.identifier.urihttps://hdl.handle.net/11441/135265
dc.description.abstractCarbapenemase-producing Klebsiella pneumoniae infections are an increasing global threat with scarce and uncertain treatment options. In this context, combination therapies are often used for these infections. The bactericidal and synergistic activity of fosfomycin plus amikacin and gentamicin was studied trough time–kill assays against four clonally unrelated clinical isolates of carbapenemase-producing K. pneumoniae, VIM-1, VIM-1 plus DHA-1, OXA-48 plus CTXM-15, and KPC-3, respectively. The efficacy of antimicrobials that showed synergistic activity in vitro against all the carbapenemase-producing K. pneumoniae were tested in monotherapy and in combination, in a murine peritoneal sepsis model. In vitro, fosfomycin plus amikacin showed synergistic and bactericidal effect against strains producing VIM-1, VIM-1 plus DHA-1, and OXA-48 plus CTX-M-15. Fosfomycin plus gentamicin had in vitro synergistic activity against the strain producing KPC-3. In vivo, fosfomycin and amikacin and its combination reduced the spleen bacterial concentration compared with controls groups in animals infected by K. pneumoniae producing VIM-1 and OXA-48 plus CTX-M-15. Moreover, amikacin alone and its combination with fosfomycin reduced the bacteremia rate against the VIM-1 producer strain. Contrary to the in vitro results, no in vivo efficacy was found with fosfomycin plus amikacin against the VIM-1 plus DHA-1 producer strain. Finally, fosfomycin plus gentamicin reduced the bacterial concentration in spleen against the KPC-3 producer strain. In conclusion, our results suggest that fosfomycin plus aminoglycosides has a dissimilar efficacy in the treatment of this severe experimental infection, when caused by different carbapenemase-producing K. pneumoniae strains. Fosfomycin plus amikacin or plus gentamycin may be useful to treat infections by OXA-48 plus CTX-M-15 or KPC-3 producer strains, respectively.es
dc.description.sponsorshipJunta de Andalucía PI-0622-2012es
dc.description.sponsorshipMinisterio de Economía, Industria y Competitividad co-financed by FEDER - RD16/0016/0001, RD16/0016/0009es
dc.formatapplication/pdfes
dc.format.extent8 p.es
dc.language.isoenges
dc.publisherFrontiers Mediaes
dc.relation.ispartofFrontiers in Medicine, 8, 615540.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectFosfomycines
dc.subjectAminoglycosideses
dc.subjectIn vivoes
dc.subjectTime kill curveses
dc.subjectCarbapenemase-producing Klebsiella pneumoniaees
dc.titleEfficacy of Fosfomycin and Its Combination With Aminoglycosides in an Experimental Sepsis Model by Carbapenemase-Producing Klebsiella pneumoniae Clinical Strainses
dc.typeinfo:eu-repo/semantics/articlees
dcterms.identifierhttps://ror.org/03yxnpp24
dc.type.versioninfo:eu-repo/semantics/publishedVersiones
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Microbiologíaes
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Medicinaes
dc.relation.projectIDPI-0622-2012es
dc.relation.projectIDRD16/0016/0001es
dc.relation.projectIDRD16/0016/0009es
dc.relation.publisherversionhttps://dx.doi.org/10.3389/fmed.2021.615540es
dc.identifier.doi10.3389/fmed.2021.615540es
dc.journaltitleFrontiers in Medicinees
dc.publication.volumen8es
dc.publication.initialPage615540es
dc.contributor.funderJunta de Andalucíaes
dc.contributor.funderMinisterio de Economia, Industria y Competitividad (MINECO). Españaes
dc.contributor.funderEuropean Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)es

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