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dc.contributor.authorKebriaei, Razieh
dc.contributor.authorRice, Seth A.
dc.contributor.authorStamper, Kyle
dc.contributor.authorSeepersaud, Ravin
dc.contributor.authorGarcía-De-La-Mària, Cristina
dc.contributor.authorMishra, Nagendra Nath
dc.contributor.authorMiró, José Mª
dc.contributor.authorArias, César A.
dc.contributor.authorTran, Truc T
dc.contributor.authorSullam, Paul M.
dc.contributor.authorBayer, Arnold
dc.contributor.authorRybak, Michael Joseph
dc.date.accessioned2020-05-08T00:02:31Z
dc.date.available2020-05-08T00:02:31Z
dc.identifier.issn1098-6596spa
dc.identifier.urihttp://hdl.handle.net/20.500.12495/2509
dc.format.mimetypeapplication/pdfspa
dc.language.isoengspa
dc.publisherAmerican Society for Microbiologyspa
dc.relation.ispartofseriesAntimicrobial agents and chemotherapy, 1098-6596, Vol. 63, Nro. 6, 2019, p. e00386-19spa
dc.relation.urihttps://aac.asm.org/content/63/6/e00386-19.longspa
dc.titleDaptomycin dose-ranging evaluation with single-dose versus multidose ceftriaxone combinations against streptococcus mitis/ oralis in an ex vivo simulated endocarditis vegetation modelspa
dc.typearticlespa
dc.type.localartículospa
dc.subject.decsEstreptococos viridansspa
dc.subject.decsEndocarditis bacterianaspa
dc.subject.decsResistencia betalactámicaspa
dc.identifier.doihttps://doi.org/10.1128/AAC.00386-19spa
dc.subject.armarcCeftriaxonespa
dc.subject.armarcDaptomycinspa
dc.subject.armarcSEVsspa
dc.type.hasversioninfo:eu-repo/semantics/publishedVersion
dc.publisher.journalAntimicrobial agents and chemotherapyspa
dc.description.abstractenglishT The viridans group streptococci (VGS) are a heterogeneous group of organisms which are important components of the normal human oral flora. Among the VGS, the Streptococcus mitis/oralis subgroup is one of the most common causes of infective endocarditis (IE). Daptomycin (DAP) is a potential alternative therapeutic option for invasive S. mitis infections, given high rates of -lactam resistance and vancomycin tolerance in such strains. However, the ability of these strains to rapidly evolve high-level and durable DAP resistance (DAP-R) is problematic. Recent data suggest that combination DAP--lactam therapy circumvents this issue. Humansimulated dose-escalating DAP-alone dose regimens (6, 8, 10, or 12 mg/kg/day times 4 days) versus DAP (6 mg/kg/day) plus ceftriaxone (CRO) (2 g once daily times 4 days or 0.5 g, single dose) were assessed against two prototypical DAP-susceptible (DAP-S) S. mitis/oralis strains (SF100 and 351), as measured by a pharmacokinetic/ pharmacodynamic (PK/PD) model of simulated endocardial vegetations (SEVs). No DAP-alone regimen was effective, with regrowth of high-level DAP-R isolates observed for both strains over 96-h exposures. Combinations of DAP-CRO with either single- or multidose regimens yielded significant reductions in log10 CFU/g amounts within SEVs for both strains (6 log10 CFU/g) within 24 h. In addition, no DAP-R strains were detected in either DAP-CRO combination regimens over the 96-h exposure. In contrast to prior in vitro studies, no perturbations in two key cardiolipin biosynthetic genes (cdsA and pgsA) were identified in DAP-R SEV isolates emerging from strain 351, despite defective phospholipid production. The combination of DAP-CRO warrants further investigation for treatment of IE due to S. mitis/oralisspa
dc.rights.localAcceso cerradospa
dc.date.issued2019


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