Mechanistic insights into the differential efficacy of Daptomycin Plus β-Lactam combinations against Daptomycin-Resistant Enterococcus faecium

Vista sencilla de ítem
dc.contributor.authorKebriaei, Razieh
dc.contributor.authorStamper, Kyle
dc.contributor.authorSingh, Kavindra
dc.contributor.authorKhan, Ayesha
dc.contributor.authorRice, Seth A.
dc.contributor.authorDinh, An Q
dc.contributor.authorTran, Truc T.
dc.contributor.authorMurray, Barbara E.
dc.contributor.authorArias, César A.
dc.contributor.authorRybak, Michael Joseph
dc.date.accessioned2021-02-15T13:27:04Z
dc.date.available2021-02-15T13:27:04Z
dc.date.issued2020
dc.description.abstractenglishBackground The combination of daptomycin (DAP) plus ampicillin (AMP), ertapenem (ERT), or ceftaroline has been demonstrated to be efficacious against a DAP-tolerant Enterococcus faecium strain (HOU503). However, the mechanism for the efficacy of these combinations against DAP-resistant (DAP-R) E. faecium strains is unknown. Methods We investigated the efficacy of DAP in combination with AMP, ERT, ceftaroline, ceftriaxone, or amoxicillin against DAP-R E. faecium R497 using established in vitro and in vivo models. We evaluated pbp expression, levels of penicillin-binding protein (PBP) 5 (PBP5) and β-lactam binding affinity in HOU503 versus R497. Results DAP plus AMP was the only efficacious regimen against DAP-R R497 and prevented emergence of resistance. DAP at 8, 6, and 4 mg/kg in combination with AMP was efficacious but showed delayed killing compared with 10 mg/kg. PBP5 of HOU503 exhibited amino acid substitutions in the penicillin-binding domain relative to R497. No difference in pbp mRNA or PBP5 levels was detected between HOU503 and R497. labeling of PBPs with Bocillin FL, a fluorescent penicillin derivative, showed increased β-lactam binding affinity of PBP5 of HOU503 compared with that of R497. Conclusions Only DAP (10 mg/kg) plus AMP or amoxicillin was efficacious against a DAP-R E. faecium strain, and pbp5 alleles may be important contributors to efficacy of DAP plus β-lactam therapy.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1093/infdis/jiaa319
dc.identifier.instnameinstname:Universidad El Bosquespa
dc.identifier.issn1537-6613
dc.identifier.reponamereponame:Repositorio Institucional Universidad El Bosquespa
dc.identifier.repourlrepourl:https://repositorio.unbosque.edu.co
dc.identifier.urihttps://hdl.handle.net/20.500.12495/5317
dc.language.isoeng
dc.publisherOxford University Pressspa
dc.publisher.journalJournal of infectious diseasesspa
dc.relation.ispartofseriesJournal of infectious diseases, 1537-6613, Vol. 222, Nro. 9, 2020, 1531-1539spa
dc.relation.urihttps://academic.oup.com/jid/article-abstract/222/9/1531/5854807
dc.rights.accessrightshttps://purl.org/coar/access_right/c_abf2
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.accessrightsAcceso abierto
dc.rights.creativecommons2020-11
dc.rights.localAcceso abiertospa
dc.subject.keywordsVancomycin-resistant E. faeciumspa
dc.subject.keywordsE. faeciumspa
dc.subject.keywordsDaptomycin, β-lactamspa
dc.subject.keywordsPBPspa
dc.titleMechanistic insights into the differential efficacy of Daptomycin Plus β-Lactam combinations against Daptomycin-Resistant Enterococcus faeciumspa
dc.title.translatedMechanistic insights into the differential efficacy of Daptomycin Plus β-Lactam combinations against Daptomycin-Resistant Enterococcus faeciumspa
dc.type.coarhttps://purl.org/coar/resource_type/c_6501
dc.type.driverinfo:eu-repo/semantics/article
dc.type.hasversioninfo:eu-repo/semantics/publishedVersion
dc.type.localArtículo de revista

Archivos

Bloque original
Mostrando 1 - 1 de 1
No hay miniatura disponible
Nombre:
Razieh Kebriaei, Kyle C Stamper, Kavindra V Singh_2020.pdf
Tamaño:
2.69 MB
Formato:
Adobe Portable Document Format
Descripción:
Descargar
Bloque de licencias
Mostrando 1 - 1 de 1
No hay miniatura disponible
Nombre:
license.txt
Tamaño:
1.71 KB
Formato:
Item-specific license agreed upon to submission
Descripción:
Descargar

Colecciones

Artículos