The Combination of Daptomycin plus Fosfomycin has Synergistic, Potent and Rapid Bactericidal Activity against Methicillin-ResistantStaphylococcus aureus(MRSA) in a Rabbit Model of Experimental Endocarditis (EE).

This study aims to investigate whether the addition of fosfomycin or cloxacillin to daptomycin provides better outcomes in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) experimental aortic endocarditis in rabbits. Five MRSA strains were used to perform in vitro time-kill studie...

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Autores: García de la Mària, Cristina, Gasch, Oriol, García González, Javier, Soy Muner, Dolors, Shaw Perujo, Evelyn, Ambrosioni, Juan, Almela, M. (Manel), Pericàs, Juan M., Tellez, Adrian, Falces Salvador, Carles, Hernández Meneses, Marta, Sandoval, Elena, Quintana, Eduard, Vidal, Bàrbara, Tolosana, José M. (José María), Fuster Pelfort, David, Llopis Pérez, Jaime, Pujol Rojo, Miquel, Moreno Camacho, Ma. Asunción, Marco Reverté, Francesc, Miró Meda, José M. (José María), 1956-, Hospital Clínic Endocarditis Study Group
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2018
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/184232
Acceso en línea:https://hdl.handle.net/2445/184232
Access Level:acceso abierto
Palabra clave:Endocarditis
Microbiologia
Microbiology
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repository_id_str
spelling The Combination of Daptomycin plus Fosfomycin has Synergistic, Potent and Rapid Bactericidal Activity against Methicillin-ResistantStaphylococcus aureus(MRSA) in a Rabbit Model of Experimental Endocarditis (EE).García de la Mària, CristinaGasch, OriolGarcía González, JavierSoy Muner, DolorsShaw Perujo, EvelynAmbrosioni, JuanAlmela, M. (Manel)Pericàs, Juan M.Tellez, AdrianFalces Salvador, CarlesHernández Meneses, MartaSandoval, ElenaQuintana, EduardVidal, BàrbaraTolosana, José M. (José María)Fuster Pelfort, DavidLlopis Pérez, JaimePujol Rojo, MiquelMoreno Camacho, Ma. AsunciónMarco Reverté, FrancescMiró Meda, José M. (José María), 1956-Hospital Clínic Endocarditis Study GroupEndocarditisMicrobiologiaEndocarditisMicrobiologyThis study aims to investigate whether the addition of fosfomycin or cloxacillin to daptomycin provides better outcomes in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) experimental aortic endocarditis in rabbits. Five MRSA strains were used to perform in vitro time-kill studies at standard (105) and high (108) inocula. Combined therapy was compared with daptomycin monotherapy treatment in the MRSA experimental endocarditis model. A human-like pharmacokinetics model was applied and the equivalents of cloxacillin 2g/4hiv, fosfomycin 2g/6h iv and daptomycin 6-10mg/kg/d iv were administered. The combination of daptomycin and fosfomycin or cloxacillin was synergistic in the five strains tested at both inocula. A bactericidal effect was detected in four out of five strains tested with both combinations. The MRSA-277 strain (vancomycin MIC, 2 mcg/mL) was used for the experimental endocarditis model. Daptomycin plus fosfomycin significantly improved the efficacy of daptomycin monotherapy at 6 mg/kg/d in terms of both the proportion of sterile vegetations (100% vs. 72%, P=.046) and the decrease in the density of bacteria within the vegetations (P=.025). Daptomycin plus fosfomycin was as effective as daptomycin monotherapy at 10 mg/kg/d (100% vs. 93%, P=1.00) and had similar activity to daptomycin plus cloxacillin when daptomycin was administered at 6 mg/kg/d (100% vs. 88%, P=0.48). Daptomycin non-susceptibility was not detected in any of the isolates recovered from vegetations. In conclusion, for the treatment of MRSA experimental endocarditis, the combination of daptomycin plus fosfomycin showed synergistic and bactericidal activity.Copyright © 2018 American Society for Microbiology.American Society for Microbiology2022202220182022info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion8 p.application/pdfhttps://hdl.handle.net/2445/184232Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del postprint publicat a: https://doi.org/10.1128/AAC.02633-17Antimicrobial Agents And Chemotherapy, 2018, vol 62, num 6, p. 1-8https://doi.org/10.1128/AAC.02633-17(c) American Society for Microbiology, 2018info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1842322026-05-29T05:05:01Z
dc.title.none.fl_str_mv The Combination of Daptomycin plus Fosfomycin has Synergistic, Potent and Rapid Bactericidal Activity against Methicillin-ResistantStaphylococcus aureus(MRSA) in a Rabbit Model of Experimental Endocarditis (EE).
title The Combination of Daptomycin plus Fosfomycin has Synergistic, Potent and Rapid Bactericidal Activity against Methicillin-ResistantStaphylococcus aureus(MRSA) in a Rabbit Model of Experimental Endocarditis (EE).
spellingShingle The Combination of Daptomycin plus Fosfomycin has Synergistic, Potent and Rapid Bactericidal Activity against Methicillin-ResistantStaphylococcus aureus(MRSA) in a Rabbit Model of Experimental Endocarditis (EE).
García de la Mària, Cristina
Endocarditis
Microbiologia
Endocarditis
Microbiology
title_short The Combination of Daptomycin plus Fosfomycin has Synergistic, Potent and Rapid Bactericidal Activity against Methicillin-ResistantStaphylococcus aureus(MRSA) in a Rabbit Model of Experimental Endocarditis (EE).
title_full The Combination of Daptomycin plus Fosfomycin has Synergistic, Potent and Rapid Bactericidal Activity against Methicillin-ResistantStaphylococcus aureus(MRSA) in a Rabbit Model of Experimental Endocarditis (EE).
title_fullStr The Combination of Daptomycin plus Fosfomycin has Synergistic, Potent and Rapid Bactericidal Activity against Methicillin-ResistantStaphylococcus aureus(MRSA) in a Rabbit Model of Experimental Endocarditis (EE).
title_full_unstemmed The Combination of Daptomycin plus Fosfomycin has Synergistic, Potent and Rapid Bactericidal Activity against Methicillin-ResistantStaphylococcus aureus(MRSA) in a Rabbit Model of Experimental Endocarditis (EE).
title_sort The Combination of Daptomycin plus Fosfomycin has Synergistic, Potent and Rapid Bactericidal Activity against Methicillin-ResistantStaphylococcus aureus(MRSA) in a Rabbit Model of Experimental Endocarditis (EE).
dc.creator.none.fl_str_mv García de la Mària, Cristina
Gasch, Oriol
García González, Javier
Soy Muner, Dolors
Shaw Perujo, Evelyn
Ambrosioni, Juan
Almela, M. (Manel)
Pericàs, Juan M.
Tellez, Adrian
Falces Salvador, Carles
Hernández Meneses, Marta
Sandoval, Elena
Quintana, Eduard
Vidal, Bàrbara
Tolosana, José M. (José María)
Fuster Pelfort, David
Llopis Pérez, Jaime
Pujol Rojo, Miquel
Moreno Camacho, Ma. Asunción
Marco Reverté, Francesc
Miró Meda, José M. (José María), 1956-
Hospital Clínic Endocarditis Study Group
author García de la Mària, Cristina
author_facet García de la Mària, Cristina
Gasch, Oriol
García González, Javier
Soy Muner, Dolors
Shaw Perujo, Evelyn
Ambrosioni, Juan
Almela, M. (Manel)
Pericàs, Juan M.
Tellez, Adrian
Falces Salvador, Carles
Hernández Meneses, Marta
Sandoval, Elena
Quintana, Eduard
Vidal, Bàrbara
Tolosana, José M. (José María)
Fuster Pelfort, David
Llopis Pérez, Jaime
Pujol Rojo, Miquel
Moreno Camacho, Ma. Asunción
Marco Reverté, Francesc
Miró Meda, José M. (José María), 1956-
Hospital Clínic Endocarditis Study Group
author_role author
author2 Gasch, Oriol
García González, Javier
Soy Muner, Dolors
Shaw Perujo, Evelyn
Ambrosioni, Juan
Almela, M. (Manel)
Pericàs, Juan M.
Tellez, Adrian
Falces Salvador, Carles
Hernández Meneses, Marta
Sandoval, Elena
Quintana, Eduard
Vidal, Bàrbara
Tolosana, José M. (José María)
Fuster Pelfort, David
Llopis Pérez, Jaime
Pujol Rojo, Miquel
Moreno Camacho, Ma. Asunción
Marco Reverté, Francesc
Miró Meda, José M. (José María), 1956-
Hospital Clínic Endocarditis Study Group
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Endocarditis
Microbiologia
Endocarditis
Microbiology
topic Endocarditis
Microbiologia
Endocarditis
Microbiology
description This study aims to investigate whether the addition of fosfomycin or cloxacillin to daptomycin provides better outcomes in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) experimental aortic endocarditis in rabbits. Five MRSA strains were used to perform in vitro time-kill studies at standard (105) and high (108) inocula. Combined therapy was compared with daptomycin monotherapy treatment in the MRSA experimental endocarditis model. A human-like pharmacokinetics model was applied and the equivalents of cloxacillin 2g/4hiv, fosfomycin 2g/6h iv and daptomycin 6-10mg/kg/d iv were administered. The combination of daptomycin and fosfomycin or cloxacillin was synergistic in the five strains tested at both inocula. A bactericidal effect was detected in four out of five strains tested with both combinations. The MRSA-277 strain (vancomycin MIC, 2 mcg/mL) was used for the experimental endocarditis model. Daptomycin plus fosfomycin significantly improved the efficacy of daptomycin monotherapy at 6 mg/kg/d in terms of both the proportion of sterile vegetations (100% vs. 72%, P=.046) and the decrease in the density of bacteria within the vegetations (P=.025). Daptomycin plus fosfomycin was as effective as daptomycin monotherapy at 10 mg/kg/d (100% vs. 93%, P=1.00) and had similar activity to daptomycin plus cloxacillin when daptomycin was administered at 6 mg/kg/d (100% vs. 88%, P=0.48). Daptomycin non-susceptibility was not detected in any of the isolates recovered from vegetations. In conclusion, for the treatment of MRSA experimental endocarditis, the combination of daptomycin plus fosfomycin showed synergistic and bactericidal activity.Copyright © 2018 American Society for Microbiology.
publishDate 2018
dc.date.none.fl_str_mv 2018
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/184232
url https://hdl.handle.net/2445/184232
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del postprint publicat a: https://doi.org/10.1128/AAC.02633-17
Antimicrobial Agents And Chemotherapy, 2018, vol 62, num 6, p. 1-8
https://doi.org/10.1128/AAC.02633-17
dc.rights.none.fl_str_mv (c) American Society for Microbiology, 2018
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Society for Microbiology, 2018
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 8 p.
application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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