Effectiveness of vancomycin plus cloxacillin compared with vancomycin, cloxacillin and daptomycin single therapies in the treatment of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in a rabbit model of experimental endocarditis

Objectives: To investigate if the addition of cloxacillin to vancomycin enhances the activity of both monotherapies for treating MSSA and MRSA experimental endocarditis (EE) in rabbits. Methods: Vancomycin plus cloxacillin was compared with the respective monotherapies and daptomycin. In vitro time-...

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Autores: Castañeda, Ximena, García de la Mària, Cristina, Gasch, Oriol, Pericàs, Juan M., Soy Muner, Dolors, Cañas, María Alexandra, Falces Salvador, Carles, García González, Javier, Hernández-Meneses, Marta, Vidal, Bàrbara, Almela, M. (Manel), Quintana, Eduard, Tolosana, José M. (José María), Fuster, David, Llopis, Jaume, Dahl, Anders, Moreno, Asuncion, Marco, Francesc, Miró Meda, José M. (José María), 1956-, Hospital Clínic Endocarditis Study Group
Tipo de documento: artigo
Estado:Versión aceptada para publicación
Data de publicação:2021
País:España
Recursos:Universidad de Barcelona
Repositório:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/184347
Acesso em linha:https://hdl.handle.net/2445/184347
Access Level:Acceso aberto
Palavra-chave:Endocarditis
Staphylococcus aureus
Medicaments antibacterians
Epidemiologia
Antibacterial agents
Epidemiology
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spelling Effectiveness of vancomycin plus cloxacillin compared with vancomycin, cloxacillin and daptomycin single therapies in the treatment of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in a rabbit model of experimental endocarditisCastañeda, XimenaGarcía de la Mària, CristinaGasch, OriolPericàs, Juan M.Soy Muner, DolorsCañas, María AlexandraFalces Salvador, CarlesGarcía González, JavierHernández-Meneses, MartaVidal, BàrbaraAlmela, M. (Manel)Quintana, EduardTolosana, José M. (José María)Fuster, DavidLlopis, JaumeDahl, AndersMoreno, AsuncionMarco, FrancescMiró Meda, José M. (José María), 1956-Hospital Clínic Endocarditis Study GroupEndocarditisStaphylococcus aureusMedicaments antibacteriansEpidemiologiaEndocarditisStaphylococcus aureusAntibacterial agentsEpidemiologyObjectives: To investigate if the addition of cloxacillin to vancomycin enhances the activity of both monotherapies for treating MSSA and MRSA experimental endocarditis (EE) in rabbits. Methods: Vancomycin plus cloxacillin was compared with the respective monotherapies and daptomycin. In vitro time-kill studies were performed using standard (105 cfu) and high (108 cfu) inocula of five MRSA, one glycopeptide-intermediate (GISA) and five MSSA strains. One MSSA (MSSA-678) and one MRSA (MRSA-277) strain were selected to be used in the in vivo model. A human-like pharmacokinetics model was applied and the equivalents of cloxacillin 2 g/4 h IV and daptomycin 6 mg/kg/day IV were administered. To optimize vancomycin activity, dosage was adjusted to achieve an AUC/MIC ≥400. Results: Daptomycin sterilized significantly more vegetations than cloxacillin (13/13, 100% versus 9/15, 60%; P = 0.02) and showed a trend of better activity than vancomycin (10/14, 71%; P = 0.09) and vancomycin plus cloxacillin (10/14, 71%; P = 0.09) against MSSA-678. Addition of cloxacillin to vancomycin (13/15, 87%) was significantly more effective than vancomycin (8/16, 50%; P = 0.05) and showed similar activity to daptomycin (13/18, 72%; P = 0.6) against MRSA-277. In all treatment arms, the bacterial isolates recovered from vegetations were re-tested and showed the same daptomycin susceptibility as the original strains. Conclusions: Vancomycin plus cloxacillin proved synergistic and bactericidal activity against MRSA. Daptomycin was the most efficacious option against MSSA and similar to vancomycin plus cloxacillin against MRSA. In settings with high MRSA prevalence, vancomycin plus cloxacillin might be a good alternative for empirical therapy of S. aureus IE.Oxford University Press2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/184347Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1093/jac/dkab069Journal of Antimicrobial Chemotherapy, 2021, vol. 76, num. 6, p. 1539-1546https://doi.org/10.1093/jac/dkab069(c) Castañeda, Ximena et al., 2021info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1843472026-05-27T06:46:51Z
dc.title.none.fl_str_mv Effectiveness of vancomycin plus cloxacillin compared with vancomycin, cloxacillin and daptomycin single therapies in the treatment of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in a rabbit model of experimental endocarditis
title Effectiveness of vancomycin plus cloxacillin compared with vancomycin, cloxacillin and daptomycin single therapies in the treatment of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in a rabbit model of experimental endocarditis
spellingShingle Effectiveness of vancomycin plus cloxacillin compared with vancomycin, cloxacillin and daptomycin single therapies in the treatment of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in a rabbit model of experimental endocarditis
Castañeda, Ximena
Endocarditis
Staphylococcus aureus
Medicaments antibacterians
Epidemiologia
Endocarditis
Staphylococcus aureus
Antibacterial agents
Epidemiology
title_short Effectiveness of vancomycin plus cloxacillin compared with vancomycin, cloxacillin and daptomycin single therapies in the treatment of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in a rabbit model of experimental endocarditis
title_full Effectiveness of vancomycin plus cloxacillin compared with vancomycin, cloxacillin and daptomycin single therapies in the treatment of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in a rabbit model of experimental endocarditis
title_fullStr Effectiveness of vancomycin plus cloxacillin compared with vancomycin, cloxacillin and daptomycin single therapies in the treatment of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in a rabbit model of experimental endocarditis
title_full_unstemmed Effectiveness of vancomycin plus cloxacillin compared with vancomycin, cloxacillin and daptomycin single therapies in the treatment of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in a rabbit model of experimental endocarditis
title_sort Effectiveness of vancomycin plus cloxacillin compared with vancomycin, cloxacillin and daptomycin single therapies in the treatment of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in a rabbit model of experimental endocarditis
dc.creator.none.fl_str_mv Castañeda, Ximena
García de la Mària, Cristina
Gasch, Oriol
Pericàs, Juan M.
Soy Muner, Dolors
Cañas, María Alexandra
Falces Salvador, Carles
García González, Javier
Hernández-Meneses, Marta
Vidal, Bàrbara
Almela, M. (Manel)
Quintana, Eduard
Tolosana, José M. (José María)
Fuster, David
Llopis, Jaume
Dahl, Anders
Moreno, Asuncion
Marco, Francesc
Miró Meda, José M. (José María), 1956-
Hospital Clínic Endocarditis Study Group
author Castañeda, Ximena
author_facet Castañeda, Ximena
García de la Mària, Cristina
Gasch, Oriol
Pericàs, Juan M.
Soy Muner, Dolors
Cañas, María Alexandra
Falces Salvador, Carles
García González, Javier
Hernández-Meneses, Marta
Vidal, Bàrbara
Almela, M. (Manel)
Quintana, Eduard
Tolosana, José M. (José María)
Fuster, David
Llopis, Jaume
Dahl, Anders
Moreno, Asuncion
Marco, Francesc
Miró Meda, José M. (José María), 1956-
Hospital Clínic Endocarditis Study Group
author_role author
author2 García de la Mària, Cristina
Gasch, Oriol
Pericàs, Juan M.
Soy Muner, Dolors
Cañas, María Alexandra
Falces Salvador, Carles
García González, Javier
Hernández-Meneses, Marta
Vidal, Bàrbara
Almela, M. (Manel)
Quintana, Eduard
Tolosana, José M. (José María)
Fuster, David
Llopis, Jaume
Dahl, Anders
Moreno, Asuncion
Marco, 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
dc.subject.none.fl_str_mv Endocarditis
Staphylococcus aureus
Medicaments antibacterians
Epidemiologia
Endocarditis
Staphylococcus aureus
Antibacterial agents
Epidemiology
topic Endocarditis
Staphylococcus aureus
Medicaments antibacterians
Epidemiologia
Endocarditis
Staphylococcus aureus
Antibacterial agents
Epidemiology
description Objectives: To investigate if the addition of cloxacillin to vancomycin enhances the activity of both monotherapies for treating MSSA and MRSA experimental endocarditis (EE) in rabbits. Methods: Vancomycin plus cloxacillin was compared with the respective monotherapies and daptomycin. In vitro time-kill studies were performed using standard (105 cfu) and high (108 cfu) inocula of five MRSA, one glycopeptide-intermediate (GISA) and five MSSA strains. One MSSA (MSSA-678) and one MRSA (MRSA-277) strain were selected to be used in the in vivo model. A human-like pharmacokinetics model was applied and the equivalents of cloxacillin 2 g/4 h IV and daptomycin 6 mg/kg/day IV were administered. To optimize vancomycin activity, dosage was adjusted to achieve an AUC/MIC ≥400. Results: Daptomycin sterilized significantly more vegetations than cloxacillin (13/13, 100% versus 9/15, 60%; P = 0.02) and showed a trend of better activity than vancomycin (10/14, 71%; P = 0.09) and vancomycin plus cloxacillin (10/14, 71%; P = 0.09) against MSSA-678. Addition of cloxacillin to vancomycin (13/15, 87%) was significantly more effective than vancomycin (8/16, 50%; P = 0.05) and showed similar activity to daptomycin (13/18, 72%; P = 0.6) against MRSA-277. In all treatment arms, the bacterial isolates recovered from vegetations were re-tested and showed the same daptomycin susceptibility as the original strains. Conclusions: Vancomycin plus cloxacillin proved synergistic and bactericidal activity against MRSA. Daptomycin was the most efficacious option against MSSA and similar to vancomycin plus cloxacillin against MRSA. In settings with high MRSA prevalence, vancomycin plus cloxacillin might be a good alternative for empirical therapy of S. aureus IE.
publishDate 2021
dc.date.none.fl_str_mv 2021
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/2445/184347
url https://hdl.handle.net/2445/184347
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1093/jac/dkab069
Journal of Antimicrobial Chemotherapy, 2021, vol. 76, num. 6, p. 1539-1546
https://doi.org/10.1093/jac/dkab069
dc.rights.none.fl_str_mv (c) Castañeda, Ximena et al., 2021
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Castañeda, Ximena et al., 2021
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv Articles publicats en revistes (Genètica, Microbiologia i Estadística)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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