Daptomycin plus fosfomycin versus daptomycin alone for methicillin-resistant staphylococcus aureus bacteremia and endocarditis: a randomized clinical trial

Background. We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis.Methods. A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical tri...

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Autores: Pujol, Miquel, Miró, José María, Shaw, Evelyn, Aguado, Jose María, San Juan, Rafael, Puig Asensio, Mireia, Pigrau, Carles, Calbo Sebastian, Esther, Montejo, Miguel, Rodríguez Álvarez, Regino, García Pais, María Jose, Pintado, Vicente, Escudero Sánchez, Rosa, López Contreras, Joaquín, Morata, Laura, Montero, Milagros, Andrés, Marta, Pasquau, Juan, Arenas, María del Mar, Padilla, Belén, Murillas, Javier, Jover-Saenz, Alfredo, López Cortes, Luis Eduardo, García Pardo, Graciano, Gasch, Oriol, Videla, Sebastian, Hereu, Pilar, Tebé, Cristian, Pallarès, Natalia, Sanllorente, Mireia, Domínguez, María Ángeles, Càmara, Jordi, Ferrer, Anna, Padullés, Ariadna, Cuervo, Guillermo, Carratalà, Jordi
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universitat de Lleida (UdL)
Repositorio:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/73000
Acceso en línea:https://doi.org/10.1093/cid/ciaa1081
http://hdl.handle.net/10459.1/73000
Access Level:acceso abierto
Palabra clave:MRSA
Bacteremia
Daptomycin
Fosfomycin
Clinical trial
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spelling Daptomycin plus fosfomycin versus daptomycin alone for methicillin-resistant staphylococcus aureus bacteremia and endocarditis: a randomized clinical trialPujol, MiquelMiró, José MaríaShaw, EvelynAguado, Jose MaríaSan Juan, RafaelPuig Asensio, MireiaPigrau, CarlesCalbo Sebastian, EstherMontejo, MiguelRodríguez Álvarez, ReginoGarcía Pais, María JosePintado, VicenteEscudero Sánchez, RosaLópez Contreras, JoaquínMorata, LauraMontero, MilagrosAndrés, MartaPasquau, JuanArenas, María del MarPadilla, BelénMurillas, JavierJover-Saenz, AlfredoLópez Cortes, Luis EduardoGarcía Pardo, GracianoGasch, OriolVidela, SebastianHereu, PilarTebé, CristianPallarès, NataliaSanllorente, MireiaDomínguez, María ÁngelesCàmara, JordiFerrer, AnnaPadullés, AriadnaCuervo, GuillermoCarratalà, JordiMRSABacteremiaDaptomycinFosfomycinClinical trialBackground. We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis.Methods. A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intra-venously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy.Results. Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93–1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bac-teremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) re-ceiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018).Conclusions. Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this dif-ference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacte-remia, but it was more often associated with adverse eventsThis work was supported by the Spanish Ministry of Science, Innovation and Universities (PI12/01907); Spanish Network for Research in Infectious Diseases (RD16/0016/0005); Instituto de Salud Carlos III (ISCIII); and Spanish Ministry of Economy, Industry and Competitiveness. This work was also supported by the European Development Regional Fund “A way to achieve Europe,” Operational Programme Intelligent Growth 2014–2020; Spanish Clinical Research Network (SCReN), co-financed by the Plan Nacional de I+D and ISCIII, Subdirección General de Evaluación y Fomento de la Investigación (PT13/0002/0007); and the Grupo de Estudio de la Infección Relacionada con la Asistencia Sanitaria. J. M.-M. received a personal 80:20 research grant from the Institut d’Investigacions Biomèdiques Agust Pi i Sunyer, Barcelona, Spain, during 2017–2021.Oxford University PressInfectious Diseases Society of America2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.1093/cid/ciaa1081http://hdl.handle.net/10459.1/73000reponame:Repositori Obert UdL instname:Universitat de Lleida (UdL)InglésReproducció del document publicat a: https://doi.org/10.1093/cid/ciaa1081Clinical Infectious Diseases, 2021, vol. 72, núm. 9, p. 1517-1525cc-by-nc-nd (c) authors, 2020info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/4.0/oai:repositori.udl.cat:10459.1/730002026-06-24T12:42:17Z
dc.title.none.fl_str_mv Daptomycin plus fosfomycin versus daptomycin alone for methicillin-resistant staphylococcus aureus bacteremia and endocarditis: a randomized clinical trial
title Daptomycin plus fosfomycin versus daptomycin alone for methicillin-resistant staphylococcus aureus bacteremia and endocarditis: a randomized clinical trial
spellingShingle Daptomycin plus fosfomycin versus daptomycin alone for methicillin-resistant staphylococcus aureus bacteremia and endocarditis: a randomized clinical trial
Pujol, Miquel
MRSA
Bacteremia
Daptomycin
Fosfomycin
Clinical trial
title_short Daptomycin plus fosfomycin versus daptomycin alone for methicillin-resistant staphylococcus aureus bacteremia and endocarditis: a randomized clinical trial
title_full Daptomycin plus fosfomycin versus daptomycin alone for methicillin-resistant staphylococcus aureus bacteremia and endocarditis: a randomized clinical trial
title_fullStr Daptomycin plus fosfomycin versus daptomycin alone for methicillin-resistant staphylococcus aureus bacteremia and endocarditis: a randomized clinical trial
title_full_unstemmed Daptomycin plus fosfomycin versus daptomycin alone for methicillin-resistant staphylococcus aureus bacteremia and endocarditis: a randomized clinical trial
title_sort Daptomycin plus fosfomycin versus daptomycin alone for methicillin-resistant staphylococcus aureus bacteremia and endocarditis: a randomized clinical trial
dc.creator.none.fl_str_mv Pujol, Miquel
Miró, José María
Shaw, Evelyn
Aguado, Jose María
San Juan, Rafael
Puig Asensio, Mireia
Pigrau, Carles
Calbo Sebastian, Esther
Montejo, Miguel
Rodríguez Álvarez, Regino
García Pais, María Jose
Pintado, Vicente
Escudero Sánchez, Rosa
López Contreras, Joaquín
Morata, Laura
Montero, Milagros
Andrés, Marta
Pasquau, Juan
Arenas, María del Mar
Padilla, Belén
Murillas, Javier
Jover-Saenz, Alfredo
López Cortes, Luis Eduardo
García Pardo, Graciano
Gasch, Oriol
Videla, Sebastian
Hereu, Pilar
Tebé, Cristian
Pallarès, Natalia
Sanllorente, Mireia
Domínguez, María Ángeles
Càmara, Jordi
Ferrer, Anna
Padullés, Ariadna
Cuervo, Guillermo
Carratalà, Jordi
author Pujol, Miquel
author_facet Pujol, Miquel
Miró, José María
Shaw, Evelyn
Aguado, Jose María
San Juan, Rafael
Puig Asensio, Mireia
Pigrau, Carles
Calbo Sebastian, Esther
Montejo, Miguel
Rodríguez Álvarez, Regino
García Pais, María Jose
Pintado, Vicente
Escudero Sánchez, Rosa
López Contreras, Joaquín
Morata, Laura
Montero, Milagros
Andrés, Marta
Pasquau, Juan
Arenas, María del Mar
Padilla, Belén
Murillas, Javier
Jover-Saenz, Alfredo
López Cortes, Luis Eduardo
García Pardo, Graciano
Gasch, Oriol
Videla, Sebastian
Hereu, Pilar
Tebé, Cristian
Pallarès, Natalia
Sanllorente, Mireia
Domínguez, María Ángeles
Càmara, Jordi
Ferrer, Anna
Padullés, Ariadna
Cuervo, Guillermo
Carratalà, Jordi
author_role author
author2 Miró, José María
Shaw, Evelyn
Aguado, Jose María
San Juan, Rafael
Puig Asensio, Mireia
Pigrau, Carles
Calbo Sebastian, Esther
Montejo, Miguel
Rodríguez Álvarez, Regino
García Pais, María Jose
Pintado, Vicente
Escudero Sánchez, Rosa
López Contreras, Joaquín
Morata, Laura
Montero, Milagros
Andrés, Marta
Pasquau, Juan
Arenas, María del Mar
Padilla, Belén
Murillas, Javier
Jover-Saenz, Alfredo
López Cortes, Luis Eduardo
García Pardo, Graciano
Gasch, Oriol
Videla, Sebastian
Hereu, Pilar
Tebé, Cristian
Pallarès, Natalia
Sanllorente, Mireia
Domínguez, María Ángeles
Càmara, Jordi
Ferrer, Anna
Padullés, Ariadna
Cuervo, Guillermo
Carratalà, Jordi
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
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 MRSA
Bacteremia
Daptomycin
Fosfomycin
Clinical trial
topic MRSA
Bacteremia
Daptomycin
Fosfomycin
Clinical trial
description Background. We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis.Methods. A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intra-venously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy.Results. Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93–1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bac-teremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) re-ceiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018).Conclusions. Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this dif-ference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacte-remia, but it was more often associated with adverse events
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.1093/cid/ciaa1081
http://hdl.handle.net/10459.1/73000
url https://doi.org/10.1093/cid/ciaa1081
http://hdl.handle.net/10459.1/73000
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1093/cid/ciaa1081
Clinical Infectious Diseases, 2021, vol. 72, núm. 9, p. 1517-1525
dc.rights.none.fl_str_mv cc-by-nc-nd (c) authors, 2020
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
rights_invalid_str_mv cc-by-nc-nd (c) authors, 2020
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Oxford University Press
Infectious Diseases Society of America
publisher.none.fl_str_mv Oxford University Press
Infectious Diseases Society of America
dc.source.none.fl_str_mv reponame:Repositori Obert UdL
instname:Universitat de Lleida (UdL)
instname_str Universitat de Lleida (UdL)
reponame_str Repositori Obert UdL
collection Repositori Obert UdL
repository.name.fl_str_mv
repository.mail.fl_str_mv
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