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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 tr...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096235/ https://www.ncbi.nlm.nih.gov/pubmed/32725216 http://dx.doi.org/10.1093/cid/ciaa1081 |
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author | Pujol, Miquel Miró, José-María Shaw, Evelyn Aguado, Jose-María San-Juan, Rafael Puig-Asensio, Mireia Pigrau, Carles Calbo, Esther Montejo, Miguel Rodriguez-Álvarez, Regino Garcia-Pais, María-Jose Pintado, Vicente Escudero-Sánchez, Rosa Lopez-Contreras, Joaquín Morata, Laura Montero, Milagros Andrés, Marta Pasquau, Juan Arenas, María-del-Mar Padilla, Belén Murillas, Javier Jover-Sáenz, 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_facet | Pujol, Miquel Miró, José-María Shaw, Evelyn Aguado, Jose-María San-Juan, Rafael Puig-Asensio, Mireia Pigrau, Carles Calbo, Esther Montejo, Miguel Rodriguez-Álvarez, Regino Garcia-Pais, María-Jose Pintado, Vicente Escudero-Sánchez, Rosa Lopez-Contreras, Joaquín Morata, Laura Montero, Milagros Andrés, Marta Pasquau, Juan Arenas, María-del-Mar Padilla, Belén Murillas, Javier Jover-Sáenz, 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_sort | Pujol, Miquel |
collection | PubMed |
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 intravenously 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 bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving 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 difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events. CLINICAL TRIALS REGISTRATION: NCT01898338. |
format | Online Article Text |
id | pubmed-8096235 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-80962352021-05-10 Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial Pujol, Miquel Miró, José-María Shaw, Evelyn Aguado, Jose-María San-Juan, Rafael Puig-Asensio, Mireia Pigrau, Carles Calbo, Esther Montejo, Miguel Rodriguez-Álvarez, Regino Garcia-Pais, María-Jose Pintado, Vicente Escudero-Sánchez, Rosa Lopez-Contreras, Joaquín Morata, Laura Montero, Milagros Andrés, Marta Pasquau, Juan Arenas, María-del-Mar Padilla, Belén Murillas, Javier Jover-Sáenz, 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 Clin Infect Dis Major Articles and Commentaries 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 intravenously 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 bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving 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 difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events. CLINICAL TRIALS REGISTRATION: NCT01898338. Oxford University Press 2020-07-29 /pmc/articles/PMC8096235/ /pubmed/32725216 http://dx.doi.org/10.1093/cid/ciaa1081 Text en © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Major Articles and Commentaries Pujol, Miquel Miró, José-María Shaw, Evelyn Aguado, Jose-María San-Juan, Rafael Puig-Asensio, Mireia Pigrau, Carles Calbo, Esther Montejo, Miguel Rodriguez-Álvarez, Regino Garcia-Pais, María-Jose Pintado, Vicente Escudero-Sánchez, Rosa Lopez-Contreras, Joaquín Morata, Laura Montero, Milagros Andrés, Marta Pasquau, Juan Arenas, María-del-Mar Padilla, Belén Murillas, Javier Jover-Sáenz, 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 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 |
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_short | 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 |
topic | Major Articles and Commentaries |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096235/ https://www.ncbi.nlm.nih.gov/pubmed/32725216 http://dx.doi.org/10.1093/cid/ciaa1081 |
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