{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T20:59:21Z","timestamp":1793134761055,"version":"4.5.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,1,26]],"date-time":"2018-01-26T00:00:00Z","timestamp":1516924800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,1,26]],"date-time":"2018-01-26T00:00:00Z","timestamp":1516924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    There is limited clinical evidence to support the combination of daptomycin and beta-lactam antibiotics (DAP\u2009+\u2009BLA) for treatment of vancomycin-resistant enterococci (VRE) bloodstream infections (BSI). We conducted a prospective observational cohort study of VRE-BSI during 2010\u20132015. The primary endpoint was mortality at the end of treatment. We included 114 patients who received DAP for VRE-BSI. Of these 87 (76.3%) received DAP\u2009+\u2009BLA. There were no significant differences in mortality between the DAP and DAP\u2009+\u2009BLA groups on univariable analysis (10\/27\n                    <jats:italic>vs<\/jats:italic>\n                    . 34\/87,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.85). A subgroup analysis of patients with enterococcal DAP minimum inhibitory concentrations (MICs)\u2009\u22642\u2009mg\/L, revealed that those treated with DAP\u2009+\u2009BLA had a lower mortality (adjusted hazard ratio [aHR], 0.23; 95% confidence interval [CI], 0.06\u20130.93;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.04) after adjustment for other significant predictors of mortality, including the DAP dose. In addition, patients receiving high-dose (\u22659\u2009mg\/kg) DAP\u2009+\u2009BLA independently had a better survival than those receiving low-dose DAP alone (aHR\u2009=\u20095.16), low-dose DAP\u2009+\u2009BLA (aHR\u2009=\u20095.39), and high-dose DAP alone (aHR\u2009=\u200919.01) (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.05 for all comparisons). For patients with VRE-BSIs, the DAP MIC of the isolate and the DAP dose influence the effect of DAP\u2009+\u2009BLA on outcome. A high-dose DAP\u2009+\u2009BLA might improve survival. These findings support the use of high-dose DAP\u2009+\u2009BLA for treatment of VRE-BSI.\n                  <\/jats:p>","DOI":"10.1038\/s41598-018-19986-8","type":"journal-article","created":{"date-parts":[[2018,1,22]],"date-time":"2018-01-22T05:35:26Z","timestamp":1516599326000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["A retrospective clinical comparison of daptomycin vs daptomycin and a beta-lactam antibiotic for treating vancomycin-resistant Enterococcus faecium bloodstream infections"],"prefix":"10.1038","volume":"8","author":[{"given":"Yu-Chung","family":"Chuang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pao-Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Ying","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee-Chun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jann-Tay","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan-Chwen","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,1,26]]},"reference":[{"key":"19986_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1086\/595011","volume":"48","author":"HW Boucher","year":"2009","unstructured":"Boucher, H. W. et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin. Infect. Dis. 48, 1\u201312 (2009).","journal-title":"Clin. Infect. Dis."},{"key":"19986_CR2","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1517\/14656560902811811","volume":"10","author":"JL Wang","year":"2009","unstructured":"Wang, J. L. & Hsueh, P. R. Therapeutic options for infections due to vancomycin-resistant enterococci. Expert Opin. Pharmacother. 10, 785\u2013796 (2009).","journal-title":"Expert Opin. Pharmacother."},{"key":"19986_CR3","doi-asserted-by":"publisher","first-page":"5013","DOI":"10.1128\/AAC.00714-13","volume":"57","author":"DW Whang","year":"2013","unstructured":"Whang, D. W., Miller, L. G., Partain, N. M. & McKinnell, J. A. Systematic review and meta-analysis of linezolid and daptomycin for treatment of vancomycin-resistant enterococcal bloodstream infections. Antimicrob. Agents Chemother. 57, 5013\u20135018 (2013).","journal-title":"Antimicrob. Agents Chemother."},{"key":"19986_CR4","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-014-0687-9","volume":"14","author":"YC Chuang","year":"2014","unstructured":"Chuang, Y. C., Wang, J. T., Lin, H. Y. & Chang, S. C. Daptomycin versus linezolid for treatment of vancomycin-resistant enterococcal bacteremia: systematic review and meta-analysis. BMC Infect. Dis. 14, 687 (2014).","journal-title":"BMC Infect. Dis."},{"key":"19986_CR5","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1093\/cid\/ciw815","volume":"64","author":"NS Britt","year":"2017","unstructured":"Britt, N. S., Potter, E. M., Patel, N. & Steed, M. E. Comparative Effectiveness and Safety of Standard-, Medium-, and High-Dose Daptomycin Strategies for the Treatment of Vancomycin-Resistant Enterococcal Bacteremia Among Veterans Affairs Patients. Clin. Infect. Dis. 64, 605\u2013613 (2017).","journal-title":"Clin. Infect. Dis."},{"key":"19986_CR6","doi-asserted-by":"publisher","first-page":"890 e891","DOI":"10.1016\/j.cmi.2016.07.018","volume":"22","author":"YC Chuang","year":"2016","unstructured":"Chuang, Y. C. et al. Daptomycin versus linezolid for the treatment of vancomycin-resistant enterococcal bacteraemia: implications of daptomycin dose. Clin. Microbiol. Infect. 22, 890 e891\u2013890 e897 (2016).","journal-title":"Clin. Microbiol. Infect."},{"key":"19986_CR7","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1093\/cid\/cix024","volume":"64","author":"YC Chuang","year":"2017","unstructured":"Chuang, Y. C. et al. Effect of Daptomycin Dose on the Outcome of Vancomycin-Resistant, Daptomycin-Susceptible Enterococcus faecium Bacteremia. Clin. Infect. Dis. 64, 1026\u20131034 (2017).","journal-title":"Clin. Infect. Dis."},{"key":"19986_CR8","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1128\/AAC.05551-11","volume":"56","author":"G Sakoulas","year":"2012","unstructured":"Sakoulas, G. et al. Ampicillin enhances daptomycin- and cationic host defense peptide-mediated killing of ampicillin- and vancomycin-resistant Enterococcus faecium. Antimicrob. Agents Chemother. 56, 838\u2013844 (2012).","journal-title":"Antimicrob. Agents Chemother."},{"key":"19986_CR9","doi-asserted-by":"publisher","first-page":"2148","DOI":"10.1093\/jac\/dku113","volume":"69","author":"A Hall Snyder","year":"2014","unstructured":"Hall Snyder, A., Werth, B. J., Barber, K. E., Sakoulas, G. & Rybak, M. J. Evaluation of the novel combination of daptomycin plus ceftriaxone against vancomycin-resistant enterococci in an in vitro pharmacokinetic\/pharmacodynamic simulated endocardial vegetation model. J. Antimicrob. Chemother. 69, 2148\u20132154 (2014).","journal-title":"J. Antimicrob. Chemother."},{"key":"19986_CR10","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1128\/AAC.02274-13","volume":"58","author":"G Sakoulas","year":"2014","unstructured":"Sakoulas, G. et al. Ceftaroline restores daptomycin activity against daptomycin-nonsusceptible vancomycin-resistant Enterococcus faecium. Antimicrob. Agents Chemother. 58, 1494\u20131500 (2014).","journal-title":"Antimicrob. Agents Chemother."},{"key":"19986_CR11","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1093\/jac\/dku386","volume":"70","author":"BJ Werth","year":"2015","unstructured":"Werth, B. J. et al. Ceftobiprole and ampicillin increase daptomycin susceptibility of daptomycin-susceptible and -resistant VRE. J. Antimicrob. Chemother. 70, 489\u2013493 (2015).","journal-title":"J. Antimicrob. Chemother."},{"key":"19986_CR12","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1093\/jac\/dkv007","volume":"70","author":"JR Smith","year":"2015","unstructured":"Smith, J. R. et al. beta-Lactam combinations with daptomycin provide synergy against vancomycin-resistant Enterococcus faecalis and Enterococcus faecium. J. Antimicrob. Chemother. 70, 1738\u20131743 (2015).","journal-title":"J. Antimicrob. Chemother."},{"key":"19986_CR13","doi-asserted-by":"publisher","first-page":"4279","DOI":"10.1128\/AAC.05077-14","volume":"59","author":"JA Hindler","year":"2015","unstructured":"Hindler, J. A. et al. In vitro activity of daptomycin in combination with beta-lactams, gentamicin, rifampin, and tigecycline against daptomycin-nonsusceptible enterococci. Antimicrob. Agents Chemother. 59, 4279\u20134288 (2015).","journal-title":"Antimicrob. Agents Chemother."},{"key":"19986_CR14","doi-asserted-by":"publisher","first-page":"4042","DOI":"10.1128\/AAC.02481-12","volume":"57","author":"G Sakoulas","year":"2013","unstructured":"Sakoulas, G. et al. Treatment of high-level gentamicin-resistant Enterococcus faecalis endocarditis with daptomycin plus ceftaroline. Antimicrob. Agents Chemother. 57, 4042\u20134045 (2013).","journal-title":"Antimicrob. Agents Chemother."},{"key":"19986_CR15","doi-asserted-by":"publisher","first-page":"6064","DOI":"10.1128\/AAC.01760-12","volume":"56","author":"M Sierra-Hoffman","year":"2012","unstructured":"Sierra-Hoffman, M., Iznaola, O., Goodwin, M. & Mohr, J. Combination therapy with ampicillin and daptomycin for treatment of Enterococcus faecalis endocarditis. Antimicrob. Agents Chemother. 56, 6064 (2012).","journal-title":"Antimicrob. Agents Chemother."},{"key":"19986_CR16","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1007\/s15010-015-0836-0","volume":"44","author":"S Leone","year":"2016","unstructured":"Leone, S., Noviello, S. & Esposito, S. Combination antibiotic therapy for the treatment of infective endocarditis due to enterococci. Infection 44, 273\u2013281 (2016).","journal-title":"Infection"},{"key":"19986_CR17","doi-asserted-by":"publisher","DOI":"10.1007\/s11908-014-0431-z","volume":"16","author":"M Nigo","year":"2014","unstructured":"Nigo, M., Munita, J. M., Arias, C. A. & Murray, B. E. What\u2019s New in the Treatment of Enterococcal Endocarditis? Curr. Infect. Dis. Rep. 16, 431 (2014).","journal-title":"Curr. Infect. Dis. Rep."},{"key":"19986_CR18","doi-asserted-by":"publisher","first-page":"1514","DOI":"10.1093\/cid\/ciw173","volume":"62","author":"BS Shukla","year":"2016","unstructured":"Shukla, B. S. et al. Influence of Minimum Inhibitory Concentration in Clinical Outcomes of Enterococcus faecium Bacteremia Treated With Daptomycin: Is it Time to Change the Breakpoint? Clin. Infect. Dis. 62, 1514\u20131520 (2016).","journal-title":"Clin. Infect. Dis."},{"key":"19986_CR19","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1093\/cid\/civ444","volume":"61","author":"NS Britt","year":"2015","unstructured":"Britt, N. S., Potter, E. M., Patel, N. & Steed, M. E. Comparison of the Effectiveness and Safety of Linezolid and Daptomycin in Vancomycin-Resistant Enterococcal Bloodstream Infection: A National Cohort Study of Veterans Affairs Patients. Clin. Infect. Dis. 61, 871\u2013878 (2015).","journal-title":"Clin. Infect. Dis."},{"key":"19986_CR20","unstructured":"Clinical and Laboratory Standards Institute. (CLSI, Wayne, PA., 2010)."},{"key":"19986_CR21","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.ajic.2008.03.002","volume":"36","author":"TC Horan","year":"2008","unstructured":"Horan, T. C., Andrus, M. & Dudeck, M. A. CDC\/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 36, 309\u2013332 (2008).","journal-title":"Am J Infect Control"},{"key":"19986_CR22","doi-asserted-by":"publisher","first-page":"e162","DOI":"10.1093\/cid\/cir257","volume":"52","author":"NP O\u2019Grady","year":"2011","unstructured":"O\u2019Grady, N. P. et al. Guidelines for the prevention of intravascular catheter-related infections. Clin. Infect. Dis. 52, e162\u2013193 (2011).","journal-title":"Clin. Infect. Dis."},{"key":"19986_CR23","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","volume":"40","author":"ME Charlson","year":"1987","unstructured":"Charlson, M. E., Pompei, P., Ales, K. L. & MacKenzie, C. R. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J. Chronic Dis. 40, 373\u2013383 (1987).","journal-title":"J. Chronic Dis."},{"key":"19986_CR24","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/S0924-8579(98)00060-0","volume":"11","author":"JW Chow","year":"1999","unstructured":"Chow, J. W. & Yu, V. L. Combination antibiotic therapy versus monotherapy for gram-negative bacteraemia: a commentary. Int. J. Antimicrob. Agents 11, 7\u201312 (1999).","journal-title":"Int. J. Antimicrob. Agents"},{"key":"19986_CR25","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-13-66","volume":"13","author":"CC Lai","year":"2013","unstructured":"Lai, C. C. et al. Safety and efficacy of high-dose daptomycin as salvage therapy for severe gram-positive bacterial sepsis in hospitalized adult patients. BMC Infect. Dis. 13, 66 (2013).","journal-title":"BMC Infect. Dis."},{"key":"19986_CR26","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1592\/phco.29.7.792","volume":"29","author":"JC Gallagher","year":"2009","unstructured":"Gallagher, J. C. et al. Daptomycin therapy for vancomycin-resistant enterococcal bacteremia: a retrospective case series of 30 patients. Pharmacotherapy 29, 792\u2013799 (2009).","journal-title":"Pharmacotherapy"},{"key":"19986_CR27","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1007\/BF02294361","volume":"52","author":"H Bozdogan","year":"1987","unstructured":"Bozdogan, H. Model selection and Akaike\u2019s Information Criterion (AIC): The general theory and its analytical extensions. Psychometrika 52, 345\u2013370 (1987).","journal-title":"Psychometrika"},{"key":"19986_CR28","doi-asserted-by":"publisher","first-page":"b5087","DOI":"10.1136\/bmj.b5087","volume":"340","author":"LE Levesque","year":"2010","unstructured":"Levesque, L. E., Hanley, J. A., Kezouh, A. & Suissa, S. Problem of immortal time bias in cohort studies: example using statins for preventing progression of diabetes. BMJ 340, b5087 (2010).","journal-title":"BMJ"},{"key":"19986_CR29","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1093\/jac\/dku381","volume":"70","author":"J Piszczek","year":"2015","unstructured":"Piszczek, J., Hutchinson, J. & Partlow, E. Failure of combination therapy with daptomycin and synergistic ceftriaxone for enterococcal endocarditis. J. Antimicrob. Chemother. 70, 623\u2013624 (2015).","journal-title":"J. Antimicrob. Chemother."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-19986-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-19986-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-19986-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T19:27:25Z","timestamp":1751225245000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-19986-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,26]]},"references-count":29,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["19986"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-19986-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,26]]},"assertion":[{"value":"1 June 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 January 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 January 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"1632"}}