{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:56:11Z","timestamp":1790258171947,"version":"4.1.0"},"reference-count":24,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T00:00:00Z","timestamp":1626998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Introduction: E. faecium and E. faecalis are responsible for 13.9% of hospital-acquired infections with frequent resistance to vancomycin (82.6% of E. faecium, 9.5% of E. faecalis). Medical device infections secondary to enterococci often require combination therapy due to impaired activity against biofilm embedded cells. In vitro data demonstrate synergistic activity of daptomycin combinations. Using a novel, biofilm time-kill approach, we evaluated whether daptomycin combinations maintained synergy against biofilm-producing E. faecium and E. faecalis. Methods: Broth microdilution (BMD) and biofilm MIC (bMIC) values for daptomycin, ampicillin, ceftriaxone, fosfomycin, and rifampin were determined against biofilm-producing E. faecium and E. faecalis. Daptomycin combination bMIC values were determined in the presence of biologic concentrations of other antimicrobials. Synergy was evaluated against two E. faecalis (R6981, R7808) and two E. faecium (5938 and 8019) using a previously described biofilm time-kill method. Synergy was defined as \u22652 log10 CFU\/cm2 reduction over the most active agent alone. Bactericidal activity was defined as \u22653 log10 CFU\/cm2 reduction. Results: Daptomycin bMICs were 2\u20138-fold higher than BMD. In the presence of other antimicrobials, daptomycin bMICs were reduced \u2265 two-fold in dilutions. Ceftriaxone and ampicillin demonstrated the most potent combinations with daptomycin, yielding synergy against three of four strains. Daptomycin plus rifampin was synergistic against E. faecium 5938 and E. faecalis 6981 and produced bactericidal kill. The combination of daptomycin plus fosfomycin displayed synergy solely against E. faecalis 6981. Conclusions: Daptomycin combinations with beta-lactams demonstrated promising synergistic activity against both E. faecium and E. faecalis. While daptomycin plus rifampin yielded bactericidal results, the effect was not seen across all organisms. These combinations warrant further evaluation to determine the optimal dose and response.<\/jats:p>","DOI":"10.3390\/antibiotics10080897","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T04:29:14Z","timestamp":1627014554000},"page":"897","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Biofilm Time-Kill Curves to Assess the Bactericidal Activity of Daptomycin Combinations against Biofilm-Producing Vancomycin-Resistant Enterococcus\u00a0faecium and faecalis"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8411-3111","authenticated-orcid":false,"given":"Katie E.","family":"Barber","sequence":"first","affiliation":[{"name":"Anti-Infective Research Laboratory, School of Medicine, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, MI 48201, USA"},{"name":"Department of Pharmacy Practice, School of Pharmacy, The University of Mississippi, 2500 North State Street, Jackson, MS 39216, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zade","family":"Shammout","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, School of Medicine, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1789-3517","authenticated-orcid":false,"given":"Jordan R.","family":"Smith","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, School of Medicine, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, MI 48201, USA"},{"name":"Department of Clinical Sciences, Fred Wilson School of Pharmacy, High Point University, 1 University Parkway, High Point, NC 27268, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razieh","family":"Kebriaei","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, School of Medicine, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Morrisette","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, School of Medicine, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Rybak","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, School of Medicine, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, MI 48201, USA"},{"name":"Department of Internal Medicine, School of Medicine, Wayne State University, 540 E. Canfield St., Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,23]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Antimicrobial-resistant pathogens associated with adult healthcare-associated infections: Summary of data reported to the National Healthcare Safety Network, 2015\u20132017","volume":"41","author":"Abner","year":"2020","journal-title":"Infect. Control. Hosp. Epidemiol."},{"key":"ref_2","unstructured":"Srinivasan, A., Wise, M., Bell, M., Cardo, D., Edwards, J., Fridkin, S., Jernigan, J., Kallen, A., McDonald, L.C., and Patel, P.R. (2011). Vital Signs: Central Line-Associated Blood Stream Infections\u2014United States, 2001, 2008, and 2009, Centers for Disease Control and Prevention. 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