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DAP tends to be less active against enterococci than staphylococci and may require high doses or combination therapy to be bactericidal. Fosfomycin (FOF) has activity against VRE and has demonstrated synergistic bactericidal activity with DAP\n                    <jats:italic>in vitro<\/jats:italic>\n                    . The objective of this study was to evaluate the activity of DAP alone and in combination with FOF against VRE in an\n                    <jats:italic>in vitro<\/jats:italic>\n                    pharmacokinetic\/pharmacodynamic (PK\/PD) model. The activity of DAP at 8 and 12 mg\/kg of body weight\/day (DAP 8 and DAP 12, respectively) and FOF of 40 mg\/kg intravenously every 8 h, alone and in combination, were evaluated against 2 vancomycin-resistant\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Enterococcus faecium<\/jats:named-content>\n                    strains (8019 and 5938) and 2 vancomycin-resistant\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. faecalis<\/jats:named-content>\n                    strains (V583 and R7302) in an\n                    <jats:italic>in vitro<\/jats:italic>\n                    PK\/PD model over 72 h. Cell surface charge in the presence and absence of FOF was evaluated by zeta potential analysis. Daptomycin-boron-dipyrromethene (bodipy) binding was assessed by fluorescence microscopy. The addition of FOF to DAP 8 and DAP 12 resulted in significantly increased killing over DAP alone at 72 h for 8019, V583, and R7302 (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05). Therapeutic enhancement was observed with DAP 12 plus FOF against 8019, V583, and R7302. Cell surface charge became more negative after exposure to FOF by \u223c2 to 8mV in all 4 strains. Daptomycin-bodipy binding increased by 2.6 times in the presence of fosfomycin (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001). The combination of DAP plus FOF may provide improved killing against VRE (including DAP-resistant strains) through modulation of cell surface charge. Further studies to clarify the role of intravenous FOF are warranted.\n                  <\/jats:p>","DOI":"10.1128\/aac.00687-16","type":"journal-article","created":{"date-parts":[[2016,7,18]],"date-time":"2016-07-18T22:39:00Z","timestamp":1468881540000},"page":"5716-5723","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["Fosfomycin Enhances the Activity of Daptomycin against Vancomycin-Resistant Enterococci in an\n                    <i>In Vitro<\/i>\n                    Pharmacokinetic-Pharmacodynamic Model"],"prefix":"10.1128","volume":"60","author":[{"given":"Ashley D.","family":"Hall Snyder","sequence":"first","affiliation":[{"name":"Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Werth","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poochit","family":"Nonejuie","sequence":"additional","affiliation":[{"name":"University of California San Diego Division of Biology, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"McRoberts","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Pogliano","sequence":"additional","affiliation":[{"name":"University of California San Diego Division of Biology, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Sakoulas","sequence":"additional","affiliation":[{"name":"Center for Immunity, Infection &amp; Inflammation, Division of Pediatric Pharmacology &amp; Drug Discovery, University of San Diego School of Medicine, San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juwon","family":"Yim","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nivedita","family":"Singh","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Rybak","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA"},{"name":"School of Medicine, Wayne State University, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2011.02.008"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00349-11"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0732-8893(02)00370-X"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2009.08.013"},{"key":"e_1_3_2_6_2","volume-title":"CLSI document M100-S26","author":"Clinical and Laboratory Standards Institute","year":"2016","unstructured":"Clinical and Laboratory Standards Institute. 2016. 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