{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:15:18Z","timestamp":1791825318940,"version":"4.3.4"},"reference-count":52,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2016,10,21]],"date-time":"2016-10-21T00:00:00Z","timestamp":1477008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["U54 HD071600-01"],"award-info":[{"award-number":["U54 HD071600-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Ertapenem and cefazolin were used in combination to successfully clear refractory methicillin-susceptible\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>\n            (MSSA) bacteremia. In addition, recent work has demonstrated activity of combination therapy with beta-lactams from different classes against methicillin-resistant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>\n            (MRSA). The ertapenem-plus-cefazolin combination was evaluated for synergy\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            in a murine skin infection model using an index MSSA bloodstream isolate from a patient in whom persistent bacteremia was cleared with this combination and against a cadre of well-described research strains and clinical strains of MSSA and MRSA. Against the index MSSA bloodstream isolate, ertapenem and cefazolin showed synergy using both checkerboard (fractional inhibitory concentration [FIC] index = 0.375) and time-kill assays. Using a disk diffusion ertapenem potentiation assay, the MSSA isolate showed a cefazolin disk zone increased from 34 to 40 mm.\n            <jats:italic>In vitro<\/jats:italic>\n            pharmacokinetic\/pharmacodynamic modeling at clinically relevant drug concentrations demonstrated bactericidal activity (&gt;3 log\n            <jats:sub>10<\/jats:sub>\n            -CFU\/ml reduction) of the combination but bacteriostatic activity of ether drug alone at 48 h. A disk diffusion potentiation assay showed that ertapenem increased the cefazolin zone of inhibition by &gt;3 mm for 34\/35 (97%) MSSA and 10\/15 (67%) MRSA strains. A murine skin infection model of MSSA showed enhanced activity of cefazolin plus ertapenem compared to monotherapy with these agents. After successful use in clearance of MSSA bacteremia, the combination of ertapenem and cefazolin showed synergy against MSSA\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            . This combination may warrant consideration for future clinical study in MSSA bacteremia.\n          <\/jats:p>","DOI":"10.1128\/aac.01192-16","type":"journal-article","created":{"date-parts":[[2016,8,30]],"date-time":"2016-08-30T02:03:38Z","timestamp":1472522618000},"page":"6609-6618","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":49,"title":["Cefazolin and Ertapenem, a Synergistic Combination Used To Clear Persistent Staphylococcus aureus Bacteremia"],"prefix":"10.1128","volume":"60","author":[{"given":"George","family":"Sakoulas","sequence":"first","affiliation":[{"name":"University of California San Diego School of Medicine, La Jolla, California, USA"},{"name":"Sharp Healthcare System, San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Olson","sequence":"additional","affiliation":[{"name":"University of California San Diego School of Medicine, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juwon","family":"Yim","sequence":"additional","affiliation":[{"name":"Eugene Appelbaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niedita B.","family":"Singh","sequence":"additional","affiliation":[{"name":"Eugene Appelbaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Kumaraswamy","sequence":"additional","affiliation":[{"name":"University of California San Diego School of Medicine, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana T.","family":"Quach","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Rybak","sequence":"additional","affiliation":[{"name":"Eugene Appelbaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Pogliano","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Nizet","sequence":"additional","affiliation":[{"name":"University of California San Diego School of Medicine, La Jolla, California, USA"},{"name":"Skaggs School of Pharmacy, University of California San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/598189"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.163.17.2066"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis552"},{"key":"e_1_3_3_5_2","first-page":"653","article-title":"S. aureus Endocarditis and Bacteremia Study Group","volume":"355","author":"Fowler VG","year":"2006","unstructured":"Fowler VG, Jr, Boucher HW, Corey GR, Abrutyn E, Karchmer AW, Rupp ME, Levine DP, Chambers HF, Tally FP, Vigliani GA, Cabell CH, Link AS, DeMeyer I, Filler SG, Zervos M, Cook P, Parsonnet J, Bernstein JM, Price CS, Forrest GN, F\u00e4tkenheuer G, Gareca M, Rehm SJ, Brodt HR, Tice A, Cosgrove SE. 2006. 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