{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T09:57:04Z","timestamp":1772013424025,"version":"3.50.1"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T00:00:00Z","timestamp":1467331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Ceftolozane-tazobactam (TOL-TAZ) is a novel cephalosporin\/beta-lactamase inhibitor with activity against several Gram-negative pathogens. Daptomycin (DAP) has demonstrated synergistic activity with beta-lactams against methicillin-resistant\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            (MRSA) isolates with reduced lipopeptide and glycopeptide susceptibilities. Our objective was to determine if DAP and TOL-TAZ possess synergy in hollow-fiber pharmacokinetic\/pharmacodynamic (PK\/PD) models. One isogenic pair of daptomycin-susceptible and daptomycin-nonsusceptible MRSA strains was evaluated. DAP, TOL-TAZ, and cefazolin (CFZ) MIC determinations were performed. DAP MIC determinations were also performed in the presence of subinhibitory concentrations of TOL-TAZ and CFZ. Ninety-six-hour\n            <jats:italic>in vitro<\/jats:italic>\n            models were run, simulating DAP at 10 mg\/kg of body weight\/day; TOL-TAZ at 1,500 mg every 8 h; TOL at 1,000 mg every 8 h; and DAP combined with TOL-TAZ (DAP+TOL-TAZ), DAP+TOL, DAP+TAZ, and DAP+CFZ at 2,000 mg every 8 h. DAP MICs were 0.5 and 4 \u03bcg\/ml for strains R8845 and R8846, respectively. In the presence of CFZ, R8845 and R8846 DAP MICs were reduced 8-fold and 16-fold, respectively. TOL and TAZ had no effect on DAP MICs. PK\/PD models demonstrated bactericidal activity with DAP+CFZ against both strains. The combination of DAP+TOL-TAZ was bactericidal against R8845 but was not bactericidal against daptomycin-nonsusceptible strain R8846. DAP+TOL and DAP+TAZ were not bactericidal. No other regimens were bactericidal. DAP+TOL-TAZ did not demonstrate synergistic activity against daptomycin-nonsusceptible\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            but prevented daptomycin-nonsusceptible MRSA emergence. Because DAP+TOL or TAZ alone did not prevent daptomycin-nonsusceptible MRSA emergence, the combination TOL-TAZ may be necessary for synergy with DAP. DAP+CFZ demonstrated enhancement against both strains. The combination of DAP+CFZ warrants further clinical study.\n          <\/jats:p>","DOI":"10.1128\/aac.01666-15","type":"journal-article","created":{"date-parts":[[2016,4,19]],"date-time":"2016-04-19T03:28:50Z","timestamp":1461036530000},"page":"3970-3975","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Daptomycin in Combination with Ceftolozane-Tazobactam or Cefazolin against Daptomycin-Susceptible and -Nonsusceptible Staphylococcus aureus in an\n            <i>In Vitro<\/i>\n            , Hollow-Fiber Model"],"prefix":"10.1128","volume":"60","author":[{"given":"Jordan R.","family":"Smith","sequence":"first","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anu","family":"Arya","sequence":"additional","affiliation":[{"name":"Cubist Pharmaceuticals, Lexington, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juwon","family":"Yim","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katie E.","family":"Barber","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Hallesy","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nivedita B.","family":"Singh","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Rybak","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Detroit, Michigan, USA"},{"name":"Wayne State University School of Medicine, Detroit, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/668770"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2013.03.047"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/383472"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2014.01.018"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.4.1581-1585.2006"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2014.05.061"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00660-07"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00536-10"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01185-12"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00088-14"},{"key":"e_1_3_3_12_2","volume-title":"Abstr 53rd Intersci Conf Antimicrob Agents Chemother","author":"Barber K","year":"2013","unstructured":"Barber K, Werth BJ, Rybak MJ. 2013. 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