{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T18:41:11Z","timestamp":1788892871667,"version":"build-2803163510"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","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":[[2018,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Combination therapy is an attractive option for the treatment of multidrug-resistant (MDR)\n            <jats:named-content content-type=\"genus-species\">Pseudomonas aeruginosa<\/jats:named-content>\n            infections; however, limited data are available on combinations with ceftolozane-tazobactam (C-T). The\n            <jats:italic>in vitro<\/jats:italic>\n            pharmacodynamic chemostat model was employed to compare human-simulated exposures of C-T at 3 g every 8 h alone or in combination with amikacin at 25 mg\/kg of body weight daily or colistin at 360 mg daily against four MDR\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            isolates. C-T alone resulted in 24-h changes in the number of CFU of \u22120.02 \u00b1 0.21, \u22121.81 \u00b1 0.55, \u22121.44 \u00b1 0.40, and +0.62 \u00b1 0.05 log\n            <jats:sub>10<\/jats:sub>\n            CFU\/ml against isolates with C-T MICs of 4, 4, 8, and 16 \u03bcg\/ml, respectively. Amikacin and colistin monotherapy displayed various results. The addition of amikacin to C-T resulted in \u22122.00 \u00b1 0.23 (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001, additive)-, \u22121.50 \u00b1 0.83 (\n            <jats:italic>P<\/jats:italic>\n            = 0.687, indifferent)-, \u22122.84 \u00b1 0.08 (\n            <jats:italic>P<\/jats:italic>\n            = 0.079, indifferent)-, and \u22122.67 \u00b1 0.54 (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001, synergy)-log\n            <jats:sub>10<\/jats:sub>\n            CFU\/ml reductions, respectively. The addition of colistin to C-T resulted in \u22123.02 \u00b1 0.22 (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001, additive)-, \u22123.21 \u00b1 0.24 (\n            <jats:italic>P<\/jats:italic>\n            &gt; 0.05, indifferent)-, \u22124.6 \u00b1 0.11 (\n            <jats:italic>P<\/jats:italic>\n            = 0.002, synergy)-, and \u22123.01 \u00b1 0.28 (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001, synergy)-log\n            <jats:sub>10<\/jats:sub>\n            CFU\/ml reductions, respectively, against the MDR\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            isolates with these MICs. Greater overall reductions in bacterial burden, including additive or synergistic interactions at 24 h, with C-T plus amikacin or colistin were observed against 3 out of 4 MDR\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            strains tested, particularly those strains that were intermediate or resistant to C-T. Further studies assessing combination regimens containing C-T against MDR\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            are warranted.\n          <\/jats:p>","DOI":"10.1128\/aac.02384-17","type":"journal-article","created":{"date-parts":[[2018,3,28]],"date-time":"2018-03-28T16:15:29Z","timestamp":1522253729000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":31,"title":["Efficacy of Human-Simulated Exposures of Ceftolozane-Tazobactam Alone and in Combination with Amikacin or Colistin against Multidrug-Resistant Pseudomonas aeruginosa in an\n            <i>In Vitro<\/i>\n            Pharmacodynamic Model"],"prefix":"10.1128","volume":"62","author":[{"given":"Veronica","family":"Rico Caballero","sequence":"first","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safa","family":"Almarzoky Abuhussain","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"},{"name":"Umm Al-Qura University, Makkah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph L.","family":"Kuti","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2016.12.016"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2015.993381"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/595011"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/504477"},{"key":"e_1_3_2_6_2","volume-title":"Antimicrobial resistance surveillance in Europe\u20142016","author":"European Centre for Disease Prevention and Control","year":"2017","unstructured":"European Centre for Disease Prevention and Control. 2017. Antimicrobial resistance surveillance in Europe\u20142016. European Centre for Disease Prevention and Control, Stockholm, Sweden. https:\/\/ecdc.europa.eu\/en\/publications-data\/antimicrobial-resistance-surveillance-europe-2016. Accessed 15 November 2017."},{"key":"e_1_3_2_7_2","volume-title":"Antibiotic resistance threats in the United States, 2013","author":"CDC","year":"2013","unstructured":"CDC. 2013. Antibiotic resistance threats in the United States, 2013. CDC, Atlanta, GA. https:\/\/www.cdc.gov\/drugresistance\/threat-report-2013\/pdf\/ar-threats-2013-508.pdf#page=69. 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Pharmacokinetics\/pharmacodynamics and safety of 3 g ceftolozane\/tazobactam in critically ill adult patients, abstr 1882. IDWeek Abstr 2017."},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12941-016-0155-z"},{"key":"e_1_3_2_30_2","first-page":"285","article-title":"Influence of sepsis on higher daily dose of amikacin pharmacokinetics in critically ill patients","volume":"17","author":"Mahmoudi L","year":"2013","unstructured":"Mahmoudi L, Mohammadpour AH, Ahmadi A, Niknam R, Mojtahedzadeh M. 2013. Influence of sepsis on higher daily dose of amikacin pharmacokinetics in critically ill patients. 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