{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:55:30Z","timestamp":1787068530270,"version":"build-2736575974"},"reference-count":73,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"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":["R01 AI111965"],"award-info":[{"award-number":["R01 AI111965"]}],"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":[[2018,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Polymyxins are increasingly used as a last-resort class of antibiotics against extensively drug-resistant (XDR) Gram-negative bacteria. However, resistance to polymyxins can emerge with monotherapy. As nephrotoxicity is the major dose-limiting factor for polymyxin monotherapy, dose escalation to suppress the emergence of polymyxin resistance is not a viable option. Therefore, novel approaches are needed to preserve this last-line class of antibiotics. This study aimed to investigate the antimicrobial synergy of polymyxin B combined with enrofloxacin against\n                    <jats:named-content content-type=\"genus-species\">Pseudomonas aeruginosa<\/jats:named-content>\n                    . Static time-kill studies were conducted over 24 h with polymyxin B (1 to 4 mg\/liter) and enrofloxacin (1 to 4 mg\/liter) alone or in combination. Additionally,\n                    <jats:italic>in vitro<\/jats:italic>\n                    one-compartment model (IVM) and hollow-fiber infection model (HFIM) experiments were performed against\n                    <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n                    12196. Polymyxin B and enrofloxacin in monotherapy were ineffective against all of the\n                    <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n                    isolates examined, whereas polymyxin B-enrofloxacin in combination was synergistic against\n                    <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n                    , with \u22652 to 4 log\n                    <jats:sub>10<\/jats:sub>\n                    kill at 24 h in the static time-kill studies. In both IVM and HFIM, the combination was synergistic, and the bacterial counting values were below the limit of quantification on day 5 in the HFIM. A population analysis profile indicated that the combination inhibited the emergence of polymyxin resistance in\n                    <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n                    12196. The mechanism-based modeling suggests that the synergistic killing is a result of the combination of mechanistic and subpopulation synergy. Overall, this is the first preclinical study to demonstrate that the polymyxin-enrofloxacin combination is of considerable utility for the treatment of XDR\n                    <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n                    infections and warrants future clinical evaluations.\n                  <\/jats:p>","DOI":"10.1128\/aac.00028-18","type":"journal-article","created":{"date-parts":[[2018,4,5]],"date-time":"2018-04-05T06:48:04Z","timestamp":1522910884000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Polymyxin B in Combination with Enrofloxacin Exerts Synergistic Killing against Extensively Drug-Resistant Pseudomonas aeruginosa"],"prefix":"10.1128","volume":"62","author":[{"given":"Yu-Wei","family":"Lin","sequence":"first","affiliation":[{"name":"Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi H.","family":"Yu","sequence":"additional","affiliation":[{"name":"Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Ling","family":"Han","sequence":"additional","affiliation":[{"name":"Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesmin","family":"Akter","sequence":"additional","affiliation":[{"name":"Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasini","family":"Wickremasinghe","sequence":"additional","affiliation":[{"name":"Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasini","family":"Walpola","sequence":"additional","affiliation":[{"name":"Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Wirth","sequence":"additional","affiliation":[{"name":"Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gauri G.","family":"Rao","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Forrest","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Velkov","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr239"},{"key":"e_1_3_3_3_2","volume-title":"Antimicrobial resistance: 2014 global report on surveillance","author":"World Health Organization","year":"2014","unstructured":"World Health Organization. 2014. 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