{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T02:24:05Z","timestamp":1778811845553,"version":"3.51.4"},"reference-count":20,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2016,12,27]],"date-time":"2016-12-27T00:00:00Z","timestamp":1482796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Cardeas Pharma"},{"DOI":"10.13039\/501100001794","name":"The University of Queensland","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001794","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1048652"],"award-info":[{"award-number":["APP1048652"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1099452"],"award-info":[{"award-number":["APP1099452"]}],"id":[{"id":"10.13039\/501100000925","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":[[2017,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            There has been a resurgence of interest in aerosolization of antibiotics for treatment of patients with severe pneumonia caused by multidrug-resistant pathogens. A combination formulation of amikacin-fosfomycin is currently undergoing clinical testing although the exposure-response relationships of these drugs have not been fully characterized. The aim of this study was to describe the individual and combined antibacterial effects of simulated epithelial lining fluid exposures of aerosolized amikacin and fosfomycin against resistant clinical isolates of\n            <jats:named-content content-type=\"genus-species\">Pseudomonas aeruginosa<\/jats:named-content>\n            (MICs of 16 mg\/liter and 64 mg\/liter) and\n            <jats:named-content content-type=\"genus-species\">Klebsiella pneumoniae<\/jats:named-content>\n            (MICs of 2 mg\/liter and 64 mg\/liter) using a dynamic hollow-fiber infection model over 7 days. Targeted peak concentrations of 300 mg\/liter amikacin and\/or 1,200 mg\/liter fosfomycin as a 12-hourly dosing regimens were used. Quantitative cultures were performed to describe changes in concentrations of the total and resistant bacterial populations. The targeted starting inoculum was 10\n            <jats:sup>8<\/jats:sup>\n            CFU\/ml for both strains. We observed that neither amikacin nor fosfomycin monotherapy was bactericidal against\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            while both were associated with rapid amplification of resistant\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            strains (about 10\n            <jats:sup>8<\/jats:sup>\n            to 10\n            <jats:sup>9<\/jats:sup>\n            CFU\/ml within 24 to 48 h). For\n            <jats:named-content content-type=\"genus-species\">K. pneumoniae<\/jats:named-content>\n            , amikacin but not fosfomycin was bactericidal. When both drugs were combined, a rapid killing was observed for\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            and\n            <jats:named-content content-type=\"genus-species\">K. pneumoniae<\/jats:named-content>\n            (6-log kill within 24 h). Furthermore, the combination of amikacin and fosfomycin effectively suppressed growth of resistant strains of\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            and\n            <jats:named-content content-type=\"genus-species\">K. pneumoniae<\/jats:named-content>\n            . In conclusion, the combination of amikacin and fosfomycin was effective at maximizing bacterial killing and suppressing emergence of resistance against these clinical isolates.\n          <\/jats:p>","DOI":"10.1128\/aac.01763-16","type":"journal-article","created":{"date-parts":[[2016,10,25]],"date-time":"2016-10-25T03:09:14Z","timestamp":1477364954000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["Pharmacodynamics of Aerosolized Fosfomycin and Amikacin against Resistant Clinical Isolates of Pseudomonas aeruginosa and Klebsiella pneumoniae in a Hollow-Fiber Infection Model: Experimental Basis for Combination Therapy"],"prefix":"10.1128","volume":"61","author":[{"given":"Fekade Bruck","family":"Sime","sequence":"first","affiliation":[{"name":"Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia"},{"name":"Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia"},{"name":"Department of Molecular and Clinical Pharmacology, The University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, The University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Whalley","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, The University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anahi","family":"Santoyo-Castelazo","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, The University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. Bruce","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Cardeas Pharma Corporation, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathie Ann","family":"Walters","sequence":"additional","affiliation":[{"name":"Cardeas Pharma Corporation, Seattle, Washington, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Lipman","sequence":"additional","affiliation":[{"name":"Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William W.","family":"Hope","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, The University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason A.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia"},{"name":"Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia"},{"name":"Department of Molecular and Clinical Pharmacology, The University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.2165\/11592900-000000000-00000"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/CPM.0b013e31828fc646"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201311-395FR"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0000000000000004"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/jamp.2013.1100"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-016-0140-x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-011-2420-0"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.2.479-487.2005"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1974.tb43277.x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05958-11"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00752-15"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv221"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr466"},{"key":"e_1_3_2_15_2","volume-title":"CLSI document M100-S24","author":"CLSI","year":"2014","unstructured":"CLSI. 2014. Performance standards for antimicrobial susceptibility testing; twenty-fourth informational supplement. CLSI document M100-S24. Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-0691.2003.00790.x"},{"key":"e_1_3_2_17_2","first-page":"007","article-title":"The hollow fiber infection model for antimicrobial pharmacodynamics and pharmacokinetics","volume":"1","author":"Cadwell JJS","year":"2012","unstructured":"Cadwell JJS . 2012. The hollow fiber infection model for antimicrobial pharmacodynamics and pharmacokinetics. 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U.S. Food and Drug Administration, Rockville, MD. http:\/\/www.fda.gov\/downloads\/Drugs\/Guidances\/ucm070107.pdf."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01763-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01763-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:42:07Z","timestamp":1645476127000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01763-16"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,1]]}},"alternative-id":["10.1128\/AAC.01763-16"],"URL":"https:\/\/doi.org\/10.1128\/aac.01763-16","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1]]},"assertion":[{"value":"2016-08-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-10-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-12-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01763-16"}}