{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:05:37Z","timestamp":1791299137487,"version":"4.1.0"},"reference-count":26,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2012,9,1]],"date-time":"2012-09-01T00:00:00Z","timestamp":1346457600000},"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":[[2012,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Colistin resistance, although uncommon, is increasingly being reported among Gram-negative clinical pathogens, and an understanding of its impact on the activity of antimicrobials is now evolving. We evaluated the potential for synergy of colistin plus trimethoprim, trimethoprim-sulfamethoxazole (1\/19 ratio), or vancomycin against 12 isolates of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Acinetobacter baumannii<\/jats:named-content>\n            (\n            <jats:italic>n<\/jats:italic>\n            = 4),\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pseudomonas aeruginosa<\/jats:named-content>\n            (\n            <jats:italic>n<\/jats:italic>\n            = 4), and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Klebsiella pneumoniae<\/jats:named-content>\n            (\n            <jats:italic>n<\/jats:italic>\n            = 4). The strains included six multidrug-resistant clinical isolates,\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">K. pneumoniae<\/jats:named-content>\n            ATCC 700603,\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">A. baumannii<\/jats:named-content>\n            ATCC 19606,\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. aeruginosa<\/jats:named-content>\n            ATCC 27853, and their colistin-resistant derivatives (KPm1, ABm1, and PAm1, respectively). Antimicrobial susceptibilities were assessed by broth microdilution and population analysis profiles. The potential for synergy of colistin combinations was evaluated using a checkerboard assay, as well as static time-kill experiments at 0.5\u00d7 and 0.25\u00d7 MIC. The MIC ranges of vancomycin, trimethoprim, and trimethoprim-sulfamethoxazole (1\/19) were \u2265128, 4 to \u2265128, and 2\/38 to &gt;128\/2,432 \u03bcg\/ml, respectively. Colistin resistance demonstrated little impact on vancomycin, trimethoprim, or trimethoprim-sulfamethoxazole MIC values. Isolates with subpopulations heterogeneously resistant to colistin were observed to various degrees in all tested isolates. In time-kill assays, all tested combinations were synergistic against KPm1 at 0.25\u00d7 MIC and 0.5\u00d7 MIC and ABm1 and PAm1 at 0.5\u00d7 MIC. In contrast, none of the tested combinations demonstrated synergy against any colistin-susceptible\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. aeruginosa<\/jats:named-content>\n            isolates and clinical strains of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">K. pneumoniae<\/jats:named-content>\n            isolates. Only colistin plus trimethoprim or trimethoprim-sulfamethoxazole was synergistic and bactericidal at 0.5\u00d7 MIC against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">K. pneumoniae<\/jats:named-content>\n            ATCC 700603. Colistin resistance seems to promote the\n            <jats:italic>in vitro<\/jats:italic>\n            activity of unconventional colistin combinations. Additional experiments are warranted to understand the clinical significance of these observations.\n          <\/jats:p>","DOI":"10.1128\/aac.05996-11","type":"journal-article","created":{"date-parts":[[2012,7,3]],"date-time":"2012-07-03T02:37:25Z","timestamp":1341283045000},"page":"4856-4861","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":117,"title":["<i>In Vitro<\/i>\n            Synergy of Colistin Combinations against Colistin-Resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae Isolates"],"prefix":"10.1128","volume":"56","author":[{"given":"C\u00e9line","family":"Vidaillac","sequence":"first","affiliation":[{"name":"SRSMC, UMR CNRS 7565"},{"name":"ABC Platform, Universit\u00e9 de Lorraine, Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lothaire","family":"Benichou","sequence":"additional","affiliation":[{"name":"SRSMC, UMR CNRS 7565"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rapha\u00ebl E.","family":"Duval","sequence":"additional","affiliation":[{"name":"SRSMC, UMR CNRS 7565"},{"name":"ABC Platform, Universit\u00e9 de Lorraine, Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00284-09"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl562"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr296"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05028-11"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05298-11"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.7.3018-3020.2005"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.116.3003.45"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.24.1.5"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/j.1574-695X.2012.00929.x","article-title":"The metabolically active subpopulation in Pseudomonas aeruginosa biofilms survives exposure to membrane-targeting antimicrobials via distinct molecular mechanisms","volume":"65","author":"Chiang WC","year":"2012","unstructured":"ChiangWC PampSJ NilssonM GivskovM Tolker-NielsenT. 2012. The metabolically active subpopulation in Pseudomonas aeruginosa biofilms survives exposure to membrane-targeting antimicrobials via distinct molecular mechanisms. FEMS Immunol. Med. Microbiol. 65:245\u2013256.","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"e_1_3_2_11_2","unstructured":"Clinical and Laboratory Standards Institute. 2009. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard 9th ed. CLSI Wayne PA."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.148.2.487-497.1981"},{"key":"e_1_3_2_13_2","first-page":"432","volume-title":"Antibiotics in laboratory medicine","author":"Eliopoulos GM","year":"1991","unstructured":"EliopoulosGM MoelleringRC. 1991. Antimicrobial combinations, p 432\u2013492. In LorianV (ed), Antibiotics in laboratory medicine. 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April 2010, Vienna, Austria."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00103-06"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(09)70054-4"},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1136\/jcp.23.9.757","article-title":"Colistin, sulphamethoxazole, and trimethoprim in synergy against Gram-negative bacteria","volume":"23","author":"Simmons NA","year":"1970","unstructured":"SimmonsNA. 1970. Colistin, sulphamethoxazole, and trimethoprim in synergy against Gram-negative bacteria. J. Clin. Pathol. 23:757\u2013764.","journal-title":"J. Clin. 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