{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:58:52Z","timestamp":1791385132991,"version":"4.3.3"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2013,11,1]],"date-time":"2013-11-01T00:00:00Z","timestamp":1383264000000},"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":[[2013,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Doripenem-colistin exerts synergy against some, but not all,\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                    carbapenemase (KPC)-producing\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                    strains\n                    <jats:italic>in vitro<\/jats:italic>\n                    . We determined if doripenem MICs and\/or\n                    <jats:italic>ompK36<\/jats:italic>\n                    porin gene mutations impacted the responses of 23 sequence type 258 (ST258), KPC-2-producing strains to the combination of doripenem (8 \u03bcg\/ml) and colistin (2 \u03bcg\/ml) during time-kill assays. The median doripenem and colistin MICs were 32 and 4 \u03bcg\/ml. Doripenem MICs did not correlate with KPC-2 expression levels. Five and 18 strains had wild-type and mutant\n                    <jats:italic>ompK36<\/jats:italic>\n                    , respectively. The most common mutations were IS\n                    <jats:italic>5<\/jats:italic>\n                    promoter insertions (\n                    <jats:italic>n<\/jats:italic>\n                    = 7) and insertions encoding glycine and aspartic acid at amino acid (aa) positions 134 and 135 (ins aa134-135 GD;\n                    <jats:italic>n<\/jats:italic>\n                    = 8), which were associated with higher doripenem MICs than other mutations or wild-type\n                    <jats:italic>ompK36<\/jats:italic>\n                    (all\n                    <jats:italic>P<\/jats:italic>\n                    values \u2264 0.04). Bactericidal activity (24 h) was achieved by doripenem-colistin against 12%, 43%, and 75% of ins aa134-135 GD, IS\n                    <jats:italic>5<\/jats:italic>\n                    , and wild-type\/other mutants, respectively (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.04). Doripenem-colistin was more active in time-kill studies than colistin at 12 and 24 h if the doripenem MIC was \u22648 \u03bcg\/ml (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.0007 and 0.09, respectively), but not if the MIC was &gt;8 \u03bcg\/ml (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.10 and 0.16). Likewise, doripenem-colistin was more active at 12 and 24 h against the wild type\/other mutants than ins aa134-135 GD or IS\n                    <jats:italic>5<\/jats:italic>\n                    mutants (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.007 and 0.0007). By multivariate analysis, the absence of ins aa134-135 GD or IS\n                    <jats:italic>5<\/jats:italic>\n                    mutations was the only independent predictor of doripenem-colistin responses at 24 h (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.002). In conclusion,\n                    <jats:italic>ompK36<\/jats:italic>\n                    genotypes identified ST258 KPC-\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                    strains that were most likely to respond to doripenem-colistin.\n                  <\/jats:p>","DOI":"10.1128\/aac.01069-13","type":"journal-article","created":{"date-parts":[[2013,8,12]],"date-time":"2013-08-12T23:35:50Z","timestamp":1376350550000},"page":"5258-5265","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":99,"title":["Mutations of the\n                    <i>ompK36<\/i>\n                    Porin Gene and Promoter Impact Responses of Sequence Type 258, KPC-2-Producing Klebsiella pneumoniae Strains to Doripenem and Doripenem-Colistin"],"prefix":"10.1128","volume":"57","author":[{"given":"Cornelius J.","family":"Clancy","sequence":"first","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"},{"name":"Pittsburgh VA Healthcare System, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, New Jersey Medical School-University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae H.","family":"Hong","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoji","family":"Cheng","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binghua","family":"Hao","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan K.","family":"Shields","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie N.","family":"Farrell","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Doi","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, New Jersey Medical School-University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Perlin","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, New Jersey Medical School-University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry N.","family":"Kreiswirth","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, New Jersey Medical School-University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Hong","family":"Nguyen","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.165.12.1430"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/595011"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(09)70054-4"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2009.01.010"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00011-10"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1609.091389"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/649865"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1710.110655"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir202"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01103-07"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1086\/648451"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03514.x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1086\/605922"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.06268-11"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq108"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis588"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01064-12"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.06364-11"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2011.05.003"},{"key":"e_1_3_2_21_2","article-title":"Epidemiology and molecular characterization of bacteremia due to carbapenem-resistant Klebsiella pneumoniae in transplant recipients","author":"Clancy CJ","unstructured":"ClancyCJChenLShieldsRKZhaoYChengSChavdaKDHaoBHongJHDoiYKwakEJSilveiraFPAbdel-MassihRBogdanovichTHumarAPerlinDSKreiswirthBNNguyenMH. 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