{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:41:09Z","timestamp":1790178069928,"version":"4.1.0"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"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":[[2013,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    We characterized carbapenem resistance mechanisms among 12\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                    (referred to here as 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                    ) clinical isolates and evaluated their effects on the activity of 2- and 3-drug combinations of colistin, doripenem, and ertapenem. All isolates were resistant to ertapenem and doripenem; 75% (9\/12) were resistant to colistin. Isolates belonged to the ST258 clonal group and harbored\n                    <jats:italic>bla<\/jats:italic>\n                    <jats:sub>KPC-2<\/jats:sub>\n                    ,\n                    <jats:italic>bla<\/jats:italic>\n                    <jats:sub>SHV-12<\/jats:sub>\n                    , and\n                    <jats:italic>bla<\/jats:italic>\n                    <jats:sub>TEM-1<\/jats:sub>\n                    . As determined by time-kill assays, doripenem (8 \u03bcg\/ml) and ertapenem (2 \u03bcg\/ml) were inactive against 92% (11\/12) and 100% (12\/12) of isolates, respectively. Colistin (2.5 \u03bcg\/ml) exerted some activity (range, 0.39 to 2.5 log\n                    <jats:sub>10<\/jats:sub>\n                    ) against 78% (7\/9) of colistin-resistant isolates. Colistin-ertapenem, colistin-doripenem, and colistin-doripenem-ertapenem exhibited synergy against 42% (5\/12), 50% (6\/12), and 67% (8\/12) of isolates, respectively. Expression of\n                    <jats:italic>ompK35<\/jats:italic>\n                    and\n                    <jats:italic>ompK36<\/jats:italic>\n                    porins correlated with each other (\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    = 0.80). Levels of porin expression did not correlate with colistin-doripenem or colistin-ertapenem synergy. However, synergy with colistin-doripenem-ertapenem was more likely against isolates with high porin expression than those with low expression (100% [8\/8] versus 0% [0\/4];\n                    <jats:italic>P<\/jats:italic>\n                    = 0.002). Moreover, bactericidal activity (area under the bacterial killing curve) against isolates with high porin expression was greater for colistin-doripenem-ertapenem than colistin-doripenem or colistin-ertapenem (\n                    <jats:italic>P<\/jats:italic>\n                    \u2264 0.049). In conclusion, colistin-carbapenem combinations may provide optimal activity against 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                    , including colistin-resistant isolates. Screening for porin expression may identify isolates that are most likely to respond to a triple combination of colistin-doripenem-ertapenem. In the future, molecular characterization of 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                    isolates may be a practical tool for identifying effective combination regimens.\n                  <\/jats:p>","DOI":"10.1128\/aac.02411-12","type":"journal-article","created":{"date-parts":[[2013,3,5]],"date-time":"2013-03-05T06:26:17Z","timestamp":1362464777000},"page":"2147-2153","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":48,"title":["Characterization of Porin Expression in Klebsiella pneumoniae Carbapenemase (KPC)-Producing K. pneumoniae Identifies Isolates Most Susceptible to the Combination of Colistin and Carbapenems"],"prefix":"10.1128","volume":"57","author":[{"given":"Jae H.","family":"Hong","sequence":"first","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelius J.","family":"Clancy","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"Pittsburgh VA Health System, 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":"Ryan K.","family":"Shields","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, 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, 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, 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, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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