{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:24:12Z","timestamp":1790173452322,"version":"4.1.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2014,8,1]],"date-time":"2014-08-01T00:00:00Z","timestamp":1406851200000},"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":[[2014,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            We measured\n            <jats:italic>in vitro<\/jats:italic>\n            activity of plazomicin, a next-generation aminoglycoside, and other aminoglycosides against 50 carbapenem-resistant\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            strains from two centers and correlated the results with the presence of various aminoglycoside-modifying enzymes (AMEs). Ninety-four percent of strains were sequence type 258 (ST258) clones, which exhibited 5\n            <jats:italic>ompK36<\/jats:italic>\n            genotypes; 80% and 10% of strains produced\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 2 (KPC-2) and KPC-3, respectively. Ninety-eight percent of strains possessed AMEs, including AAC(6\u2032)-Ib (98%), APH(3\u2032)-Ia (56%), AAC(3)-IV (38%), and ANT(2\u2033)-Ia (2%). Gentamicin, tobramycin, and amikacin nonsusceptibility rates were 40, 98, and 16%, respectively. Plazomicin MICs ranged from 0.25 to 1 \u03bcg\/ml. Tobramycin and plazomicin MICs correlated with gentamicin MICs (\n            <jats:italic>r<\/jats:italic>\n            = 0.75 and 0.57, respectively). Plazomicin exerted bactericidal activity against 17% (1\u00d7 MIC) and 94% (4\u00d7 MIC) of strains. All strains with AAC(6\u2032)-Ib were tobramycin-resistant; 16% were nonsusceptible to amikacin. AAC(6\u2032)-Ib combined with another AME was associated with higher gentamicin, tobramycin, and plazomicin MICs than AAC(6\u2032)-Ib alone (\n            <jats:italic>P<\/jats:italic>\n            = 0.01, 0.0008, and 0.046, respectively). The presence of AAC(3)-IV in a strain was also associated with higher gentamicin, tobramycin, and plazomicin MICs (\n            <jats:italic>P<\/jats:italic>\n            = 0.0006,\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.0001, and\n            <jats:italic>P<\/jats:italic>\n            = 0.01, respectively). The combination of AAC(6\u2032)-Ib and another AME, the presence of AAC(3)-IV, and the presence of APH(3\u2032)-Ia were each associated with gentamicin resistance (\n            <jats:italic>P<\/jats:italic>\n            = 0.0002, 0.003, and 0.01, respectively). In conclusion, carbapenem-resistant\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 (including ST258 clones) exhibit highly diverse antimicrobial resistance genotypes and phenotypes. Plazomicin may offer a treatment option against strains resistant to other aminoglycosides. The development of molecular assays that predict antimicrobial responses among carbapenem-resistant\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 should be a research priority.\n          <\/jats:p>","DOI":"10.1128\/aac.00099-14","type":"journal-article","created":{"date-parts":[[2014,5,28]],"date-time":"2014-05-28T07:08:08Z","timestamp":1401260888000},"page":"4443-4451","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":113,"title":["Carbapenem-Resistant Klebsiella pneumoniae Strains Exhibit Diversity in Aminoglycoside-Modifying Enzymes, Which Exert Differing Effects on Plazomicin and Other Agents"],"prefix":"10.1128","volume":"58","author":[{"given":"Reem","family":"Almaghrabi","sequence":"first","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelius J.","family":"Clancy","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"},{"name":"Pittsburgh VA Healthcare System, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Doi","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binghua","family":"Hao","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"},{"name":"XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, New Jersey Medical School-Rutgers University, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan K.","family":"Shields","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"},{"name":"XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen G.","family":"Press","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole M.","family":"Iovine","sequence":"additional","affiliation":[{"name":"University of Florida College of Medicine, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethany M.","family":"Townsend","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn M.","family":"Wagener","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"},{"name":"Pittsburgh VA Healthcare System, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Kreiswirth","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, New Jersey Medical School-Rutgers University, Newark, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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