{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T13:35:41Z","timestamp":1762004141015},"reference-count":24,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2009,7,1]],"date-time":"2009-07-01T00:00:00Z","timestamp":1246406400000},"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":[[2009,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Tigecycline is a glycylcycline with activity against\n            <jats:italic>Enterobacteriaceae<\/jats:italic>\n            , including multidrug-resistant isolates of\n            <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n            and\n            <jats:italic>Escherichia coli<\/jats:italic>\n            producing extended-spectrum beta-lactamase (ESBL) and carbapenemases. Herein, we used an in vivo murine thigh model to characterize the pharmacodynamic profile of tigecycline against genotypically and phenotypically diverse\n            <jats:italic>K. pneumoniae<\/jats:italic>\n            and\n            <jats:italic>E. coli<\/jats:italic>\n            isolates. Doses of 3.125 to 300 mg\/kg, divided 1 to 6 times daily, were administered subcutaneously against six (two nonresistant, one carbapenemase, and three ESBL producing)\n            <jats:italic>K. pneumoniae<\/jats:italic>\n            strains and five (two nonresistant and three ESBL producing)\n            <jats:italic>E. coli<\/jats:italic>\n            strains. The phenotypic profile (reported tigecycline MIC) for all isolates ranged from 0.125 to 2 \u03bcg\/ml. Mean correlation coefficients of free (\n            <jats:italic>f<\/jats:italic>\n            ) drug exposures (percentage of the dosing interval that free drug concentration remained above the MIC [\n            <jats:italic>fT<\/jats:italic>\n            &gt;MIC], the ratio of the free drug area under the concentration-time curve\/MIC [\n            <jats:italic>f<\/jats:italic>\n            AUC\/MIC], and the ratio of maximum concentration of free drug in serum\/MIC) for all 11 isolates were 0.595, 0.969, and 0.897, respectively. The\n            <jats:italic>f<\/jats:italic>\n            AUC\/MIC was the pharmacodynamic parameter that best described the efficacy of tigecycline against both\n            <jats:italic>E. coli<\/jats:italic>\n            and\n            <jats:italic>K. pneumoniae<\/jats:italic>\n            . Interestingly, reductions in the number of CFU were noted even though doses achieved an\n            <jats:italic>fT<\/jats:italic>\n            &gt;MIC of 0%. With respect to\n            <jats:italic>f<\/jats:italic>\n            AUC\/MIC in the neutropenic model, the cumulative 80% and 50% effective pharmacodynamic indexes (EI\n            <jats:sub>80<\/jats:sub>\n            and EI\n            <jats:sub>50<\/jats:sub>\n            ) for all 11 isolates were 8.4 and 4.7, respectively. An experiment in nonneutropenic mice infected with an ESBL-producing\n            <jats:italic>E. coli<\/jats:italic>\n            and\n            <jats:italic>K. pneumoniae<\/jats:italic>\n            isolate resulted in the lowest tigecycline\n            <jats:italic>f<\/jats:italic>\n            AUC\/MIC EI\n            <jats:sub>80<\/jats:sub>\n            and EI\n            <jats:sub>50<\/jats:sub>\n            values at 1.8 and 1.0 for\n            <jats:italic>E. coli<\/jats:italic>\n            and 1.7 and 1.6 for\n            <jats:italic>K. pneumoniae<\/jats:italic>\n            . While the phenotypic profile of tigecycline appeared to drive efficacy irrespective of ESBL or carbapenemase production, the presence of a competent immune system markedly reduced this required exposure.\n          <\/jats:p>","DOI":"10.1128\/aac.01678-08","type":"journal-article","created":{"date-parts":[[2009,4,14]],"date-time":"2009-04-14T00:33:44Z","timestamp":1239669224000},"page":"2756-2761","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["In Vivo Pharmacodynamic Profile of Tigecycline against Phenotypically Diverse\n            <i>Escherichia coli<\/i>\n            and\n            <i>Klebsiella pneumoniae<\/i>\n            Isolates"],"prefix":"10.1128","volume":"53","author":[{"given":"Anthony M.","family":"Nicasio","sequence":"first","affiliation":[{"name":"Center for Anti-Infective Research and Development"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jared L.","family":"Crandon","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David P.","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development"},{"name":"Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.9.3903-3909.2005"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01114-07"},{"key":"e_1_3_2_4_2","unstructured":"Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard 2007"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.diagmicrobio.2008.01.023","volume":"61","year":"2008","unstructured":"Conejo, M. C., J. R. Hern\u00e1ndez, and A. Pascual. 2008. Effect of porin loss on the activity of tigecycline against Klebsiella pneumoniae producing extended-spectrum beta-lactamases or plasmid-mediated AmpC-type beta-lactamases. Diagn. Microbiol. Infect. Dis.61:343-345.","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00647-08"},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1590\/S1413-86702008000300007","volume":"12","year":"2008","unstructured":"Curcio, D., F. Fern\u00e1ndez, A. Can\u00e9, L. Barcelona, and D. Stamboulian. 2008. Indications of a new antibiotic in clinical practice: results of the tigecycline initial use registry. Braz. J. Infect. Dis.12:198-201.","journal-title":"Braz. J. Infect. Dis."},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.ijantimicag.2006.10.019","volume":"29","year":"2007","unstructured":"DiPersio, J. R., and M. J. Dowzicky. 2007. Regional variations in multidrug resistance among Enterobacteriaceae in the USA and comparative activity of tigecycline, a new glycylcycline antimicrobial. Int. J. Antimicrob. Agents29:518-527.","journal-title":"Int. J. Antimicrob. Agents"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.diagmicrobio.2007.10.017","volume":"60","year":"2008","unstructured":"Gales, A. C., H. S. Sader, and T. R. Fritsche. 2008. Tigecycline activity tested against 11,808 bacterial pathogens recently collected from US medical centers. Diagn. Microbiol. Infect. Dis.60:421-427.","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1093\/jac\/dkl414","volume":"58","year":"2006","unstructured":"Hope, R., M. Warner, N. A. C. Potz, E. J. Fagan, D. James, and D. M. Livermore. 2006. Activity of tigecycline against ESBL-producing and AmpC-hyperproducing Enterobacteriaceae from south-east England. J. Antimicrob. Chemother.58:1312-1314.","journal-title":"J. Antimicrob. Chemother."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn311"},{"key":"e_1_3_2_12_2","first-page":"332","volume":"41","year":"2008","unstructured":"Ku, Y. H., Y. C. Chuang, and W. L. Yu. 2008. In vitro activity of tigecycline against clinical isolates of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae,Serratia marcescens and Enterobacter cloacae. J. Microbiol. Immunol. Infect.41:332-336.","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1179\/joc.2008.20.1.69","volume":"20","year":"2008","unstructured":"Kuti, J. L., M. Dowzicky, and D. P. Nicolau. 2008. A pharmacodynamic simulation to assess tigecycline efficacy for hospital-acquired pneumonia compared with other common intravenous antibiotics. J. Chemother.20:69-76.","journal-title":"J. Chemother."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1570-0232(04)00745-7"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/431674"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01084-06"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.1.220-229.2005"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-008-0629-9"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.28.2.235"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00813-07"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01099-06"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.4.943-949.2000"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01636-05"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn249"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn396"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01678-08","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01678-08","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:08:24Z","timestamp":1645474104000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01678-08"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,7]]},"references-count":24,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2009,7]]}},"alternative-id":["10.1128\/AAC.01678-08"],"URL":"https:\/\/doi.org\/10.1128\/aac.01678-08","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,7]]},"assertion":[{"value":"2008-12-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-04-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-07-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}