{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:32:41Z","timestamp":1787016761042,"version":"build-2736575974"},"reference-count":24,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2017,7,1]],"date-time":"2017-07-01T00:00:00Z","timestamp":1498867200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Paratek","award":["1"],"award-info":[{"award-number":["1"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Eravacycline is a novel fluorocycline antibiotic with potent activity against a broad range of pathogens, including strains with tetracycline and other drug resistance phenotypes. The goal of the studies was to determine which pharmacokinetic\/pharmacodynamic (PK\/PD) parameter and magnitude best correlated with efficacy in the murine thigh infection model. Six\n                    <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n                    isolates were utilized for the studies. MICs were determined using CLSI methods and ranged from 0.125 to 0.25 mg\/liter. A neutropenic murine thigh infection model was utilized for all treatment studies. Single-dose plasma pharmacokinetics were determined in mice after administration of 2.5, 5, 10, 20, 40, and 80 mg\/kg of body weight. Pharmacokinetic studies exhibited maximum plasma concentration (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    ) values of 0.34 to 2.58 mg\/liter, area under the concentration-time curve (AUC) from time zero to infinity (AUC\n                    <jats:sub>0\u2013\u221e<\/jats:sub>\n                    ) values of 2.44 to 57.6 mg \u00b7 h\/liter, and elimination half-lives of 3.9 to 17.6 h. Dose fractionation studies were performed using total drug doses of 6.25 mg\/kg to 100 mg\/kg fractionated into 6-, 8-, 12-, or 24-h regimens. Nonlinear regression analysis demonstrated that the 24-h free drug AUC\/MIC (\n                    <jats:italic>f<\/jats:italic>\n                    AUC\/MIC) was the PK\/PD parameter that best correlated with efficacy (\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    = 0.80). In subsequent studies, we used the neutropenic murine thigh infection model to determine if the magnitude of the AUC\/MIC needed for the efficacy of eravacycline varied among pathogens. Mice were treated with 2-fold increasing doses (range, 3.125 to 50 mg\/kg) of eravacycline every 12 h. The mean\n                    <jats:italic>f<\/jats:italic>\n                    AUC\/MIC magnitudes associated with the net stasis and the 1-log-kill endpoints were 27.97 \u00b1 8.29 and 32.60 \u00b1 10.85, respectively.\n                  <\/jats:p>","DOI":"10.1128\/aac.00250-17","type":"journal-article","created":{"date-parts":[[2017,4,17]],"date-time":"2017-04-17T20:55:21Z","timestamp":1492462521000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":47,"title":["<i>In Vivo<\/i>\n                    Pharmacodynamic Target Assessment of Eravacycline against Escherichia coli in a Murine Thigh Infection Model"],"prefix":"10.1128","volume":"61","author":[{"given":"Miao","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA"},{"name":"William S. Middleton Memorial VA Hospital, Madison, Wisconsin, USA"},{"name":"Institute of Antibiotics, Hua-shan Hospital, Fudan University, and Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J.","family":"Lepak","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Marchillo","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA"},{"name":"William S. Middleton Memorial VA Hospital, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"VanHecker","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA"},{"name":"William S. Middleton Memorial VA Hospital, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Andes","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA"},{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin, USA"},{"name":"William S. Middleton Memorial VA Hospital, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01614-13"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-016-0545-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2015.12.021"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiac.2016.04.004"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/516284"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00813-07"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01084-06"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.4.943-949.2000"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsle.2005.02.034"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-009-0172-6"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-8579(09)70005-6"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm201465w"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04354-14"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00366-16"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01046-07"},{"key":"e_1_3_2_17_2","volume-title":"Abstr 39th Infect Dis Soc Am Annu Meet, San Francisco, CA","author":"Christianson J","year":"2001","unstructured":"Christianson J AndesDCraigW. 2001. Magnitude of the 24-h AUC\/MIC required for efficacy of doxycycline (doxy) against Streptococcus pneumoniae (SP) in a murine thigh-infection model, abstr 475. Abstr 39th Infect Dis Soc Am Annu Meet, San Francisco, CA. Infectious Diseases Society of America,Arlington, VA."},{"key":"e_1_3_2_18_2","volume-title":"Abstr 50th Intersci Conf Antimicrob Agents ChemotherAmerican Society for Microbiology","author":"Weiss WJ","year":"2010","unstructured":"Weiss WJ PulseMRenickPSutcliffeJ. 2010. Efficacy of fluorocyclines TP-434 in the neutropenic thigh infection model is predicted by AUC\/MIC, abstr F1-2164. Abstr 50th Intersci Conf Antimicrob Agents Chemother,Boston, MA. American Society for Microbiology,Washington, DC."},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00277-10"},{"key":"e_1_3_2_20_2","volume-title":"CLSI document M07-A10","author":"Clinical and Laboratory Standards Institute","year":"2015","unstructured":"Clinical and Laboratory Standards Institute. 2015. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard,10th ed. CLSI document M07-A10. Clinical and Laboratory Standards Institute Wayne,PA.","edition":"10"},{"key":"e_1_3_2_21_2","volume-title":"CLSI supplement M100S","author":"Clinical and Laboratory Standards Institute","year":"2016","unstructured":"Clinical and Laboratory Standards Institute. 2016. Performance standards for antimicrobial susceptibility testing,26th ed. CLSI supplement M100S. Clinical and Laboratory Standards Institute,Wayne, PA.","edition":"26"},{"key":"e_1_3_2_22_2","volume-title":"Guide for the care and use of laboratory animals","author":"National Research Council Committee on the Care and Use of Laboratory Animals, Institute of Laboratory Animal Resources, and Commission on Life Sciences","year":"1996","unstructured":"National Research Council Committee on the Care and Use of Laboratory Animals, Institute of Laboratory Animal Resources, and Commission on Life Sciences. 1996. Guide for the care and use of laboratory animals. National Academy Press,Washington, DC."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/159.2.281"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00240-16"},{"key":"e_1_3_2_25_2","volume-title":"Applied biopharmaceutics and pharmacokinetics","author":"Shargel L","year":"1993","unstructured":"Shargel L YuA. 1993. Applied biopharmaceutics and pharmacokinetics,3rd ed. 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