{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:18:32Z","timestamp":1783606712518,"version":"3.55.0"},"reference-count":26,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2017,5,1]],"date-time":"2017-05-01T00:00:00Z","timestamp":1493596800000},"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":[[2017,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Omadacycline is a novel aminomethylcycline antibiotic in clinical development for community-acquired bacterial pneumonia (CABP). We used a neutropenic murine pneumonia infection model to characterize the\n            <jats:italic>in vivo<\/jats:italic>\n            pharmacodynamic activity of omadacycline against\n            <jats:named-content content-type=\"genus-species\">Streptococcus pneumoniae<\/jats:named-content>\n            . Four strains with various phenotypic resistances to other antimicrobials, including tetracyclines, were utilized. Drug concentration measurements were performed in the plasma and epithelial lining fluid (ELF) after administration of 0.5, 2, 8, and 32 mg\/kg. Pharmacokinetic parameters were calculated using a noncompartmental model and were linear over the dose range. Penetration into ELF ranged from 72 to 102%. Omadacycline demonstrated net cidal activity in relation to the initial burden against all four strains. The pharmacokinetic\/pharmacodynamic index AUC\/MIC correlated well with efficacy (\n            <jats:italic>R<\/jats:italic>\n            <jats:sup>2<\/jats:sup>\n            = 0.74). The plasma 24-h static dose AUC\/MIC values were 16 to 20 (24-h ELF AUC\/MIC of 14 to 18). A 1-log\n            <jats:sub>10<\/jats:sub>\n            kill was achieved at 24-h plasma AUC\/MIC values of 6.1 to 180 (24-h ELF AUC\/MIC values 6.0 to 200). A 2-log\n            <jats:sub>10<\/jats:sub>\n            kill was achieved at 24-h plasma AUC\/MIC values of 19 to 56 (24-h ELF AUC\/MIC of 17 to 47). The targets identified in this study in combination with\n            <jats:italic>in vitro<\/jats:italic>\n            potency and favorable human pharmacokinetics make omadacycline an attractive candidate for further development and study in patients with CABP.\n          <\/jats:p>","DOI":"10.1128\/aac.02368-16","type":"journal-article","created":{"date-parts":[[2017,2,14]],"date-time":"2017-02-14T01:55:24Z","timestamp":1487037324000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":48,"title":["<i>In Vivo<\/i>\n            Pharmacodynamic Evaluation of Omadacycline (PTK 0796) against Streptococcus pneumoniae in the Murine Pneumonia Model"],"prefix":"10.1128","volume":"61","author":[{"given":"Alexander J.","family":"Lepak","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Zhao","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":"Karen","family":"Marchillo","sequence":"additional","affiliation":[{"name":"William S. Middleton Memorial VA Hospital, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"VanHecker","sequence":"additional","affiliation":[{"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":"10.1016\/S0140-6736(14)61682-2"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/1469-0691.12461"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2004.05.003"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2009.129502"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1508.081187"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2012.08.024"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(16)00051-7"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.NAJ.0000494687.10004.61"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01536-15"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01242-13"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb-2016-0100"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01066-13"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2016.07.029"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl224"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3109\/9781420017137.013","volume-title":"Antimicrobial pharmacodynamics in theory and clinical practice","author":"Andes D","year":"2007","unstructured":"Andes D CraigW. 2007. Pharmacokinetics and pharmacodynamics of tetracyclines, p 267\u2013278. InNightingaleCHAmbrosePGDrusanoGLMurakawaT (ed), Antimicrobial pharmacodynamics in theory and clinical practice,2nd ed. Informa Healthcare USA,New York, NY.","edition":"2"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.4.943-949.2000"},{"key":"e_1_3_2_18_2","volume-title":"39th Infectious Diseases Society of America Annual Meeting","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. 39th Infectious Diseases Society of America Annual Meeting. Infectious Disease Society of America,San Francisco, CA."},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00647-08"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00985-09"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01678-08"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01084-06"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00277-10"},{"key":"e_1_3_2_24_2","volume-title":"Document M07-A9","author":"Clinical and Laboratory Standards Institute","year":"2012","unstructured":"Clinical and Laboratory Standards Institute. 2012. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard,9th ed. Document M07-A9. 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