{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T22:52:07Z","timestamp":1773787927654,"version":"3.50.1"},"reference-count":37,"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":"Theravance","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            The pharmacodynamics of telavancin and vancomycin were compared using neutropenic murine thigh and lung infection models. Four\n            <jats:named-content content-type=\"genus-species\">Staphylococcus aureus<\/jats:named-content>\n            strains were included. The telavancin MIC ranged from 0.06 to 0.25 mg\/liter, and the vancomycin MIC ranged from 1 to 4 mg\/liter. The plasma pharmacokinetics of escalating doses (1.25, 5, 20, and 80 mg\/kg of body weight) of telavancin and vancomycin were linear over the dose range. Epithelial lining fluid (ELF) pharmacokinetics for each drug revealed that penetration into the ELF mirrored the percentage of the free fraction (the fraction not protein bound) in plasma for each drug. Telavancin (0.3125 to 80 mg\/kg\/6 h) and vancomycin (0.3125 to 1,280 mg\/kg\/6 h) were administered by the subcutaneous route in treatment studies. Dose-dependent bactericidal activity against all four strains was observed in both models. A sigmoid maximum-effect model was used to determine the area under the concentration-time curve (AUC)\/MIC exposure associated with net stasis and 1-log\n            <jats:sub>10<\/jats:sub>\n            kill relative to the burden at the start of therapy. The 24-h plasma free drug AUC (\n            <jats:italic>f<\/jats:italic>\n            AUC)\/MIC values associated with stasis and 1-log kill were remarkably congruent. Net stasis for telavancin was noted at\n            <jats:italic>f<\/jats:italic>\n            AUC\/MIC values of 83 and 40.4 in the thigh and lung, respectively, and 1-log kill was noted at\n            <jats:italic>f<\/jats:italic>\n            AUC\/MIC values of 215 and 76.4, respectively. For vancomycin, the\n            <jats:italic>f<\/jats:italic>\n            AUC\/MIC values for stasis were 77.9 and 45.3, respectively, and those for 1-log kill were 282 and 113, respectively. The 24-h ELF total drug AUC\/MIC targets in the lung model were very similar to the 24-h plasma free drug AUC\/MIC targets for each drug. Integration of human pharmacokinetic data for telavancin, the results of the MIC distribution studies, and the pharmacodynamic targets identified in this study suggests that the current dosing regimen of telavancin is optimized to obtain drug exposures sufficient to treat\n            <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n            infections.\n          <\/jats:p>","DOI":"10.1128\/aac.00281-17","type":"journal-article","created":{"date-parts":[[2017,4,18]],"date-time":"2017-04-18T00:55:21Z","timestamp":1492476921000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Comparative Pharmacodynamics of Telavancin and Vancomycin in the Neutropenic Murine Thigh and Lung Infection Models against Staphylococcus aureus"],"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Zhao","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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ534"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.3.1127-1134.2005"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01710-08"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/587896"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciq031"},{"key":"e_1_3_2_7_2","volume-title":"Vibativ (telavancin) prescribing information","author":"Food and Drug Administration","year":"2017","unstructured":"Food and Drug Administration. 2017. Vibativ (telavancin) prescribing information. Food and Drug Administration, Silver Spring, MD. http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2014\/022110s011lbl.pdf. Accessed 29 February 2017."},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/516284"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.2014.979789"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.8.3043-3050.2004"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr437"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciq146"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01264-06"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01717-15"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.5.1700-1706.2003"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis001"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5520(20)30278-6"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01433-10"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200443130-00005"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05609-11"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01485-12"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.29.11.1275"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.1.195-201.2005"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01110-07"},{"key":"e_1_3_2_25_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_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03172-14"},{"key":"e_1_3_2_27_2","unstructured":"EUCAST. Breakpoint tables for interpretation of MICs and zone diameters version 6.0. http:\/\/www.eucast.org\/fileadmin\/src\/media\/PDFs\/EUCAST_files\/Breakpoint_tables\/v_6.0_Breakpoint_table.pdf. Accessed 29 February 2017."},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2014.12.011"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1179\/1973947815Y.0000000050"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04616-14"},{"key":"e_1_3_2_31_2","volume-title":"M100-S24","author":"Clinical and Laboratory Standards Institute","year":"2014","unstructured":"Clinical and Laboratory Standards Institute. 2014. Performance standards for antimicrobial susceptibility testing, 24th informational supplement. M100-S24. Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_2_32_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_33_2","first-page":"603","volume-title":"Antibiotics in laboratory medicine","author":"Andes DR","year":"2015","unstructured":"Andes DR LepakAJ Frimodt-MollerN. 2015. Evaluation of antimicrobials in experimental animal infections, p 603\u2013677. InAmsterdamD (ed), Antibiotics in laboratory medicine, 6th ed. Wolters Kluwer, Philadelphia, PA.","edition":"6"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl222"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.9.1910"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1086\/491712"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.1.63-68.2004"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5520(03)00065-5"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00281-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00281-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T21:04:00Z","timestamp":1645477440000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00281-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7]]},"references-count":37,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2017,7]]}},"alternative-id":["10.1128\/AAC.00281-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.00281-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7]]},"assertion":[{"value":"2017-02-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-04-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-06-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00281-17"}}