{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T02:50:38Z","timestamp":1772679038004,"version":"3.50.1"},"reference-count":21,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"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":[[2024,9,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Pharmacokinetic-pharmacodynamic (PK-PD) relationships for efficacy were evaluated using data from omadacycline-treated patients with acute bacterial skin and skin structure infections (ABSSSI) enrolled in two phase 3 studies. Patients received omadacycline 100 mg intravenously (IV) every 12 hours for two doses, followed by 100 mg IV every 24 hours (q24h), with the option to switch to 300 mg oral (PO) q24h after 3 days or 450 mg PO q24h for two doses, followed by 300 mg PO q24h for a total duration of 7\u201314 days. Clinical response was evaluated at 48\u201372 hours [early clinical response (ECR)], end of treatment (EOT), and 7\u201314 days after EOT. Using a population pharmacokinetic (PK) model and PK data from patients with\n              <jats:italic>Staphylococcus aureus<\/jats:italic>\n              at baseline, omadacycline free-drug plasma area under the concentration-time curve (AUC) values were determined, and the relationships between free-drug plasma AUC:MIC ratio and dichotomous efficacy endpoints were evaluated. Using these relationships, the population PK model, simulation, and an omadacycline MIC distribution for\n              <jats:italic>S. aureus<\/jats:italic>\n              , mean percent probabilities of response were evaluated. Statistically significant PK-\u00adPD relationships were identified for ECR (\n              <jats:italic>P<\/jats:italic>\n              = 0.016 and 0.013 for optimized two- and three-group free-drug plasma AUC:MIC ratios, respectively). At an MIC value of 0.5 \u00b5g\/mL, percent probabilities of model-predicted success for ECR based on the univariable PK-PD relationships using continuous and two-group free-drug plasma AUC:MIC ratio variables were 91.9 and 95.6%, respectively, for the IV-to-PO dosing regimen and 89.3 and 88.4%, respectively, for the PO-only dosing regimen. These data support for omadacycline IV-to-PO and PO-only dosing regimens for ABSSSI and an omadacycline susceptibility breakpoint of 0.5 \u00b5g\/mL for\n              <jats:italic>S. aureus<\/jats:italic>\n              .\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01281-23","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T13:57:11Z","timestamp":1722434231000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Assessment of pharmacokinetics-pharmacodynamics to support omadacycline dosing regimens for the treatment of patients with acute bacterial skin and skin structure infections"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4891-6467","authenticated-orcid":true,"given":"Sujata M.","family":"Bhavnani","sequence":"first","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Inc., Schenectady, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey P.","family":"Hammel","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Inc., Schenectady, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A.","family":"Lakota","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Inc., Schenectady, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn","family":"Liolios","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Inc., Schenectady, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3468-3343","authenticated-orcid":true,"given":"Michael","family":"Trang","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Inc., Schenectady, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3172-0847","authenticated-orcid":true,"given":"Christopher M.","family":"Rubino","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Inc., Schenectady, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith N.","family":"Steenbergen","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., King of Prussia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence","family":"Friedrich","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., King of Prussia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evan","family":"Tzanis","sequence":"additional","affiliation":[{"name":"Paratek Pharmaceuticals, Inc., King of Prussia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2230-1125","authenticated-orcid":true,"given":"Paul G.","family":"Ambrose","sequence":"additional","affiliation":[{"name":"Institute for Clinical Pharmacodynamics, Inc., Schenectady, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02327-17."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2021.09.011."},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-78538-7_22"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2017.09.009."},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1800201."},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1800170."},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30275-0."},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02263-19."},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02201-21."},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02397-21."},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00624-19."},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.4.943-949.2000."},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.3109\/9781420017137.013"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00250-17."},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1086\/510079."},{"key":"e_1_3_3_23_2","unstructured":"United States Department of Health and Human Services Food and Drug Administration. Omadacycline injection and oral products. FDA Identified breakpoints for omadacycline. Available from: https:\/\/www.fda.gov\/drugs\/development-resources\/omadacycline-injection-and-oral-products. Retrieved 6 Feb 2024."},{"key":"e_1_3_3_24_2","unstructured":"Paratek Pharmaceuticals Inc. 2017. A phase 3 randomized double-blind multi-center study to compare the safety and efficacy of oral omadacycline to oral linezolid for treating adult subjects with acute bacterial skin and skin structure infection (ABSSSI). Study Number PTK0796-ABSI-16301. Available from: https:\/\/clinicaltrials.gov\/ProvidedDocs\/27\/NCT02877927\/SAP_001.pdf"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02083-18."},{"key":"e_1_3_3_27_2","volume-title":"R: a language and environment for statistical computing","author":"R Development Core Team","year":"2016","unstructured":"R Development Core Team. 2016. R: a language and environment for statistical computing. R. Foundation for Statistical Computing, Vienna, Austria."},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01784-16."},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02213-21."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01281-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01281-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T15:07:32Z","timestamp":1726672052000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01281-23"}},"subtitle":[],"editor":[{"given":"James E.","family":"Leggett","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,9,4]]},"references-count":21,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9,4]]}},"alternative-id":["10.1128\/aac.01281-23"],"URL":"https:\/\/doi.org\/10.1128\/aac.01281-23","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,4]]},"assertion":[{"value":"2023-10-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01281-23"}}