{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T11:05:23Z","timestamp":1788174323943,"version":"build-2803163510"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T00:00:00Z","timestamp":1729814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>Lefamulin is the first pleuromutilin antibiotic approved for the treatment of community-acquired bacterial pneumonia (CABP). However, the pharmacokinetic\/pharmacodynamic (PK\/PD) characteristics in Chinese CABP patients are not fully understood. This study aimed to evaluate its microbiological efficacy against <jats:italic>Streptococcus pneumoniae<\/jats:italic> and <jats:italic>Staphylococcus aureus<\/jats:italic> via PK\/PD analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The population PK (PopPK) model, established with foreign data was validated using data from Chinese CABP patients. PK\/PD analysis was conducted for the intravenous administration of 150\u00a0mg q12\u00a0h for 1-h, 1.5-h and extended 2-h infusion. Oral administrations of 600\u00a0mg q12\u00a0h were assessed, considering original and higher plasma protein binding.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Lefamulin displayed similar PK characteristics in both Chinese and Western populations. The PopPK model effectively predicted lefamulin concentrations in Chinese CABP patients. Under the dosage regimen of 150\u00a0mg q12\u00a0h via intravenous infusion for 1\/1.5\/2\u00a0h, the probability of target attainments reached 98% at the minimum inhibitory concentration for both 90% <jats:italic>S. pneumoniae<\/jats:italic> and <jats:italic>S. aureus,<\/jats:italic> considering both original and higher protein binding rates. It is advisable to extend the infusion duration from 1\/1.5 h\u20132\u00a0h to minimize the risk of adverse effects at the infusion site. Regardless of fasted or fed conditions, the PTAs for 600\u00a0mg q12\u00a0h lefamulin via oral administration proved comparable to those for intravenous administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study proved that intravenous and oral administrations of lefamulin can reach preclinical PK\/PD targets of <jats:italic>S. pneumoniae<\/jats:italic> and <jats:italic>S. aureus<\/jats:italic>. These findings support the optimal use of lefamulin for the safe and effective treatment of Chinese CABP patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2024.1456741","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T08:05:39Z","timestamp":1729843539000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Lefamulin dosing optimization using population pharmacokinetic and pharmacokinetic\/pharmacodynamic assessment in Chinese patients with community-acquired bacterial pneumonia"],"prefix":"10.3389","volume":"15","author":[{"given":"Xingchen","family":"Bian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jicheng","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoying","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jufang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"iii35","DOI":"10.1093\/jac\/dkz089","article-title":"Pharmacokinetic\/pharmacodynamic target attainment analyses to support intravenous and oral lefamulin dose selection for the treatment of patients with community-acquired bacterial pneumonia","volume":"74","author":"Bhavnani","year":"2019","journal-title":"J. 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