{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T12:32:36Z","timestamp":1793968356112,"version":"4.8.0"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100003347","name":"Fudan University","doi-asserted-by":"crossref","award":["Scientific Research Foundation for Talented Scholars (JIF301052)"],"award-info":[{"award-number":["Scientific Research Foundation for Talented Scholars (JIF301052)"]}],"id":[{"id":"10.13039\/501100003347","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shanghai Municipal Health Commision Clinical Research Youth Project","award":["2022Y0121"],"award-info":[{"award-number":["2022Y0121"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,3,5]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n Eravacycline is a broad-spectrum fluorocycline currently approved for complicated intra-abdominal infections (cIAIs). In lung-infection models, it is effective against methicillin-resistant\n Staphylococcus aureus<\/jats:italic>\n (MRSA) and tetracycline-resistant MRSA. As such, we aimed to develop a population pharmacokinetic\/pharmacodynamic (PK\/PD) model to evaluate eravacycline\u2019s pulmonary distribution and kinetics. Data were extracted from a Phase I study (\n NCT01989949<\/jats:ext-link>\n ) which assessed the bronchopulmonary disposition of intravenous eravacycline to construct the population PK model that could adequately describe the drug\u2019s pulmonary kinetics. Eravacycline lung PK was best described by a three-compartment model with allometric scaling, with the epithelial lining fluid (ELF) component parameterized as the ELF distribution ratio (\n \n \n \n \n \n \n \n R<\/mml:mi>\n a<\/mml:mi>\n t<\/mml:mi>\n i<\/mml:mi>\n o<\/mml:mi>\n <\/mml:mrow>\n =<\/mml:mo>\n \n \n C<\/mml:mi>\n \n \n f<\/mml:mi>\n r<\/mml:mi>\n e<\/mml:mi>\n e<\/mml:mi>\n <\/mml:mrow>\n ,<\/mml:mo>\n \n E<\/mml:mi>\n L<\/mml:mi>\n F<\/mml:mi>\n <\/mml:mrow>\n <\/mml:mrow>\n <\/mml:msub>\n \n C<\/mml:mi>\n \n \n f<\/mml:mi>\n r<\/mml:mi>\n e<\/mml:mi>\n e<\/mml:mi>\n <\/mml:mrow>\n ,<\/mml:mo>\n \u00a0<\/mml:mtext>\n \n c<\/mml:mi>\n e<\/mml:mi>\n n<\/mml:mi>\n t<\/mml:mi>\n r<\/mml:mi>\n a<\/mml:mi>\n l<\/mml:mi>\n <\/mml:mrow>\n <\/mml:mrow>\n <\/mml:msub>\n <\/mml:mfrac>\n <\/mml:mrow>\n <\/mml:mstyle>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n , unbound concentration in ELF over central compartment). The estimated ELF distribution ratio was 8.26 (95% confidence interval = 6.8\u20139.8). Besides allometrically scaled weight, no other significant covariate was found. MIC\n 90<\/jats:sub>\n was 0.5 mg\/L (\n Escherichia coli<\/jats:italic>\n ), 2 mg\/L (\n Klebsiella pneumoniae<\/jats:italic>\n ), 0.5 mg\/L (\n Acinetobacter baumannii<\/jats:italic>\n ), and 0.12 mg\/L (\n S. aureus<\/jats:italic>\n ). At the approved cIAI dosage or higher (1 mg\/kg or 1.5 mg\/kg q12h), a PK\/PD cutoff value of 2 mg\/L was appropriate for\n E. coli<\/jats:italic>\n , while a lower value of 1 mg\/L was selected for\n K. pneumoniae<\/jats:italic>\n ,\n A. baumannii<\/jats:italic>\n , and\n S. aureus<\/jats:italic>\n . For lower doses, the cutoff value was reduced to 0.5 mg\/L for\n K. pneumoniae<\/jats:italic>\n ,\n A. baumannii<\/jats:italic>\n , and\n S. aureus<\/jats:italic>\n . The study showed eravacycline was widely distributed into the lungs with promising antibacterial efficacy, thus justifying further investigations into its uses for pulmonary infections.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1128\/aac.01065-24","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T14:00:22Z","timestamp":1738159222000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["Population pharmacokinetics and pulmonary modeling of eravacycline and the determination of microbiological breakpoint and cutoff of PK\/PD"],"prefix":"10.1128","volume":"69","author":[{"given":"Xi-wei","family":"Ji","sequence":"first","affiliation":[{"name":"Institute of Clinical Pharmacology, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8346-2934","authenticated-orcid":false,"given":"Wen Yao","family":"Mak","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Xue","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-yu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle Hui-San","family":"Kuan","sequence":"additional","affiliation":[{"name":"Momentum Metrix","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-qiang","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1173-1282","authenticated-orcid":false,"given":"Yun","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology, Peking University First Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3295-619X","authenticated-orcid":true,"given":"Xiao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy1029"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01614-13"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamasurg.2016.4237"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb-2019-0135"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04354-14"},{"key":"e_1_3_3_7_2","unstructured":"Tetraphase Pharmaceuticals Inc.. 2023. Full prescribing information: Xerava. Available from: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/211109lbl.pdf"},{"key":"e_1_3_3_8_2","unstructured":"Everest Medicines. 2023. Everest medicine announces the approval of Xerava (Eravacycline) in China for the treatment of complicated intra-abdominal infections in adults. Available from: https:\/\/www.everestmedicines.com\/CN\/News_detail.aspx?nid=533"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02036-13"},{"key":"e_1_3_3_10_2","unstructured":"CLSI. 2018. Development of in vitro susceptibility testing criteria and quality control parameters. 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University of North Texas Health Science Center Preclinical Services, Fort Worth, Texas."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01065-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01065-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T05:10:52Z","timestamp":1743743452000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01065-24"}},"subtitle":[],"editor":[{"given":"James E.","family":"Leggett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,3,5]]},"references-count":43,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3,5]]}},"alternative-id":["10.1128\/aac.01065-24"],"URL":"https:\/\/doi.org\/10.1128\/aac.01065-24","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,5]]},"assertion":[{"value":"2024-07-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01065-24"}}