{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:00:49Z","timestamp":1790362849210,"version":"4.1.0"},"reference-count":22,"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"}],"funder":[{"DOI":"10.13039\/100015237","name":"The Medicines Company","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015237","id-type":"DOI","asserted-by":"crossref"}]}],"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><jats:p>Multidrug-resistant (MDR)<jats:named-content content-type=\"genus-species\">Acinetobacter baumannii<\/jats:named-content>is increasingly more prevalent in nosocomial infections. Although<jats:italic>in vitro<\/jats:italic>susceptibility of<jats:named-content content-type=\"genus-species\">A. baumannii<\/jats:named-content>to minocycline is promising, the<jats:italic>in vivo<\/jats:italic>efficacy of minocycline has not been well established. In this study, the<jats:italic>in vivo<\/jats:italic>activity of minocycline was evaluated in a neutropenic murine pneumonia model. Specifically, we investigated the relationship between minocycline exposure and bactericidal activity using five<jats:named-content content-type=\"genus-species\">A. baumannii<\/jats:named-content>isolates with a broad range of susceptibility (MIC ranged from 0.25 mg\/liter to 16 mg\/liter). The pharmacokinetics of minocycline (single dose of 25 mg\/kg of body weight, 50 mg\/kg, 100 mg\/kg, and a humanized regimen, given intraperitoneally) in serum and epithelial lining fluid (ELF) were characterized. Dose linearity was observed for doses up to 50 mg\/kg and pulmonary penetration ratios (area under the concentration-time curve in ELF from 0 to 24 h [AUC<jats:sub>ELF,0\u201324<\/jats:sub>]\/area under the concentration time curve in serum from 0 to 24 h [AUC<jats:sub>serum,0\u201324<\/jats:sub>]) ranged from 2.5 to 2.8. Pharmacokinetic-pharmacodynamics (PK-PD) index values in ELF for various dose regimens against different<jats:named-content content-type=\"genus-species\">A. baumannii<\/jats:named-content>isolates were calculated. The maximum efficacy at 24 h was approximately 1.5-log-unit reduction of pulmonary bacterial burdens from baseline. The AUC\/MIC ratio was the PK-PD index most closely correlating to the bacterial burden (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>= 0.81). The required AUC<jats:sub>ELF,0\u201324<\/jats:sub>\/MIC for maintaining stasis and achieving 1-log-unit reduction were 140 and 410, respectively. These findings could guide the treatment of infections caused by<jats:named-content content-type=\"genus-species\">A. baumannii<\/jats:named-content>using minocycline in the future. Additional studies to examine resistance development during therapy are warranted.<\/jats:p>","DOI":"10.1128\/aac.02371-16","type":"journal-article","created":{"date-parts":[[2017,3,7]],"date-time":"2017-03-07T01:40:36Z","timestamp":1488850836000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Pharmacokinetics and Pharmacodynamics of Minocycline against Acinetobacter baumannii in a Neutropenic Murine Pneumonia Model"],"prefix":"10.1128","volume":"61","author":[{"given":"Jian","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly R.","family":"Ledesma","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Tai","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrietta","family":"Abodakpi","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent H.","family":"Tam","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, Texas, USA"},{"name":"Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/653617"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-007-0371-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajic.2013.01.006"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl224"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1159\/000048494"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu706"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu593"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws072"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04110-14"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-0711-12-24"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.2460\/ajvr.71.9.1062"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-3306.2011.00459.x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/S0090-9556(25)07851-1","article-title":"Metabolism of minocycline in humans","volume":"10","author":"Nelis HJ","year":"1982","unstructured":"Nelis HJ De LeenheerAP. 1982. 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