{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:19:17Z","timestamp":1753881557419,"version":"3.41.2"},"reference-count":29,"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":[{"name":"National Key Research and Development Program of China","award":["2016YFD0501300"],"award-info":[{"award-number":["2016YFD0501300"]}]},{"name":"Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education of China","award":["IRT13063"],"award-info":[{"award-number":["IRT13063"]}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["S2012030006590"],"award-info":[{"award-number":["S2012030006590"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"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>\n          <jats:p>\n            Antofloxacin is a novel broad-spectrum fluoroquinolone under development for the treatment of infections caused by a diverse group of bacterial species. We explored the pharmacodynamic (PD) profile and targets of antofloxacin against seven\n            <jats:named-content content-type=\"genus-species\">Klebsiella pneumoniae<\/jats:named-content>\n            isolates by using a neutropenic murine lung infection model. Plasma and bronchopulmonary pharmacokinetic (PK) studies were conducted at single subcutaneous doses of 2.5, 10, 40, and 160 mg\/kg of body weight. Mice were infected intratracheally with\n            <jats:named-content content-type=\"genus-species\">K. pneumoniae<\/jats:named-content>\n            and treated using 2-fold-increasing total doses of antofloxacin ranging from 2.5 to 160 mg\/kg\/24 h administered in 1, 2, 3, or 4 doses. The\n            <jats:italic>E<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            Hill equation was used to model the dose-response data. Antofloxacin could penetrate the lung epithelial lining fluid (ELF) with pharmacokinetics similar to those in plasma with linear elimination half-lives over the dose range. All study strains showed a 3-log\n            <jats:sub>10<\/jats:sub>\n            or greater reduction in bacterial burden and prolonged postantibiotic effects (PAEs) ranging from 3.2 to 5.3 h. Dose fractionation response curves were steep, and the free-drug area under the concentration-time curve over 24 h (AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            )\/MIC ratio was the PD index most closely linked to efficacy (\n            <jats:italic>R<\/jats:italic>\n            <jats:sup>2<\/jats:sup>\n            = 0.96). The mean free-drug AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            \/MIC ratios required to achieve net bacterial stasis, a 1-log\n            <jats:sub>10<\/jats:sub>\n            kill, and a 2-log\n            <jats:sub>10<\/jats:sub>\n            kill for each isolate were 52.6, 89.9, and 164.9, respectively. When integrated with human PK data, these PD targets could provide a framework for further optimization of dosing regimens. This could make antofloxacin an attractive option for the treatment of respiratory tract infections involving\n            <jats:named-content content-type=\"genus-species\">K. pneumoniae<\/jats:named-content>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.02691-16","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":11,"title":["<i>In Vivo<\/i>\n            Pharmacokinetic and Pharmacodynamic Profiles of Antofloxacin against Klebsiella pneumoniae in a Neutropenic Murine Lung Infection Model"],"prefix":"10.1128","volume":"61","author":[{"given":"Yu-Feng","family":"Zhou","sequence":"first","affiliation":[{"name":"National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, China"},{"name":"Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng-Ting","family":"Tao","sequence":"additional","affiliation":[{"name":"National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, China"},{"name":"Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Huo","sequence":"additional","affiliation":[{"name":"National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, China"},{"name":"Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Ping","family":"Liao","sequence":"additional","affiliation":[{"name":"National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, China"},{"name":"Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Sun","sequence":"additional","affiliation":[{"name":"National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, China"},{"name":"Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-Hong","family":"Liu","sequence":"additional","affiliation":[{"name":"National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, China"},{"name":"Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.157.5.9709032"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61380-4"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.117.5_suppl_2.380S"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3978\/j.issn.2072-1439.2013.11.12"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2003.09.012"},{"key":"e_1_3_3_7_2","first-page":"1236","article-title":"Treating acute exacerbations of chronic bronchitis and community-acquired pneumonia: how effective are respiratory fluoroquinolones?","volume":"52","author":"Balter M","year":"2006","unstructured":"Balter M WeissK. 2006. Treating acute exacerbations of chronic bronchitis and community-acquired pneumonia: how effective are respiratory fluoroquinolones?Can Fam Physician52:1236\u20131242.","journal-title":"Can Fam Physician"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1159\/000317581"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.600"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00393-16"},{"key":"e_1_3_3_11_2","volume-title":"CLSI document M100-S25","author":"Clinical and Laboratory Standards Institute","year":"2015","unstructured":"Clinical and Laboratory Standards Institute. 2015. Performance standards for antimicrobial susceptibility testing; 25th informational supplement. CLSI document M100-S25. Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7254.2008.00872.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl356"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2012.68"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00133-06"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200262010-00002"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1159\/000007181"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04627-14"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-8579(02)00022-5"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.11.3028"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1086\/516284"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1135(01)00349-2"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2011.78"},{"key":"e_1_3_3_24_2","volume-title":"CLSI document M07-A9","author":"Clinical and Laboratory Standards Institute","year":"2012","unstructured":"Clinical and Laboratory Standards Institute. 2012. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard, 9th ed. CLSI document M07-A9. 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