{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T06:39:24Z","timestamp":1781332764608,"version":"3.54.1"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"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":[[2017,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Pharmacodynamics are especially important in the treatment of multidrug- and extensively drug-resistant tuberculosis (M\/XDR-TB). The free area under the concentration time curve in relation to MIC (\n            <jats:italic>f<\/jats:italic>\n            AUC\/MIC) is the most relevant pharmacokinetic (PK)-pharmacodynamic (PD) parameter for predicting the efficacy of levofloxacin (LFX). The objective of our study was to assess LFX PK variability in M\/XDR-TB patients and its potential consequence for\n            <jats:italic>f<\/jats:italic>\n            AUC\/MIC ratios. Patients with pulmonary M\/XDR-TB received LFX as part of the treatment regimen at a dose of 15 mg\/kg administered once daily. Blood samples obtained at steady state before and 1, 2, 3, 4, 7, and 12 h after drug administration were measured by validated liquid chromatography-tandem mass spectrometry. The MIC values of LFX were determined by the agar dilution method on Middlebrook 7H10 and the MGIT960 system. Twenty patients with a mean age of 31 years (interquartile range [IQR] = 27 to 35 years) were enrolled in this study. The median AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            was 98.8 mg\/h\/liter (IQR = 84.8 to 159.6 mg\/h\/liter). The MIC median value for LFX was 0.5 mg\/liter with a range of 0.25 to 2.0 mg\/liter, and the median\n            <jats:italic>f<\/jats:italic>\n            AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            \/MIC ratio was 109.5 (IQR = 48.5 to 399.4). In 4 of the 20 patients, the value was below the target value of \u2265100. When MICs of 0.25, 0.5, 1.0, and 2.0 mg\/liter were applicable, 19, 18, 3, and no patients, respectively, had an\n            <jats:italic>f<\/jats:italic>\n            AUC\/MIC ratio that exceeded 100. We observed a large variability in AUC. An\n            <jats:italic>f<\/jats:italic>\n            AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            \/MIC of \u2265100 was only observed when the MIC values for LFX were 0.25 to 0.5 mg\/liter. Dosages exceeding 15 mg\/kg should be considered for target attainment if exposures are assumed to be safe. (This study has been registered at ClinicalTrials.gov under registration no. NCT02169141.)\n          <\/jats:p>","DOI":"10.1128\/aac.00343-17","type":"journal-article","created":{"date-parts":[[2017,5,16]],"date-time":"2017-05-16T00:50:18Z","timestamp":1494895818000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Pharmacokinetics of Levofloxacin in Multidrug- and Extensively Drug-Resistant Tuberculosis Patients"],"prefix":"10.1128","volume":"61","author":[{"given":"Natasha","family":"van't Boveneind-Vrubleuskaya","sequence":"first","affiliation":[{"name":"Department of Public Health TB Control, Metropolitan Public Health Service Haaglanden, The Hague, The Netherlands"},{"name":"University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Seuruk","sequence":"additional","affiliation":[{"name":"Republican Research and Practical Centre for Pulmonology and Tuberculosis, Minsk, Republic of Belarus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"van Hateren","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tridia","family":"van der Laan","sequence":"additional","affiliation":[{"name":"National Tuberculosis Reference Laboratory, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos G. W.","family":"Kosterink","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tjip S.","family":"van der Werf","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Departments of Pulmonary Diseases and Tuberculosis, and Internal Medicine\/Infectious Diseases, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dick","family":"van Soolingen","sequence":"additional","affiliation":[{"name":"National Tuberculosis Reference Laboratory, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands"},{"name":"Radboud University Nijmegen Medical Center, Departments of Pulmonary Diseases and Medical Microbiology, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"van den Hof","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands"},{"name":"KNCV Tuberculosis Foundation, The Hague, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Skrahina","sequence":"additional","affiliation":[{"name":"Republican Research and Practical Centre for Pulmonology and Tuberculosis, Minsk, Republic of Belarus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Willem C.","family":"Alffenaar","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"WHO | global tuberculosis report","author":"World Health Organization","year":"2016","unstructured":"World Health Organization. 2016. 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