{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T06:40:24Z","timestamp":1781332824922,"version":"3.54.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T00:00:00Z","timestamp":1614643200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bill & Melinda Gates Foundation, Grand Challenges Program","award":["OPP1191221"],"award-info":[{"award-number":["OPP1191221"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DA044137"],"award-info":[{"award-number":["R01 DA044137"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5T32 A1007046"],"award-info":[{"award-number":["5T32 A1007046"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Early detection and correction of low fluoroquinolone exposure may improve treatment of MDR-TB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To explore a recently developed portable, battery-powered, UV spectrophotometer for measuring levofloxacin in saliva of people treated for MDR-TB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients treated with levofloxacin as part of a regimen for MDR-TB in Northern Tanzania had serum and saliva collected concurrently at 1 and 4\u2009h after 2\u2009weeks of observed levofloxacin administration. Saliva levofloxacin concentrations were quantified in the field via spectrophotometry, while serum was analysed at a regional laboratory using HPLC. A Bayesian population pharmacokinetics model was used to estimate the area under the concentration\u2013time curve (AUC0\u201324). Subtarget exposures of levofloxacin were defined by serum AUC0\u201324 &amp;lt;80\u2009mg\u00b7h\/L. The study was registered at Clinicaltrials.gov with clinical trial identifier NCT04124055.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 45 patients, 11 (25.6%) were women and 16 (37.2%) were living with HIV. Median AUC0\u201324 in serum was 140 (IQR\u2009=\u2009102.4\u2013179.09) mg\u00b7h\/L and median AUC0\u201324 in saliva was 97.10 (IQR\u2009=\u200974.80\u2013121.10) mg\u00b7h\/L. A positive linear correlation was observed with serum and saliva AUC0\u201324, and a receiver operating characteristic curve constructed to detect serum AUC0\u201324 below 80\u2009mg\u00b7h\/L demonstrated excellent prediction [AUC 0.80 (95% CI\u2009=\u20090.62\u20130.94)]. Utilizing a saliva AUC0\u201324 cut-off of 91.6\u2009mg\u00b7h\/L, the assay was 88.9% sensitive and 69.4% specific in detecting subtarget serum AUC0\u201324 values, including identifying eight of nine patients below target.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Portable UV spectrophotometry as a point-of-care screen for subtarget levofloxacin exposure was feasible. Use for triage to other investigation or personalized dosing strategy should be tested in a randomized study.<\/jats:p><\/jats:sec>","DOI":"10.1093\/jac\/dkab057","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T13:21:10Z","timestamp":1613136070000},"page":"1547-1552","source":"Crossref","is-referenced-by-count":24,"title":["Levofloxacin pharmacokinetics in saliva as measured by a mobile microvolume UV spectrophotometer among people treated for rifampicin-resistant TB in Tanzania"],"prefix":"10.1093","volume":"76","author":[{"given":"Sagal","family":"Mohamed","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Happiness C","family":"Mvungi","sequence":"additional","affiliation":[{"name":"Kibong'oto Infectious Diseases Hospital, Sanya Juu, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaretha","family":"Sariko","sequence":"additional","affiliation":[{"name":"Kilimanjaro Clinical Research Institute, Moshi, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakruti","family":"Rao","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Mbelele","sequence":"additional","affiliation":[{"name":"Kibong'oto Infectious Diseases Hospital, Sanya Juu, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin M","family":"Jongedijk","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia A J","family":"van Winkel","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daan J","family":"Touw","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Stroup","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Willem C","family":"Alffenaar","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, Australia"},{"name":"Westmead Hospital, Sydney, Australia"},{"name":"Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stellah","family":"Mpagama","sequence":"additional","affiliation":[{"name":"Kilimanjaro Clinical Research Institute, Moshi, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott K","family":"Heysell","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,3,1]]},"reference":[{"key":"2021051408574568200_dkab057-B1","year":"2019"},{"key":"2021051408574568200_dkab057-B2","year":"2019"},{"key":"2021051408574568200_dkab057-B3","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1164\/rccm.200906-0863ED","article-title":"How are we creating fluoroquinolone-resistant tuberculosis?","volume":"180","author":"Bernardo","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"key":"2021051408574568200_dkab057-B4","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s40265-018-1043-y","article-title":"The role of fluoroquinolones in the treatment of tuberculosis in 2019","volume":"79","author":"Pranger","year":"2019","journal-title":"Drugs"},{"key":"2021051408574568200_dkab057-B5","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1164\/rccm.201303-0604OC","article-title":"Comparison of levofloxacin versus moxifloxacin for multidrug-resistant tuberculosis","volume":"188","author":"Koh","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"2021051408574568200_dkab057-B6","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/S0140-6736(18)31644-1","article-title":"Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis","volume":"392","author":"Ahmad","year":"2018","journal-title":"Lancet"},{"key":"2021051408574568200_dkab057-B7","doi-asserted-by":"crossref","first-page":"e1001300","DOI":"10.1371\/journal.pmed.1001300","article-title":"Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients","volume":"9","author":"Ahuja","year":"2012","journal-title":"PLoS Med"},{"key":"2021051408574568200_dkab057-B8","year":"2019"},{"key":"2021051408574568200_dkab057-B9","doi-asserted-by":"crossref","first-page":"e01092-18","DOI":"10.1128\/AAC.01092-18","article-title":"Population pharmacokinetic model and limited sampling strategies for personalized dosing of levofloxacin in tuberculosis patients","volume":"62","author":"van den Elsen","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"2021051408574568200_dkab057-B10","doi-asserted-by":"crossref","first-page":"e00770-18","DOI":"10.1128\/AAC.00770-18","article-title":"Increased doses lead to higher drug exposures of levofloxacin for treatment of tuberculosis","volume":"62","author":"Peloquin","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"2021051408574568200_dkab057-B11","doi-asserted-by":"crossref","first-page":"3800","DOI":"10.1128\/AAC.00341-15","article-title":"Limited sampling strategy and target attainment analysis for levofloxacin in patients with tuberculosis","volume":"59","author":"Alsultan","year":"2015","journal-title":"Antimicrob Agents Chemother"},{"key":"2021051408574568200_dkab057-B12","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1093\/jac\/dkw164","article-title":"Pharmacokinetic\/pharmacodynamic-based optimization of levofloxacin administration in the treatment of MDR-TB","volume":"71","author":"Ghimire","year":"2016","journal-title":"J Antimicrob Chemother"},{"key":"2021051408574568200_dkab057-B13","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1128\/AAC.01549-13","article-title":"Plasma drug activity in patients on treatment for multidrug-resistant tuberculosis","volume":"58","author":"Mpagama","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"key":"2021051408574568200_dkab057-B14","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1186\/1471-2334-13-432","article-title":"Application of quantitative second-line drug susceptibility testing at a multidrug-resistant tuberculosis hospital in Tanzania","volume":"13","author":"Mpagama","year":"2013","journal-title":"BMC Infect Dis"},{"key":"2021051408574568200_dkab057-B15","doi-asserted-by":"crossref","first-page":"7104","DOI":"10.1128\/AAC.01117-15","article-title":"Sensititre MycoTB Plate compared to Bactec MGIT 960 for first- and second-line antituberculosis drug susceptibility testing in tanzania: a call to operationalize MICs","volume":"59","author":"Heysell","year":"2015","journal-title":"Antimicrob Agents Chemother"},{"key":"2021051408574568200_dkab057-B16","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2165\/00003088-199732020-00002","article-title":"The clinical pharmacokinetics of levofloxacin","volume":"32","author":"Fish","year":"1997","journal-title":"Clin Pharmacokinet"},{"key":"2021051408574568200_dkab057-B17","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1093\/cid\/ciu572","article-title":"Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis","volume":"59","author":"Cegielski","year":"2014","journal-title":"Clin Infect Dis"},{"key":"2021051408574568200_dkab057-B18","doi-asserted-by":"crossref","first-page":"S293","DOI":"10.1093\/cid\/ciy611","article-title":"Levofloxacin pharmacokinetics\/pharmacodynamics, dosing, susceptibility breakpoints, and artificial intelligence in the treatment of multidrug-resistant tuberculosis","volume":"67","author":"Deshpande","year":"2018","journal-title":"Clin Infect Dis"},{"key":"2021051408574568200_dkab057-B19","doi-asserted-by":"crossref","first-page":"e93","DOI":"10.1164\/rccm.201909-1874ST","article-title":"Treatment of drug-resistant tuberculosis. an official ATS\/CDC\/ERS\/IDSA clinical practice guideline","volume":"200","author":"Nahid","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"key":"2021051408574568200_dkab057-B20","doi-asserted-by":"crossref","first-page":"e00384-19","DOI":"10.1128\/AAC.00384-19","article-title":"Limited sampling strategies using linear regression and the Bayesian approach for therapeutic drug monitoring of moxifloxacin in tuberculosis patients","volume":"63","author":"van den Elsen","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2021051408574568200_dkab057-B21","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1097\/FTD.0000000000000462","article-title":"Systematic review of salivary versus blood concentrations of antituberculosis drugs and their potential for salivary therapeutic drug monitoring","volume":"40","author":"van den Elsen","year":"2018","journal-title":"Ther Drug Monit"},{"key":"2021051408574568200_dkab057-B22","doi-asserted-by":"crossref","first-page":"39","DOI":"10.2165\/00003088-197803010-00003","article-title":"Therapeutic drug monitoring in saliva","volume":"3","author":"Danhof","year":"1978","journal-title":"Clin Pharmacokinet"},{"key":"2021051408574568200_dkab057-B23","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/j.1875-9114.1998.tb03824.x","article-title":"Penetration of levofloxacin into lung tissue after oral administration to subjects undergoing lung biopsy or lobectomy","volume":"18","author":"Lee","year":"1998","journal-title":"Pharmacotherapy"},{"key":"2021051408574568200_dkab057-B24","doi-asserted-by":"crossref","first-page":"e02379-18","DOI":"10.1128\/AAC.02379-18","article-title":"Evaluation of saliva as a potential alternative sampling matrix for therapeutic drug monitoring of levofloxacin in patients with multidrug-resistant tuberculosis","volume":"63","author":"Ghimire","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"2021051408574568200_dkab057-B25","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1093\/jac\/dkaa420","article-title":"A mobile microvolume-UV\/VIS spectrophotometer for the measurement of levofloxacin in saliva","volume":"76","author":"Alffenaar","year":"2020","journal-title":"J Antimicrob Chemother"},{"key":"2021051408574568200_dkab057-B26","doi-asserted-by":"crossref","first-page":"3292","DOI":"10.1128\/JCM.01248-17","article-title":"Membrane filtration is suitable for reliable elimination of Mycobacterium tuberculosis from saliva for therapeutic drug monitoring","volume":"55","author":"van den Elsen","year":"2017","journal-title":"J Clin Microbiol"},{"key":"2021051408574568200_dkab057-B27","doi-asserted-by":"crossref","first-page":"e0170663","DOI":"10.1371\/journal.pone.0170663","article-title":"Determination of plasma concentrations of levofloxacin by high performance liquid chromatography for use at a multidrug-resistant tuberculosis hospital in Tanzania","volume":"12","author":"Ebers","year":"2017","journal-title":"PLoS One"},{"key":"2021051408574568200_dkab057-B28","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/1471-2105-12-77","article-title":"pROC: an open-source package for R and S+ to analyze and compare ROC curves","volume":"12","author":"Robin","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"2021051408574568200_dkab057-B29","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/S0140-6736(20)30049-0","article-title":"Challenging the management of drug-resistant tuberculosis","volume":"395","author":"Kim","year":"2020","journal-title":"Lancet"},{"key":"2021051408574568200_dkab057-B30","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1093\/cid\/ciy787","article-title":"Therapeutic drug monitoring: the need for practical guidance","volume":"68","author":"Alffenaar","year":"2019","journal-title":"Clin Infect Dis"},{"key":"2021051408574568200_dkab057-B31","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/(SICI)1099-081X(199905)20:4<183::AID-BDD178>3.0.CO;2-B","article-title":"Kinetics of 4-fluoroquinolones permeation into saliva","volume":"20","author":"Kozjek","year":"1999","journal-title":"Biopharm Drug Dispos"},{"key":"2021051408574568200_dkab057-B32","doi-asserted-by":"crossref","first-page":"655","DOI":"10.4155\/bio-2017-0010","article-title":"Saliva: a reliable sample matrix in bioanalytics","volume":"9","author":"Gr\u00f6schl","year":"2017","journal-title":"Bioanalysis"},{"key":"2021051408574568200_dkab057-B33","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1093\/cid\/ciz942","article-title":"Integrating pharmacokinetics and pharmacodynamics in operational research to end tuberculosis","volume":"70","author":"Alffenaar","year":"2020","journal-title":"Clin Infect Dis"},{"key":"2021051408574568200_dkab057-B34","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1093\/cid\/cix992","article-title":"Bedaquiline resistance: its emergence, mechanism, and prevention","volume":"66","author":"Nguyen","year":"2018","journal-title":"Clin Infect Dis"},{"key":"2021051408574568200_dkab057-B35","article-title":"Determination of rifampin concentrations by urine colorimetry and mobile phone readout for personalized dosing in tuberculosis treatment","author":"Szipszky","year":"2020","journal-title":"J Pediatr Infect Dis Soc"},{"key":"2021051408574568200_dkab057-B36","doi-asserted-by":"crossref","first-page":"411","DOI":"10.4103\/ijmy.ijmy_186_20","article-title":"Urine colorimetry for levofloxacin pharmacokinetics and personalized dosing in people with drug-resistant tuberculosis","volume":"9","author":"Rao","year":"2020","journal-title":"Int J Mycobacteriology"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jac\/article-pdf\/76\/6\/1547\/37927450\/dkab057.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jac\/article-pdf\/76\/6\/1547\/37927450\/dkab057.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T06:09:17Z","timestamp":1698646157000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/76\/6\/1547\/6155895"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,1]]},"references-count":36,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,3,1]]},"published-print":{"date-parts":[[2021,5,12]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkab057","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,6,1]]},"published":{"date-parts":[[2021,3,1]]}}}