{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T11:11:16Z","timestamp":1769944276856,"version":"3.49.0"},"reference-count":49,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T00:00:00Z","timestamp":1592265600000},"content-version":"unspecified","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2020,5,21]]},"published-print":{"date-parts":[[2020,6]]},"abstract":"\n Introduction<\/jats:title>\n Global multidrug-resistant tuberculosis (MDR-TB) treatment success rates remain suboptimal. Highly active WHO group A drugs moxifloxacin and levofloxacin show intraindividual and interindividual pharmacokinetic variability which can cause low drug exposure. Therefore, therapeutic drug monitoring (TDM) of fluoroquinolones is recommended to personalise the drug dosage, aiming to prevent the development of drug resistance and optimise treatment. However, TDM is considered laborious and expensive, and the clinical benefit in MDR-TB has not been extensively studied. This observational multicentre study aims to determine the feasibility of centralised TDM and to investigate the impact of fluoroquinolone TDM on sputum conversion rates in patients with MDR-TB compared with historical controls.<\/jats:p>\n <\/jats:sec>\n \n Methods and analysis<\/jats:title>\n Patients aged 18 years or older with sputum smear and culture-positive pulmonary MDR-TB will be eligible for inclusion. Patients receiving TDM using a limited sampling strategy (t=0\u2009and t=5\u2009hours) will be matched to historical controls without TDM in a 1:2 ratio. Sample analysis and dosing advice will be performed in a centralised laboratory. Centralised TDM will be considered feasible if >80% of the dosing recommendations are returned within 7\u2009days after sampling and 100% within 14 days. The number of patients who are sputum smear and culture-negative after 2\u2009months of treatment will be determined in the prospective TDM group and will be compared with the control group without TDM to determine the impact of TDM.<\/jats:p>\n <\/jats:sec>\n \n Ethics and dissemination<\/jats:title>\n Ethical clearance was obtained by the ethical review committees of the 10 participating hospitals according to local procedures or is pending (online supplementary file 1). Patients will be included after obtaining written informed consent. We aim to publish the study results in a peer-reviewed journal.<\/jats:p>\n <\/jats:sec>\n \n Trial registration number<\/jats:title>\n \n ClinicalTrials.gov Registry (\n NCT03409315<\/jats:ext-link>\n ).\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/bmjopen-2019-035350","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T07:05:57Z","timestamp":1592377557000},"page":"e035350","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Prospective evaluation of improving fluoroquinolone exposure using centralised therapeutic drug monitoring (TDM) in patients with tuberculosis (PERFECT): a study protocol of a prospective multicentre cohort study"],"prefix":"10.1136","volume":"10","clinical-trial-number":[{"clinical-trial-number":"nct03409315","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Simone HJ","family":"van den Elsen","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marieke GG","family":"Sturkenboom","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Onno","family":"Akkerman","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"},{"name":"Tuberculosis Center Beatrixoord, University of Groningen, University Medical Center Groningen, Haren, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Barkane","sequence":"additional","affiliation":[{"name":"Department of Multidrug Resistant Tuberculosis, Riga East University Hospital TB and Lung Disease Clinic, Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith","family":"Bruchfeld","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey","family":"Eather","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Metro South Clinical Tuberculosis Service, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott K","family":"Heysell","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henadz","family":"Hurevich","sequence":"additional","affiliation":[{"name":"The Republican Scientific and Practical Center for Pulmonology and Tuberculosis, Minsk, Belarus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liga","family":"Kuksa","sequence":"additional","affiliation":[{"name":"Department of Multidrug Resistant Tuberculosis, Riga East University Hospital TB and Lung Disease Clinic, Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heinke","family":"Kunst","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Blizard Institute, Queen Mary University of London, Barts Health NHS Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Kuhlin","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katerina","family":"Manika","sequence":"additional","affiliation":[{"name":"Pulmonary Department, Respiratory Infections Unit, G. Papanikolaou Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charalampos","family":"Moschos","sequence":"additional","affiliation":[{"name":"Drug-Resistant Tuberculosis Unit, 'Sotiria' Hospital for Chest Diseases, Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stellah G","family":"Mpagama","sequence":"additional","affiliation":[{"name":"Kibong'oto Infectious Diseases Hospital, Kilimanjaro, United Republic of Tanzania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcela","family":"Mu\u00f1oz Torrico","sequence":"additional","affiliation":[{"name":"Cl\u00ednica de Tuberculosis, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alena","family":"Skrahina","sequence":"additional","affiliation":[{"name":"The Republican Scientific and Practical Center for Pulmonology and Tuberculosis, Minsk, Belarus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Sotgiu","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Experimental Sciences, Clinical Epidemiology and Medical Statistics Unit, University of Sassari, Sassari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Tadolini","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Unit of Infectious Diseases, Alma Mater Studiorum University of Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Tiberi","sequence":"additional","affiliation":[{"name":"Department of Infection, Blizard Institute, Queen Mary University of London, Barts Health NHS Trust, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Volpato","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Unit of Infectious Diseases, Alma Mater Studiorum University of Bologna, Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tjip S","family":"van der Werf","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"},{"name":"Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malcolm R","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Metro South Clinical Tuberculosis Service, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joaquin","family":"Z\u00fa\u00f1iga","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico"},{"name":"Tecnologico de Monterrey, Escuela de Medicina y Ciencias de Salud, Mexico City, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daan J","family":"Touw","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni B","family":"Migliori","sequence":"additional","affiliation":[{"name":"Servizio di Epidemiologia Clinica delle Malattie Respiratorie, Istituti Clinici Scientifici Maugeri IRCCS, Tradate, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6703-0288","authenticated-orcid":false,"given":"Jan-Willem","family":"Alffenaar","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"},{"name":"Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2020,6,16]]},"reference":[{"key":"2025121407430836000_10.6.e035350.1","unstructured":"World Health Organization . 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