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128 results on '"Kuksa, L."'

1. Drug-associated adverse events in the treatment of multidrug-resistant tuberculosis: an individual patient data meta-analysis

Author

Lan, Zhiyi, Ahmad, Nafees, Baghaei, Parvaneh, Barkane, Linda, Benedetti, Andrea, Brode, Sarah K, Brust, James CM, Campbell, Jonathon R, Chang, Vicky Wai Lai, Falzon, Dennis, Guglielmetti, Lorenzo, Isaakidis, Petros, Kempker, Russell R, Kipiani, Maia, Kuksa, Liga, Lange, Christoph, Laniado-Laborín, Rafael, Nahid, Payam, Rodrigues, Denise, Singla, Rupak, Udwadia, Zarir F, Menzies, Dick, 2017, The Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB treatment, Ahmad, N, Baghaei, P, Barkane, L, Benedetti, A, Brode, SK, Brust, JCM, Campbell, Chang, VWL, Falzon, D, Guglielmetti, L, Isaakidis, P, Kempker, RR, Kipiani, M, Kuksa, L, Lan, Z, Lange, C, Laniado-Laborín, R, Nahid, P, Rodrigues, D, Singla, R, Udwadia, ZF, and Menzies, D

Subjects
Emerging Infectious Diseases, Orphan Drug, Antimicrobial Resistance, Lung, Rare Diseases, Infectious Diseases, Tuberculosis, Prevention, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Good Health and Well Being, Adult, Aminosalicylic Acid, Antitubercular Agents, Canada, Clofazimine, Diarylquinolines, Drug-Related Side Effects and Adverse Reactions, Female, Fluoroquinolones, Humans, Incidence, Linezolid, Male, Mycobacterium tuberculosis, Tuberculosis, Multidrug-Resistant, Tuberculosis, Pulmonary, Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB treatment 2017, Clinical Sciences, Public Health and Health Services, Other Medical and Health Sciences
Abstract

BackgroundTreatment of multidrug-resistant tuberculosis requires long-term therapy with a combination of multiple second-line drugs. These drugs are associated with numerous adverse events that can cause severe morbidity, such as deafness, and in some instances can lead to death. Our aim was to estimate the absolute and relative frequency of adverse events associated with different tuberculosis drugs to provide useful information for clinicians and tuberculosis programmes in selecting optimal treatment regimens.MethodsWe did a meta-analysis using individual-level patient data that were obtained from studies that reported adverse events that resulted in permanent discontinuation of anti-tuberculosis medications. We used a database created for our previous meta-analysis of multidrug-resistant tuberculosis treatment and outcomes, for which we did a systematic review of literature published between Jan 1, 2009, and Aug 31, 2015 (updated April 15, 2016), and requested individual patient-level information from authors. We also considered for this analysis studies contributing patient-level data in response to a public call made by WHO in 2018. Meta-analysis for proportions and arm-based network meta-analysis were done to estimate the incidence of adverse events for each tuberculosis drug.Findings58 studies were identified, including 50 studies from the updated individual patient data meta-analysis for multidrug-resistant tuberculosis treatment. 35 of these studies, with 9178 patients, were included in our analysis. Using meta-analysis of proportions, drugs with low risks of adverse event occurrence leading to permanent discontinuation included levofloxacin (1·3% [95% CI 0·3-5·0]), moxifloxacin (2·9% [1·6-5·0]), bedaquiline (1·7% [0·7-4·2]), and clofazimine (1·6% [0·5-5·3]). Relatively high incidence of adverse events leading to permanent discontinuation was seen with three second-line injectable drugs (amikacin: 10·2% [6·3-16·0]; kanamycin: 7·5% [4·6-11·9]; capreomycin: 8·2% [6·3-10·7]), aminosalicylic acid (11·6% [7·1-18·3]), and linezolid (14·1% [9·9-19·6]). Risk of bias in selection of studies was judged to be low because there were no important differences between included and excluded studies. Variability between studies was significant for most outcomes analysed.InterpretationFluoroquinolones, clofazimine, and bedaquiline had the lowest incidence of adverse events leading to permanent drug discontinuation, whereas second-line injectable drugs, aminosalicylic acid, and linezolid had the highest incidence. These results suggest that close monitoring of adverse events is important for patients being treated for multidrug-resistant tuberculosis. Our results also underscore the urgent need for safer and better-tolerated drugs to reduce morbidity from treatment itself for patients with multidrug-resistant tuberculosis.FundingCanadian Institutes of Health Research, Centers for Disease Control and Prevention (USA), American Thoracic Society, European Respiratory Society, and Infectious Diseases Society of America.

Published
2020

2. Outcome of treatment of MDR-TB or drug-resistant patients treated with bedaquiline and delamanid: Results from a large global cohort

Author

Koirala, S., Borisov, S., Danila, E., Mariandyshev, A., Shrestha, B., Lukhele, N., Dalcolmo, M., Shakya, S.R., Miliauskas, S., Kuksa, L., Manga, S., Aleksa, A., Denholm, J.T., Khadka, H.B., Skrahina, A., Diktanas, S., Ferrarese, M., Bruchfeld, J., Koleva, A., Piubello, A., Koirala, G.S., Udwadia, Z.F., Palmero, D.J., Munoz-Torrico, M., GC, R., Gualano, G., Grecu, V.I., Motta, I., Papavasileiou, A., Li, Y., Hoefsloot, W., Kunst, H., Mazza-Stalder, J., Payen, M.-C., Akkerman, O.W., Bernal, E., Manfrin, V., Matteelli, A., Mustafa Hamdan, H., Nieto Marcos, M., Cadiñanos Loidi, J., Cebrian Gallardo, J.J., Duarte, R., Escobar Salinas, N., Gomez Rosso, R., Laniado-Laborín, R., Martínez Robles, E., Quirós Fernandez, S., Rendon, A., Solovic, I., Tadolini, M., Viggiani, P., Belilovski, E., Boeree, M.J., Cai, Q., Davidavičienė, E., Forsman, L.D., De Los Rios, J., Drakšienė, J., Duga, A., Elamin, S.E., Filippov, A., Garcia, A., Gaudiesiute, I., Gavazova, B., Gayoso, R., Gruslys, V., Jonsson, J., Khimova, E., Madonsela, G., Magis-Escurra, C., Marchese, V., Matei, M., Moschos, C., Nakčerienė, B., Nicod, L., Palmieri, F., Pontarelli, A., Šmite, A., Souleymane, M.B., Vescovo, M., Zablockis, R., Zhurkin, D., Alffenaar, J.-W., Caminero, J.A., Codecasa, L.R., García-García, J.-M., Esposito, S., Saderi, L., Spanevello, A., Visca, D., Tiberi, S., Pontali, E., Centis, R., D'Ambrosio, L., van den Boom, M., Sotgiu, G., and Migliori, G.B.

Published
2021
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3. Drug-associated adverse events in the treatment of multidrug-resistant tuberculosis: an individual patient data meta-analysis

Author

Ahmad, N, Baghaei, P, Barkane, L, Benedetti, A, Brode, SK, Brust, JCM, Campbell, JR, Chang, VWL, Falzon, D, Guglielmetti, L, Isaakidis, P, Kempker, RR, Kipiani, M, Kuksa, L, Lan, Z, Lange, C, Laniado-Laborín, R, Nahid, P, Rodrigues, D, Singla, R, Udwadia, ZF, Menzies, D, Lan, Zhiyi, Ahmad, Nafees, Baghaei, Parvaneh, Barkane, Linda, Benedetti, Andrea, Brode, Sarah K, Brust, James C M, Campbell, Jonathon R, Chang, Vicky Wai Lai, Falzon, Dennis, Guglielmetti, Lorenzo, Isaakidis, Petros, Kempker, Russell R, Kipiani, Maia, Kuksa, Liga, Lange, Christoph, Laniado-Laborín, Rafael, Nahid, Payam, Rodrigues, Denise, Singla, Rupak, Udwadia, Zarir F, and Menzies, Dick

Published
2020
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4. MDR/XDR-TB management of patients and contacts: Challenges facing the new decade. The 2020 clinical update by the Global Tuberculosis Network

Author

Arkub, T. Abu, Akkerman, O.W., Aleksa, A., Belilovski, E., Bernal, E., Blanc, F-X., Boeree, M., Borisov, S., Bruchfeld, J., Cadiñanos Loidi, J., Caminero, J.A., Carvalho, A.C., Cebrian Gallardo, J.J., Charalampos, Danila, E., Davies Forsman, L., Denholm, J., Dheda, K., Diel, R., Diktanas, S., Dobler, C., Enwerem, M., Esposito, S., Escobar Salinas, N., Filippov, A., Formenti, B., García García, J.M., Goletti, D., Gomez Rosso, R., Gualano, G., Isaakidis, P., Kaluzhenina, A., Koirala, S., Kuksa, L., Kunst, H., Li, Y., Magis-Escurra, C., Manfrin, V., Manga, S., Manika, K., Marchese, V., Martínez Robles, E., Maryandyshev, A., Matteelli, A., Mariani, A., Mazza-Stalder, J., Mello, F., Mendoza, L., Mesi, A., Miliauskas, S., Mustafa Hamdan, H., Ndjeka, N., Nieto Marcos, M., Ottenhoff, T.H.M., Palmero, D.J., Palmieri, F., Papavasileiou, A., Payen, M.C., Pontarelli, A., Pretti Dalcolmo, M., Quirós Fernandez, S., Romero, R., Rossato Silva, D., Santos, A.P., Seaworth, B., Sinitsyn, M., Skrahina, A., Solovic, I., Spanevello, A., Tadolini, M., Torres, C., Udwadia, Z., van den Boom, M., Volchenkov, G.V., Yedilbayev, A., Zaleskis, R., Zellweger, J.P., Migliori, Giovanni Battista, Tiberi, Simon, Zumla, Alimuddin, Petersen, Eskild, Chakaya, Jeremiah Muhwa, Wejse, Christian, Muñoz Torrico, Marcela, Duarte, Raquel, Alffenaar, Jan Willem, Schaaf, H. Simon, Marais, Ben J., Cirillo, Daniela Maria, Alagna, Riccardo, Rendon, Adrian, Pontali, Emanuele, Piubello, Alberto, Figueroa, José, Ferlazzo, Gabriella, García-Basteiro, Alberto, Centis, Rosella, Visca, Dina, D’Ambrosio, Lia, and Sotgiu, Giovanni

Published
2020
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5. Association of smoking and alcohol use with rifampin-resistant TB treatment outcomes

Author

Campbell, J. R., primary, Chan, E. D., additional, Anderson, L. F., additional, Bonnet, M., additional, Brode, S. K., additional, Cegielski, J. P., additional, Guglielmetti, L., additional, Singla, R., additional, Fox, G. J., additional, Skrahina, A., additional, Rodrigues, D., additional, Kuksa, L., additional, Viiklepp, P., additional, and Menzies, D., additional

Published
2023
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6. Tuberculosis incidence in foreign-born people residing in European countries in 2020.

Author

Vasiliu, A., Köhler, N., Altpeter, E., Ægisdóttir, T.R., Amerali, M., Oñate, W.A. de, Bakos, Á., D'Amato, S., Cirillo, D.M., Crevel, R. van, Davidaviciene, E., Demuth, I., Domínguez, J., Duarte, R., Günther, G., Guthmann, J.P., Hatzianastasiou, S., Holm, L.H., Herrador, Z., Hribar, U., Huberty, C., Ibraim, E., Jackson, S., Jensenius, M., Josefsdottir, K.S., Koch, A., Korzeniewska-Kosela, M., Kuksa, L., Kunst, H., Lienhardt, C., Mahler, B., Makek, M.J., Muylle, I., Normark, J., Pace-Asciak, A., Petrović, G., Pieridou, D., Russo, G., Rzhepishevska, O., Salzer, H.J.F., Marques, M.S., Schmid, D., Solovic, I., Sukholytka, M., Svetina, P., Tyufekchieva, M., Vasankari, T., Viiklepp, P., Villand, K., Wallenfels, J., Wesolowski, S., Mandalakas, A.M., Martinez, L., Zenner, D., Lange, C., Vasiliu, A., Köhler, N., Altpeter, E., Ægisdóttir, T.R., Amerali, M., Oñate, W.A. de, Bakos, Á., D'Amato, S., Cirillo, D.M., Crevel, R. van, Davidaviciene, E., Demuth, I., Domínguez, J., Duarte, R., Günther, G., Guthmann, J.P., Hatzianastasiou, S., Holm, L.H., Herrador, Z., Hribar, U., Huberty, C., Ibraim, E., Jackson, S., Jensenius, M., Josefsdottir, K.S., Koch, A., Korzeniewska-Kosela, M., Kuksa, L., Kunst, H., Lienhardt, C., Mahler, B., Makek, M.J., Muylle, I., Normark, J., Pace-Asciak, A., Petrović, G., Pieridou, D., Russo, G., Rzhepishevska, O., Salzer, H.J.F., Marques, M.S., Schmid, D., Solovic, I., Sukholytka, M., Svetina, P., Tyufekchieva, M., Vasankari, T., Viiklepp, P., Villand, K., Wallenfels, J., Wesolowski, S., Mandalakas, A.M., Martinez, L., Zenner, D., and Lange, C.

Abstract

Item does not contain fulltext, BackgroundEuropean-specific policies for tuberculosis (TB) elimination require identification of key populations that benefit from TB screening.AimWe aimed to identify groups of foreign-born individuals residing in European countries that benefit most from targeted TB prevention screening.MethodsThe Tuberculosis Network European Trials group collected, by cross-sectional survey, numbers of foreign-born TB patients residing in European Union (EU) countries, Iceland, Norway, Switzerland and the United Kingdom (UK) in 2020 from the 10 highest ranked countries of origin in terms of TB cases in each country of residence. Tuberculosis incidence rates (IRs) in countries of residence were compared with countries of origin.ResultsData on 9,116 foreign-born TB patients in 30 countries of residence were collected. Main countries of origin were Eritrea, India, Pakistan, Morocco, Romania and Somalia. Tuberculosis IRs were highest in patients of Eritrean and Somali origin in Greece and Malta (both > 1,000/100,000) and lowest among Ukrainian patients in Poland (3.6/100,000). They were mainly lower in countries of residence than countries of origin. However, IRs among Eritreans and Somalis in Greece and Malta were five times higher than in Eritrea and Somalia. Similarly, IRs among Eritreans in Germany, the Netherlands and the UK were four times higher than in Eritrea.ConclusionsCountry of origin TB IR is an insufficient indicator when targeting foreign-born populations for active case finding or TB prevention policies in the countries covered here. Elimination strategies should be informed by regularly collected country-specific data to address rapidly changing epidemiology and associated risks.

Published
2023

7. Prospective evaluation of improving fluoroquinolone exposure using centralised therapeutic drug monitoring (TDM) in patients with tuberculosis (PERFECT)

Author

Van Den Elsen S. H. J., Sturkenboom M. G. G., Akkerman O., Barkane L., Bruchfeld J., Eather G., Heysell S. K., Hurevich H., Kuksa L., Kunst H., Kuhlin J., Manika K., Moschos C., Mpagama S. G., Munoz Torrico M., Skrahina A., Sotgiu G., Tadolini M., Tiberi S., Volpato F., Van Der Werf T. S., Wilson M. R., Zuniga J., Touw D. J., Migliori G. B., Alffenaar J. -W., Microbes in Health and Disease (MHD), Biopharmaceuticals, Discovery, Design and Delivery (BDDD), Groningen Research Institute for Asthma and COPD (GRIAC), Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Pharmaceutical Analysis, Medicinal Chemistry and Bioanalysis (MCB), Van Den Elsen S.H.J., Sturkenboom M.G.G., Akkerman O., Barkane L., Bruchfeld J., Eather G., Heysell S.K., Hurevich H., Kuksa L., Kunst H., Kuhlin J., Manika K., Moschos C., Mpagama S.G., Munoz Torrico M., Skrahina A., Sotgiu G., Tadolini M., Tiberi S., Volpato F., Van Der Werf T.S., Wilson M.R., Zuniga J., Touw D.J., Migliori G.B., and Alffenaar J.-W.

Subjects
medicine.medical_specialty, infectious disease, lcsh:Medicine, organisation of health service, organisation of health services, law.invention, Fluoroquinolone, Moxifloxacin, Informed consent, law, Anti-Bacterial Agent, Tuberculosis, Multidrug-Resistant, medicine, Humans, Multicenter Studies as Topic, tuberculosi, Dosing, Prospective Studies, Precision Medicine, Intensive care medicine, Prospective cohort study, Clinical pharmacology, medicine.diagnostic_test, business.industry, lcsh:R, Sputum, General Medicine, Anti-Bacterial Agents, Prospective Studie, Observational Studies as Topic, Infectious Diseases, tuberculosis, Therapeutic drug monitoring, Research Design, Observational study, clinical pharmacology, Drug Monitoring, business, Human, medicine.drug, Cohort study, Fluoroquinolones
Abstract

IntroductionGlobal 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.Methods and analysisPatients 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 and t=5 hours) 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 days after sampling and 100% within 14 days. The number of patients who are sputum smear and culture-negative after 2 months 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.Ethics and disseminationEthical 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.Trial registration numberClinicalTrials.gov Registry (NCT03409315).

Published
2020

8. TB and COVID-19 co-infection: rationale and aims of a global study

Author

Casco, N., Jorge, A. L., Palmero, D., Alffenaar, J. -W., Fox, G., Ezz, W., Cho, J. -G., Skrahina, A., Solodovnikova, V., Bachez, P., Arbex, M. A., Galvao, T., Rabahi, M., Pereira, G. R., Sales, R., Silva, D. R., Saffie, M. M., Miranda, R. C., Cancino, V., Carbonell, M., Cisterna, C., Concha, C., Cruz, A., Salinas, N. E., Revillot, M. E., Farias, J., Fernandez, I., Flores, X., Gallegos, P., Garavagno, A., Guajardo, C., Bahamondes, M. H., Merino, L. M., Munoz, E., Munoz, C., Navarro, I., Navarro, J., Ortega, C., Palma, S., Pardenas, A. M., Pereira, G., Castillo, P. P., Pinto, M., Pizarro, R., Rivas, F., Rodriguez, P., Sanchez, C., Serrano, A., Soto, A., Taiba, C., Venegas, M., Vergara, M. S., Vilca, E., Villalon, C., Yucra, E., Li, Y., Guelvez, B., Plaza, R., Tello, K., Andrejak, C., Blanc, F. -X., Dourmane, S., Froissart, A., Izadifar, A., Riviere, F., Schlemmer, F., Gupta, N., Ish, P., Mishra, G., Sharma, S., Singla, R., Udwadia, Z. F., Manika, K., Diallo, B. D., Hassane-Harouna, S., Artiles, N., Mejia, L. A., Alladio, F., Calcagno, A., Centis, R., Codecasa, L. R., D'Ambrosio, L., Formenti, B., Gaviraghi, A., Giacomet, V., Goletti, D., Gualano, G., Matteelli, A., Migliori, G. B., Motta, I., Palmieri, F., Prestileo, T., Riccardi, N., Saderi, L., Saporiti, M., Sotgiu, G., Stochino, C., Tadolini, M., Torre, A., Visca, D., Villa, S., Kuksa, L., Danila, E., Diktanas, S., Miliauskas, S., Ridaura, R. L., Lopez, F. L. L., Torrico, M. M., Rendon, A., Akkerman, O. W., Piubello, A., Souleymane, M. B., Aizpurua, E., Gonzales, R., Jurado, J., Loban, A., Aguirre, S., De Egea, V., Irala, S., Medina, A., Sequera, G., Sosa, N., Vazquez, F., Manga, S., Villanueva, R., Araujo, D., Duarte, R., Marques, T. S., Grecu, V. I., Socaci, A., Barkanova, O., Bogorodskaya, M., Borisov, S., Mariandyshev, A., Kaluzhenina, A., Stosic, M., Beh, D., Ng, D., Ong, C. W. M., Solovic, I., Dheda, D., Gina, P., Caminero, J. A., Cardoso-Landivar, J., De Souza Galvao, M. L., Dominguez-Castellano, A., Garcia-Garcia, J. -M., Pinargote, I. M., Fernandez, S. Q., Sanchez-Montalva, A., Huguet, E. T., Murguiondo, M. Z., Bruchfeld, J., Bart, P. -A., Mazza-Stalder, J., Tiberi, S., Arrieta, F., Heysell, S., Logsdon, J., Young, L., Department of Physics [Glasgow], University of Strathclyde [Glasgow], Instituto de Fisica Corpuscular (IFIC), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Universitat de València (UV), Laboratoire d'Etude des Mécanismes Cognitifs (EMC), Université Lumière - Lyon 2 (UL2), Added Value Solutions (AVS), Universidade de Santiago de Compostela [Spain] (USC ), Departamento de Ingeniería Térmica y de Fluidos, Avda. Universidad 30, University Medical Center Göttingen (UMG), CHU Amiens-Picardie, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Réanimation Médicale [CHU Henri Mondor - APHP] (DHU A-TVB), CHU Henri Mondor-Université Paris-Est Créteil, Faculté de Médecine [Créteil] (UPEC-Médecine), Inter-University Centre for Astronomy and Astrophysics [Pune] (IUCAA), Alma Mater Studiorum University of Bologna (UNIBO), Laboratoire des EcoSystèmes et des Sociétés en Montagne (UR LESSEM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università degli Studi di Milano = University of Milan (UNIMI), Vilnius University [Vilnius], Instituto de Ciencias Nucleares [Mexico], Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Instituto Mexicano del Petróleo (IMP), University of Cadiz, Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], Bart's and The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), Southwest Research Institute [Boulder] (SwRI), BIOLOGICAL AND AGRICULTURAL ENGINEERING NORTH CAROLINA STATE UNIVERSITY RALEIGH USA, Partenaires IRSTEA, Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Microbes in Health and Disease (MHD), Université Paris-Est Créteil, Faculté de Médecine [Créteil] (UPEC-Médecine)-CHU Henri Mondor, Università degli Studi di Milano [Milano] (UNIMI), and Universidad Nacional Autónoma de México (UNAM)

Subjects
Pulmonary and Respiratory Medicine, Research design, medicine.medical_specialty, Tuberculosis, Coronavirus disease 2019 (COVID-19), [SDV]Life Sciences [q-bio], MEDLINE, Global Health, medicine, Global health, Humans, Multicenter Studies as Topic, Prospective Studies, Intensive care medicine, Prospective cohort study, Tuberculosis, Pulmonary, ComputingMilieux_MISCELLANEOUS, business.industry, Coinfection, COVID-19, Pulmonary, medicine.disease, Infectious Diseases, Research Design, business, Co infection
Abstract

International audience

Published
2021

9. Outcome of treatment of MDR-TB or drug-resistant patients treated with bedaquiline and delamanid: Results from a large global cohort

Author

Koirala, S, Borisov, S, Danila, E, Mariandyshev, A, Shrestha, B, Lukhele, N, Dalcolmo, M, Shakya, SR, Miliauskas, S, Kuksa, L, Manga, S, Aleksa, A, Denholm, JT, Khadka, HB, Skrahina, A, Diktanas, S, Ferrarese, M, Bruchfeld, J, Koleva, A, Piubello, A, Koirala, GS, Udwadia, ZF, Palmero, DJ, Munoz-Torrico, M, Gc, R, Gualano, G, Grecu, V, Motta, I, Papavasileiou, A, Li, Y, Hoefsloot, W, Kunst, H, Mazza-Stalder, J, Payen, M-C, Akkerman, OW, Bernal, E, Manfrin, V, Matteelli, A, Hamdan, HM, Marcos, MN, Cadinanos Loidi, J, Cebrian Gallardo, JJ, Duarte, R, Escobar Salinas, N, Gomez Rosso, R, Laniado-Laborin, R, Martinez Robles, E, Quiros Fernandez, S, Rendon, A, Solovic, I, Tadolini, M, Viggiani, P, Belilovski, E, Boeree, MJ, Cai, Q, Davidaviciene, E, Forsman, LD, De Los Rios, J, Draksiene, J, Duga, A, Elamin, SE, Filippov, A, Garcia, A, Gaudiesiute, I, Gavazova, B, Gayoso, R, Gruslys, V, Jonsson, J, Khimova, E, Madonsela, G, Magis-Escurra, C, Marchese, V, Matei, M, Moschos, C, Nakceriene, B, Nicod, L, Palmieri, F, Pontarelli, A, Smite, A, Souleymane, MB, Vescovo, M, Zablockis, R, Zhurkin, D, Alffenaar, J-W, Caminero, JA, Codecasa, LR, Garcia-Garcia, J-M, Esposito, S, Saderi, L, Spanevello, A, Visca, D, Tiberi, S, Pontali, E, Centis, R, D'Ambrosio, L, van den Boom, M, Sotgiuw, G, Migliori, GB, Koirala, S, Borisov, S, Danila, E, Mariandyshev, A, Shrestha, B, Lukhele, N, Dalcolmo, M, Shakya, SR, Miliauskas, S, Kuksa, L, Manga, S, Aleksa, A, Denholm, JT, Khadka, HB, Skrahina, A, Diktanas, S, Ferrarese, M, Bruchfeld, J, Koleva, A, Piubello, A, Koirala, GS, Udwadia, ZF, Palmero, DJ, Munoz-Torrico, M, Gc, R, Gualano, G, Grecu, V, Motta, I, Papavasileiou, A, Li, Y, Hoefsloot, W, Kunst, H, Mazza-Stalder, J, Payen, M-C, Akkerman, OW, Bernal, E, Manfrin, V, Matteelli, A, Hamdan, HM, Marcos, MN, Cadinanos Loidi, J, Cebrian Gallardo, JJ, Duarte, R, Escobar Salinas, N, Gomez Rosso, R, Laniado-Laborin, R, Martinez Robles, E, Quiros Fernandez, S, Rendon, A, Solovic, I, Tadolini, M, Viggiani, P, Belilovski, E, Boeree, MJ, Cai, Q, Davidaviciene, E, Forsman, LD, De Los Rios, J, Draksiene, J, Duga, A, Elamin, SE, Filippov, A, Garcia, A, Gaudiesiute, I, Gavazova, B, Gayoso, R, Gruslys, V, Jonsson, J, Khimova, E, Madonsela, G, Magis-Escurra, C, Marchese, V, Matei, M, Moschos, C, Nakceriene, B, Nicod, L, Palmieri, F, Pontarelli, A, Smite, A, Souleymane, MB, Vescovo, M, Zablockis, R, Zhurkin, D, Alffenaar, J-W, Caminero, JA, Codecasa, LR, Garcia-Garcia, J-M, Esposito, S, Saderi, L, Spanevello, A, Visca, D, Tiberi, S, Pontali, E, Centis, R, D'Ambrosio, L, van den Boom, M, Sotgiuw, G, and Migliori, GB

Abstract

The World Health Organization (WHO) recommends countries introduce new anti-TB drugs in the treatment of multidrug-resistant tuberculosis. The aim of the study is to prospectively evaluate the effectiveness of bedaquiline (and/or delamanid)- containing regimens in a large cohort of consecutive TB patients treated globally. This observational, prospective study is based on data collected and provided by Global Tuberculosis Network (GTN) centres and analysed twice a year. All consecutive patients (including children/adolescents) treated with bedaquiline and/or delamanid were enrolled, and managed according to WHO and national guidelines. Overall, 52 centres from 29 countries/regions in all continents reported 883 patients as of January 31st 2021, 24/29 countries/regions providing data on 100% of their consecutive patients (10-80% in the remaining 5 countries). The drug-resistance pattern of the patients was severe (>30% with extensively drug-resistant -TB; median number of resistant drugs 5 (3-7) in the overall cohort and 6 (4-8) among patients with a final outcome). For the patients with a final outcome (477/883, 54.0%) the median (IQR) number of months of anti-TB treatment was 18 (13-23) (in days 553 (385-678)). The proportion of patients achieving sputum smear and culture conversion ranged from 93.4% and 92.8% respectively (whole cohort) to 89.3% and 88.8% respectively (patients with a final outcome), a median (IQR) time to sputum smear and culture conversion of 58 (30-90) days for the whole cohort and 60 (30-100) for patients with a final outcome and, respectively, of 55 (30-90) and 60 (30-90) days for culture conversion. Of 383 patients treated with bedaquiline but not delamanid, 284 (74.2%) achieved treatment success, while 25 (6.5%) died, 11 (2.9%) failed and 63 (16.5%) were lost to follow-up.

Published
2021

11. Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report

Author

Borisov, S., Danila, E., Maryandyshev, A., Dalcolmo, M., Miliauskas, S., Kuksa, L., Manga, S., Skrahina, A., Diktanas, S., Codecasa, L.R., Aleksa, A., Bruchfeld, J., Koleva, A., Piubello, A., Udwadia, Z.F., Akkerman, O.W., Belilovski, E., Bernal, E., Boeree, M.J., Loidi, J., Cai, Q., Gallardo, J.J. Cebrian, Dara, M., Davidaviciene, E., Forsman, L.D., Rios, J. De Los, Denholm, J., Draksiene, J., Duarte, R., Elamin, S.E., Salinas, N. Escobar, Ferrarese, M., Filippov, A., Garcia, A., Garcia-Garcia, J.M., Gaudiesiute, I., Gavazova, B., Gayoso, R., Rosso, R., Gruslys, V., Gualano, G., Hoefsloot, W., Jonsson, J., Khimova, E., Kunst, H., Laniado-Laborin, R., Li, Y, Magis-Escurra, C., Manfrin, V., Marchese, V., Robles, E. Martinez, Matteelli, A., Mazza-Stalder, J., Moschos, C., Munoz-Torrico, M., Hamdan, H. Mustafa, Nakceriene, B., Nicod, L., Marcos, M., Palmero, D.J., Palmieri, F., Papavasileiou, A., Payen, M.C., Pontarelli, A., Quiros, S., Rendon, A., Saderi, L., Smite, A., Solovic, I., Souleymane, M.B., Tadolini, M., Boom, M. van den, Vescovo, M., Viggiani, P., Yedilbayev, A., Zablockis, R., Zhurkin, D., Zignol, M., Visca, D., Spanevello, A., Caminero, J.A., Alffenaar, J.W.C., Tiberi, S., Centis, R., D'Ambrosio, L., Pontali, E., Sotgiu, G., Migliori, G.B., Borisov, S., Danila, E., Maryandyshev, A., Dalcolmo, M., Miliauskas, S., Kuksa, L., Manga, S., Skrahina, A., Diktanas, S., Codecasa, L.R., Aleksa, A., Bruchfeld, J., Koleva, A., Piubello, A., Udwadia, Z.F., Akkerman, O.W., Belilovski, E., Bernal, E., Boeree, M.J., Loidi, J., Cai, Q., Gallardo, J.J. Cebrian, Dara, M., Davidaviciene, E., Forsman, L.D., Rios, J. De Los, Denholm, J., Draksiene, J., Duarte, R., Elamin, S.E., Salinas, N. Escobar, Ferrarese, M., Filippov, A., Garcia, A., Garcia-Garcia, J.M., Gaudiesiute, I., Gavazova, B., Gayoso, R., Rosso, R., Gruslys, V., Gualano, G., Hoefsloot, W., Jonsson, J., Khimova, E., Kunst, H., Laniado-Laborin, R., Li, Y, Magis-Escurra, C., Manfrin, V., Marchese, V., Robles, E. Martinez, Matteelli, A., Mazza-Stalder, J., Moschos, C., Munoz-Torrico, M., Hamdan, H. Mustafa, Nakceriene, B., Nicod, L., Marcos, M., Palmero, D.J., Palmieri, F., Papavasileiou, A., Payen, M.C., Pontarelli, A., Quiros, S., Rendon, A., Saderi, L., Smite, A., Solovic, I., Souleymane, M.B., Tadolini, M., Boom, M. van den, Vescovo, M., Viggiani, P., Yedilbayev, A., Zablockis, R., Zhurkin, D., Zignol, M., Visca, D., Spanevello, A., Caminero, J.A., Alffenaar, J.W.C., Tiberi, S., Centis, R., D'Ambrosio, L., Pontali, E., Sotgiu, G., and Migliori, G.B.

Abstract

Item does not contain fulltext, The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1-2) and 57 (11.3%) as serious (grade 3-5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.

Published
2019

12. Surveillance of adverse events in the treatment of drug-resistant tuberculosis: A global feasibility study

Author

Akkerman, O., Aleksa, A., Alffenaar, J.W.C., Al-Marzouqi, N.H., Arias-Guillen, M., Belilovski, E., Bernal, E., Boeree, M.J., Borisov, S.E., Bruchfeld, J., Loidi, J., Cai, Q., Caminero, J.A., Gallardo, J.J. Cebrian, Centis, R., Codecasa, L.R., D'Ambrosio, L., Dalcolmo, M., Danila, E., Dara, M., Davidaviciene, E., Forsman, L. Davies, Jefe, J. De Los Rios, Denholm, J., Duarte, R., Elamin, S.E., Ferrarese, M., Filippov, A., Ganatra, S., Garcia, A., Garcia-Garcia, J.M., Gayoso, R., Montoya, A.M. Giraldo, Rosso, R.G. Gomez, Gualano, G., Hoefsloot, W., Ilievska-Poposka, B., Jonsson, J., Khimova, E., Kuksa, L., Kunst, H., Laniado-Laborin, R., Li, Y., Magis-Escurra, C., Manfrin, V., Manga, S., Marchese, V., Robles, E. Martinez, Maryandyshev, A., Matteelli, A., Migliori, G.B., Mullerpattan, J.B., Munoz-Torrico, M., Hamdan, H. Mustafa, Marcos, M., Noordin, N.M., Palmero, D.J., Palmieri, F., Payen, M.C., Piubello, A., Pontali, E., Pontarelli, A., Quiros, S., Rendon, A., Skrahina, A., Smite, A., Solovic, I., Sotgiu, G., Souleymane, M.B., Spanevello, A., Stosic, M., Tadolini, M., Tiberi, S., Udwadia, Z.F., Boom, M. van den, Vescovo, M., Viggiani, P., Visca, D., Zhurkin, D., Zignol, M., Akkerman, O., Aleksa, A., Alffenaar, J.W.C., Al-Marzouqi, N.H., Arias-Guillen, M., Belilovski, E., Bernal, E., Boeree, M.J., Borisov, S.E., Bruchfeld, J., Loidi, J., Cai, Q., Caminero, J.A., Gallardo, J.J. Cebrian, Centis, R., Codecasa, L.R., D'Ambrosio, L., Dalcolmo, M., Danila, E., Dara, M., Davidaviciene, E., Forsman, L. Davies, Jefe, J. De Los Rios, Denholm, J., Duarte, R., Elamin, S.E., Ferrarese, M., Filippov, A., Ganatra, S., Garcia, A., Garcia-Garcia, J.M., Gayoso, R., Montoya, A.M. Giraldo, Rosso, R.G. Gomez, Gualano, G., Hoefsloot, W., Ilievska-Poposka, B., Jonsson, J., Khimova, E., Kuksa, L., Kunst, H., Laniado-Laborin, R., Li, Y., Magis-Escurra, C., Manfrin, V., Manga, S., Marchese, V., Robles, E. Martinez, Maryandyshev, A., Matteelli, A., Migliori, G.B., Mullerpattan, J.B., Munoz-Torrico, M., Hamdan, H. Mustafa, Marcos, M., Noordin, N.M., Palmero, D.J., Palmieri, F., Payen, M.C., Piubello, A., Pontali, E., Pontarelli, A., Quiros, S., Rendon, A., Skrahina, A., Smite, A., Solovic, I., Sotgiu, G., Souleymane, M.B., Spanevello, A., Stosic, M., Tadolini, M., Tiberi, S., Udwadia, Z.F., Boom, M. van den, Vescovo, M., Viggiani, P., Visca, D., Zhurkin, D., and Zignol, M.

Abstract

Contains fulltext : 207083.pdf (publisher's version ) (Open Access), The World Health Organization launched a global initiative, known as aDSM (active TB drug safety monitoring and management) to better describe the safety profile of new treatment regimens for drug-resistant tuberculosis (TB) in real-world settings. However, comprehensive surveillance is difficult to implement in several countries. The aim of the aDSM project is to demonstrate the feasibility of implementing national aDSM registers and to describe the type and the frequency of adverse events (AEs) associated with exposure to the new anti-TB drugs. Following a pilot study carried out in 2016, official involvement of TB reference centres/countries into the project was sought and cases treated with bedaquiline- and/or delamanid-containing regimens were consecutively recruited. AEs were prospectively collected ensuring potential attribution of the AE to a specific drug based on its known safety profile. A total of 309 cases were fully reported from 41 centres in 27 countries (65% males; 268 treated with bedaquiline, 20 with delamanid, and 21 with both drugs) out of an estimated 781 cases the participating countries had committed to report by the first quarter of 2019.

Published
2019

13. Management of patients with multidrug-resistant tuberculosis

Author

Lange, C., Aarnoutse, R. E., Alffenaar, J. W. C., Bothamley, G., Brinkmann, F., Costa, J., Chesov, D., van Crevel, R., Dedicoat, M., Dominguez, J., Duarte, R., Grobbel, H. P., Guenther, G., Guglielmetti, L., Heyckendorf, J., Kay, A. W., Kirakosyan, O., Kirk, O., Koczulla, R. A., Kudriashov, G. G., Kuksa, L., van Leth, F., Magis-Escurra, C., Mandalakas, A. M., Molina-Moya, B., Peloquin, C. A., Reimann, M., Rumetshofer, R., Schaaf, H. S., Schön, Thomas, Tiberi, S., Valda, J., Yablonskii, P. K., Dheda, K., Lange, C., Aarnoutse, R. E., Alffenaar, J. W. C., Bothamley, G., Brinkmann, F., Costa, J., Chesov, D., van Crevel, R., Dedicoat, M., Dominguez, J., Duarte, R., Grobbel, H. P., Guenther, G., Guglielmetti, L., Heyckendorf, J., Kay, A. W., Kirakosyan, O., Kirk, O., Koczulla, R. A., Kudriashov, G. G., Kuksa, L., van Leth, F., Magis-Escurra, C., Mandalakas, A. M., Molina-Moya, B., Peloquin, C. A., Reimann, M., Rumetshofer, R., Schaaf, H. S., Schön, Thomas, Tiberi, S., Valda, J., Yablonskii, P. K., and Dheda, K.

Abstract

The emergence of multidrug-resistant tuberculosis (MDR-TB; defined as resistance to at least rifampicin and isoniazid) represents a growing threat to public health and economic growth. Never before in the history of mankind have more patients been affected by MDR-TB than is the case today. The World Health Organization reports that MDR-TB outcomes are poor despite staggeringly high management costs. Moreover, treatment is prolonged, adverse events are common, and the majority of affected patients do not receive adequate treatment. As MDR-TB strains are often resistant to one or more second-line anti-TB drugs, in-depth genotypic and phenotypic drug susceptibility testing is needed to construct personalised treatment regimens to improve treatment outcomes. For the first time in decades, the availability of novel drugs such as bedaquiline allow us to design potent and well-tolerated personalised MDR-TB treatment regimens based solely on oral drugs. In this article, we present management guidance to optimise the diagnosis, algorithm-based treatment, drug dosing and therapeutic drug monitoring, and the management of adverse events and comorbidities, associated with MDR-TB. We also discuss the role of surgery, physiotherapy, rehabilitation, palliative care and smoking cessation in patients with MDR-TB. We hope that incorporating these recommendations into patient care will be helpful in optimising treatment outcomes, and lead to more MDR-TB patients achieving a relapse-free cure., Funding Agencies|German Center for Infection Research (DZIF); Swedish Heart and Lung Foundation; Swedish Research Council; South African Medical Research Council; European Union (EDCTP)

Published
2019
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16. Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis : an individual patient data meta-analysis

Author

Ahmad, N., Ahuja, S. D., Akkerman, O. W., Alffenaar, J. W. C., Anderson, L. F., Baghaei, P., Bang, D., Barry, P. M., Bastos, M. L., Behera, D., Benedetti, A., Bisson, G. P., Boeree, M. J., Bonnet, Maryline, Brode, S. K., Brust, J. C. M., Cai, Y., Caumes, E., Cegielski, J. P., Centis, R., Chan, P. C., Chan, E. D., Chang, K. C., Charles, M., Cirule, A., Dalcolmo, M. P., D'Ambrosio, L., de Vries, G., Dheda, K., Esmail, A., Flood, J., Fox, G. J., Frechet-Jachym, M., Fregona, G., Gayoso, R., Gegia, M., Gler, M. T., Gu, S., Guglielmetti, L., Holtz, T. H., Hughes, J., Isaakidis, P., Jarlsberg, L., Kempker, R. R., Keshavjee, S., Khan, F. A., Kipiani, M., Koenig, S. P., Koh, W. J., Kritski, A., Kuksa, L., Kvasnovsky, C. L., Kwak, N., Lan, Z. Y., Lange, C., Laniado-Laborin, R., Lee, M., Leimane, V., Leung, C. C., Leung, E. C. C., Li, P. Z., Lowenthal, P., Maciel, E. L., Marks, S. M., Mase, S., Mbuagbaw, L., Migliori, G. B., Milanov, V., Miller, A. C., Mitnick, C. D., Modongo, C., Mohr, E., Monedero, I., Nahid, P., Ndjeka, N., O'Donnell, M. R., Padayatchi, N., Palmero, D., Pape, J. W., Podewils, L. J., Reynolds, I., Riekstina, V., Robert, J., Rodriguez, M., Seaworth, B., Seung, K. J., Schnippel, K., Shim, T. S., Singla, R., Smith, S. E., Sotgiu, G., Sukhbaatar, G., Tabarsi, P., Tiberi, S., Trajman, A., Trieu, L., Udwadia, Z. F., van der Werf, T. S., Veziris, N., Viiklepp, P., Vilbrun, S. C., Walsh, K., Westenhouse, J., Yew, W. W., Yim, J. J., Zetola, N. M., Zignol, M., Menzies, D., and Collaborative Group Meta-Analysis

Abstract

Background Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis. Methods In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration. Findings Of 12030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0.15, 95% CI 0.11 to 0.18), levofloxacin (0.15, 0.13 to 0.18), carbapenems (0.14,0.06 to 0.21), moxifloxacin (0.11, 0.08 to 0.14), bedaquiline (0.10, 0.05 to 0.14), and clofazimine (0.06, 0.01 to 0.10). There was a significant association between reduced mortality and use of linezolid (-0.20, -0.23 to -0.16), levofloxacin (-0.06, -0.09 to -0.04), moxifloxacin (-0.07, -0.10 to -0.04), or bedaquiline (-0.14, -0.19 to -0.10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I-2 method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses. Interpretation Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition.

Published
2018

18. Management of patients with multidrug-resistant tuberculosis

Author

Lange, C., primary, Aarnoutse, R. E., additional, Alffenaar, J. W. C., additional, Bothamley, G., additional, Brinkmann, F., additional, Costa, J., additional, Chesov, D., additional, van Crevel, R., additional, Dedicoat, M., additional, Dominguez, J., additional, Duarte, R., additional, Grobbel, H. P., additional, Günther, G., additional, Guglielmetti, L., additional, Heyckendorf, J., additional, Kay, A. W., additional, Kirakosyan, O., additional, Kirk, O., additional, Koczulla, R. A., additional, Kudriashov, G. G., additional, Kuksa, L., additional, van Leth, F., additional, Magis-Escurra, C., additional, Mandalakas, A. M., additional, Molina-Moya, B., additional, Peloquin, C. A., additional, Reimann, M., additional, Rumetshofer, R., additional, Schaaf, H. S., additional, Schön, T., additional, Tiberi, S., additional, Valda, J., additional, Yablonskii, P. K., additional, and Dheda, K., additional

Published
2019
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36. Management of patients with multidrug-resistant tuberculosis

Author

Lange, C, Aarnoutse, R E, Alffenaar, J W C, Bothamley, G, Brinkmann, F, Costa, J, Chesov, D, Van Crevel, R, Dedicoat, M, Dominguez, J, Duarte, R, Grobbel, H P, Günther, Gunar, Guglielmetti, L, Heyckendorf, J, Kay, A W, Kirakosyan, O, Kirk, O, Koczulla, R A, Kudriashov, G G, Kuksa, L, Van Leth, F, Magis-Escurra, C, Mandalakas, A M, Molina-Moya, B, Peloquin, C A, Reimann, M, Rumetshofer, R, Schaaf, H S, Schön, T, Tiberi, S, Valda, J, Yablonskii, P K, and Dheda, K

Subjects
610 Medicine & health, 3. Good health
Abstract

The emergence of multidrug-resistant tuberculosis (MDR-TB; defined as resistance to at least rifampicin and isoniazid) represents a growing threat to public health and economic growth. Never before in the history of mankind have more patients been affected by MDR-TB than is the case today. The World Health Organization reports that MDR-TB outcomes are poor despite staggeringly high management costs. Moreover, treatment is prolonged, adverse events are common, and the majority of affected patients do not receive adequate treatment. As MDR-TB strains are often resistant to one or more second-line anti-TB drugs, in-depth genotypic and phenotypic drug susceptibility testing is needed to construct personalised treatment regimens to improve treatment outcomes. For the first time in decades, the availability of novel drugs such as bedaquiline allow us to design potent and well-tolerated personalised MDR-TB treatment regimens based solely on oral drugs. In this article, we present management guidance to optimise the diagnosis, algorithm-based treatment, drug dosing and therapeutic drug monitoring, and the management of adverse events and comorbidities, associated with MDR-TB. We also discuss the role of surgery, physiotherapy, rehabilitation, palliative care and smoking cessation in patients with MDR-TB. We hope that incorporating these recommendations into patient care will be helpful in optimising treatment outcomes, and lead to more MDR-TB patients achieving a relapse-free cure.

37. Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report

Author

José-María García-García, Jerker Jonsson, Fabrizio Palmieri, Luigi Codecasa, Matteo Zignol, Andrei Maryandyshev, Qingshan Cai, Domingo Palmero, Magnolia Nieto Marcos, Seifeldin Eltaeb Elamin, Enrique Bernal, Simon Tiberi, Alberto Matteelli, Marisa Vescovo, Judith Bruchfeld, Edita Davidavičienė, Saulius Diktanas, Skaidrius Miliauskas, Rolandas Zablockis, Raquel Duarte, R. Rosso, Martin J. Boeree, Marcela Muñoz-Torrico, Valentina Marchese, Adrian Rendon, Evgeny Belilovski, Sergey Borisov, Zarir F Udwadia, Antoniya Koleva, Jorge De Los Rios, Giovanni Battista Migliori, Ana Garcia, Elena Martínez Robles, Hamdan Mustafa Hamdan, Vygantas Gruslys, Marina Tadolini, Laurent P. Nicod, Laura Saderi, Alena Aleksa, Mahamadou Bassirou Souleymane, Rafael Laniado-Laborín, Vinicio Manfrin, Jesica Mazza-Stalder, Alberto Piubello, Charalampos Moschos, Liga Kuksa, Alexey Filippov, Giovanni Sotgiu, Lia D'Ambrosio, Agostina Pontarelli, Heinke Kunst, Pietro Viggiani, Jan-Willem C. Alffenaar, Emanuele Pontali, Maurizio Ferrarese, Regina Gayoso, Ieva Gaudiesiute, Onno W. Akkerman, Agnese Šmite, Edvardas Danila, Marie-Christine Payen, Justin T Denholm, Jacinta Drakšienė, Blagovesta Gavazova, Wouter Hoefsloot, Elena Khimova, Dina Visca, Askar Yedilbayev, Nadia Escobar Salinas, Julen Cadiñanos Loidi, Sarai Quirós, Ivan Solovic, Jose A. Caminero, Margareth Pretti Dalcolmo, Apostolos Papavasileiou, Gina Gualano, Birutė Nakčerienė, Martin van den Boom, Lina Davies Forsman, Dmitry Zhurkin, Yang Li, Alena Skrahina, Antonio Spanevello, Cecile Magis-Escurra, Masoud Dara, Selene Manga, Jose Joaquin Cebrian Gallardo, Rosella Centis, Microbes in Health and Disease (MHD), Borisov S., Danila E., Maryandyshev A., Dalcolmo M., Miliauskas S., Kuksa L., Manga S., Skrahina A., Diktanas S., Codecasa L.R., Aleksa A., Bruchfeld J., Koleva A., Piubello A., Udwadia Z.F., Akkerman O.W., Belilovski E., Bernal E., Boeree M.J., Loidi J.C., Cai Q., Gallardo J.J.C., Dara M., Davidaviciene E., Forsman L.D., de Los Rios J., Denholm J., Draksiene J., Duarte R., Elamin S.E., Salinas N.E., Ferrarese M., Filippov A., Garcia A., Garcia-Garcia J.-M., Gaudiesiute I., Gavazova B., Gayoso R., Rosso R.G., Gruslys V., Gualano G., Hoefsloot W., Jonsson J., Khimova E., Kunst H., Laniado-Laborin R., Li Y., Magis-Escurra C., Manfrin V., Marchese V., Robles E.M., Matteelli A., Mazza-Stalder J., Moschos C., Munoz-Torrico M., Hamdan H.M., Nakceriene B., Nicod L., Marcos M.N., Palmero D.J., Palmieri F., Papavasileiou A., Payen M.-C., Pontarelli A., Quiros S., Rendon A., Saderi L., Smite A., Solovic I., Souleymane M.B., Tadolini M., Boom M.V.D., Vescovo M., Viggiani P., Yedilbayev A., Zablockis R., Zhurkin D., Zignol M., Visca D., Spanevello A., Caminero J.A., Alffenaar J.-W., Tiberi S., Centis R., D'Ambrosio L., Pontali E., Sotgiu G., and Migliori G.B.

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Tuberculosis, Drug-Related Side Effects and Adverse Reactions, Antitubercular Agents, Terizidone, Clofazimine, Antitubercular Agent, Pharmacovigilance, chemistry.chemical_compound, Internal medicine, Tuberculosis, Multidrug-Resistant, medicine, Humans, Prospective Studies, Adverse effect, Aged, business.industry, Middle Aged, medicine.disease, Prospective Studie, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], chemistry, Tolerability, Female, Delamanid, Bedaquiline, Drug-Related Side Effects and Adverse Reaction, business, Human, medicine.drug
Abstract

The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1–2) and 57 (11.3%) as serious (grade 3–5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.

Published
2019

38. Effectiveness and safety of modified fully oral 9-month treatment regimens for rifampicin-resistant tuberculosis: a prospective cohort study.

Author

Korotych O, Achar J, Gurbanova E, Hovhannesyan A, Lomtadze N, Ciobanu A, Skrahina A, Dravniece G, Kuksa L, Rich M, Khachatryan N, Germanovych M, Kadyrov A, Terleieva I, Akhundova I, Adenov M, Durdyeva M, Kiria N, Parpieva N, Yatskevich N, Jumayev R, Nurov R, Diktanas S, Vilc V, Migliori GB, and Yedilbayev A

Subjects
Humans, Prospective Studies, Male, Female, Adult, Child, Adolescent, Child, Preschool, Middle Aged, Young Adult, Infant, Administration, Oral, Treatment Outcome, Drug Therapy, Combination, Aged, Tuberculosis, Pulmonary drug therapy, Infant, Newborn, Europe, Cohort Studies, Antitubercular Agents therapeutic use, Antitubercular Agents adverse effects, Antitubercular Agents administration & dosage, Rifampin therapeutic use, Rifampin adverse effects, Rifampin administration & dosage, Tuberculosis, Multidrug-Resistant drug therapy
Abstract

Background: In 2020, WHO guidelines prioritised the use of a standard fully oral short treatment regimen (STR) consisting of bedaquiline, levofloxacin or moxifloxacin, ethionamide, ethambutol, high-dose isoniazid, pyrazinamide, and clofazimine for the management of rifampicin-resistant tuberculosis. A high prevalence of resistance to constituent drugs precluded its widespread use by countries in the WHO European region. We evaluated three 9-month fully oral modified STRs (mSTRs) in which ethionamide, ethambutol, isoniazid, and pyrazinamide were replaced by linezolid, cycloserine, or delamanid (or a combination)., Methods: This multicountry, prospective, single-arm, cohort study examined the effectiveness and safety of mSTRs for fluoroquinolone-susceptible, rifampicin-resistant pulmonary tuberculosis in 13 countries in the WHO European region during 2020-23. We enrolled adults and children of all ages with bacteriologically confirmed rifampicin-resistant, fluoroquinolone-susceptible pulmonary tuberculosis, and children (aged 0-18 years) with clinically diagnosed disease and a confirmed contact with rifampicin-resistant, fluoroquinolone-susceptible tuberculosis. Participants aged 6 years or older received one of two regimens: bedaquiline, linezolid, levofloxacin, clofazimine, and cycloserine; or bedaquiline, linezolid, levofloxacin, clofazimine, and delamanid. Children younger than 6 years received delamanid, linezolid, levofloxacin, and clofazimine. Participants were followed up for 12 months after successful treatment completion to detect recurrence and death. The primary outcome was the cumulative probability of not having an unsuccessful study outcome (defined as treatment failure, on-treatment loss to follow-up, death, or recurrence) before 22 months of study follow-up. The primary safety outcome was the incidence of each adverse event of interest (peripheral neuropathy, optic neuritis, myelosuppression, hepatitis, prolonged QT interval, hypokalaemia, and acute kidney injury) of grade 3 or higher severity during the treatment course., Findings: Between Aug 28, 2020 and May 26, 2021, 7272 patients were screened and 2636 were included in the treatment cohort. 1966 (74·6%) were male, 670 (25·4%) were female, and median age was 43 years (IQR 33-53). Treatment success was recorded for 2181 (82·7%) participants. The cumulative probability of not having an unsuccessful study outcome 22 months after treatment initiation was 79% (95% CI 78-81). Increasing age (adjusted hazard ratio 2·61 [95% CI 1·70-4·04] for people aged >64 years vs 35-44 years), HIV-positive status (1·53 [1·16-2·01]), presence of bilateral cavities (1·68 [1·29-2·19]), smoking history (1·34 [1·05-1·71]), baseline anaemia (1·46 [1·15-1·86]), unemployment (1·37 [1·04-1·80]), elevated baseline liver enzymes (1·40 [1·13-1·73]), and excessive alcohol use (1·47 [1·14-1·89]) were positively associated with unsuccessful study outcomes. In the safety cohort of 2813 participants who received at least one dose, 301 adverse events of interest were recorded in 252 (9·0%) participants with the most frequent being myelosuppression (139 [4·9%] participants, 157 [52·2%] events)., Interpretation: The high treatment success and good safety results indicate considerable potential for the use of mSTRs in programmatic conditions, especially for individuals not eligible for the current WHO-recommended 6-month regimen and in settings with a need for alternative options., Funding: The Global Fund to Fight AIDS, Tuberculosis and Malaria; United States Agency for International Development; Government of Germany; and WHO., Translation: For the Russian translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 World Health Organization. Published by Elsevier Ltd. All rights reserved. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Published
2024
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39. Operational research as a mechanism to improve treatment outcomes for drug-resistant TB in the WHO European Region.

Author

Migliori GB, Korotych O, Achar J, Ciobanu A, Dravniece G, Germanovych M, Gurbanova E, Hovhannesyan A, Khachatryan N, Kuksa L, Lomtadze N, Rich ML, Skrahina A, and Yedilbayev A

Abstract

In 2022, the WHO European Region accounted for 15.1% of all incident rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB) cases. Most occurred in 18 high-priority countries of eastern Europe and central Asia, many of which joined an initiative led by the WHO Regional Office for Europe. The aim was to introduce three, fully oral, 9-month modified shorter treatment regimens (mSTR) to treat RR/MDR-TB under operational research conditions. The three regimens were: 1) bedaquiline + linezolid + levofloxacin + clofazimine + cycloserine (BdqLzdLfxCfzCs); 2) BdqLzdLfxCfz + delamanid (Dlm) for children over 6 years of age and adults; and 3) DlmLzdLfxCfz for children under 6 years of age. The project aimed to enhance treatment success, facilitate mSTR implementation, promote quality of care and build research capacity, while also contributing to global knowledge on all-oral mSTR use. Between April 2020 and June 2022, >2,800 patients underwent mSTR treatment in the WHO European Region. This unique experience promoted further collaboration with national tuberculosis programmes, health authorities, experts and donors within and outside Europe, with a focus on implementing operational research and improving the quality of care in high TB burden countries of the region. In the hope of encouraging others to adopt this model, we have described the principles of the initiative, its strengths and weaknesses and next steps., Competing Interests: Conflicts of interest: none declared., (© 2024 The Authors.)

Published
2024
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40. Tuberculosis incidence in foreign-born people residing in European countries in 2020.

Author

Vasiliu A, Köhler N, Altpeter E, Ægisdóttir TR, Amerali M, de Oñate WA, Bakos Á, D'Amato S, Cirillo DM, van Crevel R, Davidaviciene E, Demuth I, Domínguez J, Duarte R, Günther G, Guthmann JP, Hatzianastasiou S, Holm LH, Herrador Z, Hribar U, Huberty C, Ibraim E, Jackson S, Jensenius M, Josefsdottir KS, Koch A, Korzeniewska-Kosela M, Kuksa L, Kunst H, Lienhardt C, Mahler B, Makek MJ, Muylle I, Normark J, Pace-Asciak A, Petrović G, Pieridou D, Russo G, Rzhepishevska O, Salzer HJF, Marques MS, Schmid D, Solovic I, Sukholytka M, Svetina P, Tyufekchieva M, Vasankari T, Viiklepp P, Villand K, Wallenfels J, Wesolowski S, Mandalakas AM, Martinez L, Zenner D, and Lange C

Subjects
Humans, Incidence, Cross-Sectional Studies, Somalia, Europe epidemiology, Tuberculosis diagnosis, Tuberculosis epidemiology
Abstract

BackgroundEuropean-specific policies for tuberculosis (TB) elimination require identification of key populations that benefit from TB screening.AimWe aimed to identify groups of foreign-born individuals residing in European countries that benefit most from targeted TB prevention screening.MethodsThe Tuberculosis Network European Trials group collected, by cross-sectional survey, numbers of foreign-born TB patients residing in European Union (EU) countries, Iceland, Norway, Switzerland and the United Kingdom (UK) in 2020 from the 10 highest ranked countries of origin in terms of TB cases in each country of residence. Tuberculosis incidence rates (IRs) in countries of residence were compared with countries of origin.ResultsData on 9,116 foreign-born TB patients in 30 countries of residence were collected. Main countries of origin were Eritrea, India, Pakistan, Morocco, Romania and Somalia. Tuberculosis IRs were highest in patients of Eritrean and Somali origin in Greece and Malta (both > 1,000/100,000) and lowest among Ukrainian patients in Poland (3.6/100,000). They were mainly lower in countries of residence than countries of origin. However, IRs among Eritreans and Somalis in Greece and Malta were five times higher than in Eritrea and Somalia. Similarly, IRs among Eritreans in Germany, the Netherlands and the UK were four times higher than in Eritrea.ConclusionsCountry of origin TB IR is an insufficient indicator when targeting foreign-born populations for active case finding or TB prevention policies in the countries covered here. Elimination strategies should be informed by regularly collected country-specific data to address rapidly changing epidemiology and associated risks.

Published
2023
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41. Rifapentine access in Europe: growing concerns over key tuberculosis treatment component.

Author

Guglielmetti L, Günther G, Leu C, Cirillo D, Duarte R, Garcia-Basteiro AL, Goletti D, Jankovic M, Kuksa L, Maurer FP, Méchaï F, Tiberi S, van Leth F, Veziris N, and Lange C

Subjects
Antitubercular Agents therapeutic use, Drug Therapy, Combination, Europe, Humans, Rifampin analogs & derivatives, Rifampin therapeutic use, Antibiotics, Antitubercular therapeutic use, Tuberculosis drug therapy, Tuberculosis epidemiology
Abstract

Competing Interests: Conflict of interest: L. Guglielmetti is the co-principal investigator of two MSF-sponsored clinical trials testing shorter MDR-TB regimens, and has no other competing interests to disclose. All other authors have no competing interests.

Published
2022
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42. TB and COVID-19 co-infection: rationale and aims of a global study.

Author

Casco N, Jorge AL, Palmero D, Alffenaar JW, Fox G, Ezz W, Cho JG, Skrahina A, Solodovnikova V, Bachez P, Arbex MA, Galvão T, Rabahi M, Pereira GR, Sales R, Silva DR, Saffie MM, Miranda RC, Cancino V, Carbonell M, Cisterna C, Concha C, Cruz A, Salinas NE, Revillot ME, Farias J, Fernandez I, Flores X, Gallegos P, Garavagno A, Guajardo C, Bahamondes MH, Merino LM, Muñoz E, Muñoz C, Navarro I, Navarro J, Ortega C, Palma S, Pardenas AM, Pereira G, Castillo PP, Pinto M, Pizarro R, Rivas F, Rodriguez P, Sánchez C, Serrano A, Soto A, Taiba C, Venegas M, Vergara MS, Vilca E, Villalon C, Yucra E, Li Y, Cruz A, Guelvez B, Plaza R, Tello K, Andréjak C, Blanc FX, Dourmane S, Froissart A, Izadifar A, Rivière F, Schlemmer F, Gupta N, Ish P, Mishra G, Sharma S, Singla R, Udwadia ZF, Manika K, Diallo BD, Hassane-Harouna S, Artiles N, Mejia LA, Alladio F, Calcagno A, Centis R, Codecasa LR, D Ambrosio L, Formenti B, Gaviraghi A, Giacomet V, Goletti D, Gualano G, Kuksa L, Danila E, Diktanas S, Miliauskas S, Ridaura RL, López F, Torrico MM, Rendon A, Akkerman OW, Piubello A, Souleymane MB, Aizpurua E, Gonzales R, Jurado J, Loban A, Aguirre S, de Egea V, Irala S, Medina A, Sequera G, Sosa N, Vázquez F, Manga S, Villanueva R, Araujo D, Duarte R, Marques TS, Grecu VI, Socaci A, Barkanova O, Bogorodskaya M, Borisov S, Mariandyshev A, Kaluzhenina A, Stosic M, Beh D, Ng D, Ong C, Solovic I, Dheda D, Gina P, Caminero JA, Cardoso-Landivar J, de Souza Galvão ML, Dominguez-Castellano A, García-García JM, Pinargote IM, Fernandez SQ, Sánchez-Montalvá A, Huguet ET, Murguiondo MZ, Bruchfeld J, Bart PA, Mazza-Stalder J, Tiberi S, Arrieta F, Heysell S, Logsdon J, and Young L

Subjects
Coinfection, Global Health, Humans, Multicenter Studies as Topic, Prospective Studies, Research Design, COVID-19 complications, Tuberculosis, Pulmonary complications
Published
2021
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43. Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report.

Author

Borisov S, Danila E, Maryandyshev A, Dalcolmo M, Miliauskas S, Kuksa L, Manga S, Skrahina A, Diktanas S, Codecasa LR, Aleksa A, Bruchfeld J, Koleva A, Piubello A, Udwadia ZF, Akkerman OW, Belilovski E, Bernal E, Boeree MJ, Cadiñanos Loidi J, Cai Q, Cebrian Gallardo JJ, Dara M, Davidavičienė E, Forsman LD, De Los Rios J, Denholm J, Drakšienė J, Duarte R, Elamin SE, Escobar Salinas N, Ferrarese M, Filippov A, Garcia A, García-García JM, Gaudiesiute I, Gavazova B, Gayoso R, Gomez Rosso R, Gruslys V, Gualano G, Hoefsloot W, Jonsson J, Khimova E, Kunst H, Laniado-Laborín R, Li Y, Magis-Escurra C, Manfrin V, Marchese V, Martínez Robles E, Matteelli A, Mazza-Stalder J, Moschos C, Muñoz-Torrico M, Mustafa Hamdan H, Nakčerienė B, Nicod L, Nieto Marcos M, Palmero DJ, Palmieri F, Papavasileiou A, Payen MC, Pontarelli A, Quirós S, Rendon A, Saderi L, Šmite A, Solovic I, Souleymane MB, Tadolini M, van den Boom M, Vescovo M, Viggiani P, Yedilbayev A, Zablockis R, Zhurkin D, Zignol M, Visca D, Spanevello A, Caminero JA, Alffenaar JW, Tiberi S, Centis R, D'Ambrosio L, Pontali E, Sotgiu G, and Migliori GB

Subjects
Adult, Aged, Female, Humans, Male, Middle Aged, Pharmacovigilance, Prospective Studies, Antitubercular Agents adverse effects, Drug-Related Side Effects and Adverse Reactions diagnosis, Drug-Related Side Effects and Adverse Reactions epidemiology, Tuberculosis, Multidrug-Resistant drug therapy
Abstract

The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new ( i.e. bedaquiline, delamanid) and repurposed ( i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1-2) and 57 (11.3%) as serious (grade 3-5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care., Competing Interests: Conflict of interest: S. Borisov has nothing to disclose. Conflict of interest: E. Danila has nothing to disclose. Conflict of interest: A. Maryandyshev has nothing to disclose. Conflict of interest: M. Dalcolmo has nothing to disclose. Conflict of interest: S. Miliauskas has nothing to disclose. Conflict of interest: L. Kuksa reports personal fees for trial participation from Otsuka and Tibotec, personal fees for lectures from Johnson and Johnson Services Inc., outside the submitted work. Conflict of interest: S. Manga has nothing to disclose. Conflict of interest: A. Skrahina has nothing to disclose. Conflict of interest: S. Diktanas reports personal fees for trial participation from Otsuka, grants for meeting attendance from Janssen (Sirturo), outside the submitted work. Conflict of interest: L.R. Codecasa has nothing to disclose. Conflict of interest: A. Aleksa has nothing to disclose. Conflict of interest: J. Bruchfeld has nothing to disclose. Conflict of interest: A. Koleva has nothing to disclose. Conflict of interest: A. Piubello has nothing to disclose. Conflict of interest: Z.F. Udwadia has nothing to disclose. Conflict of interest: O.W. Akkerman has nothing to disclose. Conflict of interest: E. Belilovski has nothing to disclose. Conflict of interest: E. Bernal has nothing to disclose. Conflict of interest: M.J. Boeree has nothing to disclose. Conflict of interest: J. Cadiñanos Loidi has nothing to disclose. Conflict of interest: Q. Cai has nothing to disclose. Conflict of interest: J.J. Cebrian Gallardo has nothing to disclose. Conflict of interest: M. Dara has nothing to disclose. Conflict of interest: E. Davidavičienė has nothing to disclose. Conflict of interest: L. Davies Forsman has nothing to disclose. Conflict of interest: J. De Los Rios has nothing to disclose. Conflict of interest: J. Denholm has nothing to disclose. Conflict of interest: J. Drakšienė has nothing to disclose. Conflict of interest: R. Duarte has nothing to disclose. Conflict of interest: S.E. Elamin has nothing to disclose. Conflict of interest: N. Escobar Salinas has nothing to disclose. Conflict of interest: M. Ferrarese has nothing to disclose. Conflict of interest: A. Filippov has nothing to disclose. Conflict of interest: A. Garcia has nothing to disclose. Conflict of interest: J.M. García-García has nothing to disclose. Conflict of interest: I. Gaudiesiute has nothing to disclose. Conflict of interest: B. Gavazova has nothing to disclose. Conflict of interest: R. Gayoso has nothing to disclose. Conflict of interest: R. Gomez Rosso has nothing to disclose. Conflict of interest: V. Gruslys has nothing to disclose. Conflict of interest: G. Gualano has nothing to disclose. Conflict of interest: W. Hoefsloot has nothing to disclose. Conflict of interest: J. Jonsson has nothing to disclose. Conflict of interest: E. Khimova has nothing to disclose. Conflict of interest: H. Kunst has nothing to disclose. Conflict of interest: R. Laniado-Laborín has nothing to disclose. Conflict of interest: Y. Li has nothing to disclose. Conflict of interest: C. Magis-Escurra has nothing to disclose. Conflict of interest: V. Manfrin has nothing to disclose. Conflict of interest: V. Marchese has nothing to disclose. Conflict of interest: E. Martínez Robles has nothing to disclose. Conflict of interest: A. Matteelli has nothing to disclose. Conflict of interest: J. Mazza-Stalder has nothing to disclose. Conflict of interest: C. Moschos has nothing to disclose. Conflict of interest: M. Muñoz-Torrico has nothing to disclose. Conflict of interest: H. Mustafa Hamdan has nothing to disclose. Conflict of interest: B. Nakčerienė has nothing to disclose. Conflict of interest: L. Nicod has nothing to disclose. Conflict of interest: M. Nieto Marcos has nothing to disclose. Conflict of interest: D.J. Palmero has nothing to disclose. Conflict of interest: F. Palmieri has nothing to disclose. Conflict of interest: A. Papavasileiou has nothing to disclose. Conflict of interest: M-C. Payen has nothing to disclose. Conflict of interest: A. Pontarelli has nothing to disclose. Conflict of interest: S. Quirós has nothing to disclose. Conflict of interest: A. Rendon has nothing to disclose. Conflict of interest: L. Saderi has nothing to disclose. Conflict of interest: A. Šmite has nothing to disclose. Conflict of interest: I. Solovic has nothing to disclose. Conflict of interest: M.B. Souleymane has nothing to disclose. Conflict of interest: M. Tadolini has nothing to disclose. Conflict of interest: M. van den Boom has nothing to disclose. Conflict of interest: M. Vescovo has nothing to disclose. Conflict of interest: P. Viggiani has nothing to disclose. Conflict of interest: A. Yedilbayev has nothing to disclose. Conflict of interest: R. Zablockis has nothing to disclose. Conflict of interest: D. Zhurkin has nothing to disclose. Conflict of interest: M. Zignol has nothing to disclose. Conflict of interest: D. Visca has nothing to disclose. Conflict of interest: A. Spanevello has nothing to disclose. Conflict of interest: J.A. Caminero has nothing to disclose. Conflict of interest: J-W. Alffenaar has nothing to disclose. Conflict of interest: S. Tiberi has nothing to disclose. Conflict of interest: R. Centis has nothing to disclose. Conflict of interest: L. D'Ambrosio has nothing to disclose. Conflict of interest: E. Pontali has nothing to disclose. Conflict of interest: G. Sotgiu has nothing to disclose. Conflict of interest: G.B. Migliori has nothing to disclose., (Copyright ©ERS 2019.)

Published
2019
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44. Surveillance of adverse events in the treatment of drug-resistant tuberculosis: A global feasibility study.

Author

Akkerman O, Aleksa A, Alffenaar JW, Al-Marzouqi NH, Arias-Guillén M, Belilovski E, Bernal E, Boeree MJ, Borisov SE, Bruchfeld J, Cadiñanos Loidi J, Cai Q, Caminero JA, Cebrian Gallardo JJ, Centis R, Codecasa LR, D'Ambrosio L, Dalcolmo M, Danila E, Dara M, Davidavičienė E, Davies Forsman L, De Los Rios Jefe J, Denholm J, Duarte R, Elamin SE, Ferrarese M, Filippov A, Ganatra S, Garcia A, García-García JM, Gayoso R, Giraldo Montoya AM, Gomez Rosso RG, Gualano G, Hoefsloot W, Ilievska-Poposka B, Jonsson J, Khimova E, Kuksa L, Kunst H, Laniado-Laborín R, Li Y, Magis-Escurra C, Manfrin V, Manga S, Marchese V, Martínez Robles E, Maryandyshev A, Matteelli A, Migliori GB, Mullerpattan JB, Munoz-Torrico M, Mustafa Hamdan H, Nieto Marcos M, Noordin NM, Palmero DJ, Palmieri F, Payen MC, Piubello A, Pontali E, Pontarelli A, Quirós S, Rendon A, Skrahina A, Šmite A, Solovic I, Sotgiu G, Souleymane MB, Spanevello A, Stošić M, Tadolini M, Tiberi S, Udwadia ZF, van den Boom M, Vescovo M, Viggiani P, Visca D, Zhurkin D, and Zignol M

Subjects
Diarylquinolines administration & dosage, Drug Therapy, Combination, Feasibility Studies, Female, Humans, Male, Nitroimidazoles administration & dosage, Oxazoles administration & dosage, Pilot Projects, Tuberculosis drug therapy, World Health Organization, Antitubercular Agents adverse effects, Diarylquinolines adverse effects, Nitroimidazoles adverse effects, Oxazoles adverse effects, Tuberculosis, Multidrug-Resistant drug therapy
Abstract

The World Health Organization launched a global initiative, known as aDSM (active TB drug safety monitoring and management) to better describe the safety profile of new treatment regimens for drug-resistant tuberculosis (TB) in real-world settings. However, comprehensive surveillance is difficult to implement in several countries. The aim of the aDSM project is to demonstrate the feasibility of implementing national aDSM registers and to describe the type and the frequency of adverse events (AEs) associated with exposure to the new anti-TB drugs. Following a pilot study carried out in 2016, official involvement of TB reference centres/countries into the project was sought and cases treated with bedaquiline- and/or delamanid-containing regimens were consecutively recruited. AEs were prospectively collected ensuring potential attribution of the AE to a specific drug based on its known safety profile. A total of 309 cases were fully reported from 41 centres in 27 countries (65% males; 268 treated with bedaquiline, 20 with delamanid, and 21 with both drugs) out of an estimated 781 cases the participating countries had committed to report by the first quarter of 2019., (Copyright © 2019. Published by Elsevier Ltd.)

Published
2019
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45. The Tuberculosis Network European Trials group (TBnet) ERS Clinical Research Collaboration: addressing drug-resistant tuberculosis through European cooperation.

Author

van Leth F, Brinkmann F, Cirillo DM, Dheda K, Duarte R, Guglielmetti L, Kuksa L, Lange C, Mitnick C, Skrahina A, Zaman K, and Bothamley G

Subjects
Europe, Humans, Antitubercular Agents therapeutic use, International Cooperation, Tuberculosis, Multidrug-Resistant diagnosis, Tuberculosis, Multidrug-Resistant drug therapy
Abstract

Competing Interests: Conflict of interest: F. van Leth has nothing to disclose. Conflict of interest: F. Brinkmann has nothing to disclose. Conflict of interest: D.M. Cirillo has nothing to disclose. Conflict of interest: K. Dheda has nothing to disclose. Conflict of interest: R. Duarte has nothing to disclose. Conflict of interest: L. Guglielmetti has nothing to disclose. Conflict of interest: L. Kuksa has nothing to disclose. Conflict of interest: C. Lange reports personal fees (sponsorship for independent lectures at sponsored symposia) from Chiesi, Gilead, Abbvie, MSD, Becton Dickinson, Janssen, Lucane, Novartis and Thermofisher, outside the submitted work. Conflict of interest: C. Mitnick has nothing to disclose. Conflict of interest: A. Skrahina has nothing to disclose. Conflict of interest: K. Zaman has nothing to disclose. Conflict of interest: G. Bothamley reports that the TBnet ERS CRC receives a grant from the ERS.

Published
2019
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46. Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis.

Author

Ahmad N, Ahuja SD, Akkerman OW, Alffenaar JC, Anderson LF, Baghaei P, Bang D, Barry PM, Bastos ML, Behera D, Benedetti A, Bisson GP, Boeree MJ, Bonnet M, Brode SK, Brust JCM, Cai Y, Caumes E, Cegielski JP, Centis R, Chan PC, Chan ED, Chang KC, Charles M, Cirule A, Dalcolmo MP, D'Ambrosio L, de Vries G, Dheda K, Esmail A, Flood J, Fox GJ, Fréchet-Jachym M, Fregona G, Gayoso R, Gegia M, Gler MT, Gu S, Guglielmetti L, Holtz TH, Hughes J, Isaakidis P, Jarlsberg L, Kempker RR, Keshavjee S, Khan FA, Kipiani M, Koenig SP, Koh WJ, Kritski A, Kuksa L, Kvasnovsky CL, Kwak N, Lan Z, Lange C, Laniado-Laborín R, Lee M, Leimane V, Leung CC, Leung EC, Li PZ, Lowenthal P, Maciel EL, Marks SM, Mase S, Mbuagbaw L, Migliori GB, Milanov V, Miller AC, Mitnick CD, Modongo C, Mohr E, Monedero I, Nahid P, Ndjeka N, O'Donnell MR, Padayatchi N, Palmero D, Pape JW, Podewils LJ, Reynolds I, Riekstina V, Robert J, Rodriguez M, Seaworth B, Seung KJ, Schnippel K, Shim TS, Singla R, Smith SE, Sotgiu G, Sukhbaatar G, Tabarsi P, Tiberi S, Trajman A, Trieu L, Udwadia ZF, van der Werf TS, Veziris N, Viiklepp P, Vilbrun SC, Walsh K, Westenhouse J, Yew WW, Yim JJ, Zetola NM, Zignol M, and Menzies D

Subjects
Amikacin therapeutic use, Antitubercular Agents administration & dosage, Capreomycin therapeutic use, Carbapenems therapeutic use, Clofazimine therapeutic use, Diarylquinolines therapeutic use, Drug Therapy, Combination, Fluoroquinolones therapeutic use, Humans, Kanamycin therapeutic use, Levofloxacin therapeutic use, Linezolid therapeutic use, Moxifloxacin, Recurrence, Treatment Failure, Antitubercular Agents therapeutic use, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Multidrug-Resistant mortality, Tuberculosis, Pulmonary drug therapy, Tuberculosis, Pulmonary mortality
Abstract

Background: Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis., Methods: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration., Findings: Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0·15, 95% CI 0·11 to 0·18), levofloxacin (0·15, 0·13 to 0·18), carbapenems (0·14, 0·06 to 0·21), moxifloxacin (0·11, 0·08 to 0·14), bedaquiline (0·10, 0·05 to 0·14), and clofazimine (0·06, 0·01 to 0·10). There was a significant association between reduced mortality and use of linezolid (-0·20, -0·23 to -0·16), levofloxacin (-0·06, -0·09 to -0·04), moxifloxacin (-0·07, -0·10 to -0·04), or bedaquiline (-0·14, -0·19 to -0·10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I 2 method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses., Interpretation: Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition., Funding: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Published
2018
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47. Safety and efficacy of exposure to bedaquiline-delamanid in multidrug-resistant tuberculosis: a case series from France and Latvia.

Author

Guglielmetti L, Barkane L, Le Dû D, Marigot-Outtandy D, Robert J, Veziris N, Yazdanpanah Y, Kuksa L, Caumes E, and Fréchet-Jachym M

Subjects
Adult, Antitubercular Agents adverse effects, Clinical Trials as Topic, Diarylquinolines adverse effects, Drug Administration Schedule, France, Humans, Latvia, Male, Nitroimidazoles adverse effects, Oxazoles adverse effects, Patient Safety, Treatment Outcome, Antitubercular Agents administration & dosage, Diarylquinolines administration & dosage, Nitroimidazoles administration & dosage, Oxazoles administration & dosage, Tuberculosis, Multidrug-Resistant drug therapy
Abstract

Competing Interests: Conflict of interest: L. Guglielmetti belonged to a research team that received research grants from Janssen Pharmaceuticals, outside the submitted work. Conflict of interest: L. Barkane was sub-investigator in the delamanid trial 213 and presented the Latvian experience with delamanid in the ERS congress 2016. Conflict of interest: J. Robert belonged to a research team that received research grants from Janssen Pharmaceuticals, outside the submitted work. Conflict of interest: N. Veziris received financial support for attending the 48th Union World Conference on Lung Health from Otsuka, outside the submitted work. Conflict of interest: Y. Yazdanpanah has been a board member receiving consultancy fees from ABBVIE, BMS, Gilead, MSD, J&J, Pfizer and ViiV Healthcare until November 2016. Conflict of interest: L. Kuksa was an investigator in the delamanid trials 204, 208 and 213 and presented Latvia experience with the compound at the launching conference in Korea.

Published
2018
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48. Final treatment outcomes of multidrug- and extensively drug-resistant tuberculosis patients in Latvia receiving delamanid-containing regimens.

Author

Kuksa L, Barkane L, Hittel N, and Gupta R

Subjects
Adolescent, Adult, Aged, Child, Female, Humans, Latvia, Male, Middle Aged, Mycobacterium tuberculosis drug effects, Retrospective Studies, Treatment Outcome, Young Adult, Antitubercular Agents therapeutic use, Extensively Drug-Resistant Tuberculosis drug therapy, Nitroimidazoles therapeutic use, Oxazoles therapeutic use, Tuberculosis, Multidrug-Resistant drug therapy
Abstract

Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com

Published
2017
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49. Decreased Time to Treatment Initiation for Multidrug-Resistant Tuberculosis Patients after Use of Xpert MTB/RIF Test, Latvia.

Author

Stagg HR, White PJ, Riekstiņa V, Cīrule A, Šķenders Ģ, Leimane V, Kuksa L, Dravniece G, Brown J, and Jackson C

Subjects
Adolescent, Adult, Antibiotics, Antitubercular pharmacology, Drug Resistance, Microbial, Female, Humans, Latvia, Male, Middle Aged, Rifampin pharmacology, Young Adult, Mycobacterium tuberculosis drug effects, Time-to-Treatment, Tuberculin Test methods, Tuberculosis, Multidrug-Resistant diagnosis, Tuberculosis, Multidrug-Resistant drug therapy
Abstract

Few studies have examined whether the Xpert MTB/RIF test improves time to treatment initiation for persons with multidrug-resistant tuberculosis (MDR TB). We determined the impact of this test in Latvia, where it was introduced in 2010. After descriptive analyses of pulmonary MDR TB patients in Latvia during 2009-2012, time to treatment initiation was calculated, and univariate and multivariable accelerated failure time models were constructed. Univariate results showed strong evidence of an association between having rifampin-resistant TB detected by Xpert MTB/RIF and reduced time to treatment initiation versus the test not being used. A multivariable model stratifying by previous TB showed similar results. Our finding that in Latvia, time to treatment initiation was decreased for MDR TB cases that were rifampin-resistant TB by XpertMTB/RIF has implications for the use of this test in other settings with a high burden of MDR TB in which rifampin resistance is highly predictive of MDR TB.

Published
2016
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50. Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance.

Author

Cegielski JP, Kurbatova E, van der Walt M, Brand J, Ershova J, Tupasi T, Caoili JC, Dalton T, Contreras C, Yagui M, Bayona J, Kvasnovsky C, Leimane V, Kuksa L, Chen MP, Via LE, Hwang SH, Wolfgang M, Volchenkov GV, Somova T, Smith SE, Akksilp S, Wattanaamornkiet W, Kim HJ, Kim CK, Kazennyy BY, Khorosheva T, Kliiman K, Viiklepp P, Jou R, Huang AS, Vasilyeva IA, Demikhova OV, Lancaster J, Odendaal R, Diem L, Perez TC, Gler T, Tan K, Bonilla C, Jave O, Asencios L, Yale G, Suarez C, Walker AT, Norvaisha I, Skenders G, Sture I, Riekstina V, Cirule A, Sigman E, Cho SN, Cai Y, Eum S, Lee J, Park S, Jeon D, Shamputa IC, Metchock B, Kuznetsova T, Akksilp R, Sitti W, Inyapong J, Kiryanova EV, Degtyareva I, Nemtsova ES, Levina K, Danilovits M, Kummik T, Lei YC, Huang WL, Erokhin VV, Chernousova LN, Andreevskaya SN, Larionova EE, and Smirnova TG

Subjects
Adolescent, Adult, Aged, Drug Resistance, Multiple, Bacterial, Female, Humans, Male, Middle Aged, Mycobacterium tuberculosis isolation & purification, Prospective Studies, Sputum microbiology, Treatment Outcome, Young Adult, Antitubercular Agents therapeutic use, Mycobacterium tuberculosis drug effects, Tuberculosis, Multidrug-Resistant drug therapy
Abstract

Background: Resistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined., Methods: Patients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectable drugs (SLIs) and (2) treatment regimens., Results: Of 1244 patients with MDR tuberculosis, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR tuberculosis, 69.7% with initial resistance to either a fluoroquinolone or an SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial and 13.0% with acquired extensively drug-resistant tuberculosis (P < .001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of drugs proven effective increased from ≤1 to ≥5 (P < .001 for trend), while acquired drug resistance decreased from 12% to 16% range, depending on the drug, down to 0%-2% (P < .001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (95% confidence interval, .56-.69) for each increment in drug resistance and increased 2.1-fold (1.40-3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient, and program variables were also associated with treatment outcome., Conclusions: Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance., (Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Published
2016
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