25 results on '"Danilovits, M."'
Search Results
2. Resistance to second-line injectables and treatment outcomes in multidrug-resistant and extensively drug-resistant tuberculosis cases
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Migliori, G. B., Lange, C., Centis, R., Sotgiu, G., Mutterlein, R., Hoffmann, H., Kliiman, K., De Iaco, G., Lauria, F. N., Richardson, M. D., Spanevello, A., Cirillo, D. M., Ortmann, J., Kirsten, D., Ruesch Gerdes, S., Piana, F., Gori, A., Codecasa, L. R., Ferrarese, M., Toungoussova, O. S., Ferrara, Giovanni, Matteelli, A., De Lorenzo, S., Troupioti, P., Besozzi, G., Fattorini, L., Iona, E., Gualano, A., De Mori, P., Bevilacqua, N., Girardi, E., Danilovits, M., Hollo, V., and Mariandyshev, A.
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Estonia ,Pulmonary and Respiratory Medicine ,Drug ,medicine.medical_specialty ,Tuberculosis ,Settore MED/17 - Malattie Infettive ,Capreomycin ,FLUOROQUINOLONES ,Extensively Drug-Resistant Tuberculosis ,media_common.quotation_subject ,Drug Resistance ,Antitubercular Agents ,Drug resistance ,Injections ,Russia ,Mycobacterium tuberculosis ,Multidrug-resistant tuberculosis ,Drug Resistance, Multiple, Bacterial ,Germany ,Internal medicine ,tuberculosis MYCOBACTERIUM-TUBERCULOSIS ,Humans ,Medicine ,Registries ,Treatment Failure ,XDR-TB ,media_common ,biology ,business.industry ,Bacterial ,Extensively drug-resistant tuberculosis ,Odds ratio ,biology.organism_classification ,medicine.disease ,Survival Analysis ,Injectable second-line drugs ,Injections, Intravenous ,Italy ,Surgery ,Multiple drug resistance ,drug resistance, extensively drug-resistant tuberculosis, injectable second-line drugs, multidrug-resistant tuberculosis, tuberculosis MYCOBACTERIUM-TUBERCULOSIS, XDR-TB, FLUOROQUINOLONES ,Intravenous ,business ,Multiple ,medicine.drug - Abstract
No information is currently available on the influence of injectable second-line drugs on treatment outcomes of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) patients. To investigate this issue, a large series of MDR- and XDR-TB cases diagnosed in Estonia, Germany, Italy and the Russian Federation (Archangels Oblast) between 1999 and 2006 were analysed. All study sites performed drug susceptibility testing for first- and second-line anti-TB drugs, laboratory quality assurance and treatment delivery according to World Health Organization recommendations. Out of 4,583 culture-confirmed cases, 240 MDR- and 48 XDR-TB cases had a definitive outcome recorded (treatment success, death, failure). Among MDR- and XDR-TB cases, capreomycin resistance yielded a higher proportion of failure and death than capreomycin-susceptible cases. Resistance to capreomycin was independently associated with unfavourable outcome (logistic regression analysis: odds ratio 3.51). In the treatment of patients with multidrug-resistant and extensively drug-resistant tuberculosis, resistance to the injectable drug capreomycin was an independent predictor for therapy failure in this cohort. As Mycobacterium tuberculosis drug resistance is increasing worldwide, there is an urgent need for novel interventions in the fight against tuberculosis.
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- 2008
3. Treatment Outcomes in Multidrug-Resistant Tuberculosis
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Gunther, G., Lange, C., Alexandru, S., Altet, N., Avsar, K., Bang, D., Barbuta, R., Bothamley, G., Ciobanu, A., Crudu, V., Danilovits, M., Dedicoat, M., Duarte, R., Gualano, G., Kunst, H., Lange, W. de, Leimane, V., Magis-Escurra Ibanez, C., McLaughlin, A.M., Muylle, I., Polcova, V., Popa, C, Rumetshofer, R., Skrahina, A., Solodovnikova, V., Spinu, V., Tiberi, S., Viiklepp, P., Leth, F. van, Gunther, G., Lange, C., Alexandru, S., Altet, N., Avsar, K., Bang, D., Barbuta, R., Bothamley, G., Ciobanu, A., Crudu, V., Danilovits, M., Dedicoat, M., Duarte, R., Gualano, G., Kunst, H., Lange, W. de, Leimane, V., Magis-Escurra Ibanez, C., McLaughlin, A.M., Muylle, I., Polcova, V., Popa, C, Rumetshofer, R., Skrahina, A., Solodovnikova, V., Spinu, V., Tiberi, S., Viiklepp, P., and Leth, F. van
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Item does not contain fulltext
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- 2016
4. Tuberculosis elimination: theory and practice in Europe
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D'Ambrosio, L., Dara, M., Tadolini, M., Centis, R., Sotgiu, G., Van Der Werf, M. J., Gaga, M., Cirillo, D., Spanevello, Antonio, Raviglione, M., Blasi, F., Migliori, G. B., Hafizi, H., Wanlin, M., Oñate, W. A., Groenen, G., Janković, V. K., Šimunović, A., Wallenfels, J., Voniatis, C., Andersen, P. H., Viiklepp, P., Danilovits, M., Kummik, T., Ruutu, P., Comolet, T. M., Haas, W., Korr, G., Rüsch Gerdes, S., Bauer, T., Hauer, B., Brodhun, B., Papavenstsis, K., Papadima, S., Pusztai, Z., O'Donnell, J., Chemtob, D., Girardi, E., Mehmeti, R., Riekstina, V., Asciak, A. P., Arnesen, T. M., Augustynowicz Kopeć, E., Korzeniewska Kosela, M., Miskiewicz, P. M., Miecznikowska, D., Duarte, R., Correia, A. M., Diniz, A. M. S. C., Talevski, S., Zakoska, M., Popescu, G., Chiotan, D., Asic, . R. J., Solovic, I., Ivanuša, M., Košnik, M., Valín, E. R., Anchuela, O. T., Jonsson, J., Helbling, P., Zellweger, J. P., De Vries, G., Erkens, C., Anderson, L., Laurenson, I., European National Programme Representatives, D'Ambrosio, Lia, Dara, Masoud, Tadolini, Marina, Centis, Rosella, Sotgiu, Giovanni, Van Der Werf, Marieke J., Gaga, Mina, Cirillo, Daniela, Spanevello, Antonio, Raviglione, Mario, Blasi, Francesco, Migliori, Giovanni Battista, Hafizi, Hasan, Wanlin, Maryse, Oñate, Wouter Arrazolade, Groenen, Guido, Janković, Vera Katalinić, Šimunović, Aleksandar, Wallenfels, Jiri, Voniatis, Constantia, Andersen, Peter Henrik, Viiklepp, Piret, Danilovits, Manfred, Kummik, Tiina, Ruutu, Petri, Comolet, Thierry M., Haas, Walter, Korr, Gerit, Rüsch-Gerdes, Sabine, Bauer, Torsten, Hauer, Barbara, Brodhun, Bonita, Papavenstsis, Konstantinou, Papadima, Spala, Pusztai, Zsofia, O'Donnell, Joan, Chemtob, Daniel, Girardi, Enrico, Mehmeti, Rukije, Riekstina, Vija, Asciak, Analita Pace, Arnesen, Trude M., Augustynowicz-Kopeć, Ewa, Korzeniewska-Kosela, Maria, Miskiewicz, Paulina Marianna, Miecznikowska, Dominika, Duarte, Raquel, Correia, Ana Maria, Diniz, Antonio Manuel S.C., Talevski, Stefan, Zakoska, Maja, Popescu, Gilda, Chiotan, Domnica, Asic, Gordana Radosavl Jevic, Solovic, Ivan, Ivanuša, Marijan, Košnik, Mitja, Valín, Elena Rodríguez, Anchuela, Odorina Tello, Jonsson, Jerker, Helbling, Peter, Zellweger, Jean Pierre, De Vries, Gerard, Erkens, Connie, Anderson, Laura, and Laurenson, Ian
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Pulmonary and Respiratory Medicine ,tuberculosis eradication ,Tuberculosis ,Tuberculosi ,International Cooperation ,Population ,HIV Infections ,World Health Organization ,World health ,Health services ,Environmental health ,Surveys and Questionnaires ,medicine ,Surveys and Questionnaire ,Humans ,HIV Infection ,Disease Eradication ,education ,tuberculosis control ,education.field_of_study ,Infectious Disease Medicine ,Group screening ,business.industry ,Incidence (epidemiology) ,Incidence ,Monitoring and evaluation ,medicine.disease ,Drug Resistance, Multiple ,Europe ,Treatment Outcome ,Preparedness ,Communicable Disease Control ,Practice Guidelines as Topic ,Health Services Research ,business ,Human - Abstract
Although Europe identified the pathway to tuberculosis (TB) elimination in 1990, no information on programmes for country preparedness is available. A questionnaire investigating TB elimination activities was submitted to 38 national TB programme representatives of low TB incidence (
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- 2014
5. Extensively drug-resistant tuberculosis is worse than multidrug-resistant tuberculosis: different methodology and settings, same results
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Migliori, G. B., Lange, C., Girardi, E., Centis, R., Besozzi, G., Kliiman, K., Ortmann, J., Matteelli, A., Spanevello, A., Cirillo, D. M., Kirsten, D., Codecasa, L. R., Gori, A., De Lorenzo, S., Troupioti, P., De Iaco, G., Gualano, G., De Mori, P., Fattorini, L., Iona, E., Ferrara, G., Sotgiu, G., Danilovits, M., Hollo, V., Mariandyshev, A., and Toungoussova, O.
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Microbiology (medical) ,medicine.medical_specialty ,Tuberculosis ,Extensively Drug-Resistant Tuberculosis ,Treatment outcome ,MEDLINE ,Antitubercular Agents ,Drug Resistance ,Drug resistance ,Microbial Sensitivity Tests ,Treatment failure ,Mycobacterium tuberculosis ,Internal medicine ,medicine ,Humans ,Treatment Failure ,biology ,business.industry ,Bacterial ,Extensively drug-resistant tuberculosis ,Multidrug-Resistant ,medicine.disease ,biology.organism_classification ,Multiple drug resistance ,Infectious Diseases ,Treatment Outcome ,Regression Analysis ,Drug Resistance, Multiple, Bacterial ,Tuberculosis, Multidrug-Resistant ,business ,Multiple - Published
- 2008
6. Clinical and operational value of the extensively drug-resistant tuberculosis definition
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Migliori, G. B., Besozzi, G., Girardi, E., Kliiman, K., Lange, C., Toungoussova, O. S., Ferrara, G., Cirillo, D. M., Gori, A., Matteelli, A., Spanevello, A., Codecasa, L. R., Raviglione, M. C., Ortmann, J., Kirsten, D., Ruesch-Gerdes, S., Piana, F., Ferrarese, M., De Iaco, G., De Lorenzo, S., Troupioti, P., Fattorini, L., Iona, E., Gualano, A., De Mori, P., Centis, R., Danilovits, M., Hollo, V., and Mariandyshev, A.
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Pulmonary and Respiratory Medicine ,Risk ,medicine.medical_specialty ,Tuberculosis ,Time Factors ,medicine.medical_treatment ,Extensively Drug-Resistant Tuberculosis ,Antitubercular Agents ,Drug Resistance ,Drug resistance ,Global Health ,Communicable Diseases ,Russia ,Multidrug-resistant tuberculosis ,Isoniazid ,Medicine ,tuberculosis MYCOBACTERIUM-TUBERCULOSIS ,Humans ,Clinical value ,Extensively drug-resistant tuberculosis ,Drug Resistance, Multiple ,Population Surveillance ,Public Health ,Rifampin ,Treatment Outcome ,Intensive care medicine ,Ethambutol ,business.industry ,Pyrazinamide ,medicine.disease ,Surgery ,clinical value, drug resistance, extensively drug-resistant tuberculosis, multidrug-resistant tuberculosis, tuberculosis MYCOBACTERIUM-TUBERCULOSIS ,Tuberculosis management ,business ,Multiple ,Rifampicin ,medicine.drug - Abstract
Currently, no information is available on the effect of resistance/susceptibility to first-line drugs different from isoniazid and rifampicin in determining the outcome of extensively drug-resistant tuberculosis (XDR-TB) patients, and whether being XDR-TB is a more accurate indicator of poor clinical outcome than being resistant to all first-line anti-tuberculosis (TB) drugs. To investigate this issue, a large series of multidrug-resistant TB (MDR-TB) and XDR-TB cases diagnosed in Estonia, Germany, Italy and the Russian Federation during the period 1999-2006 were analysed. Drug-susceptibility testing for first- and second-line anti-TB drugs, quality assurance and treatment delivery was performed according to World Health Organization recommendations in all study sites. Out of 4,583 culture-positive TB cases analysed, 361 (7.9%) were MDR and 64 (1.4%) were XDR. XDR-TB cases had a relative risk (RR) of 1.58 to have an unfavourable outcome compared with MDR-TB cases resistant to all first-line drugs (isoniazid, rifampicin ethambutol, streptomycin and, when tested, pyrazinamide), and an RR of 2.61 compared with "other" MDR-TB cases (those susceptible to at least one first-line anti-TB drug among ethambutol, pyrazinamide and streptomycin, regardless of resistance to the second-line drugs not defining XDR-TB). The emergence of extensively drug-resistant tuberculosis confirms that problems in tuberculosis management are still present in Europe. While waiting for new tools which will facilitate management of extensively drug-resistant tuberculosis, accessibility to quality diagnostic and treatment services should be urgently ensured and adequate public health policies should be rapidly implemented to prevent further development of drug resistance.
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- 2007
7. European Union Standards for Tuberculosis Care
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Migliori, G.B., primary, Zellweger, J.P., additional, Abubakar, I., additional, Ibraim, E., additional, Caminero, J.A., additional, De Vries, G., additional, D'Ambrosio, L., additional, Centis, R., additional, Sotgiu, G., additional, Menegale, O., additional, Kliiman, K., additional, Aksamit, T., additional, Cirillo, D.M., additional, Danilovits, M., additional, Dara, M., additional, Dheda, K., additional, Dinh-Xuan, A.T., additional, Kluge, H., additional, Lange, C., additional, Leimane, V., additional, Loddenkemper, R., additional, Nicod, L.P., additional, Raviglione, M.C., additional, Spanevello, A., additional, Thomsen, V.Ø., additional, Villar, M., additional, Wanlin, M., additional, Wedzicha, J.A., additional, Zumla, A., additional, Blasi, F., additional, Huitric, E., additional, Sandgren, A., additional, and Manissero, D., additional
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- 2012
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8. A prioritised research agenda for DOTS-Plus for multidrug-resistant tuberculosis (MDR-TB)
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Beggs, A., Laing, R., Preger, J., Castro, K., Cegielski, J. P., Luca, N., Laserson, K., Walton, W., Wells, C., Erokhin, V., Mishin, V., Vassilieva, I., Karataev, O. N., Drobniewski, F., Brander, L., Katila, M. -L, Malakhov, I., Safonova, S., Sheyanenko, O., Starchenkova, N., Farmer, P., Hiatt, H., Kim, J., Mukherjee, J., Murray, M., Becerra, M., Nardell, E., Palmero, D. J., Bonilla, C., Solovic, I., Mahmud, A. M., Rahman, A., Melnyk, V. M., Portaels, F., Creach, P., Billo, N., Repina, E., Rakhishev, G., Pechiorina, I., Squire, S. B., Coker, R., Arora, V. K., Sloutsky, A., Timperi, R., Henkens, M., Lafontaine, D., Slavuckij, A., Vezhnina, N., Cullinan, T., Healing, T., Weyer, K., Heifets, L., Iseman, M., Lee, D. -H, Park, S. -K, Chaulet, P., Zúñiga Gajardo, M., Mata, Z., Danilovits, M., Vink, K., Khechinashvili, G., Louissant, M., Ismailov, S., Kibuga, D., Leimane, V., Davidaviciene, E., Ferreira, E., Macarthur, A., Bam, D. S., Alarcón, E., Pedro G Suarez, Rodriguez Marco, J., Reichmann, L. B., Salfinger, M., Hasler, T., Ovreberg, K., Ringdal, T., Bayona García, J., Barry, D., Castro, A., Mitnick, C., Rich, M., Seung, K., Livchane, E., Passetchnikov, A., Ponomarenko, O., Trusov, A., Mariandyshev, A., Strelis, A. K., Lambregts-Van Weezenbeek, C., Perelmann, M. I., Borstchevsky, V., Törün, T., Hoffner, S., Sillastu, H., Barid, S., Hinman, A., Rosenberg, M. L., Schieffelbein, C., Arnadottir, T., Peremitin, G., Tonkel, T., Tupasi, T., Lechuga Perez, H., Burgos, M., Jurkuvenas, V., Kimerling, M., Hopewell, P., Bacheller, S., Bloom, A., St Antoine, J. -J, Tayler, Y., Weil, D., Aziz, M., Ramon Cruz, J., Espinal, M., Figueroa, R., Gupta, R., Lee, J. -W, Ottmani, S. -E, Raviglione, M., Seita, A., Smith, I., Zaleskis, R., and Cho, S. -N
9. Delamanid for multidrug-resistant pulmonary tuberculosis.
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Gler MT, Skripconoka V, Sanchez-Garavito E, Xiao H, Cabrera-Rivero JL, Vargas-Vasquez DE, Gao M, Awad M, Park SK, Shim TS, Suh GY, Danilovits M, Ogata H, Kurve A, Chang J, Suzuki K, Tupasi T, Koh WJ, Seaworth B, and Geiter LJ
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- 2012
10. Real-life use of delamanid: results from the European post-authorisation safety study.
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Schönfeld N, Barkane L, Davoliene I, Danilovits M, Miliauskas S, Ader F, Kon OM, Lange C, Duvignaud A, Heiss-Neumann M, Hittel N, Lazarević N, Knebel I, Martin A, Eschenbach B, van Heumen E, and George V
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Background: A post-authorisation safety study (PASS) on delamanid (DLM) was conducted as part of a post-approval commitment to the European Medicines Agency. The aim of this study was to evaluate the use of DLM in a real-life setting, its safety, and treatment outcomes in patients with multidrug-resistant TB (MDR-TB)., Methods: This was a prospective, multicentric, non-interventional study conducted in the European Union. MDR-TB Regimen selection and patient monitoring were conducted in accordance with existing medical practices. Data on the use of DLM, related adverse events, and treatment outcomes were collected for up to 30 months after the first DLM dose. Descriptive summary statistics were used for continuous and categorical variables., Results: Out of 86 patients, one had extrapulmonary TB. Two-thirds of the patients were treated with DLM for more than 24 weeks. The most frequent adverse drug reaction to DLM was QT interval prolongation. Resistance to DLM was detected in one patient during treatment. The treatment success rate was 77%., Conclusion: No new safety concerns were revealed, including in patients treated with DLM for more than 24 weeks. QT interval prolongations were well managed and did not lead to any clinically significant cardiac effects. The treatment outcomes were in line with the WHO target for Europe., Competing Interests: Conflicts of interest: NS, LB, ID, MD, SM, FA, OMK, CL, AD, and MHN are participating physicians of this study; sponsored by Otsuka Novel Products, Munich, Germany. NH, NL and AM are employees of Otsuka Novel Products. IK is a paid consultant to Otsuka Novel Products. BE and EvH. are employees of Otsuka Pharma, Frankfurt, Germany. VG is an employee of Otsuka Pharmaceutical Development and Commercialization, Princeton, NJ, USA., (© 2024 The Authors.)
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- 2024
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11. Efficacy and safety of delamanid in combination with an optimised background regimen for treatment of multidrug-resistant tuberculosis: a multicentre, randomised, double-blind, placebo-controlled, parallel group phase 3 trial.
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von Groote-Bidlingmaier F, Patientia R, Sanchez E, Balanag V Jr, Ticona E, Segura P, Cadena E, Yu C, Cirule A, Lizarbe V, Davidaviciene E, Domente L, Variava E, Caoili J, Danilovits M, Bielskiene V, Staples S, Hittel N, Petersen C, Wells C, Hafkin J, Geiter LJ, and Gupta R
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- Antitubercular Agents administration & dosage, Antitubercular Agents adverse effects, Double-Blind Method, Drug Administration Schedule, Drug Monitoring methods, Drug Therapy, Combination methods, Female, Humans, Male, Middle Aged, Treatment Outcome, Isoniazid administration & dosage, Isoniazid adverse effects, Nitroimidazoles administration & dosage, Nitroimidazoles adverse effects, Oxazoles administration & dosage, Oxazoles adverse effects, Rifampin administration & dosage, Rifampin adverse effects, Sputum microbiology, Tuberculosis, Multidrug-Resistant diagnosis, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Multidrug-Resistant microbiology, Tuberculosis, Pulmonary diagnosis, Tuberculosis, Pulmonary drug therapy, Tuberculosis, Pulmonary microbiology
- Abstract
Background: Delamanid is one of two recently approved drugs for the treatment of multidrug-resistant tuberculosis. We aimed to evaluate the safety and efficacy of delamanid in the first 6 months of treatment., Methods: This randomised, double-blind, placebo-controlled, phase 3 trial was done at 17 sites in seven countries (Estonia, Latvia, Lithuania, Moldova, Peru, the Philippines, and South Africa). We enrolled eligible adults (>18 years) with pulmonary multidrug-resistant tuberculosis to receive, in combination with an optimised background regimen developed according to WHO and national guidelines, either oral delamanid (100 mg twice daily) for 2 months followed by 200 mg once daily for 4 months or placebo (same regimen). Patients were centrally randomised (2:1) and stratified by risk category for delayed sputum culture conversion. Primary outcomes were the time to sputum culture conversion over 6 months and the difference in the distribution of time to sputum culture conversion over 6 months between the two groups, as assessed in the modified intention-to-treat population. The trial is registered at ClinicalTrials.gov, number NCT01424670., Findings: Between Sept 2, 2011, and Nov 27, 2013, we screened 714 patients, of whom 511 were randomly assigned (341 to delamanid plus optimised background regimen [delamanid group] and 170 to placebo plus optimised background regimen [placebo group]) and formed the safety analysis population. 327 patients were culture-positive for multidrug-resistant tuberculosis at baseline and comprised the efficacy analysis population (226 in the delamanid group and 101 in the placebo group). Median time to sputum culture conversion did not differ between the two groups (p=0·0562; modified Peto-Peto), with 51 days (IQR 29-98) in the delamanid group and 57 days (43-85) in the placebo group; the hazard ratio was 1·17 (95% CI 0·91-1·51, p=0·2157). 501 (98·0%) of 511 patients had at least one treatment-emergent adverse event. 136 (26·6%) of 511 patients had at least one serious treatment-emergent adverse event; the incidence was similar between treatment groups (89 [26·1%] of 341 patients for delamanid and 47 [27·6%] of 170 for placebo). Deaths related to treatment-emergent adverse events were similar between groups (15 [4·4%] of 341 for delamanid and six [3·5%] of 170 for placebo). No deaths were considered to be related to delamanid., Interpretation: The reduction in median time to sputum culture conversion over 6 months was not significant in the primary analysis. Delamanid was well tolerated with a highly characterised safety profile. Further evaluation of delamanid is needed to determine its role in a rapidly evolving standard of care., Funding: Otsuka Pharmaceutical., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
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- 2019
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12. Clinical Management of Multidrug-Resistant Tuberculosis in 16 European Countries.
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Günther G, van Leth F, Alexandru S, Altet N, Avsar K, Bang D, Barbuta R, Bothamley G, Ciobanu A, Crudu V, Danilovits M, Dedicoat M, Duarte R, Gualano G, Kunst H, de Lange W, Leimane V, McLaughlin AM, Magis-Escurra C, Muylle I, Polcová V, Popa C, Rumetshofer R, Skrahina A, Solodovnikova V, Spinu V, Tiberi S, Viiklepp P, and Lange C
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- Cohort Studies, Europe epidemiology, Humans, Incidence, Prospective Studies, Treatment Outcome, Antitubercular Agents therapeutic use, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Multidrug-Resistant epidemiology
- Abstract
Rationale: Multidrug-resistant tuberculosis (MDR-TB) is a major burden to public health in Europe. Reported treatment success rates are around 50% or less, and cure rates are even lower., Objectives: To document the management and treatment outcome in patients with MDR-TB in Europe., Methods: We performed a prospective cohort study, analyzing management and treatment outcomes stratified by incidence of patients with MDR-TB in Europe. Treatment outcomes were compared by World Health Organization and alternative simplified definitions by the Tuberculosis Network European Trialsgroup (TBNET)., Measurements and Main Results: A total of 380 patients with MDR-TB were recruited and followed up between 2010 and 2014 in 16 European countries. Patients in high-incidence countries compared with low-incidence countries were treated more frequently with standardized regimen (83.2% vs. 9.9%), had delayed treatment initiation (median, 111 vs. 28 d), developed more additional drug resistance (23% vs. 5.8%), and had increased mortality (9.4% vs. 1.9%). Only 20.1% of patients using pyrazinamide had proven susceptibility to the drug. Applying World Health Organization outcome definitions, frequency of cure (38.7% vs. 9.7%) was higher in high-incidence countries. Simplified outcome definitions that include 1 year of follow-up after the end of treatment showed similar frequency of relapse-free cure in low- (58.3%), intermediate- (55.8%), and high-incidence (57.1%) countries, but highest frequency of failure in high-incidence countries (24.1% vs. 14.6%)., Conclusions: Conventional standard MDR-TB treatment regimens resulted in a higher frequency of failure compared with individualized treatments. Overall, cure from MDR-TB is substantially more frequent than previously anticipated, and poorly reflected by World Health Organization outcome definitions.
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- 2018
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13. Multidrug-resistant TB in Eastern region of the EU: is the shorter regimen an exception or a rule?
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Balabanova Y, Fiebig L, Ignatyeva O, Riekstina V, Danilovits M, Jaama K, Davidaviciene E, Radiulyte B, Popa CM, Nikolayevskyy V, and Drobniewski F
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- Adult, Drug Administration Schedule, Drug Resistance, Multiple, Bacterial, Drug Therapy, Combination, Europe, Eastern, Female, Humans, Male, Middle Aged, Antitubercular Agents administration & dosage, Tuberculosis, Multidrug-Resistant drug therapy
- Abstract
WHO recently recommended the use of a shorter multidrug-resistant TB (MDR-TB) regimen under programmatic conditions. We assessed eligibility for this regimen in a cohort of 737 adult patients with MDR-TB from Latvia, Lithuania, Estonia and Bucharest city recruited in 2007 and 2009. Only 4.2% of the patients were eligible for this regimen. Ethambutol (64%), pyrazinamide resistance (58%) and previous exposure to second-line TB drugs were major reasons for non-eligibility. High-level resistance to isoniazid is expected due to widespread prevalence of katG mutations. In Eastern Europe, the use of the shorter regimen might be an exception rather than a rule., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)
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- 2017
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14. Treatment Outcomes in Multidrug-Resistant Tuberculosis.
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Günther G, Lange C, Alexandru S, Altet N, Avsar K, Bang D, Barbuta R, Bothamley G, Ciobanu A, Crudu V, Danilovits M, Dedicoat M, Duarte R, Gualano G, Kunst H, de Lange W, Leimane V, Magis-Escurra C, McLaughlin AM, Muylle I, Polcová V, Popa C, Rumetshofer R, Skrahina A, Solodovnikova V, Spinu V, Tiberi S, Viiklepp P, and van Leth F
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- Humans, Mycobacterium tuberculosis isolation & purification, Treatment Outcome, World Health Organization, Outcome Assessment, Health Care methods, Tuberculosis, Multidrug-Resistant drug therapy
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- 2016
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15. Safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in adults with tuberculosis: A phase II randomised study.
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Gillard P, Yang PC, Danilovits M, Su WJ, Cheng SL, Pehme L, Bollaerts A, Jongert E, Moris P, Ofori-Anyinam O, Demoitié MA, and Castro M
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- Adolescent, Adult, Antibodies, Bacterial biosynthesis, CD4-Positive T-Lymphocytes immunology, Erythema etiology, Female, Humans, Immunity, Cellular immunology, Male, Middle Aged, Mycobacterium tuberculosis immunology, Pain etiology, Single-Blind Method, Young Adult, Tuberculosis immunology, Tuberculosis Vaccines adverse effects, Tuberculosis Vaccines immunology
- Abstract
Previous studies have shown that the M72/AS01E candidate tuberculosis vaccine is immunogenic with a clinically acceptable safety profile in healthy and Mycobacterium tuberculosis-infected adults. This phase II, observer-blind, randomised study compared the safety, reactogenicity, and immunogenicity of M72/AS01E in 3 cohorts: tuberculosis-naïve adults (n = 80), adults previously treated for tuberculosis (n = 49), and adults who have completed the intensive phase of tuberculosis treatment (n = 13). In each cohort, 18-59-year-old adults were randomised (1:1) to receive two doses of M72/AS01E (n = 71) or placebo (n = 71) and followed-up until six months post-dose 2. Safety and reactogenicity were assessed as primary objective. Recruitment in the study ended prematurely because of a high incidence of large injection site redness/swelling reactions in M72/AS01E-vaccinated adults undergoing tuberculosis treatment. No additional clinically relevant adverse events were observed, except one possibly vaccine-related serious adverse event (hypersensitivity in a tuberculosis-treated-M72/AS01E participant). Robust and persistent M72-specific humoral and polyfunctional CD4(+) T-cell-mediated immune responses were observed post-M72/AS01E vaccination in each cohort. In conclusion, the M72/AS01E vaccine was immunogenic in adults previously or currently treated for tuberculosis, but further analyses are needed to explain the high local reactogenicity in adults undergoing tuberculosis treatment. ClinicalTrials.gov: NCT01424501., (Copyright © 2016 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.)
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- 2016
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16. Survival of patients with multidrug-resistant TB in Eastern Europe: what makes a difference?
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Balabanova Y, Ignatyeva O, Fiebig L, Riekstina V, Danilovits M, Jaama K, Davidaviciene E, Radiulyte B, Popa CM, Nikolayevskyy V, and Drobniewski F
- Subjects
- Adolescent, Adult, Antitubercular Agents therapeutic use, Drug Resistance, Multiple, Bacterial, Drug Therapy, Combination, Europe, Eastern epidemiology, Extensively Drug-Resistant Tuberculosis drug therapy, Extensively Drug-Resistant Tuberculosis mortality, Female, Humans, Male, Middle Aged, Prospective Studies, Risk Factors, Survival Analysis, Tuberculosis, Multidrug-Resistant drug therapy, Young Adult, Tuberculosis, Multidrug-Resistant mortality, Tuberculosis, Pulmonary mortality
- Abstract
Background: The quality of care for patients with TB in Eastern Europe has improved significantly; nevertheless drug resistance rates remain high. We analysed survival in a cohort of patients with multidrug-resistant and extensively drug-resistant (MDR-/XDR-) TB from Latvia, Lithuania, Estonia and Bucharest city., Methods: Consecutive adult new and retreatment patients with culture-confirmed pulmonary MDR-TB registered for treatment in 2009 (and in 2007 in Latvia) were enrolled; prospective survival information was collected., Results: A total of 737 patients were included into the cohort. Of all MDR-TB cases, 46% were newly diagnosed; 56% of all MDR-TB cases had no additional resistance to fluoroquinolones or injectable agents, 33% had pre-XDR-TB and 11% XDR-TB. Median survival was 5.9 years in patients with MDR-TB and XDR-TB; 1.9 years in patients coinfected with HIV. Older age, male gender, alcohol abuse, retirement, co-morbidities, extrapulmonary involvement and HIV coinfection independently worsened survival. Inclusion of fluoroquinolones and injectable agents improves survival in patients with MDR-TB. Pre-XDR and XDR status did not significantly shorten survival as long as fluoroquinolones and injectable agents were part of the regimen. Moxifloxacin seems to improve survival in ofloxacin-susceptible patients when compared with older generation fluoroquinolones., Conclusions: The burden of additional resistances in patients with MDR-TB is high likely due to primary transmission of resistant strains. Social and programmatic factors including management of alcohol dependency, expansion of HIV testing and antiretroviral treatment need to be addressed in order to achieve cure and to interrupt transmission. The role of last generation fluoroquinolones and injectable agents in treatment of patients with pre-XDR and XDR-TB needs to be further investigated., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)
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- 2016
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17. Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance.
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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.)
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- 2016
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18. Building clinical trial capacity to develop a new treatment for multidrug-resistant tuberculosis.
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Tupasi T, Gupta R, Danilovits M, Cirule A, Sanchez-Garavito E, Xiao H, Cabrera-Rivero JL, Vargas-Vasquez DE, Gao M, Awad M, Gentry LM, Geiter LJ, and Wells CD
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- Capacity Building standards, Clinical Protocols, Documentation, Drug Approval, Humans, Antitubercular Agents therapeutic use, Capacity Building organization & administration, International Cooperation, Nitroimidazoles therapeutic use, Oxazoles therapeutic use, Research Design, Tuberculosis, Multidrug-Resistant drug therapy
- Abstract
Problem: New drugs for infectious diseases often need to be evaluated in low-resource settings. While people working in such settings often provide high-quality care and perform operational research activities, they generally have less experience in conducting clinical trials designed for drug approval by stringent regulatory authorities., Approach: We carried out a capacity-building programme during a multi-centre randomized controlled trial of delamanid, a new drug for the treatment of multidrug-resistant tuberculosis. The programme included: (i) site identification and needs assessment; (ii) achieving International Conference on Harmonization - Good Clinical Practice (ICH-GCP) standards; (iii) establishing trial management; and (iv) increasing knowledge of global and local regulatory issues., Local Setting: Trials were conducted at 17 sites in nine countries (China, Egypt, Estonia, Japan, Latvia, Peru, the Philippines, the Republic of Korea and the United States of America). Eight of the 10 sites in low-resource settings had no experience in conducting the requisite clinical trials., Relevant Changes: Extensive capacity-building was done in all 10 sites. The programme resulted in improved local capacity in key areas such as trial design, data safety and monitoring, trial conduct and laboratory services., Lessons Learnt: Clinical trials designed to generate data for regulatory approval require additional efforts beyond traditional research-capacity strengthening. Such capacity-building approaches provide an opportunity for product development partnerships to improve health systems beyond the direct conduct of the specific trial.
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- 2016
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19. Bedaquiline in the treatment of multidrug- and extensively drug-resistant tuberculosis.
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Pym AS, Diacon AH, Tang SJ, Conradie F, Danilovits M, Chuchottaworn C, Vasilyeva I, Andries K, Bakare N, De Marez T, Haxaire-Theeuwes M, Lounis N, Meyvisch P, Van Baelen B, van Heeswijk RP, and Dannemann B
- Subjects
- Adolescent, Adult, Aged, Female, Humans, Male, Middle Aged, Treatment Outcome, Tuberculosis, Multidrug-Resistant drug therapy, Young Adult, Antitubercular Agents therapeutic use, Diarylquinolines therapeutic use, Extensively Drug-Resistant Tuberculosis drug therapy
- Abstract
Bedaquiline, a diarylquinoline, improved cure rates when added to a multidrug-resistant tuberculosis (MDR-TB) treatment regimen in a previous placebo-controlled, phase 2 trial (TMC207-C208; NCT00449644). The current phase 2, multicenter, open-label, single-arm trial (TMC207-C209; NCT00910871) reported here was conducted to confirm the safety and efficacy of bedaquiline.Newly diagnosed or previously treated patients with MDR-TB (including pre-extensively drug-resistant (pre-XDR)-TB or extensively drug-resistant (XDR)-TB) received bedaquiline for 24 weeks with a background regimen of anti-TB drugs continued according to National TB Programme treatment guidelines. Patients were assessed during and up to 120 weeks after starting bedaquiline.Of 233 enrolled patients, 63.5% had MDR-TB, 18.9% had pre-XDR-TB and 16.3% had XDR-TB, with 87.1% having taken second-line drugs prior to enrolment. 16 patients (6.9%) died. 20 patients (8.6%) discontinued before week 24, most commonly due to adverse events or MDR-TB-related events. Adverse events were generally those commonly associated with MDR-TB treatment. In the efficacy population (n=205), culture conversion (missing outcome classified as failure) was 72.2% at 120 weeks, and 73.1%, 70.5% and 62.2% in MDR-TB, pre-XDR-TB and XDR-TB patients, respectively.Addition of bedaquiline to a background regimen was well tolerated and led to good outcomes in this clinically relevant patient cohort with MDR-TB., (Copyright ©ERS 2016.)
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- 2016
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20. Resistance profile and risk factors of drug resistant tuberculosis in the Baltic countries.
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Ignatyeva O, Balabanova Y, Nikolayevskyy V, Koshkarova E, Radiulyte B, Davidaviciene E, Riekstina V, Jaama K, Danilovits M, Popa CM, and Drobniewski FA
- Subjects
- Adult, Baltic States epidemiology, Comorbidity, Extensively Drug-Resistant Tuberculosis diagnosis, Extensively Drug-Resistant Tuberculosis microbiology, Female, Humans, Male, Middle Aged, Mycobacterium tuberculosis isolation & purification, Mycobacterium tuberculosis pathogenicity, Retrospective Studies, Risk Factors, Socioeconomic Factors, Treatment Failure, Tuberculosis, Multidrug-Resistant diagnosis, Tuberculosis, Multidrug-Resistant microbiology, Antitubercular Agents therapeutic use, Drug Resistance, Multiple, Bacterial, Extensively Drug-Resistant Tuberculosis drug therapy, Extensively Drug-Resistant Tuberculosis epidemiology, Mycobacterium tuberculosis drug effects, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Multidrug-Resistant epidemiology
- Abstract
The rates of multi- and extensively drug-resistant tuberculosis (X/MDRTB) in the Baltic countries are the highest within the European Union hampering recent achievements of national TB control programmes. We included all consecutive culture-confirmed X/MDRTB patients registered for treatment in 2009 in Latvia, Lithuania and Estonia into this multicenter case-control study. Cases were compared with randomly selected controls with non-MDRTB registered for treatment in the same year across these sites. Of 495 MDRTB patients, 243 (49.7%) showed resistance to at least one second-line drug, 206 (42.1%) had pre-XDRTB (i.e. MDRTB with additional resistance to a second-line injectable or fluoroquinolones) and 64 (13.1%) had XDRTB. Younger age, male gender and known contact with an MDRTB case were associated with increased risk of primary infection with X/MDRTB strains. Previous treatment and alcohol abuse were strong predictors for MDRTB acquisition; defaults and failures in the past triggered XDRTB development. All patients received appropriate therapy; less than half of the patients were fully adherent. An erroneous treatment strategy is unlikely to drive resistance development. Increasing patients' compliance, addressing issues of social support, rapid detection of drug resistance and improving infection control is crucial for prevention of further spread of X/MDRTB and achieving higher cure rates., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
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- 2015
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21. Sputum culture conversion as a prognostic marker for end-of-treatment outcome in patients with multidrug-resistant tuberculosis: a secondary analysis of data from two observational cohort studies.
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Kurbatova EV, Cegielski JP, Lienhardt C, Akksilp R, Bayona J, Becerra MC, Caoili J, Contreras C, Dalton T, Danilovits M, Demikhova OV, Ershova J, Gammino VM, Gelmanova I, Heilig CM, Jou R, Kazennyy B, Keshavjee S, Kim HJ, Kliiman K, Kvasnovsky C, Leimane V, Mitnick CD, Quelapio I, Riekstina V, Smith SE, Tupasi T, van der Walt M, Vasilyeva IA, Via LE, Viiklepp P, Volchenkov G, Walker AT, Wolfgang M, Yagui M, and Zignol M
- Subjects
- Adolescent, Adult, Aged, Humans, Middle Aged, Mycobacterium tuberculosis isolation & purification, Prospective Studies, Treatment Outcome, Young Adult, Sputum microbiology, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Pulmonary drug therapy
- Abstract
Background: Sputum culture conversion is often used as an early microbiological endpoint in phase 2 clinical trials of tuberculosis treatment on the basis of its assumed predictive value for end-of-treatment outcome, particularly in patients with drug-susceptible tuberculosis. We aimed to assess the validity of sputum culture conversion on solid media at varying timepoints, and the time to conversion, as prognostic markers for end-of-treatment outcome in patients with multidrug-resistant (MDR) tuberculosis., Methods: We analysed data from two large cohort studies of patients with MDR tuberculosis. We defined sputum culture conversion as two or more consecutive negative cultures from sputum samples obtained at least 30 days apart. To estimate the association of 2 month and 6 month conversion with successful treatment outcome, we calculated odds ratios (ORs) and 95% CIs with random-effects multivariable logistic regression. We calculated predictive values with bivariate random-effects generalised linear mixed modelling., Findings: We assessed data for 1712 patients who had treatment success, treatment failure, or who died. Among patients with treatment success, median time to sputum culture conversion was significantly shorter than in those who had poor outcomes (2 months [IQR 1-3] vs 7 months [3 to ≥24]; log-rank p<0·0001). Furthermore, conversion status at 6 months (adjusted OR 14·07 [95% CI 10·05-19·71]) was significantly associated with treatment success compared with failure or death. Sputum culture conversion status at 2 months was significantly associated with treatment success only in patients who were HIV negative (adjusted OR 4·12 [95% CI 2·25-7·54]) or who had unknown HIV infection (3·59 [1·96-6·58]), but not in those who were HIV positive (0·38 [0·12-1·18]). Thus, the overall association of sputum culture conversion with a successful outcome was substantially greater at 6 months than at 2 months. 2 month conversion had low sensitivity (27·3% [95% confidence limit 16·6-41·4]) and high specificity (89·8% [82·3-94·4]) for prediction of treatment success. Conversely, 6 month sputum culture conversion status had high sensitivity (91·8% [85·9-95·4]), but moderate specificity (57·8% [42·5-71·6]). The maximum combined sensitivity and specificity for sputum culture conversion was reached between month 6 and month 10 of treatment., Interpretation: Time to sputum culture conversion, conversion status at 6 months, and conversion status at 2 months in patients without known HIV infection can be considered as proxy markers of end-of-treatment outcome in patients with MDR tuberculosis, although the overall association with treatment success is substantially stronger for 6 month than for 2 month conversion status. Investigators should consider these results regarding the validity of sputum culture conversion at various timepoints as an early predictor of treatment efficacy when designing phase 2 studies before investing substantial resources in large, long-term, phase 3 trials of new treatments for MDR tuberculosis., Funding: US Agency for International Development, US Centers for Disease Control and Prevention, Division of Intramural Research of the US National Institute of Allergy and Infectious Diseases, Korea Centers for Disease Control and Prevention., (Copyright © 2015 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2015
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22. Delamanid improves outcomes and reduces mortality in multidrug-resistant tuberculosis.
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Skripconoka V, Danilovits M, Pehme L, Tomson T, Skenders G, Kummik T, Cirule A, Leimane V, Kurve A, Levina K, Geiter LJ, Manissero D, and Wells CD
- Subjects
- Adolescent, Adult, Drug Administration Schedule, Extensively Drug-Resistant Tuberculosis mortality, Female, Follow-Up Studies, Humans, Male, Middle Aged, Randomized Controlled Trials as Topic, Treatment Outcome, Tuberculosis, Multidrug-Resistant mortality, Young Adult, Antitubercular Agents therapeutic use, Extensively Drug-Resistant Tuberculosis drug therapy, Nitroimidazoles therapeutic use, Oxazoles therapeutic use, Tuberculosis, Multidrug-Resistant drug therapy
- Abstract
Multidrug-resistant and extensively drug-resistant tuberculosis (TB) are associated with worse treatment outcomes for patients, including higher mortality, than for drug-sensitive tuberculosis. Delamanid (OPC-67683) is a novel anti-TB medication with demonstrated activity against multidrug-resistant disease. Patients who participated in the previously reported randomised, placebo-controlled trial of delamanid and the subsequent open-label extension trial were eligible to participate in a 24-month observational study designed to capture treatment outcomes. Treatment outcomes, as assessed by clinicians and defined by the World Health Organization, were categorised as favourable and unfavourable. Delamanid treatment groups were combined for analysis, based on their duration of treatment. In total, for 421 (87.5%) out of 481 patients from the original randomised controlled trial, consent was granted for follow-up assessments. Favourable outcomes were observed in 143 (74.5%) out of 192 patients who received delamanid for ≥6 months, compared to 126 (55%) out of 229 patients who received delamanid for ≤2 months. Mortality was reduced to 1.0% among those receiving long-term delamanid versus short-term/no delamanid (8.3%; p<0.001). Treatment benefit was also seen among patients with extensively drug-resistant TB. This analysis suggests that treatment with delamanid for 6 months in combination with an optimised background regimen can improve outcomes and reduce mortality among patients with both multidrug-resistant and extensively drug-resistant TB.
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- 2013
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23. Cost and cost-effectiveness of multidrug-resistant tuberculosis treatment in Estonia and Russia.
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Floyd K, Hutubessy R, Kliiman K, Centis R, Khurieva N, Jakobowiak W, Danilovits M, Peremitin G, Keshavjee S, and Migliori GB
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- Adolescent, Adult, Antitubercular Agents therapeutic use, Cohort Studies, Cost-Benefit Analysis, Estonia, Female, Humans, Male, Middle Aged, Quality-Adjusted Life Years, Russia, Treatment Outcome, Tuberculosis, Multidrug-Resistant drug therapy, World Health Organization, Young Adult, Antitubercular Agents economics, Health Care Costs, Tuberculosis, Multidrug-Resistant economics
- Abstract
Evidence on the cost and cost-effectiveness of treatment of multidrug-resistant tuberculosis (MDR-TB) is limited, and no published data are available from former Soviet Union countries, where rates of MDR-TB are highest globally. We evaluated the cost and cost-effectiveness of MDR-TB treatment in Estonia and Russia (Tomsk Oblast), comparing cohorts enrolled on treatment according to World Health Organization (WHO) guidelines in 2001 and 2002 with cohorts treated in previous years. Costs were assessed from a health system perspective in 2003 US$; effects were measured as cures, deaths averted and disability-adjusted life-years (DALYs) averted. Cure rates when WHO guidelines were followed were 61% (90 out of 149) in Estonia and 76% (76 out of 100) in Tomsk Oblast, with a cost per patient treated of US$8,974 and US$10,088, respectively. Before WHO guidelines were followed, cure rates were 52% in Estonia and 15% in Tomsk Oblast; the cost per patient treated was US$4,729 and US$2,282, respectively. Drugs and hospitalisation accounted for 69-90% of total costs. The cost per DALY averted by treatment following WHO guidelines was US$579 (range US$297-US$902) in Estonia and US$429 (range US$302-US$546) in Tomsk Oblast. Treatment of patients with MDR-TB can be cost-effective, but requires substantial additional investment in tuberculosis control in priority countries.
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- 2012
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24. Multidrug-resistant tuberculosis management in resource-limited settings.
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Nathanson E, Lambregts-van Weezenbeek C, Rich ML, Gupta R, Bayona J, Blöndal K, Caminero JA, Cegielski JP, Danilovits M, Espinal MA, Hollo V, Jaramillo E, Leimane V, Mitnick CD, Mukherjee JS, Nunn P, Pasechnikov A, Tupasi T, Wells C, and Raviglione MC
- Subjects
- Communicable Disease Control methods, Drug Administration Schedule, Estonia epidemiology, Humans, Latvia epidemiology, Peru epidemiology, Philippines epidemiology, Program Evaluation, Russia epidemiology, Treatment Outcome, Tuberculosis, Multidrug-Resistant microbiology, Antitubercular Agents administration & dosage, Antitubercular Agents therapeutic use, Developing Countries, Government Programs, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Multidrug-Resistant prevention & control
- Abstract
Evidence of successful management of multidrug-resistant tuberculosis (MDRTB) is mainly generated from referral hospitals in high-income countries. We evaluate the management of MDRTB in 5 resource-limited countries: Estonia, Latvia, Peru, the Philippines, and the Russian Federation. All projects were approved by the Green Light Committee for access to quality-assured second-line drugs provided at reduced price for MDRTB management. Of 1047 MDRTB patients evaluated, 119 (11%) were new, and 928 (89%) had received treatment previously. More than 50% of previously treated patients had received both first- and second-line drugs, and 65% of all patients had infections that were resistant to both first- and second-line drugs. Treatment was successful in 70% of all patients, but success rate was higher among new (77%) than among previously treated patients (69%). In resource-limited settings, treatment of MDRTB provided through, or in collaboration with, national TB programs can yield results similar to those from wealthier settings.
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- 2006
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25. Spread of drug-resistant pulmonary tuberculosis in Estonia.
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Krüüner A, Hoffner SE, Sillastu H, Danilovits M, Levina K, Svenson SB, Ghebremichael S, Koivula T, and Källenius G
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- Adult, Bacterial Typing Techniques, Estonia epidemiology, Female, Humans, Male, Microbial Sensitivity Tests, Mycobacterium tuberculosis classification, Mycobacterium tuberculosis genetics, Mycobacterium tuberculosis isolation & purification, Oligonucleotides analysis, Tuberculosis, Multidrug-Resistant epidemiology, Tuberculosis, Multidrug-Resistant microbiology, Tuberculosis, Pulmonary epidemiology, Tuberculosis, Pulmonary microbiology, Antitubercular Agents pharmacology, DNA Transposable Elements genetics, Mycobacterium tuberculosis drug effects, Polymorphism, Restriction Fragment Length, Tuberculosis, Multidrug-Resistant transmission, Tuberculosis, Pulmonary transmission
- Abstract
Restriction fragment length polymorphism (RFLP) analysis of 209 Mycobacterium tuberculosis clinical isolates obtained from newly detected pulmonary tuberculosis patients (151 male and 58 female; mean age, 41 years) in Estonia during 1994 showed that 61 isolates (29%) belonged to a genetically closely related group of isolates, family A, with a predominant IS6110 banding pattern. These strains shared the majority of their IS6110 DNA-containing restriction fragments, representing a predominant banding pattern (similarity, >65%). This family A comprised 12 clusters of identical isolates, and the largest cluster comprised 10 strains. The majority (87.5%) of all multidrug-resistant (MDR) isolates, 67.2% of all isolates with any drug resistance, but only 12% of the fully susceptible isolates of M. tuberculosis belonged to family A. These strains were confirmed by spoligotyping as members of the Beijing genotype family. The spread of Beijing genotype MDR M. tuberculosis strains was also frequently seen in 1997 to 1999. The members of this homogenous group of drug-resistant M. tuberculosis strains have contributed substantially to the continual emergence of drug-resistant tuberculosis all over Estonia.
- Published
- 2001
- Full Text
- View/download PDF
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