Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB treatment–2017, Ahmad Nafees, Ahuja Shama D, Akkerman Onno W, Alffenaar Jan-Willem C, Anderson Laura F, Baghaei Parvaneh, Bang Didi, Barry Pennan M, Bastos Mayara L, Behera Digamber, Benedetti Andrea, Bisson Gregory P, Boeree Martin J, Bonnet Maryline, Brode Sarah K, Brust James C M, Cai Ying, Caumes Eric, Cegielski J Peter, Centis Rosella, Chan Pei-Chun, Chan Edward D, Chang Kwok-Chiu, Charles Macarthur, Cirule Andra, Dalcolmo Margareth Pretti, D'Ambrosio Lia, de Vries Gerard, Dheda Keertan, Esmail Aliasgar, Flood Jennifer, Fox Gregory J, Fréchet-Jachym Mathilde, Fregona Geisa, Gayoso Regina, Gegia Medea, Gler Maria Tarcela, Gu Sue, Guglielmetti Lorenzo, Holtz Timothy H, Hughes Jennifer, Isaakidis Petros, Jarlsberg Leah, Kempker Russell R, Keshavjee Salmaan, Khan Faiz Ahmad, Kipiani Maia, Koenig Serena P, Koh Won-Jung, Kritski Afranio, Kuksa Liga, Kvasnovsky Charlotte L, Kwak Nakwon, Lan Zhiyi, Lange Christoph, Laniado-Laborín Rafael, Lee Myungsun, Leimane Vaira, Leung Chi-Chiu, Leung Eric Chung-Ching, Li Pei Zhi, Lowenthal Phil, Maciel Ethel L, Marks Suzanne M, Mase Sundari, Mbuagbaw Lawrence, Migliori Giovanni B, Milanov Vladimir, Miller Ann C, Mitnick Carole D, Modongo Chawangwa, Mohr Erika, Monedero Ignacio, Nahid Payam, Ndjeka Norbert, O'Donnell Max R, Padayatchi Nesri, Palmero Domingo, Pape Jean William, Podewils Laura J, Reynolds Ian, Riekstina Vija, Robert Jérôme, Rodriguez Maria, Seaworth Barbara, Seung Kwonjune J, Schnippel Kathryn, Shim Tae Sun, Singla Rupak, Smith Sarah E, Sotgiu Giovanni, Sukhbaatar Ganzaya, Tabarsi Payam, Tiberi Simon, Trajman Anete, Trieu Lisa, Udwadia Zarir F, van der Werf Tjip S, Veziris Nicolas, Viiklepp Piret, Vilbrun Stalz Charles, Walsh Kathleen, Westenhouse Janice, Yew Wing-Wai, Yim Jae-Joon, Zetola Nicola M, Zignol Matteo, Menzies Dick
Аннотация
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 I2 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.