Bedaquiline–Pretomanid–Linezolid Regimens for Drug-Resistant Tuberculosis
Francesca ConradieFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JTatevik R. BagdasaryanFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JBorisov SeFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JPauline HowellFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JLali MikiashviliFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JNosipho NgubaneFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JAnastasia SamoilovaFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JSergey SkornykovaFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JElena TudorFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JEbrahim VariavaFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JP. K. YаblonskiyFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JDaniel E. EverittFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JGenevieve H. WillsFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JEugene SunFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JMorounfolu OlugbosiFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JErica EgiziFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JMengchun LiFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JAlda HolstaFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JJuliano TimmFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JMatthew BatesFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JAngela M. CrookFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JStella M. FabianeFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JRobert HuntFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JTimothy D. McHughFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JConor TweedMedical Research Council Clinical Trials Unit at University College London, University College London, LondonSalah ForaidaFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JCarl M. MendelFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., JMelvin SpigelmanFrom the Clinical HIV Research Unit (F.C., P.H.) and Klerksdorp–Tshepong Hospital Complex, Department of Internal Medicine (E.V.), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, the Clinical HIV Research Unit, King DinuZulu Hospital, Durban (N.N.), and the TB Alliance, Pretoria (M.O.) — all in South Africa; the Central TB Research Institute of the Federal Agency of Scientific Organizations Moscow (T.R.B.), Moscow City Research and Practice Tuberculosis Treatment Center (S.B.), and National Medical Research Center of Phthisiopulmonology and Infectious Diseases (A.S.), Moscow, Ural Research Institute of Phthisiopulmonology, Yekaterinburg (S.S.), and St. Petersburg Research Institute of Phthisiopulmonology, St. Petersburg (P.Y.) — all in Russia; the National Center for Tuberculosis and Lung Disease, Tbilisi, Georgia (L.M.); the Chiril Draganiuc Institute of Phthisiopneumology, Chisinau, Moldova (E.T.); the TB Alliance, New York (D.E., E.S., E.E., M.L., A.H., J
2022en
ABI
Annotatsiya
BACKGROUND: The bedaquiline-pretomanid-linezolid regimen has been reported to have 90% efficacy against highly drug-resistant tuberculosis, but the incidence of adverse events with 1200 mg of linezolid daily has been high. The appropriate dose of linezolid and duration of treatment with this agent to minimize toxic effects while maintaining efficacy against highly drug-resistant tuberculosis are unclear. METHODS: We enrolled participants with extensively drug-resistant (XDR) tuberculosis (i.e., resistant to rifampin, a fluoroquinolone, and an aminoglycoside), pre-XDR tuberculosis (i.e., resistant to rifampin and to either a fluoroquinolone or an aminoglycoside), or rifampin-resistant tuberculosis that was not responsive to treatment or for which a second-line regimen had been discontinued because of side effects. We randomly assigned the participants to receive bedaquiline for 26 weeks (200 mg daily for 8 weeks, then 100 mg daily for 18 weeks), pretomanid (200 mg daily for 26 weeks), and daily linezolid at a dose of 1200 mg for 26 weeks or 9 weeks or 600 mg for 26 weeks or 9 weeks. The primary end point in the modified intention-to-treat population was the incidence of an unfavorable outcome, defined as treatment failure or disease relapse (clinical or bacteriologic) at 26 weeks after completion of treatment. Safety was also evaluated. RESULTS: A total of 181 participants were enrolled, 88% of whom had XDR or pre-XDR tuberculosis. Among participants who received bedaquiline-pretomanid-linezolid with linezolid at a dose of 1200 mg for 26 weeks or 9 weeks or 600 mg for 26 weeks or 9 weeks, 93%, 89%, 91%, and 84%, respectively, had a favorable outcome; peripheral neuropathy occurred in 38%, 24%, 24%, and 13%, respectively; myelosuppression occurred in 22%, 15%, 2%, and 7%, respectively; and the linezolid dose was modified (i.e., interrupted, reduced, or discontinued) in 51%, 30%, 13%, and 13%, respectively. Optic neuropathy developed in 4 participants (9%) who had received linezolid at a dose of 1200 mg for 26 weeks; all the cases resolved. Six of the seven unfavorable microbiologic outcomes through 78 weeks of follow-up occurred in participants assigned to the 9-week linezolid groups. CONCLUSIONS: A total of 84 to 93% of the participants across all four bedaquiline-pretomanid-linezolid treatment groups had a favorable outcome. The overall risk-benefit ratio favored the group that received the three-drug regimen with linezolid at a dose of 600 mg for 26 weeks, with a lower incidence of adverse events reported and fewer linezolid dose modifications. (Funded by the TB Alliance and others; ZeNix ClinicalTrials.gov number, NCT03086486.).
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