Evidence map›Paper›PMID 36053506›Full record

Trial reportThe New England journal of medicine2022

Bedaquiline-Pretomanid-Linezolid Regimens for Drug-Resistant Tuberculosis.

Francesca Conradie, Tatevik R Bagdasaryan, Sergey Borisov, Pauline Howell, Lali Mikiashvili, Nosipho Ngubane, Anastasia Samoilova, Sergey Skornykova, Elena Tudor, Ebrahim Variava and 19 more

4 registry-linked trialsOpen access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 317 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
317citing papers in PubMed, 8 pooled it
49.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03086486 phase3completednot on this map

A Phase 3 Partially-blinded, Randomized Trial Assessing the Safety and Efficacy of Various Doses and Treatment Durations of Linezolid Plus Bedaquiline and Pretomanid in Participants With Pulmonary Infection of Either Extensively Drug-resistant Tuberculosis (XDR-TB), Pre-XDR-TB or Treatment Intolerant or Non-responsive Multi-drug Resistant Tuberculosis (MDR-TB)

TypeinterventionalSponsorGlobal Alliance for TB Drug DevelopmentRan2017 to 2022Enrolled181ConditionsTuberculosis, Pulmonary, Tuberculosis, Multidrug-Resistant, Tuberculosis, MDR, TuberculosisArmsPretomanid, Linezolid, Bedaquiline, Placebo Linezolid
NCT06590428 narecruitingnot on this mapstarted 2026, after this paper: background citation

Therapeutic Drug Monitoring for Linezolid in the Treatment of Rifampin-resistant Tuberculosis

TypeinterventionalSponsorAlbert Einstein College of MedicineRan2026 to 2029Enrolled280ConditionsRifampin-resistant Tuberculosis, Drug-resistant TuberculosisArmsTherapeutic Drug Monitoring for Linezolid
NCT06905522 phase3recruitingnot on this mapstarted 2025, after this paper: background citation

A Pan-Ultrashort Regimen for Drug-susceptible and Drug-resistant Pulmonary Tuberculosis: A Multi-Center Randomized Controlled Trial

TypeinterventionalSponsorShenzhen Third People's HospitalRan2025 to 2029Enrolled610ConditionsPulmonary TuberculosisArmsBedaquiline (B), Sitafloxacin (S), Linezolid (L), Pyrazinamide (Z), Isoniazid (H)
NCT07477119 phase4recruitingnot on this mapstarted 2026, after this paper: background citation

Tolérance du Linézolide Pendant le Régime BPaL Avec Personnalisation de la Posologie Basée Sur la Surveillance Thérapeutique Des Médicaments (TDM) au Cours du Traitement de la Tuberculose Multirésistante

TypeinterventionalSponsorMarco SchiumaRan2026 to 2028Enrolled150ConditionsLinezolid, Tuberculosis Multi Drug Resistant Active, Therapeutic Drug Monitoring (TDM)ArmsLinezolid dose personalization based on TDM
3 · Its place in the literature

Who cites it

317 citing papers in PubMed, 8 syntheses or guidelines pooled it, 528 citations in OpenAlex.

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  6. Bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) for multidrug- or rifampin-resistant tuberculosis: a systematic review.Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia · 2025
    Pooled it
  7. Bedaquiline and linezolid regimens for multidrug-resistant tuberculosis: a systematic review and meta-analysis.Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia · 2025
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257 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors at 9 institutions in 6 countries.

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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Tatevik 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Sergey BorisovFrom 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.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Pauline 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Lali 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Nosipho 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Anastasia 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Sergey 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Elena 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Ebrahim 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Petr YablonskiyFrom 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.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Daniel 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Genevieve 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Eugene 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Morounfolu 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Erica 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Mengchun 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Alda 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Juliano 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Anna BatesonFrom 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.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Angela 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Stella 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Robert 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Timothy 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.ORCID 0000-0003-4658-8594
Conor D TweedFrom 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.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.ORCID 0000-0001-6021-8237
Salah 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Carl 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., J.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
Melvin 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.T., S.F., C.M.M., M.S.); and the Medical Research Council Clinical Trials Unit at University College London (G.H.W., A.M.C., S.M.F., C.D.T.) and the University College London Centre for Clinical Microbiology (A.B., R.H., T.D.M.), University College London, London.
ZeNix Trial Team
TB Alliance · USPerinatal HIV Research Unit · ZAMRC Clinical Trials Unit at UCL · GBCity Clinical Hospital · RUNational Center for Tuberculosis and Lung Disease · GEPhthisiopneumology Institute "Chiril Draganiuc" · MDSaint-Petersburg Research Institute of Phthisiopulmonology · RUUniversity of the Witwatersrand · ZAUral research Institute of Phthisiopulmonology · RU

Funding

Emory-Georgia TB Research Training ProgramD43TW007124 · FIC · EMORY UNIVERSITY · PI HENRY M BLUMBERG, Nestani Tukvadze · 2004 to 2026
$4.6M
Bill and Melinda Gates Foundation OPP1129600FIC NIH HHS D43 TW007124Medical Research Council MC_UU_00004/04Medical Research Council MC_UU_12023/27
6 · The paper itself

Abstract

backgroundThe 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.

methodsWe 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.

resultsA 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.

conclusionsA 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.).

Indexed as

Antitubercular AgentsLinezolidNitroimidazolesTuberculosis, Multidrug-ResistantAminoglycosidesDiarylquinolinesFluoroquinolonesHumansRifampinRisk AssessmentTreatment OutcomeTuberculosisAminoglycosidesAntitubercular AgentsbedaquilineDiarylquinolinesFluoroquinolonesLinezolidNitroimidazolespretomanidRifampin

Identifiers

PMID36053506
PMCPMC9490302
OpenAlexW4293842430

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.