Meta-Analysis

. 2025 Aug 22;66(2):2500315.

doi: 10.1183/13993003.00315-2025. Print 2025 Aug.

Optimal dosing and duration of linezolid for the treatment of multidrug-resistant and rifampicin-resistant tuberculosis: an individual patient data meta-analysis

Nakwon Kwak^{1

2}, Joong-Yub Kim^{1

3

2}, Areum Han^{4

5}, Catherine Berry⁶, Maria Beumont⁷, Conor Tweed⁸, Angela Crook⁸, Keertan Dheda^{9

10}, Stella Fabiane⁸, Muse O Fadeyi¹¹, Salah Foraida⁷, Tinne Gils^{12

13}, Thi Thanh Thuy Hoang¹⁴, Menal A Jham¹⁵, Richard A Murphy¹⁶, Binh Hoa Nguyen¹⁴, Thi Mai Phuong Nguyen¹⁴, Bern Thomas Nyang'wa^{17

18}, Suzette Oelofse¹⁰, Seokyung Hahn^{19

20

21}, Jae-Joon Yim²²

Affiliations

¹ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
² N. Kwak and J-Y. Kim contributed equally.
³ Department of Microbiology, Harvard Medical School, Boston, MA, USA.
⁴ Interdisciplinary Program of Medical Informatics, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁵ Integrated Major in Innovative Medical Science, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁶ Médecins Sans Frontières, London, UK.
⁷ TB Alliance, New York, NY, USA.
⁸ MRC Clinical Trials Unit, University College London, London, UK.
⁹ Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
¹⁰ Centre for Lung Infection and Immunity, University of Cape Town, Cape Town, South Africa.
¹¹ Damien Foundation Belgium (Nigeria Project), Ibadan, Nigeria.
¹² Unit of HIV and Coinfections, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
¹³ Global Health Institute, University of Antwerp, Wilrijk, Belgium.
¹⁴ National Lung Hospital, Hanoi, Vietnam.
¹⁵ UMMA Community Clinic, Los Angeles, CA, USA.
¹⁶ Division of Infectious Diseases, Dartmouth Geisel School of Medicine, Hanover, NH, USA.
¹⁷ Médecins Sans Frontières, Amsterdam, The Netherlands.
¹⁸ Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK.
¹⁹ Medical Bigdata Research Center, Medical Research Center, Seoul National University, Seoul, Republic of Korea.
²⁰ Institute of Health Policy and Management, Medical Research Center, Seoul National University, Seoul, South Korea.
²¹ Department of Human Systems Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
²² Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea yimjj@snu.ac.kr.

PMID: 40675768
PMCID: PMC12371315
DOI: 10.1183/13993003.00315-2025

Meta-Analysis

Optimal dosing and duration of linezolid for the treatment of multidrug-resistant and rifampicin-resistant tuberculosis: an individual patient data meta-analysis

Nakwon Kwak et al. Eur Respir J. 2025.

. 2025 Aug 22;66(2):2500315.

doi: 10.1183/13993003.00315-2025. Print 2025 Aug.

Authors

Affiliations

¹ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
² N. Kwak and J-Y. Kim contributed equally.
³ Department of Microbiology, Harvard Medical School, Boston, MA, USA.
⁴ Interdisciplinary Program of Medical Informatics, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁵ Integrated Major in Innovative Medical Science, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁶ Médecins Sans Frontières, London, UK.
⁷ TB Alliance, New York, NY, USA.
⁸ MRC Clinical Trials Unit, University College London, London, UK.
⁹ Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
¹⁰ Centre for Lung Infection and Immunity, University of Cape Town, Cape Town, South Africa.
¹¹ Damien Foundation Belgium (Nigeria Project), Ibadan, Nigeria.
¹² Unit of HIV and Coinfections, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
¹³ Global Health Institute, University of Antwerp, Wilrijk, Belgium.
¹⁴ National Lung Hospital, Hanoi, Vietnam.
¹⁵ UMMA Community Clinic, Los Angeles, CA, USA.
¹⁶ Division of Infectious Diseases, Dartmouth Geisel School of Medicine, Hanover, NH, USA.
¹⁷ Médecins Sans Frontières, Amsterdam, The Netherlands.
¹⁸ Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK.
¹⁹ Medical Bigdata Research Center, Medical Research Center, Seoul National University, Seoul, Republic of Korea.
²⁰ Institute of Health Policy and Management, Medical Research Center, Seoul National University, Seoul, South Korea.
²¹ Department of Human Systems Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
²² Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea yimjj@snu.ac.kr.

PMID: 40675768
PMCID: PMC12371315
DOI: 10.1183/13993003.00315-2025

Abstract

Background: The optimal dosing strategy of linezolid for treating multidrug-resistant and rifampicin-resistant tuberculosis remains unclear. We conducted an individual patient data meta-analysis to determine the optimal linezolid dosing strategy.

Methods: We searched for randomised controlled trials and prospective cohort studies on short-course all‑oral regimens containing linezolid for treating multidrug-resistant and rifampicin-resistant tuberculosis in PubMed, Embase and Scopus up to 31 August 2023. Patients were grouped according to linezolid dosing patterns. Time to treatment success and adverse events of grade 3 and higher were analysed using the Fine-Gray sub-distribution hazard model.

Results: Of 12 eligible studies, eight (four randomised controlled trials, four prospective studies) were included. Overall, 945 patients were grouped as follows: group 1 (600 mg·day^-1 linezolid for 8 weeks), group 2 (600 mg·day^-1 for 16 weeks, then 300 mg·day^-1 for 8 weeks), group 3 (600 mg·day^-1 for 39 weeks) and group 4 (1200 mg·day^-1 for 25 weeks). Proportions of patients achieving treatment success were 59.1%, 90.4%, 91.3% and 96.0%, respectively. Compared with group 2, group 1 (adjusted sub-distribution hazard ratio (SHR) 0.24, 95% CI 0.08-0.71) and group 3 (adjusted SHR 0.36, 95% CI 0.16-0.81) had lower success rates. While group 4 showed no significant difference in treatment success versus group 2 (adjusted SHR 0.57, 95% CI 0.23-1.43), it had a higher rate of adverse events of grade 3 and higher (adjusted SHR 2.29, 95% CI 1.37-3.83).

Conclusion: A dosing strategy of 600 mg·day^-1 linezolid for 16 weeks then 300 mg·day^-1 for 8 weeks could be optimal for treating multidrug-resistant and rifampicin-resistant tuberculosis when considering effectiveness and safety.

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Conflict of interest statement

Conflict of interest: M. Beumont and S. Foraida are employees of TB Alliance. R.A. Murphy reports payment for expert testimony and support for attending meetings from the University of Nevada. J-J. Yim has participated or is currently participating as the overall or institutional principal investigator in multiple clinical trials sponsored by Insmed Incorporated, AN2 Therapeutics and LigaChem Biosciences Inc. The remaining authors have no potential conflicts of interest to disclose.

Figures

**FIGURE 1**
Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) individual patient data (IPD) flow diagram. TB: tuberculosis.

**FIGURE 2**
Cumulative incidence function plot for treatment success.

See this image and copyright information in PMC

Comment in

Linezolid for the treatment of drug-resistant tuberculosis.
Lange C, Barry C 3rd, Sotgiu G. Lange C, et al. Eur Respir J. 2025 Aug 22;66(2):2500927. doi: 10.1183/13993003.00927-2025. Print 2025 Aug. Eur Respir J. 2025. PMID: 40846488 No abstract available.

References

1. World Health Organization . Global Tuberculosis Report 2024. Geneva, World Health Organization, 2024.
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1. Conradie F, Bagdasaryan TR, Borisov S, et al. Bedaquiline–pretomanid–linezolid regimens for drug-resistant tuberculosis. N Engl J Med 2022; 387: 810–823. doi: 10.1056/NEJMoa2119430 - DOI - PMC - PubMed
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Optimal dosing and duration of linezolid for the treatment of multidrug-resistant and rifampicin-resistant tuberculosis: an individual patient data meta-analysis

Affiliations

Optimal dosing and duration of linezolid for the treatment of multidrug-resistant and rifampicin-resistant tuberculosis: an individual patient data meta-analysis

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

References

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MeSH terms

Substances

LinkOut - more resources

Full Text Sources