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Eur Respir J. 2025;66(2):13993003.00315-2025.

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

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제1저자 곽낙원, 김중엽 · 교신저자 임재준

PMID 40675768 PMC12371315 DOI 10.1183/13993003.00315-2025 IF 23.8 호흡기내과
소속 (22)
  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.

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.

Copyright ©The authors 2025.

Figures

FIGURE 1
FIGURE 1 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) individual patient data (IPD) flow diagram. TB: tuberculosis.
FIGURE 2
FIGURE 2 Cumulative incidence function plot for treatment success.

그림 출처: PubMed Central 공개 논문 (PMC12371315)

Comment · 정정

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.

그 밖의 정보
출판 형태
Journal Article, Meta-Analysis, Systematic Review
저널
The European respiratory journal · eISSN 1399-3003
전자 출판
2025-08-22
MeSH
Humans · Linezolid* / administration & dosage · Tuberculosis, Multidrug-Resistant* / drug therapy · Rifampin / pharmacology / therapeutic use · Antitubercular Agents* / administration & dosage · Randomized Controlled Trials as Topic · Treatment Outcome · Dose-Response Relationship, Drug
Substances
Linezolid · Rifampin · Antitubercular Agents
참고문헌
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