Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Mar 20;3(3):CD012836.
doi: 10.1002/14651858.CD012836.pub2.

Linezolid for drug-resistant pulmonary tuberculosis

Bhagteshwar Singh  1 , Derek Cocker, Hannah Ryan, Derek J Sloan
Affiliations

Linezolid for drug-resistant pulmonary tuberculosis

Bhagteshwar Singh et al. Cochrane Database Syst Rev. .

Abstract

Background: Linezolid was recently re-classified as a Group A drug by the World Health Organization (WHO) for treatment of multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), suggesting that it should be included in the regimen for all patients unless contraindicated. Linezolid use carries a considerable risk of toxicity, with the optimal dose and duration remaining unclear. Current guidelines are mainly based on evidence from observational non-comparative studies.

Objectives: To assess the efficacy of linezolid when used as part of a second-line regimen for treating people with MDR and XDR pulmonary tuberculosis, and to assess the prevalence and severity of adverse events associated with linezolid use in this patient group.

Search methods: We searched the following databases: the Cochrane Infectious Diseases Specialized Register; CENTRAL; MEDLINE; Embase; and LILACS up to 13 July 2018. We also checked article reference lists and contacted researchers in the field.

Selection criteria: We included studies in which some participants received linezolid, and others did not. We included randomized controlled trials (RCTs) of linezolid for MDR and XDR pulmonary tuberculosis to evaluate efficacy outcomes. We added non-randomized cohort studies to evaluate adverse events.Primary outcomes were all-cause and tuberculosis-associated death, treatment failure, and cure. Secondary outcomes were treatment interrupted, treatment completed, and time to sputum culture conversion. We recorded frequency of all and serious adverse events, adverse events leading to drug discontinuation or dose reduction, and adverse events attributed to linezolid, particularly neuropathy, anaemia, and thrombocytopenia.

Data collection and analysis: Two review authors (BS and DC) independently assessed the search results for eligibility and extracted data from included studies. All review authors assessed risk of bias using the Cochrane 'Risk of bias' tool for RCTs and the ROBINS-I tool for non-randomized studies. We contacted study authors for clarification and additional data when necessary.We were unable to perform a meta-analysis as one of the RCTs adopted a study design where participants in the study group received linezolid immediately and participants in the control group received linezolid after two months, and therefore there were no comparable data from this trial. We deemed meta-analysis of non-randomized study data inappropriate.

Main results: We identified three RCTs for inclusion. One of these studies had serious problems with allocation of the study drug and placebo, so we could not analyse data for intervention effect from it. The remaining two RCTs recruited 104 participants. One randomized 65 participants to receive linezolid or not, in addition to a background regimen; the other randomized 39 participants to addition of linezolid to a background regimen immediately, or after a delay of two months. We included 14 non-randomized cohort studies (two prospective, 12 retrospective), with a total of 1678 participants.Settings varied in terms of income and tuberculosis burden. One RCT and 7 out of 14 non-randomized studies commenced recruitment in or after 2009. All RCT participants and 38.7% of non-randomized participants were reported to have XDR-TB.Dosing and duration of linezolid in studies were variable and reported inconsistently. Daily doses ranged from 300 mg to 1200 mg; some studies had planned dose reduction for all participants after a set time, others had incompletely reported dose reductions for some participants, and most did not report numbers of participants receiving each dose. Mean or median duration of linezolid therapy was longer than 90 days in eight of the 14 non-randomized cohorts that reported this information.Duration of participant follow-up varied between RCTs. Only five out of 14 non-randomized studies reported follow-up duration.Both RCTs were at low risk of reporting bias and unclear risk of selection bias. One RCT was at high risk of performance and detection bias, and low risk for attrition bias, for all outcomes. The other RCT was at low risk of detection and attrition bias for the primary outcome, with unclear risk of detection and attrition bias for non-primary outcomes, and unclear risk of performance bias for all outcomes. Overall risk of bias for the non-randomized studies was critical for three studies, and serious for the remaining 11.One RCT reported higher cure (risk ratio (RR) 2.36, 95% confidence interval (CI) 1.13 to 4.90, very low-certainty evidence), lower failure (RR 0.26, 95% CI 0.10 to 0.70, very low-certainty evidence), and higher sputum culture conversion at 24 months (RR 2.10, 95% CI 1.30 to 3.40, very low-certainty evidence), amongst the linezolid-treated group than controls, with no differences in other primary and secondary outcomes. This study also found more anaemia (17/33 versus 2/32), nausea and vomiting, and neuropathy (14/33 versus 1/32) events amongst linezolid-receiving participants. Linezolid was discontinued early and permanently in two of 33 (6.1%) participants who received it.The other RCT reported higher sputum culture conversion four months after randomization (RR 2.26, 95% CI 1.19 to 4.28), amongst the group who received linezolid immediately compared to the group who had linezolid initiation delayed by two months. Linezolid was discontinued early and permanently in seven of 39 (17.9%) participants who received it.Linezolid discontinuation occurred in 22.6% (141/624; 11 studies), of participants in the non-randomized studies. Total, serious, and linezolid-attributed adverse events could not be summarized quantitatively or comparatively, due to incompleteness of data on duration of follow-up and numbers of participants experiencing events.

Authors' conclusions: We found some evidence of efficacy of linezolid for drug-resistant pulmonary tuberculosis from RCTs in participants with XDR-TB but adverse events and discontinuation of linezolid were common. Overall, there is a lack of comparative data on efficacy and safety. Serious risk of bias and heterogeneity in conducting and reporting non-randomized studies makes the existing, mostly retrospective, data difficult to interpret. Further prospective cohort studies or RCTs in high tuberculosis burden low-income and lower-middle-income countries would be useful to inform policymakers and clinicians of the efficacy and safety of linezolid as a component of drug-resistant TB treatment regimens.

PubMed Disclaimer

Conflict of interest statement

BS is a Clinical Research Fellow for the NIHR Global Health Research Group on Brain Infections at the University of Liverpool, and also works at the Royal Liverpool University Hospital, UK, and has no known conflicts of interest.

HR works at the Royal Liverpool University Hospital, UK, and has no known conflicts of interest.

DC is a PhD candidate supported by a Wellcome Trust Clinical Training Fellowship, based at the Liverpool School of Tropical Medicine, UK, and has no known conflicts of interest.

DS is a Senior Clinical Lecturer at the University of St Andrews, UK, and is a principal or co‐investigator on projects funded through grants from the Cunningham Trust, the Wellcome Trust, MRC‐Newton Fund, and EDCTP, and has no known conflicts of interest.

Figures

1
1
Study flow diagram
2
2
Risk of bias in included RCTs
3
3
Risk of bias in included non‐randomized studies
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD012836

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

References to studies included in this review

Ferlazzo 2018 {published and unpublished data}
    1. Ferlazzo G, Mohr E, Laxmeshwar C, Hewison C, Hughes J, Jonckheere S, et al. Early safety and efficacy of the combination of bedaquiline and delamanid for the treatment of patients with drug‐resistant tuberculosis in Armenia, India, and South Africa: a retrospective cohort study. Lancet Infectious Diseases 2018;18:536‐44. [DOI: 10.1016/S1473-3099(18)30100-2] - DOI - PubMed
Galli 2016 {published and unpublished data}
    1. Galli L, Lancella L, Tersigni C, Venturini E, Chiappini E, Bergamini B, et al. Pediatric tuberculosis in Italian children: epidemiological and clinical data from the Italian register of pediatric tuberculosis. International Journal of Molecular Sciences 2016;17(6):960. - PMC - PubMed
Guglielmetti 2017 {published and unpublished data}
    1. Guglielmetti L, Jaspard M, Dû D, Lachâtre M, Marigot‐Outtandy D, Bernard C, French MDR‐TB Management Group. Long‐term outcome and safety of prolonged bedaquiline treatment for multidrug‐resistant tuberculosis. European Respiratory Journal 2017;49:1601799. [DOI: 10.1183/13993003.01799-2016] - DOI - PubMed
Jensenius 2016 {published data only (unpublished sought but not used)}
    1. Jensenius M, Winje BA, Blomberg B, Mengshoel AT, Lippe BV, Hannula R, et al. Multidrug‐resistant tuberculosis in Norway: a nationwide study, 1995‐2014. International Journal of Tuberculosis and Lung Disease 2016;20(6):786‐92. - PubMed
Jeong 2015 {published data only (unpublished sought but not used)}
    1. Jeong BH, Jeon K, Park HY, Kwon OJ, Lee KS, Kim HK, et al. Outcomes of pulmonary MDR‐TB: impacts of fluoroquinolone resistance and linezolid treatment. Journal of Antimicrobial Chemotherapy 2015;70(11):3127‐33. - PubMed
Jo 2014 {published and unpublished data}
    1. Jo KW, Lee SD, Kim WS, Kim DS, Shim TS. Treatment outcomes and moxifloxacin susceptibility in ofloxacin‐resistant multidrug‐resistant tuberculosis. International Journal of Tuberculosis and Lung Disease 2014;18(1):39‐43. - PubMed
Kwak 2015 {published and unpublished data}
    1. Kwak N, Kim HR, Yoo CG, Kim YW, Han SK, Yim JJ. Changes in treatment outcomes of multidrug‐resistant tuberculosis. International Journal of Tuberculosis and Lung Disease 2015;19(5):525‐30. - PubMed
Lee 2012 {published data only}
    1. Lee M, Cho SN, Barry CE. Linezolid for XDR‐TB ‐ final study outcomes. New England Journal of Medicine 2015;373(3):290‐1. - PMC - PubMed
    1. Lee M, Lee J, Carroll MW, Choi H, Min S, Song T, et al. Linezolid for treatment of chronic extensively drug‐resistant tuberculosis. New England Journal of Medicine 2012;367(16):1508‐18. - PMC - PubMed
Migliori 2009 {published data only (unpublished sought but not used)}
    1. Migliori GB, Eker B, Richardson MD, Sotgiu G, Zellweger JP, Skrahina A, et al. A retrospective TBNET assessment of linezolid safety, tolerability and efficacy in multidrug‐resistant tuberculosis. European Respiratory Journal 2009;34(2):387‐93. - PubMed
Olayanju 2018 {published and unpublished data}
    1. Olayanju O, Limberis J, Esmail A, Oelofse S, Gina P, Pietersen E, et al. Long‐term bedaquiline‐related treatment outcomes in patients with extensively drug‐resistant tuberculosis from South Africa. European Respiratory Journal 2018;51:1800544. [DOI: 10.1183/13993003.00544-2018] - DOI - PubMed
Padayatchi 2012 {published and unpublished data}
    1. Padayatchi N, Mac Kenzie WR, Hirsch‐Moverman Y, Feng PJ, Villarino E, Saukkonen J, et al. Lessons from a randomised clinical trial for multidrug‐resistant tuberculosis. International Journal of Tuberculosis and Lung Disease 2012, issue 12:1582‐7. - PubMed
Seddon 2014 {published and unpublished data}
    1. Seddon JA, Hesseling AC, Godfrey‐Faussett P, Schaaf HS. High treatment success in children treated for multidrug‐resistant tuberculosis: an observational cohort study. Thorax 2014;69(5):471‐7. - PubMed
Tang 2015 {published data only}
    1. Tang S, Yao L, Hao X, Zhang X, Liu G, Liu X, et al. Efficacy, safety and tolerability of linezolid for the treatment of XDR‐TB: a study in China. European Respiratory Journal 2015;45(1):161‐70. - PubMed
Tiberi 2016 {published and unpublished data}
    1. Tiberi S, Payen MC, Sotgiu G, D'Ambrosio L, Guizado VA, Alffenaar JW, et al. Effectiveness and safety of meropenem/ clavulanate‐containing regimens in the treatment of MDR‐ and XDR‐TB. European Respiratory Journal 2016;47(4):1235‐43. - PubMed
    1. Tiberi S, Sotgiu G, D'Ambrosio L, Centis R, Arbex MA, Arrascue EA, et al. Comparison of effectiveness and safety of imipenem/clavulanate‐versus meropenem/clavulanate‐containing regimens in the treatment of MDR‐ and XDR‐TB. European Respiratory Journal 2016;47(6):1758‐66. - PubMed
Udwadia 2010 {published data only (unpublished sought but not used)}
    1. Udwadia ZF, Sen T, Moharil G. Assessment of linezolid efficacy and safety in MDR‐ and XDR‐TB: an Indian perspective. European Respiratory Journal 2010;35(4):936‐8; author reply 938‐40. - PubMed
Van Altena 2015 {published and unpublished data}
    1. Altena R, Vries G, Haar CH, Lange WC, Magis‐Escurra C, Hof S, et al. Highly successful treatment outcome of multidrug‐resistant tuberculosis in the Netherlands, 2000‐2009. International Journal of Tuberculosis and Lung Disease 2015;19(4):406‐12. - PubMed
Zhang 2014 {published data only (unpublished sought but not used)}
    1. Zhang L, Pang Y, Yu X, Wang Y, Gao M, Huang H, et al. Linezolid in the treatment of extensively drug‐resistant tuberculosis. Infection 2014;42(4):705‐11. - PubMed

References to studies excluded from this review

Abbate 2007 {published data only}
    1. Abbate E, Vescovo M, Natiello M, Cufré M, García A, Ambroggi M, et al. Tuberculosis treatment. A practical guide elaborated by the tuberculosis section, Argentine Association of Respiratory Medicine [Tuberculosis extensamente resistente (XDR‐TB) en Argentina: aspectos destacables epidemiológicos, bacteriológicos, terapéuticos y evolutivos]. Revista Argentina de Mediciina Respiratoria 2007;7(1):19‐25.
Abbate 2010 {published data only}
    1. Abbate E, Vescovo M, Cufré M, Natiello M, García A, González MP. Extensively drug‐resistant tuberculosis in Argentina: our experience [Experiencia Argentina en el abordaje de la tuberculosis extensamente resistente]. Salud i Ciencia 2010;17(8):778‐82.
Aggarwal 2009 {published data only}
    1. Aggarwal D, Mohapatra PR, Janmeja AK. Treatment of extensively drug‐resistant tuberculosis. Lancet 2009;373(9657):26‐7; author reply 27‐8. - PubMed
Altet 2013 {published data only}
    1. Altet MN, Vidal R, Mila C, Rodrigo T, Casals M, Mir I, et al. Monitoring changes in anti‐tuberculosis treatment: associated factors determined at the time of diagnosis. International Journal of Tuberculosis and Lung Disease 2013;17(11):1435‐41. - PubMed
Anger 2010 {published data only}
    1. Anger HA, Dworkin F, Sharma S, Munsiff SS, Nilsen DM, Ahuja SD. Linezolid use for treatment of multidrug‐resistant and extensively drug‐resistant tuberculosis, New York City, 2000‐06. Journal of Antimicrobial Chemotherapy 2010;65(4):775‐83. - PubMed
Bang 2010 {published data only}
    1. Bang D, Lillebaek T, Thomsen VO, Andersen AB. Multidrug‐resistant tuberculosis: treatment outcome in Denmark, 1992‐2007. Scandinavian Journal of Infectious Diseases 2010;42(4):288‐93. - PubMed
Berry 2016 {published data only}
    1. Berry C, Yates TA, Seddon JA, Phillips PP, du Cros P. Efficacy, safety and tolerability of linezolid for the treatment of XDR‐TB: a study in China. European Respiratory Journal 2016;47(5):1591‐2. - PubMed
Bolhuis 2012 {published data only}
    1. Bolhuis MS, Pranger AD, Alffenaar JW. Linezolid: safety and efficacy monitoring. European Respiratory Journal 2012;39(5):1275‐6; author reply 1276‐7. - PubMed
Bolhuis 2015 {published data only}
    1. Bolhuis MS, Tiberi S, Sotgiu G, Lorenzo S, Kosterink JG, Werf TS, et al. Linezolid tolerability in multidrug‐resistant tuberculosis: a retrospective study. European Respiratory Journal 2015;46(4):1205‐7. - PubMed
Cadena 2009 {published data only}
    1. Cadena J, Hartzler A, Hsue G, Longfield RN. Coccidioidomycosis and tuberculosis coinfection at a tuberculosis hospital: clinical features and literature review. Medicine 2009;88(1):66‐76. - PubMed
Carroll 2011 {published data only}
    1. Carroll MW, Lee MS, Song TS, Cai Y, Lee JS, Lee YM. Linezolid for extensively drug resistant pulmonary tuberculosis. American Journal of Respiratory and Critical Care Medicine 2011; Vol. 183:A1838.
Chan 2013 {published data only}
    1. Chan PC, Huang SH, Yu MC, Lee SW, Huang YW, Chien ST, et al. Effectiveness of a government‐organized and hospital‐initiated treatment for multidrug‐resistant tuberculosis patients ‐ a retrospective cohort study. PLoS One 2013;8(2):e57719. - PMC - PubMed
Chang 2012 {published data only}
    1. Chang KC, Leung CC, Daley CL. Linezolid for multidrug‐resistant tuberculosis. Lancet Infectious Diseases 2012;12(7):502‐3. - PubMed
Chang 2013 {published data only}
    1. Chang KC, Yew WW, Cheung SW, Leung CC, Tam CM, Chau CH, et al. Can intermittent dosing optimize prolonged linezolid treatment of difficult multidrug‐resistant tuberculosis?. Antimicrobial Agents and Chemotherapy 2013;57(7):3445‐9. - PMC - PubMed
Cherenko 2013 {published data only}
    1. Cherenko S, Kibiziva N, Pogrebnaya M, Senko J. Linezolid in the treatment of patients with MDR TB and XDR TB. European Respiratory Journal 2013;42:P2818.
Coban 2009 {published data only}
    1. Coban AY, Bilgin K, Uzun M, Durupinar B. Effect of linezolid in combination with isoniazid and rifampicin against multidrug resistant Mycobacterium tuberculosis clinical isolates. Mikrobiyoloji Bulteni 2009;43(2):293‐7. - PubMed
Coleman 2014 {published data only}
    1. Coleman MT, Chen RY, Lee M, Lin PL, Dodd LE, Maiello P, et al. PET/CT imaging reveals a therapeutic response to oxazolidinones in macaques and humans with tuberculosis. Science Translational Medicine 2014;6(265):265ra167. - PMC - PubMed
Conradie 2014 {published data only}
    1. Conradie F, Mabiletsa T, Sefoka M, Mabaso S, Louw R, Evans D, et al. Prevalence and incidence of symmetrical symptomatic peripheral neuropathy in patients with multidrug‐resistant TB. South African Medical Journal 2014;104(1):24‐6. - PubMed
Corpe 1964 {published data only}
    1. Corpe RF, Blalock FA, Gross JH, Goldhammer EJ. Re‐treatment of drug‐resistant pulmonary tuberculosis at Battey State Hospital. American Review of Respiratory Disease 1964;90:957‐60. - PubMed
Cox 2013 {published data only}
    1. Cox H, Ford N, Hughes J, Goemaere E. Linezolid for multidrug‐resistant tuberculosis. Lancet Infectious Diseases 2013;13(1):16. - PubMed
Dauby 2011 {published data only}
    1. Dauby N, Muylle I, Mouchet F, Sergysels R, Payen MC. Meropenem/clavulanate and linezolid treatment for extensively drug‐resistant tuberculosis. Pediatric Infectious Disease Journal 2011;30(9):812‐3. - PubMed
De Lorenzo 2012 {published data only}
    1. Lorenzo S, Centis R, D'Ambrosio L, Sotgiu G, Migliori GB. On linezolid efficacy and tolerability. European Respiratory Journal 2012;39(3):770‐2. - PubMed
De Lorenzo 2013 {published data only}
    1. Lorenzo S, Alffenaar JW, Sotgiu G, Centis R, D'Ambrosio L, Tiberi S, et al. Efficacy and safety of meropenem‐clavulanate added to linezolid‐containing regimens in the treatment of MDR‐/XDR‐TB. European Respiratory Journal 2013;41(6):1386‐92. - PubMed
Dheda 2017 {published data only}
    1. Dheda K, Limberis JD, Pietersen E, Phelan J, Esmail A, Lesosky M, et al. Outcomes, infectiousness, and transmission dynamics of patients with extensively drug‐resistant tuberculosis and home‐discharged patients with programmatically incurable tuberculosis: a prospective cohort study. Lancet Respiratory Medicine 2017;5:269‐81. - PubMed
Dhingra 2008 {published data only}
    1. Dhingra VK, Rajpal S, Mittal A, Hanif M. Outcome of multi‐drug resistant tuberculosis cases treated by individualized regimens at a tertiary level clinic. Indian Journal of Tuberculosis 2008;55(1):15‐21. - PubMed
Diacon 2012 {published data only}
    1. Diacon AH, Donald PR, Pym A, Grobusch M, Patientia RF, Mahanyele R, et al. Randomized pilot trial of eight weeks of bedaquiline (TMC207) treatment for multidrug‐resistant tuberculosis: long‐term outcome, tolerability, and effect on emergence of drug resistance. Antimicrobial Agents and Chemotherapy 2012; Vol. 56, issue 6:3271‐6. - PMC - PubMed
Farshidpour 2013 {published data only}
    1. Farshidpour M, Ebrahimi G, Mirsaeidi M. Multidrug‐resistant tuberculosis treatment with linezolid‐containing regimen. International Journal of Mycobacteriology 2013;2(4):233‐6. - PMC - PubMed
Fattorini 2012 {published data only}
    1. Fattorini L, Mustazzolu A, Piccaro G, Pardini M, Filippini P, Giannoni F, et al. Drug‐resistant tuberculosis among foreign‐born persons in Italy. European Respiratory Journal 2012;40(2):497‐500. - PubMed
Fortun 2005 {published data only}
    1. Fortun J, Martin‐Davila P, Navas E, Perez‐Elias M J, Cobo J, Tato M, et al. Linezolid for the treatment of multidrug‐resistant tuberculosis. Journal of Antimicrobial Chemotherapy 2005;56(1):180‐5. - PubMed
Griffith 2004 {published data only}
    1. Griffith DE. Treatment of multidrug‐resistant tuberculosis: should you try this at home?. American Journal of Respiratory and Critical Care Medicine 2004;169(10):1082‐3. - PubMed
Gunther 2015 {published data only}
    1. Gunther G, Leth F, Alexandru S, Altet N, Avsar K, Bang D, et al. Multidrug‐resistant tuberculosis in Europe, 2010‐2011. Emerging Infectious Diseases 2015;21(3):409‐16. - PMC - PubMed
Henry 2016 {published data only}
    1. Henry B, Revest M, Dournon N, Epelboin L, Mellon G, Bellaud G, et al. Preliminary favorable outcome for medically and surgically managed extensively drug‐resistant tuberculosis, France, 2009‐2014. Emerging Infectious Diseases 2016;22(3):518‐21. - PMC - PubMed
Heyckendorf 2018 {published data only}
    1. Heyckendorf J, Leth F, Avsar K, Glattki G, Günther G, Kalsdorf B, et al. Treatment responses in multidrug‐resistant tuberculosis in Germany. International Journal of Tuberculosis and Lung Disease 2018;22:399‐406. - PubMed
Huang 2012 {published data only}
    1. Huang YW, Tsai HC, Chang CN, Yang WT. Use of linezolid in complex MDRTB cases. European Respiratory Journal 2012;40(Suppl 56):P3327.
Hughes 2015 {published data only}
    1. Hughes J, Isaakidis P, Andries A, Mansoor H, Cox V, Meintjes G, et al. Linezolid for multidrug‐resistant tuberculosis in HIV‐infected and ‐uninfected patients. European Respiratory Journal 2015;46(1):271‐4. - PubMed
Jaramillo 2013 {published data only}
    1. Jaramillo E, Weyer K, Raviglione M. Linezolid for extensively drug‐resistant tuberculosis. New England Journal of Medicine 2013;368(3):290. - PubMed
Jaspard 2017 {published data only}
    1. Jaspard M, Elefant‐Amoura E, Melonio I, Montgolfier I, Veziris N, Caumes E. Bedaquiline and linezolid for extensively drug‐resistant tuberculosis in pregnant woman. Emerging Infectious Diseases 2017;23:1731‐2. - PMC - PubMed
Jiang 2013 {published data only}
    1. Jiang RH, Xu HB, Li L. Comparative roles of moxifloxacin and levofloxacin in the treatment of pulmonary multidrug‐resistant tuberculosis: a retrospective study. International Journal of Antimicrobial Agents 2013;42(1):36‐41. - PubMed
Joseph 2011 {published data only}
    1. Joseph P, Desai VB, Mohan NS, Fredrick JS, Ramachandran R, Raman B, et al. Outcome of standardized treatment for patients with MDR‐TB from Tamil Nadu, India. Indian Journal of Medical Research 2011;133:529‐34. - PMC - PubMed
Kjollerstrom 2011 {published data only}
    1. Kjollerstrom P, Brito MJ, Gouveia C, Ferreira G, Varandas L. Linezolid in the treatment of multidrug‐resistant/extensively drug‐resistant tuberculosis in paediatric patients: experience of a paediatric infectious diseases unit. Scandinavian Journal of Infectious Diseases 2011;43(6‐7):556‐9. - PubMed
Koh 2009 {published data only}
    1. Koh WJ, Kwon OJ, Gwak H, Chung JW, Cho SN, Kim WS, et al. Daily 300 mg dose of linezolid for the treatment of intractable multidrug‐resistant and extensively drug‐resistant tuberculosis. Journal of Antimicrobial Chemotherapy 2009;64(2):388‐91. - PubMed
    1. Koh WJ, Shim TS. Daily 300 mg dose of linezolid for the treatment of intractable multidrug‐resistant and extensively drug‐resistant tuberculosis ‐ Authors' response. Journal of Antimicrobial Chemotherapy 2009;64(4):883‐4. - PubMed
    1. Koh WJ, Shim TS. Daily 300 mg dose of linezolid for the treatment of intractable multidrug‐resistant and extensively drug‐resistant tuberculosis‐‐authors' response. Journal of Antimicrobial Chemotherapy 2009;64(5):1119‐20. - PubMed
Koh 2012 {published data only}
    1. Koh WJ, Kang YR, Jeon K, Kwon OJ, Lyu J, Kim WS, et al. Daily 300 mg dose of linezolid for multidrug‐resistant and extensively drug‐resistant tuberculosis: updated analysis of 51 patients. Journal of Antimicrobial Chemotherapy 2012;67(6):1503‐7. - PubMed
Lai 2008 {published data only}
    1. Lai CC, Tan CK, Huang YT, Chou CH, Hung CC, Yang PC, et al. Extensively drug‐resistant Mycobacterium tuberculosis during a trend of decreasing drug resistance from 2000 through 2006 at a Medical Center in Taiwan. Clinical Infectious Diseases 2008;47(7):e57‐63. - PubMed
Laniado‐Laborin 2012 {published data only}
    1. Laniado‐Laborin R, Estrada‐Guzman J, Perez H, Batiz‐Armenta F, Alcantar‐Schramm JM. Treatment of multidrug‐resistant tuberculosis in a high‐prevalence region through a binational consortium. International Journal of Tuberculosis and Lung Disease 2012;16(5):610‐1. - PubMed
Maartens 2015 {published data only}
    1. Maartens G, Benson CA. Linezolid for treating tuberculosis: a delicate balancing act. EBioMedicine 2015;2(11):1568‐9. - PMC - PubMed
Macedo 2012 {published data only}
    1. Macedo R, Antunes AF, Villar M, Portugal I. Multidrug and extensively drug‐resistant tuberculosis in Lisbon and Vale do Tejo, Portugal, from 2008 to 2010. International Journal of Mycobacteriology 2012;1(3):131‐6. - PubMed
Maimakov 2013 {published data only}
    1. Maimakov T, Sadykova L, Kalmataeva Z, Kurakpaev K, Smigelskas K. Treatment of tuberculosis in South Kazakhstan: clinical and economical aspects. Medicina (Kaunas, Lithuania) 2013;49(7):335‐40. - PubMed
Manfredi 2009 {published data only}
    1. Manfredi R, Nanetti A, Dal Monte P, Calza L. Increasing pathomorphism of pulmonary tuberculosis: an observational study of slow clinical, microbiological and imaging response of lung tuberculosis to specific treatment. Which role for linezolid?. Brazilian Journal of Infectious Diseases 2009;13(4):297‐303. - PubMed
Milanov 2015 {published and unpublished data}
    1. Milanov V, Falzon D, Zamfirova M, Varleva T, Bachiyska E, Koleva A, et al. Factors associated with treatment success and death in cases with multidrug‐resistant tuberculosis in Bulgaria, 2009‐2010. International Journal of Mycobacteriology 2015;4(2):131‐7. - PubMed
Mirsaeidi 2005 {published data only}
    1. Mirsaeidi SM, Tabarsi P, Khoshnood K, Pooramiri MV, Rowhani‐Rahbar A, Mansoori SD, et al. Treatment of multiple drug‐resistant tuberculosis (MDR‐TB) in Iran. International Journal of Infectious Diseases 2005;9(6):317‐22. - PubMed
Moyo 2015 {published data only}
    1. Moyo S, Cox HS, Hughes J, Daniels J, Synman L, Azevedo V, et al. Loss from treatment for drug resistant tuberculosis: risk factors and patient outcomes in a community‐based program in Khayelitsha, South Africa. PLoS One 2015;10(3):e0118919. - PMC - PubMed
Nam 2009 {published data only}
    1. Nam HS, Koh WJ, Kwon OJ, Cho SN, Shim TS. Daily half‐dose linezolid for the treatment of intractable multidrug‐resistant tuberculosis. International Journal of Antimicrobial Agents 2009;33(1):92‐3. - PubMed
Nie 2013 {published data only}
    1. Nie W J, Chu NH. The analysis of clinical data about the treatment of linezolid against tuberculosis. Zhonghua Jie He He Hu Xi Za Zhi 2013;36(8):601‐3. - PubMed
O'Donnell 2013 {published data only}
    1. O'Donnell MR, Padayatchi N, Kvasnovsky C, Werner L, Master I, Horsburgh CR Jr. Treatment outcomes for extensively drug‐resistant tuberculosis and HIV co‐infection. Emerging Infectious Diseases 2013;19(3):416‐24. - PMC - PubMed
Palmero 2004 {published data only}
    1. Palmero DJ, Ambroggi M, Brea A, Lucas M, Fulgenzi A, Martinez D, et al. Treatment and follow‐up of HIV‐negative multidrug‐resistant tuberculosis patients in an infectious diseases reference hospital, Buenos Aires, Argentina. International Journal of Tuberculosis and Lung Disease 2004;8(6):778‐84. - PubMed
Palmero 2010 {published data only}
    1. Palmero D, Cruz V, Museli T, Pavlovsky H, Fernandez J, Waisman J. Adverse drug reactions in multidrug‐resistant tuberculosis [Reacciones adversas a fármacos en tuberculosis multirresistente]. Medicina 2010;70(5):427‐33. - PubMed
Palmero 2015 {published data only}
    1. Palmero D, Gonzalez Montaner P, Cufre M, Garcia A, Vescovo M, Poggi S. First series of patients with XDR and pre‐XDR TB treated with regimens that included meropenen‐clavulanate in Argentina. Archivos de Bronconeumologia 2015;51(10):e49‐52. - PubMed
Park 2004 {published data only}
    1. Park SK, Lee WC, Lee DH, Mitnick CD, Han L, Seung KJ. Self‐administered, standardized regimens for multidrug‐resistant tuberculosis in South Korea. International Journal of Tuberculosis and Lung Disease 2004;8(3):361‐8. - PubMed
Park 2006 {published data only}
    1. Park IN, Hong SB, Oh YM, Kim MN, Lim CM, Lee SD, et al. Efficacy and tolerability of daily‐half dose linezolid in patients with intractable multidrug‐resistant tuberculosis. Journal of Antimicrobial Chemotherapy 2006;58(3):701‐4. - PubMed
Park 2010 {published data only}
    1. Park JK, Koh WJ, Kim DK, Kim EK, Kim YI, Kim HJ, et al. Treatment outcomes and prognostic factors in patients with multidrug‐resistant tuberculosis in Korean private hospitals. Tuberculosis and Respiratory Diseases 2010;69(2):95‐102.
Pasticci 2012 {published data only}
    1. Pasticci MB, Mazzolla R, Mercuri A, Gamboni G, Bombaci JC, Tiecco C, et al. Trends and challenges in tuberculosis in a medium‐sized southern European setting. International Journal of Tuberculosis and Lung Disease 2012;16(5):645‐8. - PubMed
Pawar 2009 {published data only}
    1. Pawar UM, Kundnani V, Agashe V, Nene A. Multidrug‐resistant tuberculosis of the spine‐is it the beginning of the end? A study of twenty‐five culture proven multidrug‐resistant tuberculosis spine patients. Spine 2009;34(22):E806‐10. - PubMed
Pietersen 2014 {published data only}
    1. Pietersen E, Ignatius E, Streicher EM, Mastrapa B, Padanilam X, Pooran A, et al. Long‐term outcomes of patients with extensively drug‐resistant tuberculosis in South Africa: a cohort study. Lancet 2014;383(9924):1230‐9. - PubMed
Prajapati 2017 {published data only}
    1. Prajapati K, Mishra V, Desai M, Solanki R, Naik P. Treatment outcome of patients having extensively drug‐resistant tuberculosis in Gujarat, India. International Journal of Mycobacteriology 2017;6:289‐95. - PubMed
Ralli 2011 {published data only}
    1. Ralli M, Stournara L, Tsaroucha EG, Palavra M, Karagiannis S, Sgountzos V, et al. Efficacy and safety of linezolid for the treatment of multidrug resistant tuberculosis (MDR‐TB) and disease by non tuberculous mycobacteria (NTM). European Respiratory Journal 2011;38:4398.
Roongruangpitayakul 2013 {published data only}
    1. Roongruangpitayakul C, Chuchottaworn C. Outcomes of MDR/XDR‐TB patients treated with linezolid: experience in Thailand. Chotmaihet Thangphaet [Journal of the Medical Association of Thailand] 2013;96(10):1273‐82. - PubMed
Rose 2012 {published data only}
    1. Rose PC, Hallbauer UM, Seddon JA, Hesseling AC, Schaaf HS. Linezolid‐containing regimens for the treatment of drug‐resistant tuberculosis in South African children. International Journal of Tuberculosis and Lung Disease 2012;16(12):1588‐93. - PubMed
Schecter 2010 {published data only}
    1. Schecter GF, Scott C, True L, Raftery A, Flood J, Mase S. Linezolid in the treatment of multidrug‐resistant tuberculosis. Clinical Infectious Diseases 2010;50(1):49‐55. - PubMed
Seddon 2012 {published data only}
    1. Seddon JA, Hesseling AC, Willemse M, Donald PR, Schaaf HS. Culture‐confirmed multidrug‐resistant tuberculosis in children: clinical features, treatment, and outcome. Clinical Infectious Diseases 2012;54(2):157‐66. - PubMed
Shah 2011 {published data only}
    1. Shah I, Rahangdale A. Partial extensively drug resistance (XDR) tuberculosis in children. Indian Pediatrics 2011;48(12):977‐9. - PubMed
Singla 2012 {published data only}
    1. Singla R, Caminero JA, Jaiswal A, Singla N, Gupta S, Bali RK, et al. Linezolid: an effective, safe and cheap drug for patients failing multidrug‐resistant tuberculosis treatment in India. European Respiratory Journal 2012, issue 4:956‐62. - PubMed
Slebos 2004 {published data only}
    1. Slebos DJ, Altena R, Kuijper EJ, Schippers EF, Bernards AT. Linezolid, an agent from a new class of antibiotics (multiple letters). Nederlands Tijdschrift voor Geneeskunde 2004;148(49):2462‐3. - PubMed
Sokolova 2008 {published data only}
    1. Sokolova GB, Lazareva Ia R, Kirtaeva OV, Romanova EV, Tsybane AA. Rezonizat and cycloserine in complex therapy of drug resistant tuberculosis (comparative studies). Antibiotiki i Khimioterapiia [Antibiotics and Chemoterapy] 2008;53(11‐12):25‐8. - PubMed
Sotgiu 2015 {published data only}
    1. Sotgiu G, Centis R, D'Ambrosio L, Castiglia P, Migliori GB. Low minimal inhibitory concentrations of linezolid against multidrug‐resistant tuberculosis strains. European Respiratory Journal 2015;45(1):287‐9. - PubMed
Stoltz 2017 {published data only}
    1. Stoltz AC, Kock EJ, Nathavitharana RR, Lederer P, Kruger JA, Keulder S, et al. Multi‐drug resistant TB treatment regimen, including bedaquiline and linezolid, failed to reduce transmission over 14 days. American Journal of Respiratory and Critical Care Medicine 2017;195:Np.
Tabarsi 2010 {published data only}
    1. Tabarsi P, Chitsaz E, Baghaei P, Shamaei M, Farnia P, Marjani M, et al. Impact of extensively drug‐resistant tuberculosis on treatment outcome of multidrug‐resistant tuberculosis patients with standardized regimen: report from Iran. Microbial Drug Resistance (Larchmont, N.Y.) 2010;16(1):81‐6. - PubMed
Tang 2011 {published data only}
    1. Tang S, Xiao H, Zeng L, Sun H, Gu J, Hao X, et al. Efficacy and safety of linezolid for the treatment of extensively drug resistant tuberculosis. American Journal of Respiratory and Critical Care Medicine 2011;183:A1834.
Tang 2012 {published data only}
    1. Tang S, Yao L, Xiao H, Zeng L, Sun H, Hao X, et al. Clinical efficacy and safety of linezolid for the treatment of extensively drug‐resistant tuberculosis. Clinical Microbiology and Infection 2012;18:33.
Tangg 2011 {published data only}
    1. Tangg SJ, Zhang Q, Zheng LH, Sun H, Gu J, Hao XH, et al. Efficacy and safety of linezolid in the treatment of extensively drug‐resistant tuberculosis. Japanese Journal of Infectious Diseases 2011;64(6):509‐12. - PubMed
Tiberi 2016b {published data only}
    1. Tiberi S, Sotgiu G, D'Ambrosio L, Centis R, Arbex MA, Alarcon Arrascue E, et al. Effectiveness and safety of imipenem‐clavulanate added to an optimized background regimen (OBR) versus OBR control regimens in the treatment of multidrug‐resistant and extensively drug‐resistant tuberculosis. Clinical Infectious Diseases 2016;62(9):1188‐90. - PubMed
Tortoli 2010 {published data only}
    1. Tortoli E, Rogasi PG, Fantoni E, Beltrami C, Francisci A, Mariottini A. Infection due to a novel mycobacterium, mimicking multidrug‐resistant Mycobacterium tuberculosis. Clinical Microbiology and Infection 2010;16(8):1130‐4. - PubMed
Tse‐Chang 2013 {published data only}
    1. Tse‐Chang A, Kunimoto D, Der E, Ahmed R. Assessment of linezolid efficacy, safety and tolerability in the treatment of tuberculosis: a retrospective case review. Canadian Journal of Infectious Diseases & Medical Microbiology [Journal Canadien des Maladies Infectieuses et de la Microbiologie Medicale] 2013;24(3):e50‐2. - PMC - PubMed
Udwadia 2017 {published data only}
    1. Udwadia ZF, Ganatra S, Mullerpattan JB. Compassionate use of bedaquiline in highly drug‐resistant tuberculosis patients in Mumbai, India. European Respiratory Journal 2017;49:1601699. - PubMed
Van der Walt 2013 {published data only}
    1. Walt M, Lancaster J, Odendaal R, Davis JG, Shean K, Farley J. Serious treatment related adverse drug reactions amongst anti‐retroviral naive MDR‐TB patients. PLoS One 2013;8(4):e58817. - PMC - PubMed
Van Heurck 2013 {published data only}
    1. Heurck R, Payen MC, Wit S, Clumeck N. Epidemiology of MDR‐TB in a Belgian infectious diseases unit: a 15 years review. Acta Clinica Belgica 2013;68(5):321‐4. - PubMed
Velasquez 2014 {published data only}
    1. Velasquez GE, Becerra MC, Gelmanova IY, Pasechnikov AD, Yedilbayev A, Shin SS, et al. Improving outcomes for multidrug‐resistant tuberculosis: aggressive regimens prevent treatment failure and death. Clinical Infectious Diseases 2014;59(1):9‐15. - PMC - PubMed
von der Lippe 2006 {published data only}
    1. Lippe B, Sandven P, Brubakk O. Efficacy and safety of linezolid in multidrug resistant tuberculosis (MDR‐TB)‐‐a report of ten cases. Journal of Infection 2006;52(2):92‐6. - PubMed
Ward 2005 {published data only}
    1. Ward HA, Marciniuk DD, Hoeppner VH, Jones W. Treatment outcome of multidrug‐resistant tuberculosis among Vietnamese immigrants. International Journal of Tuberculosis and Lung Disease 2005;9(2):164‐9. - PubMed
Wirth 2017 {published data only}
    1. Wirth D, Dass R, Hettle R. Cost‐effectiveness of adding novel or group 5 interventions to a background regimen for the treatment of multidrug‐resistant tuberculosis in Germany. BMC Health Services Research 2017;17:182. - PMC - PubMed
Xu 2012a {published data only}
    1. Xu HB, Jiang RH, Li L, Xiao HP. Linezolid in the treatment of MDR‐TB: a retrospective clinical study. International Journal of Tuberculosis and Lung Disease 2012;16(3):358‐63. - PubMed
Xu 2012b {published data only}
    1. Xu HB, Jiang RH, Xiao HP. Clofazimine in the treatment of multidrug‐resistant tuberculosis. Clinical Microbiology and Infection 2012;18(11):1104‐10. - PubMed
Yao 2011 {published data only}
    1. Yao L, Tang SJ, Xiao HP, Zeng LH, Sun H, Gu J, et al. Clinical efficacy and safety of linezolid for the treatment of extensively drug resistant tuberculosis. Respirology 2011;16:80. - PubMed
Yew 2008 {published data only}
    1. Yew WW, Chau CH, Wen KH. Linezolid in the treatment of ‘difficult' multidrug‐resistant tuberculosis. International Journal of Tuberculosis and Lung Disease 2008;12(3):345‐6. - PubMed
Yew 2009 {published data only}
    1. Yew WW, Chang KC, Chau CH. What is the optimal dosage of linezolid in treatment of complicated multidrug‐resistant tuberculosis?. European Respiratory Journal 2009;34(6):1492‐4. - PubMed
Yew 2014 {published data only}
    1. Yew WW, Lange C. Linezolid in the treatment of drug‐resistant tuberculosis: the way forward?. International Journal of Tuberculosis and Lung Disease 2014;18(6):631‐2. - PubMed
Yi 2017 {published data only}
    1. Yi L, Yoshiyama T, Okumura M, Morimoto K, Sasaki Y, Shiraishi Y, et al. Linezolid as a potentially effective drug for the treatment of multidrug‐resistant tuberculosis in Japan. Japanese Journal of Infectious Diseases 2017;70(1):96‐9. - PubMed

References to studies awaiting assessment

Agarwal 2005 {published data only (unpublished sought but not used)}
    1. Agarwal SK. Clinical efficacy of linezolid, clarithromycin and capreomycin in the treatment of multi‐drug resistant pulmonary tuberculosis. Chest 2005;128(4 Supplement):176S.
Agarwal 2007 {published data only (unpublished sought but not used)}
    1. Agarwal SK. Clinical efficacy of once a day linezolid and azithromycin in the treatment of multi drug resistant tuberculosis. European Respiratory Journal 2007;30(Suppl 51):454s [2683].
Anderson 2013 {published data only (unpublished sought but not used)}
    1. Anderson LF, Tamne S, Watson JP, Cohen T, Mitnick C, Brown T, et al. Treatment outcome of multi‐drug resistant tuberculosis in the United Kingdom: retrospective‐prospective cohort study from 2004 to 2007. Eurosurveillance 2013;18(40):20601. - PubMed
Arnold 2017 {published data only (unpublished sought but not used)}
    1. Arnold A, Cooke GS, Kon OM, Dedicoat M, Lipman M, Loyse A, et al. Drug resistant TB: UK multicentre study (DRUMS): treatment, management and outcomes in London and West Midlands 2008‐2014. Infection 2017;3:260‐71. - PubMed
Bionghi 2017 {published data only (unpublished sought but not used)}
    1. Bionghi N, Padayatchi N, Master I, Naidoo K, O'Donnell MR. Bedaquiline and linezolid for the operational treatment of multidrug‐resistant and extensively drug‐resistant tuberculosis in a high burden HIV setting (blix study). American Journal of Respiratory and Critical Care Medicine 2017;195:A3090. [DOI: 10.1164/ajrccm-conference.2017.B27] - DOI
Borisov 2017 {published data only (unpublished sought but not used)}
    1. Borisov SE, Dheda K, Enwerem M, Leyet RR, D'Ambrosio L, Centis R, et al. Effectiveness and safety of bedaquiline containing regimens in the treatment of MDR‐ and XDR‐TB: a multicentre study. European Respiratory Journal 2017;49:1700387. [DOI: 10.1183/13993003.00387-2017] - DOI - PubMed
Catho 2015 {published data only (unpublished sought but not used)}
    1. Catho G, Couraud S, Grard S, Bouaziz A, Senechal A, Valour F, et al. Management of emerging multidrug‐resistant tuberculosis in a low‐prevalence setting. Clinical Microbiology and Infection 2015;21(5):472.e7‐472.e10. - PubMed
Dey 2015 {published data only (unpublished sought but not used)}
    1. Dey A. Linezolid in children with drug resistant tuberculosis and associated peripheral neuropathy. Neurology 2015;84(14 Supplement):P6.319.
Ganatra 2017 {published data only (unpublished sought but not used)}
    1. Ganatra SR, Udwadia ZF, Mullerpattan JB, Banka RA, Sharma U, Kambli PG, et al. Clinical profiles of linezolid resistant tuberculosis cases in Mumbai. American Journal of Respiratory and Critical Care Medicine 2017;195:A2114. [DOI: 10.1164/ajrccm-conference.2017.A62] - DOI
Grard 2015 {published data only (unpublished sought but not used)}
    1. Grard S, Catho G, Valour F, Bouaziz A, Perpoint T, Braun E, et al. Linezolid in the starter combination for multidrug‐resistant tuberculosis: time to move on to group four?. Open Forum Infectious Diseases 2015;2(4):ofv175. - PMC - PubMed
Jeon 2009 {published data only (unpublished sought but not used)}
    1. Jeon DS, Kim DH, Kang HS, Hwang SH, Min JH, Kim JH, et al. Survival and predictors of outcomes in non‐HIV‐infected patients with extensively drug‐resistant tuberculosis. International Journal of Tuberculosis and Lung Disease 2009;13(5):594‐600. - PubMed
Kim 2007 {published data only (unpublished sought but not used)}
    1. Kim HR, Seung SH, Hyun JK, Sang ML, Yoo CG, Young WK, et al. Impact of extensive drug resistance on treatment outcomes in non‐HIV‐infected patients with multidrug‐resistant tuberculosis. Clinical Infectious Diseases 2007;45(10):1290‐5. - PubMed
Kim 2018 {published data only (unpublished sought but not used)}
    1. Kim CT, Kim TO, Shin HJ, Ko YC, Hun Choe Y, Kim HR, et al. Bedaquiline and delamanid for the treatment of multidrug‐resistant tuberculosis: a multicentre cohort study in Korea. European Respiratory Journal 2018;51(3):1702467. [DOI: 10.1183/13993003.02467-2017] - DOI - PubMed
Kuksa 2017 {published data only (unpublished sought but not used)}
    1. Kuksa L, Barkane L, Hittel N, Gupta R. Final treatment outcomes of multidrug and extensively drug‐resistant tuberculosis patients in Latvia receiving delamanid‐containing regimens. European Respiratory Journal 2017;50:1701105. [DOI: 10.1183/13993003.01105-2017] - DOI - PubMed
Lee 2017 {published data only (unpublished sought but not used)}
    1. Lee H, Ahn S, Hwang NY, Jeon K, Kwon OJ, Huh HJ, et al. Treatment outcomes of rifabutin‐containing regimens for rifabutin‐sensitive multidrug‐resistant pulmonary tuberculosis. International Journal of Infectious Diseases 2017;65:135‐41. [DOI: 10.1016/j.ijid.2017.10.013] - DOI - PubMed
Meressa 2015 {published data only (unpublished sought but not used)}
    1. Meressa D, Hurtado RM, Andrews JR, Diro E, Abato K, Daniel T, et al. Achieving high treatment success for multidrug‐resistant TB in Africa: initiation and scale‐up of MDR TB care in Ethiopia ‐ an observational cohort study. Thorax 2015;70(12):1181‐8. - PMC - PubMed
Pang 2017 {published data only (unpublished sought but not used)}
    1. Pang Y, Lu J, Huo F, Ma Y, Zhao L, Li Y, et al. Prevalence and treatment outcome of extensively drug‐resistant tuberculosis plus additional drug resistance from the National Clinical Center for Tuberculosis in China: a five‐year review. Journal of Infection 2017;75:433‐40. [DOI: 10.1016/j.jinf.2017.08.005] - DOI - PubMed
Ramirez‐Lapausa 2016 {published data only (unpublished sought but not used)}
    1. Ramirez‐Lapausa M, Pascual Pareja JF, Carrillo Gomez R, Martinez‐Prieto M, Gonzalez‐Ruano Perez P, Noguerado Asensio A. Retrospective study of tolerability and efficacy of linezolid in patients with multidrug‐resistant tuberculosis (1998‐2014). Enfermedades Infecciosas y Microbiologia Clinica 2016;34(2):85‐90. - PubMed
Soman 2014 {published data only (unpublished sought but not used)}
    1. Soman R, Pillai P, Madan S, Shetty A, Rodrigues C. Successful management of highly drug resistant tuberculosis with individualised drug susceptibility testing. Journal of the Association of Physicians of India 2014;62(7):567‐70. - PubMed
Tornheim 2017 {published data only (unpublished sought but not used)}
    1. Tornheim J, Ganatra S, Deluca A. Linezolid experience among MDR‐TB patients in Mumbai. European Respiratory Journal 2017;50(Suppl 61):PA3486. [DOI: 10.1183/1393003.congress-2017.PA3486] - DOI
Udwadia 2014 {published data only (unpublished sought but not used)}
    1. Udwadia Z, Moharil G. Multidrug‐resistant‐tuberculosis treatment in the Indian private sector: results from a tertiary referral private hospital in Mumbai. Lung India 2014;31(4):336‐41. - PMC - PubMed

References to ongoing studies

NCT02333799 {unpublished data only}
    1. NCT02333799. A phase 3 study assessing the safety and efficacy of bedaquiline plus PA‐824 plus linezolid in subjects with drug resistant pulmonary tuberculosis [A phase 3 open‐label trial assessing the safety and efficacy of bedaquiline plus PA‐824 plus linezolid in subjects with pulmonary infection of either extensively drug‐resistant tuberculosis (XDR‐TB) or treatment intolerant / non‐responsive multi‐drug resistant tuberculosis (MDR‐TB)]. clinicaltrials.gov/ct2/show/NCT02333799 (first posted 7 January 7 2015).
NCT02454205 {unpublished data only}
    1. NCT02454205. An open‐label RCT to evaluate a new treatment regimen for patients with multi‐drug resistant tuberculosis (NEXT) [Evaluating a new treatment regimen for patients with multidrug‐resistant tb (MDR‐TB) ‐ a prospective open‐label randomised controlled trial]. clinicaltrials.gov/ct2/show/NCT02454205 (first posted 27 May 2015).
NCT02589782 {unpublished data only}
    1. NCT02589782. Pragmatic clinical trial for a more effective concise and less toxic MDR‐TB treatment regimen(s) (TB‐PRACTECAL) [A randomised, controlled, open‐label, phase II‐III trial to evaluate the safety and efficacy of regimens containing bedaquiline and pretomanid for the treatment of adult patients with pulmonary multidrug resistant tuberculosis]. clinicaltrials.gov/ct2/show/NCT02589782 (first posted 28 October 2015).
NCT02619994 {unpublished data only}
    1. NCT02619994. Treatment shortening of MDR‐TB using existing and new drugs (MDR‐END) [Delamanid, linezolid, levofloxacin, and pyrazinamide for the treatment of patients with fluoroquinolone‐sensitive MDR‐TB: a phase 2/3, multicenter, randomized, open‐label, clinical trial]. clinicaltrials.gov/ct2/show/NCT02619994 (first posted 2 December 2015).
NCT02754765 {unpublished data only}
    1. NCT02754765. Evaluating newly approved drugs for multidrug‐resistant TB (endTB) [Evaluating newly approved drugs for multidrug‐resistant TB (endTB): a clinical trial]. clinicaltrials.gov/ct2/show/NCT02754765 (first posted 28 April 2016).
NCT03237182 {unpublished data only}
    1. NCT03237182. The individualized M(X) drug‐resistant TB treatment strategy study (InDEX) [The individualized M(X) drug‐resistant TB treatment strategy study a strategy to improve treatment outcomes in patients with drug‐resistant TB]. clinicaltrials.gov/ct2/show/NCT03237182 (first posted 2 August 2017).

Additional references

Ahmad 2018
    1. Ahmad N, Ahuja SD, Akkerman OW, Alffenaar JC, Anderson LF, Baghaei P, et al. Treatment correlates of successful outcomes in pulmonary multi‐drug resistant tuberculosis: an individual patient data meta‐analysis. Lancet 2018;362:821‐34. - PMC - PubMed
Caminero 2015
    1. Caminero JA, Scardigli A. Classification of antituberculosis drugs: a new proposal based on the most recent evidence. European Respiratory Journal 2015;46(4):887‐93. - PubMed
Chang 2013a
    1. Chang KC, Yew WW. Management of difficult multidrug‐resistant tuberculosis and extensively drug‐resistant tuberculosis: update 2012. Respirology 2013;18(1):8‐21. [DOI: 10.1111/j.1440-1843.2012.02257.x] - DOI - PubMed
Chang 2013b
    1. Chang KC, Yew WW, Cheung SW, Leung CC, Tam CM, Chau CH, et al. Can intermittent dosing optimize prolonged linezolid treatment of difficult multidrug‐resistant tuberculosis?. Antimicrobial Agents and Chemotherapy 2013;57(7):3445‐9. [DOI: 10.1128/AAC.00388-13] - DOI - PMC - PubMed
Chang 2013c
    1. Chang KC, Yew WW, Tam CM, Leung CC. WHO group 5 drugs and difficult multidrug‐resistant tuberculosis: a systematic review with cohort analysis and meta‐analysis. Antimicrobial Agents and Chemotherapy 2013;57(9):4097–104. - PMC - PubMed
Cox 2012
    1. Cox H, Ford N. Linezolid for the treatment of complicated drug‐resistant tuberculosis: a systematic review and meta‐analysis. International Journal of Tuberculosis and Lung Disease 2012;16(4):447‐54. [DOI: 10.5588/ijtld.11.0451] - DOI - PubMed
De Vriese 2006
    1. Vriese AS, Coster RV, Smet J, Seneca S, Lovering A, Haute LL, et al. Linezolid‐induced inhibition of mitochondrial protein synthesis. Clinical Infectious Diseases 2006;42(8):1111‐7. - PubMed
Deeks 2017
    1. Deeks JJ, Higgins JP, Altman DG (editors) on behalf of the Cochrane Statistical Methods Group. Chapter 9: Analysing data and undertaking meta‐analyses. In: Higgins JPT, Churchill R, Chandler J, Cumpston MS (editors), Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0 (updated June 2017), Cochrane, 2017. Available from www.training.cochrane.org/handbook.
Dryden 2011
    1. Dryden MS. Linezolid pharmacokinetics and pharmacodynamics in clinical treatment. Journal of Antimicrobial Chemotherapy 2011;66(Suppl 4):iv7‐15. [DOI: 10.1093/jac/dkr072] - DOI - PubMed
Erturan 2005
    1. Erturan Z, Uzun M. In vitro activity of linezolid against multidrug‐resistant Mycobacterium tuberculosis isolates. International Journal of Antimicrobial Agents 2005;26(1):78‐80. [DOI: 10.1016/j.ijantimicag.2005.03.006] - DOI - PubMed
Fox 2017
    1. Fox GJ, Benedetti A, Cox H, Koh WJ, Viiklepp P, Ahuja S, et al. on behalf of the Collaborative Group for Meta‐Analysis of Individual Patient Data in MDR‐TB. Group 5 drugs for multidrug‐resistant tuberculosis: individual patient data meta‐analysis. European Respiratory Journal 2017;49:1600993. - PubMed
GRADEpro GDT 2015 [Computer program]
    1. GRADE Working Group, McMaster University. GRADEpro GDT. Version accessed 15 May 2017. Hamilton (ON): GRADE Working Group, McMaster University, 2015.
Guyatt 2011
    1. Guyatt GH, Oxman AD, Sultan S, Glasziou P, Akl EA, Alonso‐Coello P, et al. GRADE guidelines: 9. Rating up the quality of evidence. Journal of Clinical Epidemiology 2011;64(12):1311‐6. - PubMed
Higgins 2003
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327:557‐60. - PMC - PubMed
Higgins 2011a
    1. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928. [DOI: 10.1136/bmj.d5928] - DOI - PMC - PubMed
Higgins 2011b
    1. Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Huang 2008
    1. Huang TS, Liu YC, Sy CL, Chen YS, Tu HZ, Chen BC. In vitro activities of linezolid against clinical isolates of Mycobacterium tuberculosis complex isolated in Taiwan over 10 years. Antimicrobial Agents and Chemotherapy 2008;52(6):2226‐7. [DOI: 10.1128/AAC.00414-07] - DOI - PMC - PubMed
Jüni 2001
    1. Jüni P, Altman DG, Egger M. Systematic reviews in health care: assessing the quality of controlled clinical trials. BMJ 2001;323(7303):42‐6. - PMC - PubMed
Loke 2011
    1. Loke YK, Price D, Herxheimer A. Chapter 14: Adverse effects. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.handbook.cochrane.org.
Mitnick 2015
    1. Mitnick CD, Rusen I, Bain LJ, Horsburgh CR Jr. Issues in design and interpretation of MDR‐TB clinical trials: report of the first Global MDR‐TB Clinical Trials Landscape Meeting. BMC Proceedings 2015;9(Suppl 8):S1. [DOI: 10.1186/1753-6561-9-S8-S1] - DOI
Moher 2009
    1. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred reporting items for systematic reviews and meta‐analyses: The PRISMA Statement. PLoS Medicine 6;7:e1000097. [DOI: 10.1371/journal.pmed1000097] - DOI - PMC - PubMed
Ramachandran 2015
    1. Ramachandran GS, Swaminathan S. Safety and tolerability profile of second‐line anti‐tuberculosis medications. Drug Safety 2015;38(3):253‐69. - PubMed
Review Manager 2014 [Computer program]
    1. Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Sharma 2006
    1. Sharma SK, Mohan A. Multidrug‐resistant tuberculosis: a menace that threatens to destabilize tuberculosis control. Chest 2006;130(1):261‐72. - PubMed
Sloan 2016
    1. Sloan DJ, Lewis JM. Management of multidrug‐resistant TB: novel treatments and their expansion to low resource settings. Transactions of the Royal Society of Tropical Medicine and Hygiene 2016;110(3):163‐72. [DOI: 10.1093/trstmh/trv107] - DOI - PMC - PubMed
Sotgiu 2012
    1. Sotgiu G, Centis R, D'Ambrosio L, Alffenaar JW, Anger HA, Caminero JA, et al. Efficacy, safety and tolerability of linezolid‐containing regimens in treating MDR‐TB and XDR‐TB: systematic review and meta‐analysis. European Respiratory Journal 2012;40(6):1430‐42. [DOI: 10.1183/09031936.00022912] - DOI - PubMed
Sterne 2016
    1. Sterne JA, Higgins JP, Reeves BC, Savović J, Turner L, ROBINS‐I development group. ROBINS‐I: a tool for assessing Risk Of Bias In Non‐randomized Studies of Interventions. Available from www.riskofbias.info (accessed 14 June 2016).
Vashishtha 2013
    1. Vashishtha R, Mohan K, Singh B, Devarapu SK, Sreenivas V, Ranjan S, et al. Efficacy and safety of thrice weekly DOTS in tuberculosis patients with and without HIV co‐infection: an observational study. BMC Infectious Diseases 2013;13:468. [DOI: 10.1186/1471-2334-13-468] - DOI - PMC - PubMed
WHO 2009
    1. World Health Organization. Global Tuberculosis Control Report. Geneva: World Health Organization, 2009.
WHO 2010
    1. World Health Organization. Treatment of Tuberculosis Guidelines. 4th Edition. Geneva: World Health Organization, 2010.
WHO 2011
    1. World Health Organization. Guidelines for the programmatic management of drug‐resistant tuberculosis: 2011 update. Geneva: World Health Organization, 2011. [ISBN 978 92 4 150158 3] - PubMed
WHO 2013
    1. World Health Organization. Definitions and reporting framework for tuberculosis – 2013 revision (updated December 2014). Geneva: World Health Organization, 2013.
WHO 2014
    1. World Health Organization. The End TB Strategy. Geneva: World Health Organization, 2014.
WHO 2015a
    1. World Health Organization. Global Tuberculosis Report 2015. Geneva: World Health Organization, 2015. [ISBN 978 92 4 156505 9]
WHO 2015b
    1. World Health Organization. Use of high burden country lists for TB by WHO in the post‐2015 era. Geneva: World Health Organization, 2015.
WHO 2016a
    1. World Health Organization. WHO Treatment Guidelines for Drug‐Resistant Tuberculosis – 2016 update. Geneva: World Health Organization, 2016. - PubMed
WHO 2016b
    1. World Health Organization. Global Tuberculosis Report. Geneva: World Health Organization, 2016.
WHO 2018
    1. World Health Organization. Rapid communication: key changes to treatment of multidrug‐ and rifampicin‐resistant tuberculosis (MDR/RR‐TB). Available at: www.who.int/tb/publications/2018/rapid_communications_MDR/en/ 2018.
Zhang 2015
    1. Zhang X, Falagas ME, Vardakas KZ, Wang R, Qin R, Wang J, et al. Systematic review and meta‐analysis of the efficacy and safety of therapy with linezolid containing regimens in the treatment of multidrug‐resistant and extensively drug‐resistant tuberculosis. Journal of Thoracic Disease 2015;7(4):603‐15. [DOI: 10.3978/j.issn.2072-1439.2015.03.10] - DOI - PMC - PubMed

References to other published versions of this review

Singh 2017
    1. Singh B, Cocker D, Ryan H, Sloan DJ. Linezolid for drug‐resistant tuberculosis. Cochrane Database of Systematic Reviews 2017, Issue 11. [DOI: 10.1002/14651858.CD012836] - DOI - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources