Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB: Systematic review and meta-analysis

Giovanni Sotgiu, Rosella Centis, Lia D'Ambrosio, Jan William C Alffenaar, Holly A. Anger, Jose A. Caminero, Paolo Castiglia, Saverio De Lorenzo, Giovanni Ferrara, Won Jung Koh, Giesela F. Schecter, Tae S. Shim, Rupak Singla, Alena Skrahina, Antonio Spanevello, Zarir F. Udwadia, Miquel Villar, Elisabetta Zampogna, Jean Pierre Zellweger, Alimuddin ZumlaGiovanni Battista Migliori

Research output: Contribution to journalArticle

Abstract

Linezolid is used off-label to treat multidrug-resistant tuberculosis (MDR-TB) in absence of systematic evidence. We performed a systematic review and meta-analysis on efficacy, safety and tolerability of linezolid-containing regimes based on individual data analysis. 12 studies (11 countries from three continents) reporting complete information on safety, tolerability, efficacy of linezolid-containing regimes in treating MDR-TB cases were identified based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Metaanalysis was performed using the individual data of 121 patients with a definite treatment outcome (cure, completion, death or failure). Most MDR-TB cases achieved sputum smear (86 (92.5%) out of 93) and culture (100 (93.5%) out of 107) conversion after treatment with individualised regimens containing linezolid (median (inter-quartile range) times for smear and culture conversions were 43.5 (21-90) and 61 (29-119) days, respectively) and 99 (81.8%) out of 121 patients were successfully treated. No significant differences were detected in the subgroup efficacy analysis (daily linezolid dosage ≤600 mg versus >600 mg). Adverse events were observed in 63 (58.9%) out of 107 patients, of which 54 (68.4%) out of 79 were major adverse events that included anaemia (38.1%), peripheral neuropathy (47.1%), gastro-intestinal disorders (16.7%), optic neuritis (13.2%) and thrombocytopenia (11.8%). The proportion of adverse events was significantly higher when the linezolid daily dosage exceeded 600 mg. The study results suggest an excellent efficacy but also the necessity of caution in the prescription of linezolid. Copyright

Original languageEnglish
Pages (from-to)1430-1442
Number of pages13
JournalEuropean Respiratory Journal
Volume40
Issue number6
DOIs
Publication statusPublished - Dec 1 2012

Keywords

  • Efficacy
  • Extensively drug-resistant tuberculosis
  • Linezolid
  • Multidrug-resistant tuberculosis
  • Safety
  • Tolerability

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Sotgiu, G., Centis, R., D'Ambrosio, L., Alffenaar, J. W. C., Anger, H. A., Caminero, J. A., Castiglia, P., De Lorenzo, S., Ferrara, G., Koh, W. J., Schecter, G. F., Shim, T. S., Singla, R., Skrahina, A., Spanevello, A., Udwadia, Z. F., Villar, M., Zampogna, E., Zellweger, J. P., ... Migliori, G. B. (2012). Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB: Systematic review and meta-analysis. European Respiratory Journal, 40(6), 1430-1442. https://doi.org/10.1183/09031936.00022912