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

Sotgiu, Giovanni and Centis, Rosella and D'Ambrosio, Lia and Alffenaar, Jan-William C. and Anger, Holly A. and Caminero, José A. and Castiglia, Paolo Giuseppino and De Lorenzo, Saverio and Ferrara, Giovanni and Koh, Won-Jung and Schecter, Giesela F. and Shim, Tae Sun and Singla, Rupak and Skrahina, Alena and Spanevello, Antonio and Udwadia, Zarir F. and Villar, Miguel and Zampogna, Elisabetta and Zellweger, Jean-Pierre and Zumla, Alimuddin and Migliori, Giovanni Battista (2012) Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB: systematic review and meta-analysis. European Respiratory Journal, Vol. 40 (6), p. 1430-1442. eISSN 1399-3003. Article.

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DOI: 10.1183/09031936.00022912


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. Meta-analysis 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.

Item Type:Article
ID Code:8508
Uncontrolled Keywords:Linezolid, multidrug-resistant tuberculosis (MDR-TB), meta-analyses
Subjects:Area 06 - Scienze mediche > MED/42 Igiene generale e applicata
Area 06 - Scienze mediche > MED/01 Statistica medica
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Biomediche
Publisher:European Respiratory Society
Deposited On:08 Jan 2013 13:37

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