A retrospective TBNET assessment of linezolid safety, tolerability and efficacy in multidrug-resistant tuberculosis

作者：Migliori G B; Eker B; Richardson M D; Sotgiu G; Zellweger J P; Skrahina A; Ortmann J; Girardi E; Hoffmann H; Besozzi G; Bevilacqua N; Kirsten D; Centis R; Lange C^*

来源：European Respiratory Journal, 2009, 34(2): 387-393.

DOI：10.1183/09031936.00009509

• Efficacy
• extensively drug-resistant tuberculosis
• linezolid
• multidrug-resistant tuberculosis
• safety
• tolerability

Linezolid is used to treat patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-tuberculosis (TB) cases, although clinical data on its safety, tolerability and efficacy are lacking.
We performed a retrospective, nonrandomised, unblinded observational study evaluating the safety and tolerability of linezolid at 600 mg q.d. or b.i.d. in MDR/XDR-TB treatment in four European countries. Efficacy evaluation compared end-points of 45 linezolid-treated against 110 linezolid-nontreated cases.
Out of 195 MDR/XDR-TB patients, 85 were treated with linezolid for a mean of 221 days. Of these, 35 (41.2%) out of 85 experienced major side-effects attributed to linezolid (anaemia, thrombocytopenia and/or polyneuropathy), requiring discontinuation in 27 (77%) cases. Most side-effects occurred after 60 days of treatment. Twice-daily administration produced more major side-effects than once-daily dosing (p=0.0004), with no difference in efficacy found. Outcomes were similar in patients treated with/without linezolid (p=0.8), although linezolid-treated cases had more first-line (p=0.002) and second-line (p=0.02) drug resistance and a higher number of previous treatment regimens (4.5 versus 2.3; p=0.07).
Linezolid 600 mg q.d. added to an individualised multidrug regimen may improve the chance of bacteriological conversion, providing a better chance of treatment success in only the most complicated MDR/XDR-TB cases. Its safety profile does not warrant use in cases for which there are other, safer, alternatives.

• 出版日期2009-8