title: A retrospective TBNET assessment of linezolid safety, tolerability and efficacy in multidrug-resistant tuberculosis.
abstract: 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.
authors.affiliation: WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Care and Research Institute, Tradate, Italy.
authors.forename: G B
authors.initials: GB
authors.lastname: Migliori
authors.forename: B
authors.initials: B
authors.lastname: Eker
authors.forename: M D
authors.initials: MD
authors.lastname: Richardson
authors.forename: G
authors.initials: G
authors.lastname: Sotgiu
authors.forename: J-P
authors.initials: JP
authors.lastname: Zellweger
authors.forename: A
authors.initials: A
authors.lastname: Skrahina
authors.forename: J
authors.initials: J
authors.lastname: Ortmann
authors.forename: E
authors.initials: E
authors.lastname: Girardi
authors.forename: H
authors.initials: H
authors.lastname: Hoffmann
authors.forename: G
authors.initials: G
authors.lastname: Besozzi
authors.forename: N
authors.initials: N
authors.lastname: Bevilacqua
authors.forename: D
authors.initials: D
authors.lastname: Kirsten
authors.forename: R
authors.initials: R
authors.lastname: Centis
authors.forename: C
authors.initials: C
authors.lastname: Lange
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D024881:Drug Resistance, Bacterial; D005060:Europe; D005260:Female; D006801:Humans; D000069349:Linezolid; D008297:Male; D016017:Odds Ratio; D023303:Oxazolidinones / Q000008:administration & dosage / Q000627:therapeutic use*; D012044:Regression Analysis; D012189:Retrospective Studies; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D000995:Antitubercular Agents; D023303:Oxazolidinones; D000069349:Linezolid