Linezolid safety, tolerability and efficacy to treat multidrug- and extensively drug-resistant tuberculosis

Villar, Miguęl; Sotgiu, Giovanni; D’Ambrosio, Lia; Raymundo, Elena; Fernandes, Lucas; Barbedo, J.; Diogo, Nelson; Lange, Christoph; Centis, Rosella; Migliori, Giovanni Battista

doi:10.1183/09031936.00195210

Cited by 50 publications

(41 citation statements)

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“…A series of studies evaluated the efficacy, safety and tolerability of the linezolid containing regimes for treating MDRand XDR-TB cases. However, most were restricted mainly to case reports, a retrospective analysis and small case series [14][15][16][17][18][19][28][29][30][31]. This is a prospective, multicentre, randomised study on efficacy, safety and tolerability of linezolid for treating XDR-TB.…”

Section: Discussionmentioning

confidence: 99%

Efficacy, safety and tolerability of linezolid for the treatment of XDR-TB: a study in China

et al. 2014

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Linezolid may be effective in treating multidrug-resistant tuberculosis and extensively drugresistant tuberculosis. We conducted a prospective, multicentre, randomised study to further evaluate the efficacy, safety and tolerability of linezolid in patients with extensively drug-resistant tuberculosis in China.65 patients who had culture-positive sputum for extensively drug-resistant tuberculosis were randomly assigned to a linezolid therapy group or a control group. Patients in the two groups adopted a 2-year individually based chemotherapy regimen. The linezolid therapy group was given linezolid at a start dose of 1200 mg per day for a period of 4-6 weeks and this was then followed by a dose of 300-600 mg per day.The proportion of sputum culture conversions in the linezolid therapy group was 78.8% by 24 months, significantly higher than that in the control group (37.6%, p<0.001). The treatment success rate in linezolid therapy group was 69.7%, significantly higher than that in the control group (34.4%, p=0.004). 27 (81.8%) patients had clinically significant adverse events in the linezolid group, of whom 25 (93%) patients had events that were possibly or probably related to linezolid. Most adverse events resolved after reducing the dosage of linezolid or temporarily discontinuing linezolid.Linezolid containing chemotherapy for treatment of extensively drug-resistant tuberculosis may significantly promote cavity closure, increase sputum culture-conversion rate and improve treatment success rate. @ERSpublications Prospective, multicentre, randomised study evaluating efficacy, safety and tolerability of linezolid in XDR-TB

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Section: Discussionmentioning

confidence: 99%

Efficacy, safety and tolerability of linezolid for the treatment of XDR-TB: a study in China

et al. 2014

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“…Evidence on good efficacy is accumulating, including meta-analyses [28,29] and two RCTs [30,31], in addition to observational studies [28,[32][33][34][35][36][37]. Unfortunately, the current cost and the documented toxicity [28][29][30][31][32][33][34][35][36][37] can be a barrier to its wider use. Nonetheless, the price of generic, quality-assured linezolid has reduced significantly in the last year and further cost reduction globally is expected soon [38].…”

Section: Linezolidmentioning

confidence: 99%

Classification of antituberculosis drugs: a new proposal based on the most recent evidence

Caminero

Scardigli

2015

Eur Respir J

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@ERSpublicationsThe classification of the anti-TB drugs should probably be modified to optimise the use old and new compounds http://ow.ly/QbDSP Multidrug-resistant (MDR) tuberculosis (TB) (resistance to at least isoniazid and rifampicin), with >480 000 cases in 2013, 10% of them being affected by extensively drug-resistant (XDR)-TB (MDR-TB with additional resistance to any fluoroquinolone, and to injectable second-line drugs (SLDs) (capreomycin, kanamycin or amikacin)), continues to represent a real threat to TB control [1][2][3][4]. In some high MDR-TB burden countries, the prevalence of MDR-TB among new cases exceeds 20% and among retreatment cases, reaches almost 50% [1,5].Prevention and quality diagnosis and treatment of MDR-and XDR-TB are part of the crucial interventions included in Pillar 1 of the new World Health Organization (WHO) End TB Strategy, which is focussed on the goal of TB elimination [6][7][8]. Unfortunately, the outcomes of these cases are suboptimal, with 60% success among MDR-TB cases [2], 40% among XDR-TB cases [3] and <20% among the cases with resistance patterns beyond XDR-TB [4]. This means not only high mortality but also significant human suffering and transmission of the Mycobacterium tuberculosis strains within the community [9]. Unfortunately, at present, the treatment of MDR/XDR-TB is still very long, toxic and expensive [10,11].The original WHO guidance on the management of MDR-TB was issued in 1996 [12] and since then, several updated guidelines have been published. The fundamentals on MDR/XDR-TB treatment were published in the 2006 and 2008 WHO guidelines [13,14], where the basic rationale to design therapeutic regimens for these cases was described. According to these recommendations, which are currently followed worldwide, the anti-TB drugs are classified into five main groups indirectly considering the evidence available, the safety and/or the effectiveness of the different drugs. These groups start from the most effective drugs (group 1), grouping the other drugs progressively according to decreasing order of efficacy [15].In the 2011 revision of the WHO MDR/XDR-TB guidelines [16], the composition of different groups of anti-TB drugs was not modified. Therefore, since 2006, the rationale of the classification of the anti-TB drugs has not been changed but several studies have examined the effectiveness, efficacy and safety of the group 5 drugs, and some of these drugs appear to be more effective and well tolerated than others that currently have "higher" ranking in the classification. Furthermore, promising new drugs active against M. tuberculosis have been discovered in the last couple of years [17][18][19][20] and have become progressively available in many parts of the world to treat MDR/XDR-TB.

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“…At present, only seven cohorts published on linezolid include more than 10 cases, their size ranging between 12 and 85 cases (of which only 45 had information on efficacy) [8,[30][31][32][33][34][35].…”

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confidence: 99%

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

Sotgiu¹,

Centis²,

et al. 2012

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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 f600 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.

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Linezolid safety, tolerability and efficacy to treat multidrug- and extensively drug-resistant tuberculosis

Cited by 50 publications

References 10 publications

Efficacy, safety and tolerability of linezolid for the treatment of XDR-TB: a study in China

Efficacy, safety and tolerability of linezolid for the treatment of XDR-TB: a study in China

Classification of antituberculosis drugs: a new proposal based on the most recent evidence

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

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