WHO Group 5 drugs and difficult multidrug-resistant tuberculosis: a systematic review with cohort analysis and meta-analysis
Antimicrobial agents and chemotherapy | 19 Jun 2013
KC Chang, WW Yew, CM Tam and CC Leung
It is often necessary to include WHO Group 5 drugs in the treatment of extensively drug-resistant TB (XDR-TB) and fluoroquinolone-resistant multidrug-resistant tuberculosis (MDR-TB). As clinical evidence about use of Group 5 drugs is scarce, we conducted a systematic review using published individual patient data. We searched PubMed and OvidSP through 7 April 2013 for publications in English to assemble a cohort with fluoroquinolone-resistant MDR-TB treated with Group 5 drugs. Favorable outcome was defined as sputum culture conversion, cure, or treatment completion in the absence of death, default, treatment failure, or relapse. A cohort of 194 patients was assembled from 20 articles involving 12 geographical regions. In descending order of frequency, linezolid was used in 162 (84%), macrolides in 84 (43%), clofazimine in 65 (34%), amoxicillin with clavulanate in 56 (29%), thioridazine in 18 (9%), carbapenem in 16 (8%), and high-dose isoniazid in 16 (8%). Cohort analysis with robust Poisson regression models and random-effects meta-analysis similarly suggested that linezolid use significantly increased the probability (95% confidence interval) of favorable outcome by 57% (10%, 124%) and 55% (10%, 121%), respectively. Defining significant associations by risk ratios ≥ 1.2 or ≤ 0.9, neither cohort analysis nor meta-analysis demonstrated any significant add-on benefit from the use of other Group 5 drugs on outcome of patients treated with linezolid, although selection bias might have underestimated their effects. Our findings substantiated use of linezolid in the treatment of XDR-TB or fluoroquinolone-resistant MDR-TB, and calls for further studies to evaluate the roles of other Group 5 drugs.
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