Multistudy analysis finds linezolid may be effective against XDR-TB
Meta-analysis of 20 articles involving World Health Organization (WHO) group 5 drugs suggested that linezolid significantly increases the probability of favorable outcomes in people with extensively drug-resistant tuberculosis (XDR-TB). Adding other group 5 drugs to linezolid had little impact in this analysis.
Multidrug-resistant (MDR) TB and XDR-TB have emerged as grave threats in regions of high TB prevalence, notably in people with HIV infection. WHO ranks anti-TB drugs into five groups. Although group 5 drugs are “agents with an unclear role in the treatment of drug-resistant TB,” they must often be included in regimens for XDR-TB or fluoroquinolone-resistant MDR-TB. The group 5 drugs are clofazimine, linezolid, amoxicillin with clavulanate, thioacetazone, imipenem/cilastatin, high-dose isoniazid, and clarithromycin.
To learn more about the potential value of group 5 drugs in treating XDR-TB and fluoroquinolone-resistant MDR-TB, researchers conducted a systematic review of studies including individual patient data and published through 7 April 2013. They defined a favorable outcome as sputum culture conversion, cure, or treatment completion without death, default, treatment failure, or relapse.
The investigators found 20 articles including 194 patients in 12 geographical regions. Group 5 drugs used to treat resistant TB in these patients were linezolid in 162 patients (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 Poisson regression models and random-effects meta-analysis determined that linezolid significantly increased the probability of favorable outcome by 57% (95% confidence interval 10% to 124%) and 55% (95% CI 10% to 121%) respectively.
Neither cohort analysis nor meta-analysis suggested an add-on benefit with any other group 5 drug in people already receiving linezolid, though the researchers note that selection bias could have led to underestimation of the effects of these other drugs.
The authors believe their findings “substantiated the use of linezolid in the treatment of XDR-TB or fluoroquinolone-resistant MDR-TB and call for further studies to evaluate the roles of other group 5 drugs.”
A separate review of in vitro, animal, and clinical data on group 5 drugs used for drug-resistant TB determined that linezolid “appears to be effective but is frequently discontinued due to toxicity.” This analysis also yielded evidence that clofazimine and beta-lactams “may have unrealized potential in the treatment of drug-resistant tuberculosis and warrant further study.”
Sources:
Kwok-Chiu Chang, Wing-Wai Yew, Cheuk-Ming Tam, Chi-Chiu Leung. WHO group 5 drugs and difficult multidrug-resistant tuberculosis: a systematic review with cohort analysis and meta-analysis. Antimicrobial Agents and Chemotherapy. 2013; 57: 4097-4104.
Kelly E. Dooley, Ekwaro A. Obuku, Nadza Durakovic, Vera Belitsky, Carole Mitnic, Eric L. Nuermberger on behalf of the Efficacy Subgroup, RESIST-TBWorld Health Organization group 5 drugs for the treatment of drug-resistant tuberculosis: unclear efficacy or untapped potential? Journal of Infectious Diseases. 2013; 207:1352-1358.
For the Chang article
For the Dooley article
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Source: IAS
