Mortality in Adults with MDR-TB and HIV by ART and TB Drug Use: Individual Patient Data Meta-Analysis

Evidence-based Definition for Extensively Drug-Resistant Tuberculosis

“…demonstration in an open-label, single-arm trial of the efficacy of the new BPaL regimen (bedaquiline, pretomanid and linezolid for 6-9 months) followed by its FDA approval (21,31) underlines the importance of the bedaquiline-linezolid combination in a regimen that also includes the new nitroimidazole compound pretomanid. The trial data showed also a high frequency of adverse reactions (peripheral neuropathy, bone marrow suppression), largely attributable to linezolid at the dose of 1200 mg/day, twice as high as in the IPDMA and other studies (15,32). Given the trial results leading to the FDA approval and our data confirming the importance of the bedaquiline-linezolid combination, research towards lower doses (or shorter courses) of linezolid, or new, less toxic oxazolidinones, are top priority.…”

“…We used the latest version of the IPDMA database (June 2018), following the same inclusion criteria as before (7,14). Detailed description of the IPDMA composition process (centre characteristics, outcome definition, drug susceptibility testing (DST) methods and drug dosages), and each individual study is shown elsewhere (15). The data include anonymised information for…”

“…Treatment outcomes were defined in accordance with the WHO guidelines as explained in detail elsewhere (15,16). They were summarized as unfavourable if the treatment failed, a relapse occurred or the patient died or was lost-to-follow-up; and as favourable in case of cure or completed treatment with no reported failure or relapse (15,16).…”