In 2020, an open-label, single-group study reported on the efficacy and safety of a new drug regimen (bedaquiline, pretomanid and linezolid – BPaL) taken for 6-to-9 months, in the management of 109 patients with XDR-TB or difficult-to-treat MDR-TB.118 The study found that 98 patients (90%) had a favorable treatment outcome. Adverse events, however, were frequent; all patients had at least one adverse event and 17% had a serious adverse event. Linezolid was started at 1200 mg daily, with dose adjustment for adverse events, and linezolid-related adverse events were very common; peripheral neuropathy occurred in 81% of patients, and myelosuppression in 48%. The 2020 WHO guidelines recommend use of this regimen only in operational research conditions, in MDR-TB patients with TB that is resistant to fluoroquinolones, and in those who have had no previous exposure (≤2 weeks) to bedaquiline or linezolid. Other eligibility criteria, drug dosing and monitoring are found in the WHO Operational Handbook.93 Some expert centers in other countries are using BPaL with lower doses of linezolid, guided by therapeutic drug monitoring.112 An ongoing clinical trial (ZeNix) is evaluating the BPaL regimen with a lower dose and shorter duration of linezolid.119
In addition to the ongoing studies of the BPaL regimen, there are multiple other ongoing studies of shorter treatment regimens for MDR-TB, most of which include bedaquiline.120 Numerous new anti-TB drugs are also under development.120 Only one new drug, however, is currently in use outside of clinical trials for MDR-TB management, a drug called pretomanid, which was studied as part of the BPaL regimen. Given there is no experience with pretomanid in other combinations, it is not recommended by WHO for use outside the context of the BPaL regimen.
The high number of ongoing trials of new anti-TB drugs and new regimens suggests that the optimal management of MDR-TB will continue to evolve in the near future.
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