**3. Recent WHO Recommendations for the Treatment of MDR**/**RR TB**

In the last decades, WHO made great efforts to facilitate and improve the treatment of patients with MDR-TB in high burden countries using various actions including the Directly Observed Treatment Strategy (DOTS)-Plus, to stress the use of second-line drugs in low- and middle-income settings, but the cure rate was lower than the WHO 2015 target of at least 75% to 90% [6]. For instance, treatment success for MDR/RR-TB cases started on treatment in 2016 in India, China and Russian Federation was 48%, 52% and 54%, respectively [1].

In 2018, the results from an individual patient data meta-analysis involving 12,030 patients from 25 countries showed that treatment success and death of pulmonary MDR-TB were significantly reduced after the administration of the newer or repurposed drugs linezolid (LZD), later generation FQs, bedaquiline (BDQ), clofazimine (CFZ) and carbapenems [7]. On the basis of this and other studies, in March 2019, WHO released a new drug classification and new recommendations for the treatment of MDR-TB [8–10]. The second-line drugs were reorganized into three groups, including priority drugs [Group A: LFX or MFX, BDQ, LZD], preferentially used drugs [Group B: CFZ, cycloserine (CS) or terizidone (TRD)], and other drugs [Group C: EMB, delamanid (DLM), PZA, imipenem-cilastatin (IPM-CLN) or meropenem (MPM) (administered with clavulanic acid, CLV), AM or streptomycin (SM), ethionamide (ETO) or protionamide (PTO), para-aminosalicylic acid (PAS)].

In summary, WHO recommended an injection-free therapy (groups A and B drugs) at the initiation of MDR-TB treatment. Group C agents (oral and parenteral) should be administered when groups A and B drugs cannot be used. The commonly used second-line injectable drugs KM and CM were associated with worse outcomes [7], and were no longer recommended for the treatment of MDR-TB; AK and SM may be administered only if drug susceptibility testing (DST) confirms susceptibility.

To further reduce the burden of drug-resistant TB in the near future, in December 2019, WHO also released a Rapid Communication to inform countries and stakeholders that a regimen containing BDQ, pretomanid (PRT, formerly PA-824) and LNZ (BPaL regimen) may be used under operational research conditions conforming to WHO standards for the treatment of XDR-TB patients [11]. This communication was released after a previous announcement of the Global TB Alliance in the second half of 2019, following the decision of the United States Food and Drug Administration (FDA) to administer BPaL (Nix-TB trial by the Global TB Alliance) to adults with pulmonary XDR-TB or intolerant/not responsive MDR-TB [12].
