Drug-resistant tuberculosis treatment

Section 4. The bedaquiline, pretomanid and linezolid 
(BPaL) regimen for multidrug-resistant tuberculosis 
with additional fluoroquinolone resistance
4.1 Recommendation
No.
Recommendation
4.1
A treatment regimen lasting 6–9 months, composed of bedaquiline, 
pretomanid and linezolid (BPaL), may be used under operational research 
conditions in multidrug-resistant tuberculosis (MDR-TB) patients with TB that 
is resistant to fluoroquinolones, who have either had no previous exposure 
to bedaquiline and linezolid or have been exposed for no more than 2 weeks.  
(Conditional recommendation, very low certainty in the estimates of
 
effect)
4.2 Remarks
• 
The bedaquiline, pretomanid
47
and linezolid (BPaL) regimen, which was used in the Nix-TB 
study
48
(89), may not be considered for routine programmatic use worldwide until additional 
evidence on efficacy and safety has been generated. However, in individual patients for whom the 
design of an effective regimen based on existing WHO recommendations is not possible, the BPaL 
regimen may be considered as a last resort under prevailing ethical
standards.
• 
The evidence reviewed supports the use of this regimen in certain patient subgroups, such as 
PLHIV (see 
Section 4.4
). 
4.3 Justification and evidence
The recommendation in this section addresses the following
question:
PICO question 10 (MDR/RR-TB, 2020): In XDR-TB patients or patients who are treatment 
intolerant or with non-responsive MDR-TB, does a treatment regimen lasting 6–9 months 
composed of bedaquiline, pretomanid and linezolid safely improve outcomes when compared 
with other regimens conforming to WHO
 
guidelines?
This is a new recommendation for a defined patient group; it is to be used under operational 
research conditions, and thus does not apply to routine programmatic use. Given these limitations, 
this recommendation complements other WHO recommendations on the use of longer regimens 
for patients with MDR/RR-TB (see Section 3) because individuals with MDR/RR-TB and additional 
fluoroquinolone resistance would usually receive a longer regimen comprising medicines from Groups 
A, B and C, according to their drug susceptibility profile and other parameters. Several conditions 
are therefore necessary for the implementation of this new recommendation on BPaL, and these are 
described in 
Section 4.5
. 
Treatment of XDR-TB presents multiple challenges to clinicians and NTPs, because of the limited 
range of medicines available and the life-threatening nature of the disease. Patients with MDR/RR-TB 
and additional fluoroquinolone resistance have typically experienced poor treatment outcomes since 
XDR-TB was first described in 2006 (90). Based on data reported by Member States to WHO, for the 
47 
Pretomanid is a new chemical entity and a member of a class of compounds known as nitroimidazo-oxazines, which possess significant 
anti-TB activity and a unique mechanism of
action.
48 
The protocol for the Nix-TB study is available at https://clinicaltrials.gov/ct2/show/NCT02333799.https://clinicaltrials.gov/ct2/show/
NCT02333799, and the results of the Nix-TB study have been published (90).