Drug-resistant tuberculosis treatment

Su
m
m
ar
y o
f c
ha
ng
es t
o t
he W
H
O 
M
D
R
/R
R-
TB 
tr
ea
tm
en
t r
ec
om
m
end
at
io
ns 
bet
w
een 2
01
9 a
nd 
cu
rr
en
t u
pd
at
es
No
te
: The
W
H
O c
onsolidat
ed guide
line
s on drug-
re
sist
ant
t
ube
rc
ulosis t
re
at
m
ent
w
er
e a c
om
pilat
ion o
f e
xist
ing and ne
w
r
ec
om
m
endat
io
ns on t
he
treatment and management o
f MDR/RR-TB 
and as such they included new r
ecommendations published 
in 2019 and existing r
ecommendations that had 
been pr
eviously published. In the 
curr
ent 
update (2020), 
ther
e 
ar
e 
two 
new 
recommendations 
(Recommendations 2.1 and 4.1) and a minor change to 
the 
wor
ding o
f a pr
e-existing r
ecommendation (Recommendation 3.1). 
Recommendation 2.1 is an update to a pr
evious r
ecommendation on shor
ter r
egimens 
for MDR/RR-T
B while r
ecommendation 4.1 was based on a new PIC
O question concer
ning the BP
aL r
egimen. Recommendations on the duration o
f longer 
regimens 
for 
MDR/RR-TB (Recommendations 
3.15, 3.16 and 3.17) wer
e 
combined 
into the 
section 
on the 
composition o
f longer r
egimens 
for 
MDR/RR-TB 
(Recommendations 3.1 
to 3.14), 
however the wor
ding o
f the r
ecommendations on duration 
remained unchan
ged. All other r
ecommendations r
emain 
unchanged. 
Recommendations in the 2019 updat
e
Recommendations in the curr
ent updat
e
Section 1: R
egimens for isoniazid-r
esistant tuber
culosis
Section 1: R
egimen for rifampicin-susceptible and isoniazid-r
esistant 
tuber
culosis
In patients with confir
med rifampicin-susceptible and isoniazid-
resistant tuber
culosis, tr
eatment with rifampicin, ethambutol, 
pyrazinamide and levo
flo
xacin is r
ecommended for a duration o
f 
6 months
 (conditional r
ecommendation, ver
y low cer
tainty in the 
estimates o
f
 
effect).
1.1 In patients with confir
med rifampicin-susceptible, isoniazid-r
esistant 
tuber
culosis (Hr
-TB), tr
eatment with rifampicin, ethambutol, pyrazinamide and 
levo
flo
xacin is r
ecommended for a duration o
f 6
months.
(Conditional r
ecommendation, ver
y low cer
tainty in the estimates o
f effect).
(no
 
change)
In patients with confir
med rifampicin-susceptible and isoniazid-
resistant tuber
culosis, it is not r
ecommended to add str
eptomycin 
or other injectable agents to the tr
eatment r
egimen
 (conditional 
recommendation, ver
y low cer
tainty in the estimates o
f
 
effect).
1.2. In patients with confir
med rifampicin-susceptible, isoniazid-r
esistant 
tuber
culosis, it is not r
ecommended to add str
eptomycin or other injectable 
agents to the tr
eatment
regimen.
(Conditional r
ecommendation, ver
y low cer
tainty in the estimates o
f effect). 
(no
 
change)

---

WHO consolidated 
guidelines 
on
tuberculosis: 
drug-resistant tuberculosis treatment
91
Recommendations in the 2019 updat
e
Recommendations in the curr
ent updat
e
Section 2: The composition o
f longer MDR-TB r
egimens 
Section 3: Longer r
egimens for multidrug-/ rifampicin-r
esistant 
tuber
culosis
In MDR/RR-TB patients on longer r
egimens, all thr
ee Gr
oup A 
agents and at least one Gr
oup B agent should be included to 
ensur
e that tr
eatment star
ts with at least four TB agents likely to 
be effective, and that at least thr
ee agents ar
e included for the 
rest o
f the tr
eatment af
ter bedaquiline is stopped.
68
If only one 
or two Gr
oup A agents ar
e used, both Gr
oup B agents ar
e to be 
included. If the r
egimen cannot be composed with agents fr
om 
Gr
oups A and B alone, Gr
oup C agents ar
e added to complete it 
(conditional r
ecommendation, ver
y low cer
tainty in the estimates 
of
 
effect).
3.1 In multidrug- or rifampicin-r
esistant tuber
culosis (MDR/RR-TB) patients 
on longer r
egimens, all thr
ee Gr
oup A agents and at least one Gr
oup B agent 
should be included to ensur
e that tr
eatment star
ts with at least four TB agents 
likely to be effective, and that at least thr
ee agents ar
e included for the r
est 
of tr
eatment if bedaquiline is stopped. If only one or two Gr
oup A agents 
ar
e used, both Gr
oup B agents ar
e to be included. If the r
egimen cannot be 
composed with agents fr
om Gr
oups A and B alone, Gr
oup C agents ar
e added 
to complete it. 
(Conditional r
ecommendation, ver
y low cer
tainty in the estimates o
f effect). 
(editing o
f the w
or
d “af
ter
” t
o “i
f” with r
efer
enc
e to stopping
 
bedaquiline)
Kanamycin and capr
eomycin ar
e not to be included in 
the tr
eatment o
f MDR/RR-TB patients on longer r
egimens 
(conditional r
ecommendation, ver
y low cer
tainty in the estimates 
of
 
effect).
3.2 Kanamycin and capr
eomycin ar
e not to be included in the tr
eatment o
f 
MDR/RR-TB patients on longer r
egimens. 
(Conditional r
ecommendation, ver
y low cer
tainty in the estimates o
f effect). 
(no
 
change)
Levo
flo
xacin or mo
xiflo
xacin should be included in the 
treatment o
f MDR/RR-TB patients on longer r
egimens
 (str
ong 
recommendation, moderate cer
tainty in the estimates o
f
 
effect).
3.3 Levo
flo
xacin or mo
xiflo
xacin should be included in the tr
eatment o
f MDR/
RR-TB patients on longer
regimens.
(Str
ong r
ecommendation, moderate cer
tainty in the estimates o
f effect). 
(no
 
change)
Bedaquiline should be included in longer MDR-TB r
egimens 
for patients aged 18 year
s or mor
e (str
ong r
ecommendation, 
moderate cer
tainty in the estimates o
f effect). Bedaquiline may 
also be included in longer MDR-TB r
egimens for patients aged 
6–17 year
s (conditional r
ecommendation, ver
y low cer
tainty in the 
estimates o
f
 
effect).
3.4 Bedaquiline should be included in longer multidrug-r
esistant TB (MDR-TB) 
regimens for patients aged 18 year
s or
mor
e.
(Str
ong r
ecommendation, moderate cer
tainty in the estimates o
f
 
effect)
 
Bedaquiline may also be included in longer MDR-TB r
egimens for patients aged 
6–17
year
s. 
(Conditional r
ecommendation, ver
y low cer
tainty in the estimates o
f effect). 
(no
 
change)
68
Gr
oup A = levo
flo
xacin/mo
xiflo
xacin, bedaquiline, linezolid; Gr
oup B = clo
fazimine, cycloserine/terizidone; Gr
oup C = ethambutol, delamanid, pyrazinamide, imipenem–cilastatin, mer
openem, amikacin
(str
eptomycin), ethionamide/pr
othionamide, p-aminosalicylic acid (see also 
Table 3
.1
).

---

Supplementary Table
92
Recommendations in the 2019 updat
e
Recommendations in the curr
ent updat
e
Linezolid should be included in the tr
eatment o
f MDR/RR-TB 
patients on longer r
egimens
 (str
ong r
ecommendation, moderate 
cer
tainty in the estimates o
f
 
effect).
3.5 Linezolid should be included in the tr
eatment o
f MDR/RR-TB patients on 
longer r
egimens. 
(Str
ong r
ecommendation, moderate cer
tainty in the estimates o
f effect). 
(no
 
change)
Clo
fazimine and cycloserine or terizidone may be included 
in the tr
eatment o
f MDR/RR-TB patients on longer r
egimens 
(conditional r
ecommendation, ver
y low cer
tainty in the estimates 
of
 
effect).
3.6 Clo
fazimine and cycloserine or terizidone may be included in the tr
eatment 
of MDR/RR-TB patients on longer
regimens.
(Conditional r
ecommendation, ver
y low cer
tainty in the estimates o
f effect). 
(no
 
change)
Ethambutol may be included in the tr
eatment o
f MDR/RR-TB 
patients on longer r
egimens
 (conditional r
ecommendation, ver
y 
low cer
tainty in the estimates o
f
 
effect).
3.7 Ethambutol may be included in the tr
eatment o
f MDR/RR-TB patients on 
longer
regimens.
(Conditional r
ecommendation, ver
y low cer
tainty in the estimates o
f effect). 
(no
 
change)
Delamanid may be included in the tr
eatment o
f MDR/RR-TB 
patients aged 3 year
s or mor
e on longer r
egimens
 (conditional 
recommendation, moderate cer
tainty in the estimates o
f
 
effect).
3.8 Delamanid may be included in the tr
eatment o
f MDR/RR-TB patients aged 
3 year
s or mor
e on longer
regimens.
(Conditional r
ecommendation, moderate cer
tainty in the estimates o
f effect). 
(no
 
change)
Pyrazinamide may be included in the tr
eatment o
f MDR/RR-TB 
patients on longer r
egimens 
(conditional r
ecommendation, ver
y 
low cer
tainty in the estimates o
f
 
effect).
3.9 Pyrazinamide may be included in the tr
eatment o
f MDR/RR-TB patients on 
longer
regimens.
(Conditional r
ecommendation, ver
y low cer
tainty in the estimates o
f effect).