11.1 Treatment schemes

11.1.1 Choice of the treatment scheme

Mono- and poly-drug resistant tuberculosis (PDR-TB) management is based on the PDR treatment schemes presented in Table 11.1.

Table 11.1 - Resistance pattern and recommended treatment schemes

Resistance category

H

R

E

S

Treatment scheme



H-R susceptible

Sus.

Sus.

Sus.

Sus.

New case regimen

Sus.

Sus.

Sus.

Res.

New case regimen

Sus.

Sus.

Res.

Sus.

New case regimen

Sus.

Sus.

Res.

Res.

New case regimen



H-resistance

Res.

Sus.

Sus.

Sus.

PDR Scheme A*

Res.

Sus.

Sus.

Res.

PDR Scheme A*

Res.

Sus.

Res.

Sus.

PDR Scheme B

Res.

Sus.

Res.

Res.

PDR Scheme B



R-resistance

Sus.

Res.

Sus.

Sus.

PDR Scheme C

Sus.

Res.

Sus.

Res.

PDR Scheme C

Sus.

Res.

Res.

Sus.

PDR Scheme C

Sus.

Res.

Res.

Res.

PDR Scheme C

Sus. = susceptible; Res. = resistant.
* Except previously treated patients, for whom PDR Scheme B + ethambutol is preferred.

The treatment schemes of mono/PDR-TB are based on the assumption that a full baseline drug susceptibility testing (DST) is performed before or at the start of treatment with firstline anti-TB drugs.

There is little published evidence to determine the best treatment for mono/PDR-TB. The treatment schemes are therefore based on the principles of TB treatment and expert opinion1,2,3.

At least 3, ideally 4, likely effective drugs are included in the regimen. DST results at baseline and previous treatment history are used to choose the appropriate scheme.

The use of Xpert MTB/RIF can greatly aid in getting patients on the proper regimens when isoniazid resistance is present and amplification of resistance to rifampicin is a possibility.

Perform second-line DST if patients come from a region of high second-line resistance and if there is a history of second-line anti-TB drug use. Resistance to second-line anti-TB drugs will impact the choice of regimen.

11.1.2 PDR Scheme A for cases with H or HS resistance

For new patients, the treatment regimen is 9 RZE. However, the combination HRZE can be used if more convenient since it can be given as fixed-dose combination.

At Month 2, perform smear, Xpert MTB/RIF, and culture:

Xpert
available

Xpert RIF+: switch to empiric MDR regimen while waiting for full DST results then, adapt treatment accordingly.
Xpert RIF−: continue PDR Scheme A.


Xpert
not available


Culture+: switch to empiric MDR regimen with the inclusion of R while waiting for full DST results.
• DST is unchanged (H or HS resistance only): stop the MDR regimen, and resume PDR Scheme A;
• DST has changed: adapt treatment accordingly.
Culture−: continue PDR Scheme A.

Perform smear and culture every other month. If cultures or smears are positive, switch to MDR regimen while waiting for full DST results then, adapt treatment accordingly.

For previously treated patients, it is safer to use Scheme B plus ethambutol, as DST to this drug should not be relied upon if the patient has already received it.

11.1.3 PDR Scheme B for cases with HE or HES resistance

Start patients on 3 Cm (or Km)-Lfx-RZ/7 Lfx-RZ regardless of smear status at the time of diagnosis.

At Month 2, perform smear, Xpert MTB/RIF and culture:

Xpert
available

Xpert RIF+: switch to empiric MDR regimen while waiting for full DST results then, adapt treatment accordingly.
Xpert RIF−: continue PDR Scheme B.


Xpert
not available

Culture+: switch to empiric MDR regimen with the inclusion of R while waiting for full DST results.
DST is unchanged (HE or HES resistance only): stop the MDR regimen, and resume PDR Scheme B;
DST has changed: adapt treatment accordingly.
Culture−: continue PDR Scheme B.

At Month 3, perform smear, Xpert MTB/RIF, and culture. If Xpert shows RIF+ or if the culture is still positive, this regimen is declared “failure”. Switch to MDR treatment.

Even if found susceptible, streptomycin should not be used given the high rates of resistance to this drug in patients with DR-TB and the poor reliability of the DST.

11.1.4 PDR Scheme C for cases with R or RS or RE or RES resistance

Start patient on MDR regimen until confirmation that the strain is susceptible to fluoroquinolones and injectable agents.

When DST results confirm resistance to R, RS, RE or RES and susceptibility to H, fluoroquinones and an injectable agent, there are two options:
1 - Continue the full course of MDR-TB treatment plus isoniazid. This is a reasonable consideration given that DST reliability is not 100%. This is recommended if the suspicion for MDR-TB is high (i.e. a contact of an MDR-TB patient or failure of a first-line regimen).
2 - Start PDR Scheme C: 3 Cm (or Km)-Lfx-HZ (+/-E)/12 Lfx-HZ (+/- E). Ethambutol is added if it is likely to be effective.

Even if found susceptible, streptomycin should not be used given the high rates of resistance to this drug in patients with DR-TB and the poor reliability of the DST.

At Month 2, perform smear and culture:
Culture+: start empiric MDR regimen and repeat DST.
• DST is unchanged: resume PDR Scheme C;
• DST has changed: adapt treatment accordingly.
Culture−: complete PDR Scheme C.

At Month 3, perform smear and culture. If the culture is still positive, this regimen is declared “failure.” Switch to MDR treatment.

Note: if the baseline DST is performed by LPA (Hain® test), only DST for R and H are available. In order to avoid possible resistance amplification, the worst scenario should be assumed:
– If only resistance to H is detected, treat with Scheme B, even new patients while waiting for full DST.
– If only resistance to R is detected, treat as MDR-TB as sensitivity of Hain® test for H resistance is low.