Heni Retnowulan

Pulmonary SubDepartement, Internal Medicine Departement

Medicine Faculty, Sardjito Hospital
Gadjah Mada University, Yogyakarta
Topics
• Hr TB
• RRTB - Longer Regimen
• RRTB - Shorter Regimen
• DR TB - HIV
 Hr TB
• In patients with confirmed rifampicin-susceptible and
isoniazid-resistant tuberculosis, treatment with
rifampicin, ethambutol, pyrazinamide (REZ) and
levofloxacin is recommended for a duration of 6
months

• In patients with confirmed rifampicin-susceptible and

isoniazid-resistant tuberculosis, it is not recommended
to add streptomycin or other injectable agents to the
treatment regimen
 Regimens for isoniazid-resistant
tuberculosis

Diagnostic capabilities

Rapid molecular tests such as Xpert MTB/RIF and LPAs

are preferred to guide patient selection for the
(H)REZ–levofloxacin regimen
 Regimens for isoniazid-resistant
tuberculosis

Implementation considerations

• Hr-TB is confirmed before TB treatment is started

started immediately

• Hr-TB is confirmed after the start of treatment with the 2HREZ/4HR

regimen

Rapid molecular testing for rifampicin resistance must be done (or

repeated). Once rifampicin resistance is excluded, a full 6-month
course of (H)REZ– levofloxacin is given.
If rifampicin resistance is detected  MDR-TB treatment
regimen.
 Regimens for isoniazid-resistant
tuberculosis
The addition of levofloxacin to (H)REZ is recommended in
patients with Hr-TB, with the exception of the following

• in cases where resistance to rifampicin cannot be excluded

(i.e. unknown susceptibility to rifampicin indeterminate/error
results on Xpert MTB/RIF)
• known or suspected resistance to levofloxacin
• known intolerance to fluoroquinolones
• known or suspected risk for prolonged QT-interval
• if possible in pregnancy or during breastfeeding (not an
absolute contraindication).
Topics
• Hr TB
• RRTB - Longer Regimen
• RRTB - Shorter Regimen
• DR TB - HIV
• Acid-fast smear, mycobacterial cultures & DST to R & H.
• Baseline potassium, creatinine, serum glucose & serum glutamic-pyruvic
transaminase (SGPT); alanine transaminase (ALT)).
• HIV rapid testing
• If HIV positive, refer for full blood count and CD4 (CD4% in children).
• Baseline full blood count should be performed if anaemia is suspected.
• Pregnancy test for women of childbearing age.
• Routine baseline FT4 and TSH test can be done on all patients if
resources permit.
• Audiometry.
• Chest radiograph.
• Electrocardiogram if bedaquiline is to be included in the regimen or the
patient has a history of cardiac disease.
• Baseline psychosocial assessment
• The intensive phase is recommended, including
pyrazinamide and four core secondline

• TB medicines – one chosen from Group A, one from

Group B, and at least two from Group C

• In patients with RR-TB or MDR-TB, it is recommended

that the regimen be further strengthened with high-
dose isoniazid and/or ethambutol
Z - 1A - 1B - 2C - Hh - E
Z - Lfx - Km - Eto - Cs - Hh - E
Z - 1A - 1B - 2C - Hh - E
Z - Lfx - Km - Eto - Cs - Hh - E
The composition of longer MDR-TB regimens
Grouping of medicines recommended for use in longer MDR-TB regimens
Activity of anti-tuberculosis drugs and their use

Deun AV, INT J TUBERC LUNG DIS 22(3):239–245 Q 2018 The Union
Activity of anti-tuberculosis drugs and their use

Deun AV, INT J TUBERC LUNG DIS 22(3):239–245 Q 2018 The Union
The composition of longer MDR-TB regimens
Grouping of medicines recommended for use in longer MDR-TB regimens
The composition of longer MDR-TB regimens
Grouping of medicines recommended for use in longer MDR-TB regimens
The composition of longer MDR-TB regimens
Grouping of medicines recommended for use in longer MDR-TB regimens
 The composition of longer MDR-TB regimens
• Regimens be composed of all three Group A agents and at least one Group
B agent, so that treatment starts with at least four medicines likely to be
effective and that at least three agents are continued for the remaining
duration of treatment after bedaquiline is stopped.

• If only one or two Group A agents can be used, both Group B agents are
included.

• If the regimen cannot be composed with agents from Groups A and B alone,
Group C agents are added to complete it.

• In patients in whom two agents from Group A are more likely to be stopped
before the end of treatment (e.g. pre-existing comorbidities require that
both bedaquiline and linezolid be stopped early because of health risks),
then starting with five effective agents rather than four may be advisable.

• These provisions are expected to apply to most MDR-TB patients, including

those with additional resistance to fluoroquinolones or other medicines.
The composition of longer MDR-TB regimens

3A
2B

6 Lfx – Bdq – Lzd – Cfz – Cs / 12 Lfx – Cfz - Cs

The composition of longer MDR-TB regimens

■ 3A
■
■
■ 2B

6 Lfx – Bdq – Lzd – Cfz – Cs / 12 Lfx – Cfz - Cs

The composition of longer MDR-TB regimens

■ 3A
■
■
■ 2B

6 Lfx – Bdq – Lzd – Cfz – Cs / 12 Lfx – Cfz - Cs

The composition of longer MDR-TB regimens

■ 3A
■
■
■ 2B

6 Lfx – Bdq – Lzd – Cfz – Cs / 12 Lfx – Cfz - Cs

 The duration of longer MDR-TB regimens

• A total treatment duration of 18–20 months is

suggested for most patients

• treatment duration of 15–17 months after culture

conversion is suggested for most patients

• longer regimens containing amikacin or streptomycin,

an intensive phase of 6–7 months is suggested for most
patients;
The composition of longer MDR-TB regimens

■ 3A
■
■
■ 2B

6 Lfx – Bdq – Lzd – Cfz – Cs / 12 Lfx – Cfz - Cs

The composition of longer MDR-TB regimens

■ 3A
■
■
■ 2B

6 Lfx – Bdq – Lzd – Cfz – Cs / 12 Lfx – Cfz - Cs

 The composition of longer MDR-TB regimens
• Regimens be composed of all three Group A agents and at least one Group
B agent, so that treatment starts with at least four medicines likely to be
effective and that at least three agents are continued for the remaining
duration of treatment after bedaquiline is stopped.

• If only one or two Group A agents can be used, both Group B agents are
included.

• If the regimen cannot be composed with agents from Groups A and B alone,
Group C agents are added to complete it.

• In patients in whom two agents from Group A are more likely to be stopped
before the end of treatment (e.g. pre-existing comorbidities require that
both bedaquiline and linezolid be stopped early because of health risks),
then starting with five effective agents rather than four may be advisable.

• These provisions are expected to apply to most MDR-TB patients, including

those with additional resistance to fluoroquinolones or other medicines.
 The composition of longer MDR-TB regimens
• Regimens be composed of all three Group A agents and at least one Group
B agent, so that treatment starts with at least four medicines likely to be
effective and that at least three agents are continued for the remaining
duration of treatment after bedaquiline is stopped.

• If only one or two Group A agents can be used, both Group B agents are
included.

• If the regimen cannot be composed with agents from Groups A and B alone,
Group C agents are added to complete it.

• In patients in whom two agents from Group A are more likely to be stopped
before the end of treatment (e.g. pre-existing comorbidities require that
both bedaquiline and linezolid be stopped early because of health risks),
then starting with five effective agents rather than four may be advisable.

• These provisions are expected to apply to most MDR-TB patients, including

those with additional resistance to fluoroquinolones or other medicines.
 The composition of longer MDR-TB regimens
• Regimens be composed of all three Group A agents and at least one Group
B agent, so that treatment starts with at least four medicines likely to be
effective and that at least three agents are continued for the remaining
duration of treatment after bedaquiline is stopped.

• If only one or two Group A agents can be used, both Group B agents are
included.

• If the regimen cannot be composed with agents from Groups A and B alone,
Group C agents are added to complete it.

• In patients in whom two agents from Group A are more likely to be stopped
before the end of treatment (e.g. pre-existing comorbidities require that
both bedaquiline and linezolid be stopped early because of health risks),
then starting with five effective agents rather than four may be advisable.

• These provisions are expected to apply to most MDR-TB patients, including

those with additional resistance to fluoroquinolones or other medicines.
The composition of longer MDR-TB regimens
pre XDR (FQs) or XDR

2A
2B
1C

6 Bdq – Lzd – Cfz – Cs – E / 12 Cfz – Cs - E

The composition of longer MDR-TB regimens
pre XDR (FQs) or XDR

■ 2A
■
■
■ 2B
■ 1C

6 Bdq – Lzd – Cfz – Cs – E / 12 Cfz – Cs - E

The composition of longer MDR-TB regimens
pre XDR (FQs) or XDR

■ 2A
■
■
■ 2B
■ 1C

6 Bdq – Lzd – Cfz – Cs – E / 12 Cfz – Cs - E

The composition of longer MDR-TB regimens
pre XDR (FQs) or XDR

■ 2A
■
■
■ 2B
■ 1C

6 Bdq – Lzd – Cfz – Cs – E / 12 Cfz – Cs - E

The composition of longer MDR-TB regimens
pre XDR (FQs) or XDR

■ 2A
■
■
■ 2B
■ 1C

6 Bdq – Lzd – Cfz – Cs – E / 14 Cfz – Cs - E

The composition of longer MDR-TB regimens
Bdq Intolerance
■

2A
■
■
■ 2B
■
1C

6 Lfx - Lzd – Cfz – Cs – Dlm / 12 Lfx - Cfz – Cs

The composition of longer MDR-TB regimens
Bdq Intolerance
■

2A
■
■
■ 2B
■
1C

6 Lfx - Lzd – Cfz – Cs – Dlm / 12 Lfx - Cfz – Cs

The composition of longer MDR-TB regimens
Bdq Intolerance
■

2A
■
■
■ 2B
■
1C

6 Lfx - Lzd – Cfz – Cs – Dlm / 12 Lfx - Cfz – Cs

The composition of longer MDR-TB regimens
Bdq Intolerance
■

2A
■
■
■ 2B
■
1C

6 Lfx - Lzd – Cfz – Cs – Dlm / 12 Lfx - Cfz – Cs

Topics
• Hr TB
• RRTB - Longer Regimen
• RRTB - Shorter Regimen
• DR TB - HIV
Use of the standardized shorter MDR-TB regimen

Recommendation

In MDR/RR-TB patients who have not been previously treated for more
than 1 month with second-line medicines used in the shorter MDR-TB
regimen or in whom resistance to fluoroquinolones and second-line
injectable agents has been excluded, a shorter MDR-TB regimen of 9–12
months may be used instead of the longer regimens (conditional
recommendation, low certainty in the estimates of effect).
The composition of shorter MDR-TB regimens

4-6 Km - Gfx/Mfx - Pto/Eto - Cfz - Hh - Z - E /

5 Gfx/Mfx - Cfz - Z - E

No modifications were made to the shorter

MDRTB regimen
The composition of shorter MDR-TB regimens

4-6 Km - Gfx/Mfx - Pto/Eto - Cfz - Hh - Z - E /

5 Gfx/Mfx - Cfz - Z - E

No modifications were made to the shorter

MDRTB regimen
The composition of shorter MDR-TB regimens

4-6 Km - Gfx/Mfx - Pto/Eto - Cfz - Hh - Z - E /

5 Gfx/Mfx - Cfz - Z - E

No modifications were made to the shorter

MDRTB regimen
The composition of shorter MDR-TB regimens

4-6 Amk - Gfx/Mfx - Pto/Eto - Cfz - Hh - Z - E /

5 Gfx/Mfx - Cfz - Z - E

No modifications were made to the shorter

MDRTB regimen
The composition of shorter MDR-TB regimens

4-6 Amk - Gfx/Mfx - Pto/Eto - Cfz - Hh - Z - E /

5 Gfx/Mfx - Cfz - Z - E

No modifications were made to the shorter

MDRTB regimen
Topics
• Hr TB
• RRTB - Longer Regimen
• RRTB - Shorter Regimen
• DR TB - HIV
■
■
■
■

■
■

■
■
■
1st line
TDF –3TC/ FTC –EFV/NVP
AZT – 3TC/FTC –EFV/NVP

2nd line
AZT – 3TC/FTC –LPV/r
TDF – 3TC/FTC –LPV/r

3rd line
AZT – FTC –DTG
TDF – FTC –DTG
1st line
TDF –3TC/ FTC –EFV/NVP
AZT – 3TC/FTC –EFV/NVP

2nd line
AZT – 3TC/FTC –LPV/r
TDF – 3TC/FTC –LPV/r

3rd line
AZT – FTC –DTG
TDF – FTC –DTG
Timing of ART Initiation
Topics
• Hr TB
• RRTB – Longer Regimen
• RRTB – Shorter Regimen
• DRTB - HIV