1

Constructing a regimenSession 5

USAID TB CARE II PROJECT

Principles of designing an MDR-TB treatment regimen

• Include at least four second-line anti-TB drugs likely to be effective as well as pyrazinamide during the intensive phase. More than four second-line anti-TB drugs is recommended if the effectiveness of some of the drugs is uncertain.

• The continuation phase should contain at least three second-line anti-TB drugs (pyrazinamide should also be continued in the continuation phase if extensive lung damage is present). More than three second-line anti-TB drugs is recommended if the effectiveness of some of the drugs is uncertain.

• Include a fluoroquinolone—a higher generation fluoroquinolone (levofloxacin or moxifloxacin) is strongly preferred.

• Ethambutol can be included but is not counted as a core drug in the regimen.

• Consider drug resistance data (of individual or region) and patient treatment history when designing a regimen.

USAID TB CARE II PROJECT

Duration of therapy

• The intensive phase should be at least 8 months and at least 4 months past conversion (whichever is longer).

• Total duration of treatment should be at least 20 months and at least 18 months past conversion.

USAID TB CARE II PROJECT

Constructing the regimen — Group 1

Include pyrazinamide

• Pyrazinamide should be included whenever the strain is susceptible or if susceptibility is unknown.

• DST to ethambutol is not very reliable and even if the strain is testing susceptible to ethambutol it should not be counted as a core effective drug against MDR-TB strains.

INH (H)

RIF (R)

EMB (E)

PZA (Z)

First-line

USAID TB CARE II PROJECT

Constructing the regimen — Group 2

Include an injectable for the intensive phase

• Cross resistance between KM and AMK is considered complete

• There is cross resistance of CM with KM and AMK

• All injectables must be given IM or IV (not absorbed when given orally)

• Streptomycin is considered a first-line drug by the WHO

INH (H)

RIF (R)

EMB (E)

PZA (Z)

First-line

SM

KM

AMK

CM

Injectable

Second-line

USAID TB CARE II PROJECT

Constructing the regimen — Group 3

Include a fluoroquinolone

• Highly effective

• Minimal side effects

• It is recommended to use a higher generation fluoroquinolone (levofloxacin or moxifloxacin)

INH (H)

RIF (R)

EMB (E)

PZA (Z)

First-line

SM

KM

AMK

CM

Injectable

OFX

LFX

MFX

Quinolone

Second-line

USAID TB CARE II PROJECT

Constructing the regimen — Group 4

Complete the regimen with Group 4 drugs (aiming to have four or five second-line drugs — five if you are worried about second-line resistance)

• Side effects are common • ETO/PTO may be the most effective Group 4 drugs• If INH A mutation is responsible for the isoniazid resistance, there

may be cross-resistance with ETO/PTO

INH (H)

RIF (R)

EMB (E)

PZA (Z)

First-line

SM

KM

AMK

CM

Injectable

OFX

LFX

MFX

Quinolone

ETO or PTO

CS

PAS

Other 2nd-line

Second-line

USAID TB CARE II PROJECT

Constructing the regimen — Group 5

Group 5 drugs are used in cases of extensive resistance such as XDR-TB

• Minimal clinical evidence of efficacy

• Use two or three agents from Group 5 when it has been determined that a regimen of at least four effective drugs from Groups 2 to 4 are not available.

INH (H)

RIF (R)

EMB (E)

PZA (Z)

First-line Second-line Third-line

SM

KM

AMK

CM

Injectable

OFX

LFX

MFX

Quinolone

ETO or PTO

CS

PAS

Other 2nd-line Other

agentsAmx/ClvClofazimineHigh dose HLinezolid

USAID TB CARE II PROJECT

Standardized regimens for communities with little or no second-line anti-TB drug resistance.

A common standardized regimen when very little resistance to second-line drugs exists in the population is:

Z-Km-Lfx-Eto-Cs

INH (H)

RIF (R)

EMB (E)

PZA (Z)

First-line Second-line Third-line

SM

KM

AMK

CM

Injectable

OFX

LFX

MFX

Quinolone

ETO/PTO

CS

PAS

Other 2nd-line Other

agentsAmx/ClvClofazimineHigh dose HLinezolid

USAID TB CARE II PROJECT

Standardized regimens for communities with little or no second-line anti-TB drug resistance.

A common standardized regimen when significant amounts of resistance to second-line drugs exists in the population is:

Z-Km-Lfx-Eto-Cs-PAS

INH (H)

RIF (R)

EMB (E)

PZA (Z)

First-line Second-line Third-line

Other agentsAmx/Clv

ClofazimineHigh dose HLinezolid

SM

KM

AMK

CM

Injectable

OFX

LFX

MFX

Quinolone

ETO/PTO

CS

PAS

Other 2nd-line

USAID TB CARE II PROJECT

Adjusting standardized regimens

Standardized therapies need to be adjusted in:• Pregnancy• Liver disease• Chronic kidney disease• MDR-TB contacts• History of treatment with second-line drugs