Transcript Constructing a Regimen - DR TB Training Network

Constructing a regimen
Session 5
1
Principles of designing an MDR-TB
treatment regimen
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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 antiTB 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
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The intensive phase should be at least 8 months and at
least 4 months past conversion (whichever is longer).
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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
First-line
INH (H)
RIF (R)
EMB (E)
PZA (Z)
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.
USAID TB CARE II PROJECT
Constructing the regimen — Group 2
First-line
Second-line
INH (H)
Injectable
RIF (R)
EMB (E)
PZA (Z)
SM
KM
AMK
CM
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
USAID TB CARE II PROJECT
Constructing the regimen — Group 3
First-line
Second-line
INH (H)
Injectable
RIF (R)
EMB (E)
PZA (Z)
SM
KM
AMK
CM
Quinolone
OFX
LFX
MFX
Include a fluoroquinolone
• Highly effective
• Minimal side effects
• It is recommended to use a higher generation fluoroquinolone
(levofloxacin or moxifloxacin)
USAID TB CARE II PROJECT
Constructing the regimen — Group 4
First-line
Second-line
INH (H)
Injectable
RIF (R)
EMB (E)
PZA (Z)
SM
KM
Quinolone
OFX
Other 2nd-line
ETO or PTO
AMK
LFX
CS
CM
MFX
PAS
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
USAID TB CARE II PROJECT
Constructing the regimen — Group 5
First-line
Second-line
INH (H)
Injectable
RIF (R)
EMB (E)
PZA (Z)
SM
KM
Third-line
Quinolone
OFX
Other 2nd-line
ETO or PTO
AMK
LFX
CS
CM
MFX
PAS
Other agents
Amx/Clv
Clofazimine
High dose H
Linezolid
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.
USAID TB CARE II PROJECT
Standardized regimens for communities with little
or no second-line anti-TB drug resistance.
First-line
Second-line
INH (H)
Injectable
RIF (R)
EMB (E)
PZA (Z)
SM
KM
Third-line
Quinolone
OFX
Other 2nd-line
ETO/PTO
AMK
LFX
CS
CM
MFX
PAS
Other agents
Amx/Clv
Clofazimine
High dose H
Linezolid
A common standardized regimen when very little resistance to
second-line drugs exists in the population is:
Z-Km-Lfx-Eto-Cs
USAID TB CARE II PROJECT
Standardized regimens for communities with little
or no second-line anti-TB drug resistance.
First-line
Second-line
INH (H)
Injectable
RIF (R)
EMB (E)
PZA (Z)
SM
Third-line
Quinolone
OFX
KM
Other 2nd-line
ETO/PTO
AMK
LFX
CS
CM
MFX
PAS
Other agents
Amx/Clv
Clofazimine
High dose H
Linezolid
A common standardized regimen when significant amounts of
resistance to second-line drugs exists in the population is:
Z-Km-Lfx-Eto-Cs-PAS
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
USAID TB CARE II PROJECT