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Constructing a regimen. Session 5. Principles of designing an MDR-TB treatment regimen.
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Constructing a regimen Session 5
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.
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.
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. First-line INH (H) RIF (R) EMB (E) PZA (Z)
Constructing the regimen — Group 2 Second-line 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 First-line INH (H) RIF (R) EMB (E) PZA (Z) Injectable SM KM AMK CM
Constructing the regimen — Group 3 Second-line Include a fluoroquinolone • Highly effective • Minimal side effects • It is recommended to use a higher generation fluoroquinolone (levofloxacin or moxifloxacin) First-line INH (H) RIF (R) EMB (E) PZA (Z) Injectable Quinolone SM KM AMK CM OFX LFX MFX
Constructing the regimen — Group 4 Second-line 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 First-line Injectable INH (H) RIF (R) EMB (E) PZA (Z) Quinolone SM KM AMK CM OFX LFX MFX Other 2nd-line ETO or PTO CS PAS
Constructing the regimen — Group 5 First-line Third-line Second-line 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) Injectable Quinolone Other agents SM KM AMK CM OFX LFX MFX Amx/Clv Clofazimine High dose H Linezolid Other 2nd-line ETO or PTO CS PAS
Standardized regimens for communities with little or no second-line anti-TB drug resistance. First-line Third-line Second-line 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) Injectable Quinolone Other agents SM KM AMK CM OFX LFX MFX Amx/Clv Clofazimine High dose H Linezolid Other 2nd-line ETO/PTO CS PAS
Standardized regimens for communities with little or no second-line anti-TB drug resistance. First-line Third-line Second-line 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) Injectable Quinolone Other agents SM KM AMK CM OFX LFX MFX Amx/Clv Clofazimine High dose H Linezolid Other 2nd-line ETO/PTO CS PAS
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