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APPROACH TO THE MANAGEMENT OF DR TB

APPROACH TO THE MANAGEMENT OF DR TB. Prof Frank Peters Dept Family Medicine University of Pretoria. DEFINITIONS. DS-TB: Drug susceptible TB Infection caused by M. tuberculosis which is not resistant to any anti-TB drug DR-TB:

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APPROACH TO THE MANAGEMENT OF DR TB

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  1. APPROACH TO THE MANAGEMENT OF DR TB Prof Frank Peters Dept Family Medicine University of Pretoria

  2. DEFINITIONS • DS-TB: Drug susceptible TB Infection caused by M. tuberculosis which is not resistant to any anti-TB drug • DR-TB: Infection caused by M. tuberculosis resistant to one or more anti-TB drugs.

  3. SYMPTOMS • COUGH (+2WKS) • NIGHT SWEATS • TEMPERATURE (FEVER0 • LOSS OF WEIGHT • LOSS OF APPETITE • FATIGUE

  4. RADIOLOGY CXR • Often cavitary lung lesions • Consolidation • Infiltrates • Hilar LAD • etc

  5. LABORATORY GXP AFB

  6. DS TB TREATMENT • 2 RIFAFOUR + 4 RIFINAH (OR 6 RIFINAH) • Total : 6 -8

  7. TB Treatment Regimen 2 months 4 months Rifampicin Isoniazid Pyrazinamide Ethambutol Rifampicin Isoniazid Rifampicin Inhibits RNA synthesis Binds to RNA polymerase Resistance mostly maps to rpoB Ethambutol Inhibits Arabinogalactan synthesis Targets Arabinosyltransferase Resistance maps to embB Pyrazinamide Pro-drug Complex mode of action Resistance maps to pncA mostly Isoniazid Pro-drug Inhibits mycolic acid biosynthesis Resistance maps to katG, inhA…?

  8. DR TB RR TB: Resistance to RIF • MONO RESISTANCE TB: Resistance to 1 first line drug • MDR TB: Resistance to RIF and INH • XDR-TB: Resistance to _1/RIF+ INH + _2/quinolones +Injectables (kanamycin, capreomycin, Amikacin)

  9. preXDR TB: resistant to 1st line + one of second line _1/quinolone _2/or injectables both inhA and katG mutations (INH) also considered preXDR

  10. POSSIBLE RESISTANCE • RIF • INH • EMB • PZA • MFX (Quinolones) • Km (injectables /Aminoglycoside )

  11. TB IN S.A

  12. WHO ARE LIKELY GET DR TB • NON COMPLIANT (Do not take their TB Rx regularly) • DEFAULTERS (Do not finish their TB Rx) • DIRECT CONTAMINATION (Have spent time with a DR TB person)

  13. DIAGNOSIS

  14. CLINICAL Same as DS TB: • Cough/ Fever/ Night sweats • LOW/ LOA/ Fatigue

  15. RADIOLOGICAL same as DS TB

  16. LABORATORY GXP AFB DR TB REFLEX (FL LPA + SL LPA + SMEAR + CULTURE + pDST)

  17. PREVIOUS RX of MDR TB KEMPT

  18. NEW REGIMEN

  19. BDQ= BEDAQUILINE –cidal 1 • Ln= LINEZOLID –cidal 2 • LFX= LEVOFLOXACIN –cidal 3 • CFZ= CLOFAZIMINE –cidal 4 • ETO= ETHIONAMIDE –cidal 5 • INHh= ISONIAZID HIGH DOSE –cidal 6 • PZA= PYRAZINAMIDE – static 7

  20. BDQ REGIMEN 6-9 BDQ+Ln+LFX+CFZ+ETO+INHh+PZA • LFX+CFZ+INHh+PZA TOTAL: 11-14 MONTHS

  21. MAIN SIDE EFFECTS 1/ BDQ= QT prolongation 2/ Ln= THROMBOCYTOPENIA/ ANEMIA 3/ LFX= QT prolongation (MINOR) 4/ CFZ= HYPERPIGMENTATION 5/ ETO= HYPOTHYROIDISM 6/ INHh= Peripheral neuropathy/ hepatotoxic 7/ PZA= HEPATOTOXIC

  22. BDQ ELIGIBILITY • ≥18 years of age • No history or family history of QT prolongation

  23. STEP BY STEP APPROACH

  24. 1st step : DR TB Reflex DR TB REFLEX = FL LPA + SL LPA + SMEAR + CULTURE + pDST)

  25. RR TB PROTOCOL GXP + RIF R START I. PHASE BDQ REGIMEN (7 DRUGS) :BL n L E C I P

  26. DR TB REFLEX @ 2/52

  27. CONTRAINDICATED MEDICATIONS TO BDQ • EFV (Use RTG) • MOXIFLOXACIN (Use LFX) • Antiarrhythmic (amiodarone, etc) • Tricyclic antidepressants (amitriptyline ,etc) • Neuroleptics (haloperidol ,etc) • Quinolone antimalarial (e.g.,chloroquine)

  28. PREVENTION

  29. PREVENTION • VENTILATION / FRESH AIR • N95 for health care professionals • SURGICAL MASK for patients • Educate patients about COMPLIANCE • Health care professional to prescribe the correct TB regimen with the correct doses

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