Management of Tuberculosis Dr. Uttam Kumar Dasgupta MBBS (Cal)  MD (Cal, Chest)
Introduction <ul><li>Commonest cause of death due to a single inf. agent. </li></ul><ul><li>1882 – Discovery of TB bacilli...
Statistics <ul><li>Total no. of pts. infected with TB = 2 bi. (0.3 bi.) </li></ul><ul><li>Total no. of active TB pts. = 20...
Principle of standard short course therapy <ul><li>Mycobacterial population divided into 4 groups </li></ul><ul><li>(Mitch...
Aims of treatment <ul><li>To cure pts. with least interference to their lives. </li></ul><ul><li>To prevent death from act...
Protocol of treatment with dose <ul><li>2 RHEZ / 4 RH </li></ul><ul><li>2 SRHEZ / 1 RHEZ / 5 RH </li></ul><ul><li>2RHZ / 4...
Side effect profile <ul><li>Rifampicin </li></ul><ul><li>Common </li></ul><ul><ul><li>GI toxicity (nausea, anorexia, abd. ...
Contd… <ul><li>INH </li></ul><ul><li>Peripheral neuropathy. </li></ul><ul><li>Hepatitis. </li></ul><ul><li>Rarely, giddine...
Contd… <ul><li>Ethambutol </li></ul><ul><li>Progressive loss of vision due to retrobulbar neuritis. </li></ul><ul><li>Rare...
Contd… <ul><li>Pyrazinamide </li></ul><ul><li>Hepatitis (Bilirubin,  SGPT x3 – stop) </li></ul><ul><li>Arthralgia – mild b...
Contd… <ul><li>Streptomycin </li></ul><ul><li>Auditory & vestibular nerve damage. </li></ul><ul><li>Renal damage. </li></u...
Adverse effects with management <ul><li>Pyridoxine </li></ul><ul><li>Change to Cm </li></ul><ul><li>Amitryptiline </li></u...
Contd… 1. Antipsychotics Cs FQ, H, Eto, Pto Depression <ul><li>Stop drugs – 1 to 4 weeks </li></ul><ul><li>Antipsychotics ...
Contd… PPI / Antiemetics Eto, Pto, PAS R Gastritis Thyroxine PAS, Eto, Pto Hypothyroidsm Change to Cm AG Clr Hearing loss ...
Contd… Stop E Optic neuritis NSAID Dose / Stop Z Arthralgia Replace Cm AG Electrolyte disturbances (K, Mg ) Use Cm Give bi...
Revised National Tuberculosis Control Programme (RNTCP) <ul><li>1963 – Launching of NTP. </li></ul><ul><li>1993 – NTP decl...
Setup
Categorization of TB pts. for registration on diagnosis <ul><li>New – Never ATD / < 1 month </li></ul><ul><li>Relapse – De...
Standardized treatment protocol <ul><li>Cat I – [2 (RHEZ) 3  / 4 (RH) 3 ] </li></ul><ul><li>Cat II – [2 (SRHEZ) 3  / 1 (RH...
DOTS <ul><li>Aim </li></ul><ul><ul><li>Cure at least 85% of NSSP pts. </li></ul></ul><ul><ul><li>Detect 70% of NSSP pts. <...
Contd… <ul><li>2. Components: </li></ul><ul><ul><li>Political & Administrative commitment. </li></ul></ul><ul><ul><li>Good...
Sputum Categorization 100 - NEG Nil 200 No / 200 Scanty 1 – 9 AFB / 100 OIF 100 1+ POS 10 – 99 AFB / 100 OIF 50 2+ POS 1 –...
Outcome <ul><li>Cured </li></ul><ul><li>TC </li></ul><ul><li>Died </li></ul><ul><li>Failure </li></ul><ul><li>Defaulter </...
Debates <ul><li>Cat II </li></ul><ul><li>Cat III </li></ul><ul><li>Is it only Cat I & Cat IV </li></ul>
TB & Diabetes Mellitus <ul><li>Fact Sheet: </li></ul><ul><li>TB is 2 to 7 times more common in diabetics. </li></ul><ul><l...
Points to remember in TB + DM <ul><li>Prompt initiation of Pharmacotherapy. </li></ul><ul><li>Adequate diet prescription. ...
TB & HIV ( The Deadly Duo ) <ul><li>Estimates in 2000: </li></ul><ul><li>Globally no. of people with TB + HIV = 11.4 mi. (...
Contd… <ul><li>4. 12% of 1.84 mi. deaths due to TB were due to HIV. </li></ul><ul><li>5. 11 % of all adult AIDS deaths wer...
Issues in HAART – ATD <ul><li>When to start HAART </li></ul><ul><li>‘ Virologic, immunologic & clinical responses to HAART...
Contd… <ul><li>Proposal: </li></ul><ul><li>CD 4 < 100 / µ L or in advanced AIDS – concurrent HAART as early as possible. <...
Contd… <ul><li>2.  Optimal duration of therapy </li></ul><ul><li>6 months but prolonged to 9 months in delayed clinical (s...
Overlapping adverse event profile - ZDV CTMX Valganciclovir Bone marrow dysplasia RBT, R Pancytopenia - d4T, ddl & ddc - -...
Drug – drug interaction <ul><li>R reduces PI & NNRTI by increasing CYP3A which metabolises PI & NNRTI. So R never with PI ...
IRS <ul><li>Definition : Restoration of immunity by ARV therapy leading to increased inflammation in TB resulting in signi...
BCG & HIV <ul><li>Role of BCG in preventing TB in HIV +ve pts. is not known. </li></ul><ul><li>Conversion to +ve MT after ...
MDR TB <ul><li>Definition : Resistance to H + R + / - other drugs. </li></ul><ul><li>Causes : </li></ul><ul><li>Inadequate...
Basic principles of Tt. Of MDR TB <ul><li>Tt. should be in a specialised centre with C / S facilities. </li></ul><ul><li>C...
Contd… <ul><li>Regimen should contain >= 4 drugs with certain (or nearly so) effectiveness. </li></ul><ul><li>No drug shou...
Drugs used in MDR TB <ul><li>Group 1 – 1 st  line oral ATD </li></ul><ul><li>Group 2 – Injectable ATD (Cm in cross resista...
Doses 10 – 12 g. 10 g. 8 g. 150 m/K PAS 750-1000 mg. 750 mg. 500 mg. 15-20m/K Cs 750-1000 mg. 750 mg. 500 mg. 15-20m/K Eto...
Case 1 <ul><li>42 year old male, in whom Cat I / Cat II has failed. DST done. Non diabetic. HIV –ve. </li></ul><ul><li>Res...
<ul><li>KM </li></ul><ul><li>Ofx </li></ul><ul><li>Eto </li></ul><ul><li>Cs </li></ul><ul><li>+ / - PAS </li></ul>
Case 2 <ul><li>36 year old female in whom Cat I / Cat II has failed. Non diabetic. HIV –ve. DST sent for. </li></ul><ul><l...
<ul><li>Option 1 – Cm Ofx Pto Cs </li></ul><ul><li>Option 2 – Cm Ofx Pto Cs + / - PAS </li></ul>
Case 3 <ul><li>35 year old male on Km Ofx Eto Z remains sputum +ve after eight months of treatment. DST done four months a...
<ul><li>Cm </li></ul><ul><li>Ofx </li></ul><ul><li>Cs </li></ul><ul><li>PAS </li></ul><ul><li>one of Group 5 drugs </li></ul>
Management of contacts of MDR TB patients <ul><li>Identify & Evaluate </li></ul><ul><li>If contact Sp. +ve / CXR +ve – DST...
XDR TB (Extensively drug resistant TB) <ul><li>Defintion : MDR TB + resistance to any FQ + resistance to at least one of t...
Actions to prevent XDR TB <ul><li>Strengthen basic TB care to prevent emergence of drug resistance. </li></ul><ul><li>Ensu...
DOTS PLUS & Green Light Committee <ul><li>DOTS PLUS is a comprehensive management strategy that includes five tenets of DO...
TB & Pregnancy <ul><li>Avoid. </li></ul><ul><li>No adverse effect of pregnancy on TB & vice – versa. </li></ul><ul><li>Eff...
Management of latent TB – Indications of Tt. Silicosis / DN / malignancy Chr. immunosupression Lab personnel Prior TB (fii...
Treatment of latent TB <ul><li>HIV –ve – INH 9 months </li></ul><ul><li>HIV +ve </li></ul><ul><ul><li>MT +ve – INH 9 month...
Toxicity with Tt. of latent TB <ul><li>HIV -ve – Low risk. Hepatitis (fatal), PN (use B 6 ) </li></ul><ul><li>HIV +ve – To...
Problems with treatment of latent TB <ul><li>Low rate of Tt. inititation. </li></ul><ul><li>Low Tt. completion rates. </li...
Newer drugs in TB <ul><li>Why is it required? </li></ul><ul><li>To improve current Tt. Of active TB by </li></ul><ul><ul><...
The Drugs <ul><li>Rifabutine </li></ul><ul><ul><li>First used in MAC prophylaxis. </li></ul></ul><ul><ul><li>Now, used as ...
<ul><li>Rifapentine </li></ul><ul><ul><li>It is not indicated in advanced TB & HIV infection (acquired Rifamycin resistanc...
Contd… <ul><li>5. Diarylquinoline (R 207910) </li></ul><ul><ul><li>Effective against drug sensitive bacilli & strains resi...
Contd… <ul><li>Nitroimidazopyrans (PA – 824) </li></ul><ul><ul><li>Effective against sensitive & resistant TB. </li></ul><...
Contd… <ul><li>Oxazolidinones </li></ul><ul><ul><li>It is very active against MDR TB </li></ul></ul><ul><ul><li>May rarely...
<ul><li>Where youth grows pale, and spectre-thin, and dies;          Where but to think is to be full of sorrow           ...
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MOT

  1. 1. Management of Tuberculosis Dr. Uttam Kumar Dasgupta MBBS (Cal) MD (Cal, Chest)
  2. 2. Introduction <ul><li>Commonest cause of death due to a single inf. agent. </li></ul><ul><li>1882 – Discovery of TB bacilli. </li></ul><ul><li>1944 – First Anti – TB drug, Streptomycin </li></ul><ul><li>discovered. </li></ul><ul><li>1963 – Efficacy of domiciliary treatment established. </li></ul><ul><li>1993 – WHO declares TB a global emergency. </li></ul>
  3. 3. Statistics <ul><li>Total no. of pts. infected with TB = 2 bi. (0.3 bi.) </li></ul><ul><li>Total no. of active TB pts. = 20 mi. (12 mi.) </li></ul><ul><li>Total no. of pts. dying of TB / year = 3 mi. (5 lakhs) </li></ul><ul><li>Total no. of NSSP pts. / year = 8 mi. (1.5 mi.) </li></ul>
  4. 4. Principle of standard short course therapy <ul><li>Mycobacterial population divided into 4 groups </li></ul><ul><li>(Mitchison’s Theory) </li></ul><ul><li>Grp. A – EC Bacilli in liq. caseous material (H, R) </li></ul><ul><li>Grp. B – Slow growing in macrophage (Z) </li></ul><ul><li>Grp. C – Small no. of EC Bacilli in solid caseations exhibiting brief spurts of metabolism ( R) </li></ul><ul><li>Grp. D – Dormant bacilli (nil) </li></ul>
  5. 5. Aims of treatment <ul><li>To cure pts. with least interference to their lives. </li></ul><ul><li>To prevent death from active TB or its effects. </li></ul><ul><li>To avoid relapse / recurrence. </li></ul><ul><li>To prevent development of drug resistance. </li></ul><ul><li>To decrease transmission to others. </li></ul>
  6. 6. Protocol of treatment with dose <ul><li>2 RHEZ / 4 RH </li></ul><ul><li>2 SRHEZ / 1 RHEZ / 5 RH </li></ul><ul><li>2RHZ / 4 RH </li></ul><ul><li>R = 10 mg / kg H = 5 mg / kg </li></ul><ul><li>E = 25 mg / kg 15 mg / kg Z = 25 – 35 mg / kg </li></ul><ul><li>S = 15 mg / kg </li></ul>
  7. 7. Side effect profile <ul><li>Rifampicin </li></ul><ul><li>Common </li></ul><ul><ul><li>GI toxicity (nausea, anorexia, abd. pain). </li></ul></ul><ul><li>Uncommon </li></ul><ul><ul><li>Cut. reactions (flushing, itchiness, rash). </li></ul></ul><ul><ul><li>Hepatitis. </li></ul></ul><ul><ul><li>Reduced effectiveness of oral contraceptives. </li></ul></ul><ul><ul><li>Pseudomembranous colitis, gynaecomastia. </li></ul></ul><ul><ul><li>ARF, thrombocytopenia, flu syndrome, shock, haemolytic anaemia. </li></ul></ul>
  8. 8. Contd… <ul><li>INH </li></ul><ul><li>Peripheral neuropathy. </li></ul><ul><li>Hepatitis. </li></ul><ul><li>Rarely, giddiness, convulsion, optic neuritis, psychosis. </li></ul>
  9. 9. Contd… <ul><li>Ethambutol </li></ul><ul><li>Progressive loss of vision due to retrobulbar neuritis. </li></ul><ul><li>Rarely peripheral neuropathy, joint pain, skin rash. </li></ul>
  10. 10. Contd… <ul><li>Pyrazinamide </li></ul><ul><li>Hepatitis (Bilirubin, SGPT x3 – stop) </li></ul><ul><li>Arthralgia – mild but common. Gout. </li></ul><ul><li>Rarely – GI symptoms, rash, sideroblastic anemia. </li></ul>
  11. 11. Contd… <ul><li>Streptomycin </li></ul><ul><li>Auditory & vestibular nerve damage. </li></ul><ul><li>Renal damage. </li></ul><ul><li>Rarely skin rash & anaphylaxis. </li></ul>
  12. 12. Adverse effects with management <ul><li>Pyridoxine </li></ul><ul><li>Change to Cm </li></ul><ul><li>Amitryptiline </li></ul>Cs, H AG, FQ, Eto, Pto Peripheral neuropathy <ul><li>Suspend Tt. </li></ul><ul><li>Anticonvulsant </li></ul><ul><li>Pyridoxine </li></ul>Cs H, FQ Seizures Management Drugs responsible Adverse effect
  13. 13. Contd… 1. Antipsychotics Cs FQ, H, Eto, Pto Depression <ul><li>Stop drugs – 1 to 4 weeks </li></ul><ul><li>Antipsychotics </li></ul><ul><li>Reduced dosage / stop </li></ul>Cs, H FQ, Eto, Pto Psychotic reactions Management Drugs responsible Adverse effects
  14. 14. Contd… PPI / Antiemetics Eto, Pto, PAS R Gastritis Thyroxine PAS, Eto, Pto Hypothyroidsm Change to Cm AG Clr Hearing loss Management Drugs responsible Adverse effects
  15. 15. Contd… Stop E Optic neuritis NSAID Dose / Stop Z Arthralgia Replace Cm AG Electrolyte disturbances (K, Mg ) Use Cm Give bi / tri wkly. AG Renal toxicity Management Drugs responsible Adverse effects
  16. 16. Revised National Tuberculosis Control Programme (RNTCP) <ul><li>1963 – Launching of NTP. </li></ul><ul><li>1993 – NTP declared a failure. </li></ul><ul><li>1993 – 1996 – Pilot Programme </li></ul><ul><li>1997 – Formal Launching Of RNTCP </li></ul><ul><li>2007 – 632 districts – 1114 million people covered </li></ul>
  17. 17. Setup
  18. 18. Categorization of TB pts. for registration on diagnosis <ul><li>New – Never ATD / < 1 month </li></ul><ul><li>Relapse – Declared Cured / TC, again Sp. +ve </li></ul><ul><li>Failure – Failed with previous treatment now Sp. +ve, also initially Sp. –ve now +ve </li></ul><ul><li>TAD – ATD > 1 month anywhere, then defaulted, now Sp. +ve </li></ul><ul><li>Chronic – Sp. +ve after completing rett. Regime. </li></ul><ul><li>Others – Not in the above categories </li></ul>
  19. 19. Standardized treatment protocol <ul><li>Cat I – [2 (RHEZ) 3 / 4 (RH) 3 ] </li></ul><ul><li>Cat II – [2 (SRHEZ) 3 / 1 (RHEZ) 3 / 5 (RHE) 3 ] </li></ul><ul><li>Cat III – [2 (RHZ) 3 / 4 (RH) 3 ] </li></ul><ul><li>Cat IV - Individualised </li></ul>
  20. 20. DOTS <ul><li>Aim </li></ul><ul><ul><li>Cure at least 85% of NSSP pts. </li></ul></ul><ul><ul><li>Detect 70% of NSSP pts. </li></ul></ul>
  21. 21. Contd… <ul><li>2. Components: </li></ul><ul><ul><li>Political & Administrative commitment. </li></ul></ul><ul><ul><li>Good quality diagnosis. </li></ul></ul><ul><ul><li>Good quality drugs. </li></ul></ul><ul><ul><li>Short course chemotherapy under direct supervision. </li></ul></ul><ul><ul><li>Systemic monitoring & accountability. </li></ul></ul>
  22. 22. Sputum Categorization 100 - NEG Nil 200 No / 200 Scanty 1 – 9 AFB / 100 OIF 100 1+ POS 10 – 99 AFB / 100 OIF 50 2+ POS 1 – 10 AFB / OIF 20 3+ POS >10 AFB / OIF No. of fields Grading Results If slide has
  23. 23. Outcome <ul><li>Cured </li></ul><ul><li>TC </li></ul><ul><li>Died </li></ul><ul><li>Failure </li></ul><ul><li>Defaulter </li></ul><ul><li>Transferred Out </li></ul>
  24. 24. Debates <ul><li>Cat II </li></ul><ul><li>Cat III </li></ul><ul><li>Is it only Cat I & Cat IV </li></ul>
  25. 25. TB & Diabetes Mellitus <ul><li>Fact Sheet: </li></ul><ul><li>TB is 2 to 7 times more common in diabetics. </li></ul><ul><li>30% of DM have TB which is the commonest complicating illness (5.9%). </li></ul><ul><li>Management of TB in DM is no different than in non DM patients. </li></ul><ul><li>Complication of TB in DM as in non – DM but MDR TB & mortality is more. </li></ul>
  26. 26. Points to remember in TB + DM <ul><li>Prompt initiation of Pharmacotherapy. </li></ul><ul><li>Adequate diet prescription. </li></ul><ul><li>Possible failure of sulphonylureas with Rifampicin co-administration. </li></ul><ul><li>Augmentation of hepatotoxicity of ATT (esp. with Thiazolidindiones but less with biguanides). </li></ul><ul><li>Insulin is always a good option. </li></ul>
  27. 27. TB & HIV ( The Deadly Duo ) <ul><li>Estimates in 2000: </li></ul><ul><li>Globally no. of people with TB + HIV = 11.4 mi. (2 mi.). </li></ul><ul><li>8.3 million new cases of TB (3.7 mi. is Sp. +ve). Most live in SSA, WP & S.E. Asia where 34 mi. (85%) of estimated 40 mi. people with HIV also live. </li></ul><ul><li>9% of 8.3 mi. new TB cases were due to HIV. </li></ul>
  28. 28. Contd… <ul><li>4. 12% of 1.84 mi. deaths due to TB were due to HIV. </li></ul><ul><li>5. 11 % of all adult AIDS deaths were due to TB. </li></ul><ul><li>6. HIV infected pts. has a five time risk of developing TB than non – HIV pts. </li></ul><ul><li>7. TB & HIV interaction is bi-directional. </li></ul>
  29. 29. Issues in HAART – ATD <ul><li>When to start HAART </li></ul><ul><li>‘ Virologic, immunologic & clinical responses to HAART of HIV – 1 TB patients treated concurrently with antitubercular therapy & HAART was similar to those of non TB patients’ </li></ul><ul><li>Hung C. C. et. al AIDS 2003; 17: 2615 - 2622 </li></ul>
  30. 30. Contd… <ul><li>Proposal: </li></ul><ul><li>CD 4 < 100 / µ L or in advanced AIDS – concurrent HAART as early as possible. </li></ul><ul><li>CD 4 100 – 200 / µL – Start HAART 4 – 8 weeks after ATD initiation. </li></ul><ul><li>CD 4 > 200 / µ L – initiation of HAART based on </li></ul><ul><ul><li>Further AIDS defining condition. </li></ul></ul><ul><ul><li>CD 4 counts & rate of decline. </li></ul></ul><ul><ul><li>Drug toxicity & interactions. </li></ul></ul>
  31. 31. Contd… <ul><li>2. Optimal duration of therapy </li></ul><ul><li>6 months but prolonged to 9 months in delayed clinical (sym.) / microbiologic response (culture +ve at 2 months) </li></ul><ul><li>Treatment failure & relapse is related to: </li></ul><ul><ul><li>Advanced immuno deficiency. </li></ul></ul><ul><ul><li>Acquired Rifamycin resistance (common in intt. ATD). </li></ul></ul><ul><li>So daily ATD. </li></ul>
  32. 32. Overlapping adverse event profile - ZDV CTMX Valganciclovir Bone marrow dysplasia RBT, R Pancytopenia - d4T, ddl & ddc - - H & E Peripheral neuropathy + in pts. With chr. Viral hepatitis NVP, all PI CTMX - ZRH, RBT Hepatitis - Ddl - - E, RBT Ocular Effects + Pancreatitis or Intra – abd. Adenitis ZDV, r, IDV - Do - Other opp infections - Do - Nausea Vomiting - NVP, EVP, ABC CTMX Folliculitis ZRH, RBT Skin Rash IRS ARV drugs Medication other than ARV HIV ATT Possible Causes Adverse Effects
  33. 33. Drug – drug interaction <ul><li>R reduces PI & NNRTI by increasing CYP3A which metabolises PI & NNRTI. So R never with PI & NNRTI. </li></ul><ul><li>RBT also increases CYP3A but less so, so can be used with PI. </li></ul><ul><li>PI & NNRTI alters R level by increasing or decreasing CYP3A. PI can increase levels of RBT & it’s metabolites. </li></ul><ul><li>So when using NNRTI with RBT, increase dose of RBT & while using PI reduce dose of RBT </li></ul><ul><li>H inhibits CYP3A thus increasing levels of PI & NNRTI. </li></ul>
  34. 34. IRS <ul><li>Definition : Restoration of immunity by ARV therapy leading to increased inflammation in TB resulting in significant worsening of S / S (Paradoxical reactions) </li></ul><ul><li>Onset – Within days of ARV therapy or months after ARV initiation. </li></ul><ul><li>Symptoms : Fever, adenopathy, increased pulmonary infiltrates, serositis. Less common features are worsening of meningitis, increased CNS tuberculomas, soft tissue & bone abscess & diffuse skin lesions. </li></ul><ul><li>Diagnosis : Difficult. </li></ul>
  35. 35. BCG & HIV <ul><li>Role of BCG in preventing TB in HIV +ve pts. is not known. </li></ul><ul><li>Conversion to +ve MT after BCG is less frequent but significant </li></ul><ul><li>BCG is safe in HIV </li></ul><ul><li>WHO recommendation: </li></ul><ul><li>In high prevalence – BCG except in children with S / S of HIV / AIDS </li></ul><ul><li>In low prevalence – no BCG </li></ul>
  36. 36. MDR TB <ul><li>Definition : Resistance to H + R + / - other drugs. </li></ul><ul><li>Causes : </li></ul><ul><li>Inadequate & inappropiate previous treatment with ATD. </li></ul><ul><li>Patients with extensive cavitary disease. </li></ul><ul><li>Addition syndrome </li></ul><ul><li>Ineffectual & irrational drug schedule. </li></ul><ul><li>Contact with a known MDR patient. </li></ul>
  37. 37. Basic principles of Tt. Of MDR TB <ul><li>Tt. should be in a specialised centre with C / S facilities. </li></ul><ul><li>Careful analysis of past drug history. </li></ul><ul><li>Never to add a single to a failing regimen. </li></ul><ul><li>Never combine two drugs of the same group or a drug with known cross resistance. (eg. Thioamides / TZN, Km or Am / Sm, R / RBT) </li></ul><ul><li>Intt. therapy is not effective in MDR TB </li></ul>
  38. 38. Contd… <ul><li>Regimen should contain >= 4 drugs with certain (or nearly so) effectiveness. </li></ul><ul><li>No drug should be kept in reserve & the most powerful bactericidal drugs should be used initially in maximum combination. </li></ul><ul><li>Tt. should be under direct observation throughout or at least till sputum conversion. </li></ul><ul><li>Surgical treatment may be an adjunct. </li></ul><ul><li>Injectable drugs for a min. of 6 months. Total duration 18 – 24 months after smear conversion or 12 months after culture becomes negative. Z throughout. </li></ul>
  39. 39. Drugs used in MDR TB <ul><li>Group 1 – 1 st line oral ATD </li></ul><ul><li>Group 2 – Injectable ATD (Cm in cross resistance) </li></ul><ul><li>Group 3 – Fluoroquinolones (Mx = Gx > Lx > Ox > Cx) </li></ul><ul><li>Group 4 - Oral bacteriostatic drug </li></ul><ul><ul><li>Eto / Pto – start with small dose. </li></ul></ul><ul><ul><li>PAS – Combine if imperative. </li></ul></ul><ul><ul><li>Cs </li></ul></ul><ul><ul><li>Cs + (Eto / Pto or PAS) </li></ul></ul><ul><li>Group 5 – Cfz, Amx / Clv, Clr, Lzd </li></ul><ul><li>Regimen </li></ul><ul><li>Group 2 + 3 + two to three Group 4 + / - Group 5 + Z </li></ul>
  40. 40. Doses 10 – 12 g. 10 g. 8 g. 150 m/K PAS 750-1000 mg. 750 mg. 500 mg. 15-20m/K Cs 750-1000 mg. 750 mg. 500 mg. 15-20m/K Eto / Pto 400 mg. 400 mg. 400 mg. 7.5–10m/k Mfx / Gfx 750-1000 mg. 750 mg. 750 mg. 7.5–10m/k Lfx 800-1000 mg. 800 mg. 800 mg. 15–20m/k Ofx - - - 15–20m/k AG > 70 Kg. 51-70 Kg. 33–50 Kg. < 33 Kg. Drugs
  41. 41. Case 1 <ul><li>42 year old male, in whom Cat I / Cat II has failed. DST done. Non diabetic. HIV –ve. </li></ul><ul><li>Resistant to – S R H </li></ul><ul><li>Sensitive to – E Km Ofx Eto Cs PAS </li></ul><ul><li>On RHE since DST has been sent. Sensitivity to Z was not possible. </li></ul><ul><li>What would you give? </li></ul>
  42. 42. <ul><li>KM </li></ul><ul><li>Ofx </li></ul><ul><li>Eto </li></ul><ul><li>Cs </li></ul><ul><li>+ / - PAS </li></ul>
  43. 43. Case 2 <ul><li>36 year old female in whom Cat I / Cat II has failed. Non diabetic. HIV –ve. DST sent for. </li></ul><ul><li>Resistant to – S R H E Z Km </li></ul><ul><li>Sensitive to – Cm Ofx Pto Cs PAS </li></ul><ul><li>Not on any drugs since DST was sent. </li></ul><ul><li>What would you give? </li></ul>
  44. 44. <ul><li>Option 1 – Cm Ofx Pto Cs </li></ul><ul><li>Option 2 – Cm Ofx Pto Cs + / - PAS </li></ul>
  45. 45. Case 3 <ul><li>35 year old male on Km Ofx Eto Z remains sputum +ve after eight months of treatment. DST done four months ago. </li></ul><ul><li>Resistant to – R H E Z Eto </li></ul><ul><li>Sensitive to – Km Cm Ofx Cs PAS </li></ul><ul><li>What would you give? </li></ul>
  46. 46. <ul><li>Cm </li></ul><ul><li>Ofx </li></ul><ul><li>Cs </li></ul><ul><li>PAS </li></ul><ul><li>one of Group 5 drugs </li></ul>
  47. 47. Management of contacts of MDR TB patients <ul><li>Identify & Evaluate </li></ul><ul><li>If contact Sp. +ve / CXR +ve – DST </li></ul><ul><li>If DST NA – Protocol of the index case. </li></ul><ul><li>If contact Sp. –ve (but symptomatic) & CXR –ve </li></ul><ul><li>Antibiotics </li></ul><ul><li>If symptoms persist </li></ul><ul><li>FOB / CT </li></ul><ul><li>If all NA – rpt. work-up monthly if patients remains symptomatic. </li></ul><ul><li>Chemoprophylaxis – 2 nd line not recommended – close FU. </li></ul>
  48. 48. XDR TB (Extensively drug resistant TB) <ul><li>Defintion : MDR TB + resistance to any FQ + resistance to at least one of three injectables ( Cm Am Km.) 1 to 2 % of MDR TB in India are XDR TB. This figure is 4% in the US, 19% in Latavia. </li></ul><ul><li>Causes : </li></ul><ul><li>Incorrect drug prescription by doctors. </li></ul><ul><li>Poor quality drugs. </li></ul><ul><li>Erratic supply of drugs. </li></ul><ul><li>Patient non – adherence. </li></ul>
  49. 49. Actions to prevent XDR TB <ul><li>Strengthen basic TB care to prevent emergence of drug resistance. </li></ul><ul><li>Ensure prompt diag. & Tt. of DR TB to cure existing cases & prevent further transmission. </li></ul><ul><li>Increase HIV TB control programme collaboration. </li></ul><ul><li>Increase investment in lab. infrastrutures to enable better detection & management. </li></ul>
  50. 50. DOTS PLUS & Green Light Committee <ul><li>DOTS PLUS is a comprehensive management strategy that includes five tenets of DOTS strategy. It considers specific issues (eg. use of reserve drugs) that needs to be addressed in high MDR TB areas. </li></ul><ul><li>Green Light Committee is a working group that has made arrangement with the pharmaceutical industry to provide concessionally - priced 2 nd line anti TB drugs to DOTS PLUS pilot projects for management of MDR TB. </li></ul>
  51. 51. TB & Pregnancy <ul><li>Avoid. </li></ul><ul><li>No adverse effect of pregnancy on TB & vice – versa. </li></ul><ul><li>Effect of maternal TB on baby. Examine placenta. </li></ul><ul><li>Treatment is the same (avoid Sm Eto Pto). </li></ul><ul><li>Management of new born </li></ul><ul><ul><li>Don’t separate (unless mother is desperately ill) </li></ul></ul><ul><ul><li>If mother Sp. –ve give BCG </li></ul></ul><ul><ul><li>If mother is / was Sp. +ve during pregnancy / delivery </li></ul></ul><ul><ul><ul><li>If baby ill & TB suspected – full ATD </li></ul></ul></ul><ul><ul><ul><li>If baby well - give INH 5 mg. / Kg. X2 months. Then MT done. If MT –ve – stop INH. Give BCG. If MT +ve – give INH upto 6 months. </li></ul></ul></ul><ul><li>If mother MDR – start Tt. in 2 nd trimester with 3 – 4 oral drugs (except Am, Eto, Pto) </li></ul>
  52. 52. Management of latent TB – Indications of Tt. Silicosis / DN / malignancy Chr. immunosupression Lab personnel Prior TB (fiibrosis) Residents & employees of high risk setup. Recent contact No risk persons Immigration HIV +ve 15 mm. induration 10 mm. induration 5 mm. induration
  53. 53. Treatment of latent TB <ul><li>HIV –ve – INH 9 months </li></ul><ul><li>HIV +ve </li></ul><ul><ul><li>MT +ve – INH 9 months. </li></ul></ul><ul><ul><li>MT –ve – no INH </li></ul></ul><ul><li>Shorter alternatives </li></ul><ul><ul><li>RZ x2 months – not given </li></ul></ul><ul><ul><li>RH x3 months – not given </li></ul></ul><ul><ul><li>R x4months – exclude active TB 1 st </li></ul></ul>
  54. 54. Toxicity with Tt. of latent TB <ul><li>HIV -ve – Low risk. Hepatitis (fatal), PN (use B 6 ) </li></ul><ul><li>HIV +ve – Toxicity > that of HIV –ve pts. </li></ul>
  55. 55. Problems with treatment of latent TB <ul><li>Low rate of Tt. inititation. </li></ul><ul><li>Low Tt. completion rates. </li></ul><ul><li>Monitoring for toxicity is a must. </li></ul><ul><li>Logistic difficulties. </li></ul><ul><li>Future protocol </li></ul><ul><li>RPT + INH x3 months </li></ul><ul><li>Mx </li></ul><ul><li>Special situations </li></ul><ul><li>Pregnant / breast feeding females – INH </li></ul><ul><li>Children – INH </li></ul><ul><li>Contacts with MDR – Z + E / Z + FQ x6 – 12 months </li></ul>
  56. 56. Newer drugs in TB <ul><li>Why is it required? </li></ul><ul><li>To improve current Tt. Of active TB by </li></ul><ul><ul><li>Shortening duration of treatment </li></ul></ul><ul><ul><li>Providing more widely spaced intt. therapy. </li></ul></ul><ul><li>To improve MDR TB Tt. </li></ul><ul><li>To provide more effective Tt. of latent TB. </li></ul>
  57. 57. The Drugs <ul><li>Rifabutine </li></ul><ul><ul><li>First used in MAC prophylaxis. </li></ul></ul><ul><ul><li>Now, used as a substitute for R & for patients who can’t be given R for drug drug interaction. </li></ul></ul><ul><ul><li>Given twice weekly, it increases acquired drug resistance. </li></ul></ul><ul><li>Rifalazin </li></ul><ul><ul><li>Acts by reducing enzyme induction. </li></ul></ul><ul><ul><li>Reduces drug drug interaction </li></ul></ul><ul><ul><li>Flu like syndrome </li></ul></ul>
  58. 58. <ul><li>Rifapentine </li></ul><ul><ul><li>It is not indicated in advanced TB & HIV infection (acquired Rifamycin resistance) </li></ul></ul><ul><ul><li>It’s chief indication is LTBI where it is combined with H. </li></ul></ul><ul><ul><li>Dose is 900 mg. / day. </li></ul></ul><ul><li>Moxifloxacin </li></ul><ul><ul><li>It’s bactericidal activity is better than R but = H </li></ul></ul>
  59. 59. Contd… <ul><li>5. Diarylquinoline (R 207910) </li></ul><ul><ul><li>Effective against drug sensitive bacilli & strains resistant to SRHEZFQ. </li></ul></ul><ul><ul><li>It is effective against other myco bacteria. It may be combined with any standard ATD (RHZ). </li></ul></ul><ul><ul><li>It’s ability to shorten duration is under trial. </li></ul></ul><ul><li>Pyrrole (LL 3858) – It’s a good steriliser. </li></ul><ul><li>Dihydroimidazo – oxazoles (OPC – 67683) </li></ul><ul><ul><li>No cross resistance or antagonistic action against other ATD. </li></ul></ul><ul><ul><li>Better than the first line drugs. </li></ul></ul>
  60. 60. Contd… <ul><li>Nitroimidazopyrans (PA – 824) </li></ul><ul><ul><li>Effective against sensitive & resistant TB. </li></ul></ul><ul><ul><li>It is highly selective. </li></ul></ul><ul><ul><li>Active against non replicating bacilli (cf ‘H’). </li></ul></ul><ul><ul><li>Active against MDR TB. </li></ul></ul><ul><ul><li>Does not demonstrate mutagenicity. </li></ul></ul><ul><ul><li>Min. effective dose is 12.5 mg. / day. </li></ul></ul><ul><ul><li>It is not genotoxic. </li></ul></ul><ul><li>SQ 109 – Active against MDR TB </li></ul>
  61. 61. Contd… <ul><li>Oxazolidinones </li></ul><ul><ul><li>It is very active against MDR TB </li></ul></ul><ul><ul><li>May rarely cause peripheral & optic neuropathy. </li></ul></ul>
  62. 62. <ul><li>Where youth grows pale, and spectre-thin, and dies;         Where but to think is to be full of sorrow                 And leaden-eyed despairs,     Where Beauty cannot keep her lustrous eyes,         Or new Love pine at them beyond to-morrow. </li></ul><ul><li>- John Keats (Ode To A Nightingale) </li></ul>
  63. 63. Thank You!

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