Tuberculosis- management and treatment

This deals with the management and treatment of all types of tuberculosis, and the management of adverse effect of the anti-tubercular drugs.

1. MANAGEMENT AND TREATMENT OF TUBERCULOSIS

2. INTRODUCTION Tuberculosis is the chronic granulomatous infection transmitted by ingestion or inhalation of tubercle bacilli Clinical features: Productive cough with blood. Low grade fever Loss of appetite Dyspnoea Matted lymph node Pleural & ascitic effusion

3. NON-PHARMACOLOGICAL MANAGEMENT Medical staff must wear high-efficiency disposable masks. Isolate patients with possible tuberculosis infection in a private room Encouraged patients to follow good cough hygiene. Provide vitamins & minerals supplements when required.  Integrated nutritional assessment counselling and support for the duration of the illness.

4. AIMS OF TREATMENT To cure the patient and restore quality of life & productivity. To prevent death or its late effects. To prevent relapse. To reduce transmission to others. To prevent the development and transmission of drug resistance.

5. Section 1: ANTI-TUBERCULAR DRUGS FIRST LINE DRUGS Isoniazid (H) Rifampicin (R) Pyrazinamide (Z) Ethambutol (E) Streptomysin (S) SECOND LINE DRUGS Fluoroquinolones Amikacin Capreomycin Ethionamide Para-aminosalicylic acid Cycloserine Thioacetazole NEWER DRUGS Linezolid R 207910 Clarithromycin Azithromycin

6. ISONIAZID (H) Tuberculocidal drugs Dose: 5mg/kg/day (300 mg max) 10 mg/kg (900 mg max)- thrice a week MOA: It converts into its active form by bacterial enzymes which activates kasA and inhA genes. The genes forms adducts with NAD & NADH disrupting the synthesis of cell wall and DNA of Mycobacteria . Adverse effects: Pheripheral neuritis Hepatotoxicity

7. RIFAMPICIN (R) Tuberculocidal drugs Dose: 10mg/kg/day (600 mg max) Same for thrice a week dosage MOA: Binds to β -subunit of DNA dependent RNA polymerase Inhibits polymerization of RNA Inhibits RNA synthesis Adverse effects: Red/ Orange coloured secretions Hepatitis Renal failure

8. PYRAZINAMIDE (Z) Tuberculocidal drugs Dose: 25mg/kg/day (35 mg/kg/day thrice a week) MOA: Converts into Pyrazinoic acid (by bacterial pyrazinamidase enzyme) Inhibits fatty acid synthesis Disrupts mycolic acid synthesis Also disrupts cell membrane Adverse effects: Hepatotoxicity Hyperuricaemia

9. ETHAMBUTOL (E) Tuberculostatic drug Dose: 15mg/kg/day (30mg/day thrice a week) MOA: Inhibits Arabinosyl transferase Inhibits polymerization of Arabinoglycans Inhibits mycolic acid incorporation in cell wall Adverse effects: Optic neuritis Hepatitis

10. STREPTOMYCIN (S) Tuberculocidal drugs Only injectable first line drug Dose: 15 mg/kg/day (same for thrice a week) MOA: Binds to 30s subunit prevent polysome formation inhibit protein synthesis. Adverse effects: Nephrotoxicity Ototoxicity , Dizziness Decreased urine output

11. MANAGEMENT OF ADVERSE EFFECTS Side- effects Responsible Drugs Management Skin rash Any Stop anti-TB drugs Deafness, Dizziness, decreased urine output Streptomycin Stop streptomycin Jaundice R, H, Z Stop anti-TB drugs Confusion Any Stop anti-TB drugs Visual impairment Ethambutol Stop ethambutol Shock, Purpura, Renal failure Rifampicin Stop Rifampicin Anorexia, Nausea, abdominal pain H, R, Z Symptomatic treatment, drugs with meal at bedtime Joint pains Pyrazinamide NSAIDS Burning sensation Isoniazid Pyridoxine 100 mg daily Drowsiness Isoniazid Ressurance Orange/Red urine Rifampicin Ressurance Flu syndrome Rifampicin(intermittent dose Begin daily dose

12. Section 2: Selection of Drugs New cases of TB: 2HRZE/4HR Isoniazid resistance area(probable)2HRZE/4HRE H resistant: 2HREZ/10RE R resistant: 9HEZ or 12HE Z resistant: 2HRE/7HR E resistant: 2HRZ/4HR Previously treated patients: 2HRZES/HRZE/5HRE

13. INDICATIONS FOR MDR-TB Treated in a poorly operated programme. History of using anti-tubercular drugs of poor or unknown quality. Sputum remain positive after 2-3 months of treatment. Area with very high prevalence of MDR. Patients with HIV, type-2 Diabetes Mellitus. Prior course of Rifampicin therapy.

14. GROUPS OF DRUGS TO TREAT MDR-TB GROUP Drugs Group-1: First line oral agents Pyrazinamide, Ethambutol, Rifabutin Group-2: Injectable agents Kanamycin, Amikacin, Capreomycin, Streptomycin Group-3: Fluoroquinolones Levofloxacin, Moxifloxacin, Ofloxacin Group-4: Oral bacteriostatic 2 nd line agents PAS, Cycloserine, Terizinone, Ethionamide Group-5: Others Clofazimine, Linezolid, Amoxicillin, Thioacetazone, Imipenam, Clarithromycin Principles of designing MDR-TB regimens: Use at least 4 drugs certain to be effective. Do not use drugs having possibility of cross-resistance. Eliminate drugs that are not safe. Include drugs from groups 1-5 in hierarchical order based on potency.

15. TREATMENT OF TUBERCULOSIS IN AIDS PATIENT Begin treatment as that of previously treated patient (2HRZES/HRZE/HHRE) Include cotrimoxazole. Antiviral therapy: Zidovudine + Lamivudine + Nevirapine

16. 1 . Pregnancy: All anti-tubercular drugs except streptomycin can be used. 2. Breastfeeding women: Continue breast feeding. After ruling out active TB is ruled out, baby should be given 6 months of Isoniazid therapy. 3. Renal failure: H, R, Z, E (2 months); H, R(4 months) Dose: Same for Isoniazid & Rifampicin Pyrazinamide (25mg/kg thrice weekly) Ethambutol (15 mg/kg thrice weekly) Streptomycin (15 mg/kg thrice or twice weekly)

17. 4. Liver failure: H, R, E for 9 months 2 months H, R, S, E followed by 6 months H, R 6-9 months of R, Z, E 2 months H,E, S followed by 10 months of H, R 18-24 months S, E and a fluoroquinolone.

18. TREATMENT OF EXTRAPULMONARY TUBERCULOSIS Tuberculosis of bones & joints: 9 months treatment. Also include corticosteroids. Tuberculosis meningitis or pericarditis: 9-12 months treatment. Ethambutol should be replaced by streptomycin Surgical removal of affected organ.

19. EXTREME DRUG RESISTANT TUBERCULOSIS Can be cured but likelihood of success is low. Cure depends on extent of the drug resistance the severity of the disease and Immune system of patient.  Drugs 6/4 (must include a fluoroquinolone) Surgery in case of localised tuberculosis

20. BEYOND EXTREME DRUG RESISTANT TUBERCULOSIS Very poor prognosis. Must use drugs beyond the one currently used for XDR-TB. Use AST to plan treatment.