Tuberculosis treatment


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TB treatment principles by Daniel schwartz - LSMU

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Tuberculosis treatment

  1. 1. Tuberculosis treatment: general principles and approach Lecturer: Ph.D M.G.Dolynska
  2. 2. Historical background <ul><li>Supposed incurable until XX century </li></ul><ul><li>First approach – sanatorium movement </li></ul><ul><li>First pathogenically based attempt –artificial pnemothorax (Forlanini, 1882) </li></ul><ul><li>Streptomycin discovery (Zelman Waksman, 1943) </li></ul>
  3. 3. The AIMS of treatment of tuberculosis are: <ul><li>to cure the patient of TB; </li></ul><ul><li>to prevent death from active TB or its late effects; </li></ul><ul><li>to prevent relapse of TB; </li></ul><ul><li>to decrease transmission of TB to others; </li></ul><ul><li>to prevent the development of acquired drug resistance. </li></ul>
  4. 4. DOTS ( Directly observed treatment short course ), Karel Styblo, 1972 <ul><li>The organizational principles of the DOTS are: </li></ul><ul><li>availability of a decentralized diagnostic and treatment network based on existing health facilities; </li></ul><ul><li>good programme management based on accountability and supervision of health care workers; </li></ul><ul><li>an evaluation system of case-finding and cohort analysis of treatment outcomes. </li></ul>
  5. 5. The five elements of the expanded DOTS framework are: <ul><li>1.Sustained political commitment to increase human and financial resources and make TB control a nationwide priority integral to the national health system. </li></ul><ul><li>2. Access to quality-assured TB sputum microscopy for case detection among persons presenting with, or found through screening to have, symptoms of TB (most importantly, prolonged cough). </li></ul><ul><li>3. Standardized short-course chemotherapy for all cases of TB under proper case management conditions, including direct observation of treatment. </li></ul><ul><li>4. Uninterrupted supply of quality-assured drugs with reliable drug procurement and distribution systems. </li></ul><ul><li>5. Recording and reporting system enabling outcome assessment of all patients and assessment of overall programme performance. </li></ul>
  6. 6. Dosage and abbreviation of essential antituberculosis drugs 30 (20-35) 15 (15-20) Ethambutol (E) 15 (12-18) 15 (12-18) Streptomycin (S) 35 (30-40) 25 (20-30) Pyrasinamide (Z) 10 (8-12) 10 (8-12) Rifampicin (R) 10 (8-12) 5 (4-6) Isoniasid (H) 3 times weekly Daily Recommended dosage (dose range) in md/kg Drug (abbreviation)
  7. 7. Basical treatment regimens Optional 5 (HRE) 3 Optional 2(HRZES) 3 /1HRZE 3 Preferred 5 HRE VI Preferred 2 HRZES / 1 HRZE VI Previously treated sputum smearpositive PTB: - relapse; - treatment after default II Optional 4 (HR)3 or 6 HE V Optional or 2 (HRZE) 3 or 2 HRZE IV Preferred 4 HR 4 (HR)3 Preferred 2 HRZE I New smear-positive patients; new smear-negative PTB with extensive parenchymal involvement; concomitant HIV disease or severe forms of extrapulmonary TB I Continual phase Initial phase Treatment regimen I TB patients Diagnostic category
  8. 8. Basical treatment regimens (continued) WHO/CDS/TB/2003.313 Treatment of tuberculosis:guidelines for national programmes, third edition. Revision approved by STAG, June 2004 Specially designed standardized or individualized regimens Chronic (still sputum-positive after supervised re-treatment); proven or suspected MDR TB cases. IV Optional 4 (HR)3 or 6 HE Optional 2 (HRZE)3 Preferred 4 HR Preferred 2 HRZE VIII New smear-negative PTB (other than in category I) and less severe forms of extra-pulmonary TB III Continual phase Initial phase Treatment regimen I TB patients Diagnostic category
  9. 9. Criticism concern with the DOTS strategy <ul><li>Clinical </li></ul><ul><li>Lack of smear-negative case detecting </li></ul><ul><li>Lack of case monitoring </li></ul><ul><li>Ethical </li></ul><ul><li>Treatment refusal for certain categories (especially chronic and smear-negative) </li></ul><ul><li>Epidemiological </li></ul><ul><li>Potential hazard of untreated treated in improper way patients </li></ul>
  10. 10. Expanded treatment conception <ul><li>Appropriate antibacterial treatment. </li></ul><ul><li>Hygienic and dietary regimen. </li></ul><ul><li>Pathogenetic measures: </li></ul><ul><li>desintoxication </li></ul><ul><li>hepatotropic therapy </li></ul><ul><li>tissue stimulation </li></ul><ul><li>Collapsotherapy </li></ul><ul><li>Surgical treatment. </li></ul>
  11. 11. <ul><li>For the future, the top priority remains to a dminister standardized short </li></ul><ul><li>course chemotherapy regimens to all smear positive cases (new and </li></ul><ul><li>retreatment cases). This priority requires the maximum of effort, time, </li></ul><ul><li>drugs and money in a national tuberculosis programme, without </li></ul><ul><li>diverting funds and resources to smear negative and/or chronic cases. </li></ul>
  12. 12. Drug resistance <ul><li>Primary </li></ul><ul><li>Concern with drug-resistant strains inoculation </li></ul><ul><li>Asquired </li></ul><ul><li>Produced by ineffective treatment </li></ul>
  13. 13. Drug resistance <ul><li>Simple drug resistance– resistance to more than two first line drugs including isoniasid or rifampicin </li></ul><ul><li>Multidrug-resistance (MDR) – resistance to more than two first line drugs including both isoniasid and rifampicin </li></ul>
  14. 14. Main resistance types <ul><li>XDR </li></ul>Resistance mono MDR poly
  15. 15. MDR-TB prevalence among new cases and countries in which at least one XDR-TB case has been reported At the end of 2006 year XDR-TB has been detected in 17 countries
  16. 16. Extensively drug resistance (XDR) – main definitions <ul><li>Firstly has been proposed by US Centers of Disease Control and Prevention (CDC) in March, 2006: the disease, caused by MBT, resistant to HR (MDR-TB) and to at least 3 from six classes of antituberculosis second-line drugs (aminoglycosides, polypeptide, fluoquinolones, thyamides, cyclocerine, PAS) </li></ul><ul><li>But on WHO meeting devoted to XDR problem (meeting of the WHO XDR-TB Task Force ), on October, 10-11 , 2006 difinition has been changed : the disease, caused by MBT, resistant to HR (MDR-TB) and to at least some fluoquinolones and one from 3 injectional antituberculosis drugs : cyclopentin , kanamycin, amicacin . </li></ul>
  17. 17. Second line drugs <ul><li>Less effective </li></ul><ul><li>More toxic </li></ul><ul><li>Much more expensive </li></ul>
  18. 18. Classes of second-line antituberculosis drugs <ul><li>a Aminoglycosides </li></ul><ul><li>When resistance to streptomycin is proved or highly suspected, one of </li></ul><ul><li>the other aminoglycosides can be used as a bactericidal agent against </li></ul><ul><li>actively multiplying organisms: </li></ul><ul><li>• kanamycin , the least expensive, but largely used for indications other </li></ul><ul><li>than tuberculosis in some countries. </li></ul><ul><li>• amikacin , as active as kanamycin and better tolerated, but much more </li></ul><ul><li>expensive. </li></ul><ul><li>• capreomycin ,2 very expensive but very useful in cases with tubercle </li></ul><ul><li>bacilli resistant to streptomycin, kanamycin and amikacin. </li></ul>
  19. 19. Classes of second-line antituberculosis drugs <ul><li>b Thioamides </li></ul><ul><li>Ethionamide or prothionamide are 2 different presentations of the </li></ul><ul><li>same active substance, with bactericidal activity. Prothionamide may be </li></ul><ul><li>better tolerated than ethionamide in some populations. </li></ul><ul><li>c Fluoroquinolones </li></ul><ul><li>Ofloxacin and ciprofloxacin are two different drugs, but with complete </li></ul><ul><li>cross-resistance within the group. These drugs have a low bactericidal </li></ul><ul><li>activity, and are useful in association with other drugs. The </li></ul><ul><li>pharmacokinetics of ofloxacin are better than the pharmokinetics of </li></ul><ul><li>ciprofloxacin. Sparfloxacin should be avoided because of severe </li></ul><ul><li>cutaneous side effects (photo-sensitisation). Norfloxacin should not be </li></ul><ul><li>used, because it does not give adequate serum levels . </li></ul>
  20. 20. Classes of second-line antituberculosis drugs <ul><li>d Cycloserine (or terizidone) </li></ul><ul><li>This is the same bacteriostatic agent, with 2 different formulations. It has </li></ul><ul><li>no cross-resistance with other antituberculosis agents. It might be </li></ul><ul><li>valuable to prevent resistance to other active drugs, but its use is limited </li></ul><ul><li>by its high toxicity. </li></ul>
  21. 21. Classes of second-line antituberculosis drugs <ul><li>Para-aminosalicylic acid (PAS) </li></ul><ul><li>This is a bacteriostatic agent, valuable for preventing resistance to </li></ul><ul><li>isoniazid and streptomycin in the past and to other bactericidal drugs today. </li></ul><ul><li>f Others </li></ul><ul><li>Other drugs, sometimes mentioned as second line antituberculosis </li></ul><ul><li>drugs, have no place in the treatment of MDR tuberculosis: </li></ul><ul><li>• rifampicin derivatives, like rifabutin (21), cannot be used since there is a lmost complete cross-resistance between rifabutin and rifampicin </li></ul><ul><li>(especially when there is acquired resistance to rifampicin); </li></ul><ul><li>• clofazimine has some activity against Mycobacterium leprae and </li></ul><ul><li>Mycobacterium ulcerans, but no activity against Mycobacterium </li></ul><ul><li>tuberculosis. </li></ul>
  22. 22. Acceptable regimen for the treatment of MDR Tuberculosis
  23. 23. <ul><li>It must be made clear to the patient and staff that meticulously taking the prescribed reserve regimen is all that stands between the patient and death. </li></ul>
  24. 24. Recovery criteria <ul><li>Clinical symptoms disappearing </li></ul><ul><li>Morphological changes resolving </li></ul><ul><li>Sputum conversion (by all available tests) </li></ul>
  25. 26. TB and HIV treatment sequence