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Tuberculosis treatment

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TB treatment principles by Daniel schwartz - LSMU

TB treatment principles by Daniel schwartz - LSMU


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  • 1. Tuberculosis treatment: general principles and approach Lecturer: Ph.D M.G.Dolynska
  • 2. Historical background
    • Supposed incurable until XX century
    • First approach – sanatorium movement
    • First pathogenically based attempt –artificial pnemothorax (Forlanini, 1882)
    • Streptomycin discovery (Zelman Waksman, 1943)
  • 3. The AIMS of treatment of tuberculosis are:
    • to cure the patient of TB;
    • to prevent death from active TB or its late effects;
    • to prevent relapse of TB;
    • to decrease transmission of TB to others;
    • to prevent the development of acquired drug resistance.
  • 4. DOTS ( Directly observed treatment short course ), Karel Styblo, 1972
    • The organizational principles of the DOTS are:
    • availability of a decentralized diagnostic and treatment network based on existing health facilities;
    • good programme management based on accountability and supervision of health care workers;
    • an evaluation system of case-finding and cohort analysis of treatment outcomes.
  • 5. The five elements of the expanded DOTS framework are:
    • 1.Sustained political commitment to increase human and financial resources and make TB control a nationwide priority integral to the national health system.
    • 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).
    • 3. Standardized short-course chemotherapy for all cases of TB under proper case management conditions, including direct observation of treatment.
    • 4. Uninterrupted supply of quality-assured drugs with reliable drug procurement and distribution systems.
    • 5. Recording and reporting system enabling outcome assessment of all patients and assessment of overall programme performance.
  • 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. 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. 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. Criticism concern with the DOTS strategy
    • Clinical
    • Lack of smear-negative case detecting
    • Lack of case monitoring
    • Ethical
    • Treatment refusal for certain categories (especially chronic and smear-negative)
    • Epidemiological
    • Potential hazard of untreated treated in improper way patients
  • 10. Expanded treatment conception
    • Appropriate antibacterial treatment.
    • Hygienic and dietary regimen.
    • Pathogenetic measures:
    • desintoxication
    • hepatotropic therapy
    • tissue stimulation
    • Collapsotherapy
    • Surgical treatment.
  • 11.
    • For the future, the top priority remains to a dminister standardized short
    • course chemotherapy regimens to all smear positive cases (new and
    • retreatment cases). This priority requires the maximum of effort, time,
    • drugs and money in a national tuberculosis programme, without
    • diverting funds and resources to smear negative and/or chronic cases.
  • 12. Drug resistance
    • Primary
    • Concern with drug-resistant strains inoculation
    • Asquired
    • Produced by ineffective treatment
  • 13. Drug resistance
    • Simple drug resistance– resistance to more than two first line drugs including isoniasid or rifampicin
    • Multidrug-resistance (MDR) – resistance to more than two first line drugs including both isoniasid and rifampicin
  • 14. Main resistance types
    • XDR
    Resistance mono MDR poly
  • 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. Extensively drug resistance (XDR) – main definitions
    • 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)
    • 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 .
  • 17. Second line drugs
    • Less effective
    • More toxic
    • Much more expensive
  • 18. Classes of second-line antituberculosis drugs
    • a Aminoglycosides
    • When resistance to streptomycin is proved or highly suspected, one of
    • the other aminoglycosides can be used as a bactericidal agent against
    • actively multiplying organisms:
    • • kanamycin , the least expensive, but largely used for indications other
    • than tuberculosis in some countries.
    • • amikacin , as active as kanamycin and better tolerated, but much more
    • expensive.
    • • capreomycin ,2 very expensive but very useful in cases with tubercle
    • bacilli resistant to streptomycin, kanamycin and amikacin.
  • 19. Classes of second-line antituberculosis drugs
    • b Thioamides
    • Ethionamide or prothionamide are 2 different presentations of the
    • same active substance, with bactericidal activity. Prothionamide may be
    • better tolerated than ethionamide in some populations.
    • c Fluoroquinolones
    • Ofloxacin and ciprofloxacin are two different drugs, but with complete
    • cross-resistance within the group. These drugs have a low bactericidal
    • activity, and are useful in association with other drugs. The
    • pharmacokinetics of ofloxacin are better than the pharmokinetics of
    • ciprofloxacin. Sparfloxacin should be avoided because of severe
    • cutaneous side effects (photo-sensitisation). Norfloxacin should not be
    • used, because it does not give adequate serum levels .
  • 20. Classes of second-line antituberculosis drugs
    • d Cycloserine (or terizidone)
    • This is the same bacteriostatic agent, with 2 different formulations. It has
    • no cross-resistance with other antituberculosis agents. It might be
    • valuable to prevent resistance to other active drugs, but its use is limited
    • by its high toxicity.
  • 21. Classes of second-line antituberculosis drugs
    • Para-aminosalicylic acid (PAS)
    • This is a bacteriostatic agent, valuable for preventing resistance to
    • isoniazid and streptomycin in the past and to other bactericidal drugs today.
    • f Others
    • Other drugs, sometimes mentioned as second line antituberculosis
    • drugs, have no place in the treatment of MDR tuberculosis:
    • • rifampicin derivatives, like rifabutin (21), cannot be used since there is a lmost complete cross-resistance between rifabutin and rifampicin
    • (especially when there is acquired resistance to rifampicin);
    • • clofazimine has some activity against Mycobacterium leprae and
    • Mycobacterium ulcerans, but no activity against Mycobacterium
    • tuberculosis.
  • 22. Acceptable regimen for the treatment of MDR Tuberculosis
  • 23.
    • 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.
  • 24. Recovery criteria
    • Clinical symptoms disappearing
    • Morphological changes resolving
    • Sputum conversion (by all available tests)
  • 25.  
  • 26. TB and HIV treatment sequence