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Bacillary Populations in Tuberculosis Patients - Understanding Drug Resistance Mechanisms

Explore the concept of bacillary populations in tuberculosis patients and how they impact drug resistance, varying based on location, pH, replication rate, and susceptibility to drugs. Learn about the behavior of different bacillary populations and their implications for tuberculosis treatment strategies.

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Bacillary Populations in Tuberculosis Patients - Understanding Drug Resistance Mechanisms

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  1. مفهوم مقاومت داروييدر سل دكتر مهشيد ناصحيرئيس اداره كنترل سل و جذام مركز مديريت بيماريهاي واگيرو عضو هيئت علمي دانشگاه علوم پزشكي تهران

  2. CausalAgent • - Mycobacterium tuberculosis complex • - Polyvalent • behaviour • depending • on medium.

  3. Bacillary populations ■ In a tuberculosis patient, there are different bacillary populations formed of bacilli in different situations - Location - pH - Replication rate, susceptibility to drugs, …

  4. Bacillary populations • 1. Rapidly multiplying bacilli • - Optimum medium: Extracellular. PH 6.5-7, maximum oxygenation (cavern wall) • - Large number of bacilli → High probability of spontaneous natural mutations Many Millions Natural Resistant Mutants Failure

  5. Bacillary populations 2. Slow multiplication Bacilli - Intramacrophagic location. Acid pH. Population<105 Relapses No Naturally Resistant Mutants

  6. Bacillary populations 3. Intermittently growing bacilli - Unfavourable conditions. Solid caseum. Extracellular - Population <105 - Relapse capacity Relapses No Naturally Resistant Mutants

  7. جمعيت هاي ميكروبي 1. باسيلهاي با سرعت تكثير زياد → INH 2. باسيلهاي با سرعت تكثير كم → PZ 3. باسيلهاي با رشد و تكثير متناوب → RIF يكي از دلايل ضرورت درمان تركيبي در سل در استراتژي داتس همين مسئله است

  8. ميكروب سل هر 16 تا 24 ساعت يكبار تكثير مي شود بيمار در مراجعه به واحدها و تسهيلات بهداشتي يا درماني تعلل و تاخير مي كند تاخير در تشخيص بيمار در زمان تشخيص، مدتي طولاني است كه مسري بوده و ديگران را آلوده مي كند ذات بيماريتكثير خيلي آرام ميكروب سل علائم بيماري بسيار آرام و بطئي بروز مي كند

  9. مايكوباكتريوم توبركلوزيس ديواره سلولي باسيل و نقطه هدف داروهاي ضد سل

  10. مايكوباكتريوم توبركلوزيساحتمال رخداد مقاومت دارويي در روند سير طبيعي تكثير باسيل سل • INH 1 x 105-106 Bacilli • RIF 1 x 107-108 Bacilli • SM 1 x 105-106 Bacilli • EMB 1 x 105-106 Bacilli • PZ 1 x 102-104 Bacilli ? • Quinolones 1 x 105-106 Bacilli ? • Others 1 x 105-106 Bacilli ?

  11. The possibility to generate MDR in NTP conditions The Risk to Amplify Resistances with Non Adequate Strategies

  12. Sequential Monotherapy INH Post-AntibioticEffectswith M. tuberculosis LagPeriodsbeforeCommencement of GrowthafterExposure in 7H10 Medium streptomycin Isoniazid Ethambutol Rifampicin 0 1 2 3 4 5 6 7 8 9 10 Lag after 24 hr exposure to drug (days) Mitchison DA, et al. Postgr Med J 1971;47:737-41

  13. Initial Res. H Initial MDR Pansusceptible The possibility to generate MDR in NTP conditions 2 HRZE / 4 HR

  14. The possibility to generate MDR and XDR in NTP conditions 2 HRZE / 4 HR CURE Strict DOT Pansusceptible Bad Maintained Adherence Danger ! Intermittent Tr.

  15. The possibility to generate MDR in NTP conditions 2 HRZE / 4 H R Sm (-) 2ºMonth Extend 1ª Phase Initial Res. H % CURE Sm (+) 2º M. Go to 2ª Phase ¡ High Risk MDR-TB !, but Susceptible ZE

  16. FAILURE 2. Initial Resistance to H (+%) 2 HRZE/4 HR MDR, but suscpt.Z+E 2HRZES/1HRZE/5H R E Risk to Amplify Resistance E (Avoidable if DST before 3rd Month) The Risk to Amplify Resistance in the Failures to Cat. I receiving Category II Regime (2) 2 HRZE/ 4 HR

  17. The possibility to generate MDR in NTP conditions 2 HRZE / 4 H R CURE (20-50%) Initial MDR MDR-TB, Amplifying Resist. to Z+E

  18. FAILURE 3. Initial M.D.R. (-%) 2 HRZE/4 HR Resistance to HR+E+Z Risk to Amplify Resistance to S 2HRZES/1HRZE/5HRE The Risk to Amplify Resistance in the Failures to Cat. I receiving Category II Regime (3) 2 HRZE/4 HR

  19. اگر مطمئن نباشيد كه به كجا ميرويد........ بسيار احتمال دارد كه از جاي ديگري سر در بياوريد و حتي ندانيد كه كجا هستيد

  20. >108 organisms in TB cavity 1 resistant RIF 100 resistant INH 100 resistant Strep 100 resistant EMB Likelihood of Natural Resistance Rifampin 1/108 INH, Strep, EMB 1/106

  21. For New Cases Never Treated >108 Organisms in TB Cavity 1 resistant RIF 100 resistant INH 100 resistant Strep 100 resistant EMB 0 resistant INH+Rif 0 resistant INH+Rif+EMB

  22. 100 organisms resistant to INH remain in cavity If Treated With INH Only 108 Organisms: 1 resistant RIF 100 resistant INH 100 resistant Strep 100 resistant EMB Organisms Multiply New 108 Organisms: 1 resistant Rif 108 resistant INH 100 resistant Strep 100 resistant EMB

  23. If Treated with INH and RIF 108 Organisms: 1 Resistant Rif 108 Resistant INH 100 Resistant Strep 100 Resistant EMB 1 organism resistant to RIF and INH MDR-TB Organisms Multiply

  24. The combination of drugs prevents the appearance of resistance, because it avoids the selection of naturally resistant mutants Bacteriological Fundaments of TB Treatment 1. Drug combinations

  25. به نظر شما هزينه درمان ، اميد بهبودي، طول درمان ونياز بستري يك بيمار سلي حساس به دارو با يك بيمار مقاوم به داروشبيه هم مي باشد؟؟

  26. انديكاسيون هاي آنتيبيوگرام • بیماران دچار شکست درمان در گروه 2 درمانی و موارد مزمن سل (پرخطرترین) • افراد در تماس نزدیک با بیماران مبتلا به MDR-TB شناخته شده، البته در صورتی که دچار علائم بالینی مشکوک به سل ریوی شده باشند. • بیماران دچار شکست درمان در گروه 1 درمانی • بیمارانی که اسمیر خلطشان در پایان مرحله حمله ای درمان مثبت شده یا هنوز مثبت باقی مانده است. • موارد عود و درمان بعد از غیبت (هر چند که احتمال مقاومت دارویی در آن ها نسبت به گروه- های قبلی کمتر است) • بیماران مبتلا به سل ریوی HIV+ • بیماران مبتلا به سل ریوی اسمیر خلط مثبت زندانی

  27. وب سايت اداره كنترل سل و جذام www.cdc.hbi.ir

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