Chapter 4 Drug resistant Tuberculosis.pptx

Drug resistant Tuberculosis

1. Drug-Resistant Tuberculosis

2. Introduction to Drug-resistant TB Course This course is designed to equip you with the knowledge on how to effectively and efficiently manage patients diagnosed with drug-resistant Tuberculosis disease. It will also serve as a useful resource for policy makers, those working in TB programs and those providing care to TB patients in the communities and health facilities.

3. Session 1: Pathways to Drug-resistant TB Development

4. Expected Learning Outcomes By the end of this unit,the learner will be able to: 1.Describe DRTB case finding strategies 2.Describe the approach to Diagnosing DRTB and the testing modalities available

5. Introduction The approach to diagnosis begins by identifying the high DR TB suspects or the individuals at high risk of developing DRTB and obtaining relevant samples for Mycobacteriology. Entails identifying individuals who may be at a greater risk of developing drug-resistant TB (Presumptive DR-TB) compared to the general population and evaluating them appropriately using gene-xpert, culture and Drug Susceptibility Testing (DS T).

6. DR-TB Case Finding Strategies The following individuals are at a higher risk of getting DRTB: All previously treated patients: a. failures ; b. relapses; c. treatment after loss to follow up DR TB contacts who have been diagnosed with active TB Healthcare workers with TB symptoms Patients who develop TB while on IPT Refugees with symptoms of TB Smear positive at 2 months of drug sensitive treatment Prisoners with TB symptoms

7. The definitive diagnosis of drug-resistant TB requires the detection of Mycobacterium tuberculosis bacteria and determination of resistance to anti-TB drugs using the methods outlined below: 1.Genotypic (Xpert MTB RIF assay,LPA) 2.Phenotypic culture and drug susceptibility testing .

8. Important to note the following : Patients may have a positive smear with negative cultures that may be caused by the presence of dead bacilli . That does not necessarily indicate treatment failure. Action; DISCUSS such cases with the DR TB clinical management team. In patients with repeated negative culture and smear results with no corresponding clinical and radiological improvement, consider other diseases other than MDR-TB All children presumed to have TB and are GeneXpert negative on a single Xpert - repeat Xpert. Children with high clinical suspicion of TB should be treated for TB regardless of the test results .

9. Principles and rationale for DR TB treatment Drug combinations should be used as it avoids the selection of naturally occurring mutants. Intentional or inadvertent monotherapies should NEVER be used. The regimen composition should have drugs with Sterilizing and Bactericidal effects targeting all bacillary populations Treatment should be long enough to permit action against all bacillary populations

10. Desirable characteristics of anti TB medicine s Bactericidal activity - ability to kill the rapidly multiplying, metabolically active bacilli found in cavities and sputum of smear positive pulmonary TB patients. Sterilizing activity - The ability to kill the persistent, dormant or intermittently active bacilli, which are responsible for relapses. Good sterilizing effects lead to shortening of the treatment period. Properties of anti TBs Toxicity Activity Level Prevention of Resistance Bactericidal activity Sterilizing activity Toxicity Toxicity Level High Rifampicin Isoniazid Ethambutol Isoniazid Rifampicin Lfx / Mfx Rifampicin Pyrazinamide hMfx Ethambutol Rifampicin Isoniazid Fluoroquinolones Low Moderate Injectables Fluoroquinolones Ethionamide Cycloserine PAS Linezolid Injectables Linezolid Bedaquiline Delamanid LFX Linezolid Bedaquiline Delamanid Clofazimine Injectables Pyrazinamide Linezolid Bedaquiline Delamanid Moderate Low Pyrazinamide Ethionamide/Pth High

11. Treatment regimens by resistant patterns The Injectable free treatment regimen: It is the recommended regimen for MDR/RR and Pre-XDR TB patients including adults, children and pregnant women. Drugs used in these regimens are administered orally. This regimen has two phases: 1.Intensive (6 months) 2.Continuation phase (12 months)

12. Pattern of Drug Resistance (Regimen name) Regimen Duration 1.MDR/ RR TB (Standard injectable free regimen for MDR/RR TB) Intensive phase: 6 Bdq /Lfx /Lzd /Cfz / Cs Continuation phase: 12 Lfx /Cfz / Cs   18 months 2.Paediatric MDR / RR TB ( <6yrs and <25kg) (Standard paediatric injectable free regimen for MDR/RR TB) Intensive phase: 6 Mfx/Cfz/Cs/Lzd Continuation phase: 12 Mfx/Cfz/Cs   18 months   3.Pre-XDR - Injectable resistance (Standard injectable free regimen for MDR/RR TB) Intensive phase: 6 Bdq/Lzd/Cfz/Lfx/Cs Continuation phase: 12 Cfz/Lfx/Cs 18 months

13. 4.Pre-XDR - Fluoroquinolones Resistant (Standard Pre-XDR regimen) Intensive phase: 6 Bdq/Dlm/Lzd/Cfz/Cs/ Continuation phase: 14 Dlm/Cfz/Cs 20 months   5.Pre - XDR Paediatrics* - Fluoroquinolone Resistance (Standard Paediatric Pre-XDR regimen) Intensive phase: 6 Bdq**/Dlm**/Lzd/Cfz/Cs/ Continuation phase: 14 Dlm/Cfz/Cs/   20 months 6. ISONIAZID mono resistance (Isoniazid Mono regimen) 6 (H)R/Z/E/Lfx 6 months

14. 7.Bedaquiline Intolerance (Include SAE, Hypersensitivity) Intensive Phase: 6 Dlm/Lzd/Lfx/Cfz/Cs Continuation phase: 12 Lfx/Cfz/Cs   18 months 8.PDR TB (with INH Resistance) 9 (H)R/Z/E/Lfx 9 Months   9.XDR TB Individualised regimen 18-24 months

15. 10 Z Monoresistance 2 RHZE 4 RH 6 months 11 E Monoresistance 2 RHZE 4 RH 6 months Any case excluded from any of the regimens above Individualised regimen 18-24 months