This document discusses multi-drug resistant tuberculosis (MDR-TB). It provides global statistics on TB incidence and mortality. MDR-TB is defined as disease resistant to at least two first-line anti-TB drugs. Countries with significant MDR-TB burdens are listed. The Indian scenario outlines that India has a high TB burden and accounts for 20% of global cases. A case study from Andhra Pradesh examines 75 MDR-TB patients. Clinical factors promoting drug resistance and mechanisms of resistance are reviewed. Treatment of MDR-TB and new chemotherapeutic agents are discussed. Global targets for TB control by 2015 are presented.

1. Multi drug resistant T.B. (MDR)
 Dr. Gopalrao M.D. Ph.D.
 Professor of Community Medicine
 CAR Medical College
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2. Global Fact sheet:
 T.B. Incidence: 8.8 million people
are affected by TB annually world
wide.
 1.4 million deaths occur annually
world wide.
 MDR-TB is defined as disease
having resistance to two or more of
the anti T.B. drugs with or without
resistance to other anti TB drugs
It is a major threat to TB control
program world wide.
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3. Countries having problem of MDR T.B.
 Russia
 Peoples Republic of China
 India
 Western Europe
 United states
 United Kingdom
 Germany
 Central Europe
 Lithuania
 Latvia
 Estonia
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5. Indian Scenario
 Prevalence of MDR T.B. in new smear +ve cases is less than
3% and 12 to 17% amongst previously treated PTB cases.
• India is the highest TB burden country in the world.
• India is 17th among 22 high burden countries in terms of
incidence rate
• Accounts for 20% of global burden of TB.
• Every year 1.8 million persons develop TB
• There are point eight million new smear positive cases.
• The annual risk of becoming infected with TB is 1.5 %
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6. Case study from Andhra Pradesh
 Study conducted on 75 MDR T.B. cases.
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7. 1
5 9
3 14 1
Reported 6 5
2
MDR cases 2
10 5 1
from 18
districts of 5 2
Andhra
Pradesh 2 1 2
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8. 8

12. NO. OF % OF PATIENTS
PATIENTS
SOB, Cough, fever 38 50%
Cough, fever 20 27%
SOB, cough 6 8%
Cough, fever, loss 2 3%
Complaints of appetite
SOB, cough, fever, 2 3%
loss of appetite
among cough 2 3%
SOB, Haemoptysis 1 1%
Cough, loss of 1 1%
MDRTB appetite
Cough, fever, 1 1%
haemoptysis
SOB 1 1%
Patients
SOB, cough, 1 1%
haemoptysis
Cough, fever,chest 1 1%
pain 12

13. Clinical factors promoting resistance
 Delayed diagnosis and isolation
 Inappropriate drug regimen.
 Inadequate initial therapy
 Incomplete course of treatment
 Inappropriate treatment modifications
 Adding single drug to a failing regimen
 Inappropriate use of chemoprophylaxis
 Poor adherence and incomplete Follow up
 Failure to isolate MDR TB patients
 Failure to employ DOT
 Over the counter anti TB
 Faked drugs

14. Mechanism of Resistance
 TB specific drugs
 INH, PZA, ETH
 Antibiotics with activity against TB
 RIF
 Aminogycosides
 Flouroquinolones

15. Mechanism of resistance
 INH
 Chromosomally mediated
 Loss of catalase/peroxidase
 Mutation in mycolic acid synthesis
 Regulators of peroxide response

16. Mechanism of resistance
 Rifampin
 Reduced binding to RNA polymerase
 Clusters of mutations at “Rifampin Resistance Determining
Region” (RRDR)
 Reduced Cell wall permeability

17. Treatment of MDR TB
 Factors determining Success
 Culture of MDR TB
 Reliable susceptibility
 Reliable history of previous drug regimens
 Program to assure delivery of prescribed drugs (DOT)
 Correct choice of modified treatment regimen
 Reliable follow up

18. New Chemotherapeutic Agents
 Not many. Low interest from pharmaceutical industry
 Derivatives of Rifamycin
 Rifabutin: Sensitive subset of Rifampin resistant strains
 Rifapentine: Extended half-life but more mono-resistance to
rifamycins
 KRM-1648. benzoxazinorifamycin. In vitro and animal models.
 New flouroquinolones
 Gatifloxacin, Moxifloxacin, levofloxacin, sparfloxacin
 Nitroimidazoles
 related to metronidazole. May work better against latent bacilli
 Avoiding pro-drug problems

19. Chemoprophylaxis
 Determinants of intervention
 Likelihood of infection with MDR TB
 Low
 Intermediate
 High
 Likelihood of developing MDR TB
 Immune suppression

20. Global TB control targets
2015: 50% reduction in TB prevalence and
death rates by 2015
2015: Goal 6: Combat HIV/AIDS, malaria and other
diseases
Target 8: to have halted by 2015 and begun to reverse
the incidence…
Indicator 23: prevalence and deaths associated with TB
Indicator 24: proportion of TB cases detected
and cured under DOTS
2005: World Health Assembly:
- To detect at least 70% of infectious TB cases
- To treat successfully at least 85% of detected
cases

21. Stop TB Strategy
to reach the 2015 MDGs

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24. Thank You
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