This document discusses drug resistant tuberculosis (TB) and provides definitions, mechanisms, factors, diagnostic tests, treatment principles and regimens for multi-drug resistant TB (MDR-TB). It defines MDR-TB as resistance to at least isoniazid and rifampin and notes management requires specialized treatment units, reliable drug susceptibility testing, and directly observed long-term combination drug regimens using second-line drugs. Acceptable regimens are outlined based on patterns of resistance to first-line drugs.

1. Dr. Manu Mohan K
Associate Professor
Pulmonary Medicine
DRUG RESISTANT TUBERCULOSIS

2. DEFINITIONS
• Drug resistance is defined as a decrease
in sensitivity to a drug of a sufficient
degree.
• A strain is considered resistant when 1%
or more of the bacterial population was
resistant to a designated concentration
of drug.

3. MULTI – DRUG RESISTANT
TUBERCULOSIS
• Mycobacterium tuberculosis resistant to
at least Isoniazid and Rifampicin.

4. TERMINOLOGY
• Wild strain
• Natural or Primary resistance
• Acquired resistance

5. MECHANISMS
• Mutations
• Interference in uptake, penetration
• Insusceptible metabolic pathways
• Destruction of drugs
• Fall and rise phenomenon

6. FACTORS
• Clinical
• Administrative
• Patient co-operation

7. DRUG SUSCEPTIBILITY TESTS
• Conventional methods
• Rapid methods
• Radiometric method-BACTEC
• Luciferase reporter assay

8. • Mycobacterium Growth Indicator Tube
• Gene based tests
• DNA finger printing

9. SECOND - LINE
ANTITUBERCULOSIS DRUGS
• Aminoglycosides
• Thioamides
• Fluoroquinolones
• Cycloserine
• Para Amino Salicylic acid
• Others

10. BASIC PRINCIPLES FOR
MANAGEMENT OF MDRTB
• Specialised unit
• Designing appropriate regimen
• Which regimens?
• Whether took as prescribed and how
long?
• What happened bacteriologically?

11. • Reliable susceptibility testing
• Reliable drug supplies
• Priority for prevention
• MDRTB is a consequence of poor
treatment

12. HOW TO ASSESS INDIVIDUAL
CASES?
• Think of following
• Lab report – error?
• Retreatment regimen – correct?
• Patient aware of giving true history?
• Question the family members

13. • Considering criteria of failure of
retreatment regimen
• Persistent sputum positive
• Lab report should not be considered
uncritically
• Radiological deterioration
• Clinical deterioration

14. CHOOSING CHEMOTHERAPY
REGIMEN – BASIC PRINCIPLES
• It is assumed that apparent drug
resistant tuberculosis bacilli will be
resistant to Isoniazid
• Second line drugs – less effective more
toxic

15. • Patient and staff should have clear idea
that the regimen stands between patient
and death
• Patient must try to tolerate
• Last battle – do not aim to keep drugs in
reserve

16. • Prescribe drugs which patient has not
had previously
• Initial regimen should consist of at least
3 drugs preferably 4 or 5 to which bacilli
are likely to be fully sensitive

17. • It is desirable to use in combination an
injectable aminoglycoside
• When patients sputum has converted to
negative, you can withdraw one or more
drugs, preferably weaker one causing
side effects

18. • Continuation phase should be at least 18
months after sputum conversion.
• Treatment should be daily and directly
observed

19. • Mandatory to monitor bacteriological
results (smear and culture) monthly from
2nd
month until 6th
month, and then
quarterly till the end of treatment.

20. ACCEPTABLE REGIMENS
• If susceptibility test not available start
at least 3 never used drugs
(Kanamycin, ethionamide,
fluoroquinolone and pyrazinamide)
followed by 2 drugs best tolerated and
more effective( fluoroquinolone and
ethionamide)

21. • If susceptibility test result available and
resistant to isoniazid,
• Rifampicin, aminoglycosides,
pyrazinamide, ethambutol for 2-3
months and then continued with ER
for total of 9 months

22. • Resistant to Isoniazid and Rifampicin
(with or with out streptomycin)
• 5 drug regimen mandatory.
Ethionamide, fluoroquinolone,
aminoglycoside, Pyrazinamide and
Ethambutol followed by Ethionamide,
fluoroquinolone and Ethambutol

23. • Resistance to Isoniazid, Rifampicin and
Ethambutol
• Aminoglycoside, Ethionamide,
Pyrazinamide, fluoroquinolone and
Cycloserine followed by Ethionamide,
fluoroquinolone and Cycloserine.

24. SURGERY

25. DOTS PLUS

26. HIV

27. XDR-TB