1. Treatment of Tuberculosis
Name: Razvi Janny
Roll no. 19

2. Aims of TB treatment
1) To interrupt transmission by rendering patients
noninfectious.
2) Prevent morbidity and death by curing
patients with TB while preventing emergence
of drug resistance.

3. Drugs
First line drugs Second line drugs

Well absorbed after oral
administration

Peak levels at 2 – 4 h.

Lower degree of efficacy.

Higher degree of intolerability
and toxicity.

4. 
4 major drugs are considered the first-line
agents for treatment:
1) Isoniazid
2) Rifampin
3) Pyrazinamide
4) Ethambutol

5. 
Second-line drugs:
1)Injectable aminoglycosides: streptomycin,
Kanamycin
amikacin
2)Oral agents: ethionamide
cycloserine
PAS
Third gen. fluoroquinolones

6. Isoniazid

Has bactericidal activity against actively
dividing intracellular and extracellular
organisms.

Has bacteriostatic activity against slowly
dividing organisms.

Often given together with 25-50mg pyridoxine
daily to prevent drug-related peripheral
neuropathy.

7. Mechanism of action
INH
INH+
Nicotinic acyl-
NADH
complex
Blocks InhA
Inhibit fatty acid
synthesis and mycolic
acid synthesis
which is essential
for the bacterial cell
wall.
KatG
NADH

8. Adverse effects

Drug-induced liver injury

Peripheral neuropathy

Fever

Anemia

Acne

Arthritic syndrome

SLE-like syndrome

Optic atrophy

seizures

9. Rifampin

Has bactericidal activity against both dividing
and non-dividing M.tuberculosis with sterilizing
activity.
Mechanism of action

Exerts both intracellular and extracellular
bactericidal activity.

Binds to and inhibits mycobacterial DNA-
dependent RNA polymerase, blocking RNA
synthesis.

10. Adverse effects

Hepatotoxicity in case of preexisting liver
disease.

Pruritus

Rash

Gastrointestinal symptoms

Pancytopenia

Hypersensitivity reactions.

11. Ethambutol

It is a bacteriostatic antimycobacterial agent.

Provides synergy with other drugs.

Among the first-line drugs, it is the least potent.
Mechanism of action

Inhibition of the arabinosyltransferases involved
in cell wall synthesis.
Adverse effects

Optic neuritis

Peripheral sensory neuropathy.

12. Pyrazinamide
• Bactericidal drug used in the initial phase of TB
treatment.
• Shortens duration of treatment.
• Decreases rates of relapse.

13. Mechanism of action:
• More active against slowly replicating organisms
than against actively replicating organisms.
• It is a prodrug that is converted by
mycobacterial pyrimidase to the active form,
pyrazinoic acid.
• It is active only in acidic environments as in
phagocytes or granulomas.
• Fatty acid synthetase 1 is the primary target.

14. Adverse effects
• Hepatotoxicity
• Hyperuricemia
• Teratogenicity if given during pregnancy.

15. Streptomycin
• First antimycobacterial agent used for the
treatment of TB.
• Bactericidal against dividing M.tuberculosis
organisms.
Mechanism of action:
• Inhibits protein synthesis by binding at a site on
the 30S mycobacterial ribosome.

16. Adverse effects:
• Ototoxicity (primarily vestibulotoxicity)
• Neuropathy
• Renal toxicity

17. Second-line drugs
Fluoroquinolones
Mechanism of action
• Inhibit mycobacterial DNA gyrase and
topoisomerase IV, preventing cell replication
and protein synthesis.
• Bactericidal.

18. Adverse effects:
• Gastrointestinal intolerance
• Rashes
• Dizziness
• Headache
• Cardiac arrhythmias

19. Capreomycin
Mechanism of action:
• Involves interference with the mycobacterial
ribosome and inhibition of protein synthesis.
Adverse effects:
• Hypokalemia
• Hypomagnesemia
• Ototoxicity
• Renal toxicity

20. Amikacin and kanamycin
• Exert mycobactericidal activity
• Given by IM or IV route.
Adverse effects
• Ototoxicity
• Nephrotoxicity
• Neurotoxicity

21. Ethionamide
Mechanism of action:
• Bacteriostatic against metabolically active
M.tuberculosis.
• Inhibits InhA gene product enoyl-acyl carrier
protein reductase which is involved in mycolic
acid synthesis.

22. Adverse effects:
• Gastrointestinal reactions (abdominal pain,
nausea and vomiting)
• Central and peripheral neurologic side effects.
• Reversible hepatitis
• Hypersensitivity reactions
• Hypothyroidism

23. Para-aminosalicylic acid
• Oral agent.
• Used in multiple drug resistant TB.
Mechanism of action:
• Bacteriostatic.
• Inhibition of folate synthesis and of iron uptake.

24. Adverse effects:
• Nausea, vomiting and diarrhea.
• PAS may cause hemolysis in patients with
glucose-6-phosphate dehydrogenase
deficiency.

25. Management
Chemotherapy
Initial phase
Continuation phase
Reduce bacterial
population rapidly. Destroy any remaining
bacteria.

26. • Standard treatment involves 6 months
treatment with isoniazid, rifampicin,
pyrazinamide and ethambutol.
• Fixed-dose tablets combining two or three
drugs are preferred.
• Treatment should be started immediately in any
patient who is smear-positive or smear-
negative but with typical chest x-ray changes
and no response to standard antibiotics.

27. • 6-months therapy is appropriate for new onset
pulmonary TB.
• However, a 12-months therapy is
recommended for meningeal TB, including
involvement of the spinal cord.
• Treatment may be given daily throughout the
course or intermittently (either thrice or twice
weekly)
• Patients with cavitary pulmonary TB and delayed sputum-
culture conversion should have continuation phase extended by
3 months.

28. Recommended dosage for initial
treatment of tuberculosis in adults.
Drug Daily dose Thrice-weekly dose
Isoniazid 5 mg/kg, max 300 mg 10 mg/kg, max 900 mg
Rifampin 10 mg/kg, max 600 mg 10 mg/kg, max 600 mg
Pyrazinamide 25 mg/kg, max 2 g 35 mg/kg, max 3 g
Ethambutol 15 mg/kg 30 mg/kg

29. Initial phase Continuation phase
Duration,
months
Drugs Duration,
months
Drugs
New smear or culture
positive cases
2 HRZE 4 HR
New culture negative
cases
2 HRZE 4 HR
Pregnancy 2 HRE 7 HR
Relapses and default
(pending susceptibility
testing)
3 HRZES 5 HRE
Resistance to H 6 RZE
Resistance to R 12-18 HZEQ
Resistance to all first-
line drugs.
Atleast 20
months
1 injectable agent + 3 of
these 4: E, cycloserine,
Q, PAS.

30. Management guidelines for patients
with documented XDR-TB.
1. Use any first-line oral agents that may be
effective.
2. Use an injectable agent to which the strain is
susceptible, and consider an extended duration
of use (12 months).
3. Use a later generation fluoroquinolone
(moxifloxacin).
4. Use all second-line oral agents (PAS,
cycloserine, ethinamide, prothionamide).
5. Use 2 or more of the following drugs of unclear
role: clofazimine, linezolid, thiacetazone.

31. • Administer high-dose isoniazid if low-level
resistance to this drug is documented.
• Adjuvent surgery if there is localized disease.
• Strong infection-control measures
implemented.
• Implement DOTs therapy and comprehensive
bacteriologic and clinical monitoring.

32. Treatment of HIV-associated TB
• ART is initiated early in TB therapy (within the
first 8 weeks)
• The IRIS may appear as early as 1 week after
initiation of ART. This is treated with varying
doses of glucocorticoids.

33. Regimens for the treatment of latent
TB infection in adults.
Regimen Schedule Duration
Isoniazid 300 mg daily (5
mg/kg)
9 months
Rifampin 600 mg daily (10
mg/kg)
4 months
Isoniazid plus
rifapentine
900 mg weekly +
900 mg weekly (15
mg/kg)
4 months

34. Monitering treatment response
• Patients should have their sputum examined
monthly until cultures become negative.
• Smears that are positive after 3 months of
treatment is indicative of treatment failure or
drug resistance.
• Drug susceptibility testing must then be done.

35. Monitering drug toxicity
Drug Assessment Management
Isoniazid If ALT is >5 x ULN • Obtain history of alcohol
consumption.
• Discontinue H, Z, R.
Rifampin If primary elevation is in
bilirubin and ALP, more
likely rifampin.
• Discontinue R
• Substitute it with Q.
Ethambutol Decrease in visual acuity or
color vision.
• Discontinue E and
repeat ocular exam.
Pyrazinamide If ALT is >5 x ULN Same as for H.
Fluoroquinolone If QT prolongation is
discovered on ECG.
Check audiometry, BUN
and creatinine monthly.
Aminoglycoside Abnormal results on
audiometry testing, BUN,
creatinine, electrolytes at
baseline.
• Discontinue
aminoglycosides.
• Correct electrolytes
• Seek ENT consultation.

36. Treatment failure and relapse
• Patients with treatment failure should receive
an empirical regimen, including second line
agents.
• Once drug susceptibility testing results are
available, the regimen should be adjusted
accordingly.
• Patients who have relapsed are treated with all
four first-line drugs plus streptomycin.

37. Control and prevention
Detection of latent TB
•Cases of latent TB are identified using tuberculin
skin test.
Tuberculin skin tests
Heaf test Mantoux
test
Positive when
induration is 5-14 mm.

38. BCG vaccine
• Effective in the protection of infants and young
children from relatively serious forms of TB.
• Given intradermally.
• Recommended for routine use at birth in
countries with high TB prevalence.
• Not given to immunocompromised persons.

39. Directly observed therapy (DOT)
• Involves supervised administration of therapy
by trained staff 3 times weekly to improve
adherence.
• It is an important control strategy in resource-
poor nations.

40. DOTS approach consists of:
1.Political commitment with increased and
sustained financing.
2.Case detection through quality-assured
bacteriology (sputum smear, culture and drug
susceptibility testing).
3.Administration of standardized short-course
chemotherapy, with direct supervision and
patient support.
4.Effective drug supply and management system.

41. 5. Monitoring and evaluation of treatment
outcomes.

42. THANK YOU