One-third of the world's population is latently infected with M. tuberculosis. About 5-10% of latent patients and HIV patients may develop reactivated TB within a few years. Mycobacterial infections generally result in slow-growing granulomatous lesions causing major tissue destruction, such as tuberculosis and leprosy. Current treatment recommendations for uncomplicated TB involve a 6-month regimen of isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin. The initial 2 months target actively multiplying bacilli, while the subsequent 4 months target persisters with intermittent metabolic activity.

1. latent

2. • one-third of the world's population is
infected with M. tuberculosis, and heal as
Latent infection
• 5% of latent patient may be converted to
Reactivated TB within Two years
• Another 5% may be converted to
Reactivated TB within Five years
• 10% of HIV will be converted to
Reactivated TB each year
• one-third of the world's population is
infected with M. tuberculosis, and heal as
Latent infection
• 5% of latent patient may be converted to
Reactivated TB within Two years
• Another 5% may be converted to
Reactivated TB within Five years
• 10% of HIV will be converted to
Reactivated TB each year

3. ٣

4. 4

5. ٥

6. Mycobacterial infections
• Intracellular
•Generally, result in the formation of
•slow-growing granulomatous lesions
•Responsible for major tissue destruction.
•Tuberculosis
•leprosy .
٦
Mycobacterial infections
• Intracellular
•Generally, result in the formation of
•slow-growing granulomatous lesions
•Responsible for major tissue destruction.
•Tuberculosis
•leprosy .

7. Rapidly
multiplying
1. Intracellular
2. Slowly growing
3. Easly disseminating
4. Multiple phases of
growth
Problematic infection
Time
MTb
Rapidly
multiplying
Slowly
multiplying
Dormant
A.spurt

8. CavitaryCavitary reactivation TBreactivation TB
left upper lobe cavity and localized pleural thickeningleft upper lobe cavity and localized pleural thickening

9. Who gets TB?
Children
The Sick
The Hungry

10. Transmission of TB
10
Through the airThrough the air
CoughingCoughing
SneezingSneezing

11. Potts disease of spine - gibbus
Gibbous formation
(acute angulation of spine with or without neurological damage)

12. Cervical lymph node TB progressing to abscess

13. MTB grown on biopsy by plastic surgeons (HIV neg)

14. Renal tuberculosis (may have few or no
symptoms) leading to autonephrectomy

15. Miliary TB on MRI scan
Tuberclomas on CT scan

16. SkinChest x-ray
TB Tests
Sputum
SkinChest x-ray

17. Active TB is Cured with Medicine

18. The objective of therapy is to:
• Eliminate symptoms of active disease
• prevent relapse
• prevent emergence of drug resistance.
The objective of therapy is to:
• Eliminate symptoms of active disease
• prevent relapse
• prevent emergence of drug resistance.

19. Primary VS Secondary treatment

20. To achieve these goals, the following should be
accomplished:
1.1. KillingKilling thethe ActivelyActively MultiplyingMultiplying TubercleTubercle BacilliBacilli:: initialinitial
phasephase ((11stst 22--33 months)months) ofof treatmenttreatment..
1.1. EradicatingEradicating thethe RemainingRemaining ProblematicProblematic TubercleTubercle BacilliBacilli::
22ndnd (continuation)(continuation) phasephase ((44--66 monthsmonths))
Time
MTb
Rapidly
multiplying
Slowly
multiplying
Dormant
A.spurt

21. Concepts
Of
Anti TB treatment
٢١
Concepts
Of
Anti TB treatment

22. 11. if only one antituberculous drug. if only one antituberculous drug is used there is ais used there is a
high risk thathigh risk that a druga drug--resistant mutantsresistant mutants (due to(due to
spontaneous mutation)spontaneous mutation) RifampicinRifampicin
 the possibility of bacilli to develop resistance tothe possibility of bacilli to develop resistance to
more than one drug is verymore than one drug is very low.low.ThereforeTherefore,,
treatment of two or more drugstreatment of two or more drugs reduces thereduces the
risk of developingrisk of developing drugdrug--resistanceresistance..
 Further, drugFurther, drug--combination therapy also serves tocombination therapy also serves to
reduce the incidence of relapse.reduce the incidence of relapse.
11. if only one antituberculous drug. if only one antituberculous drug is used there is ais used there is a
high risk thathigh risk that a druga drug--resistant mutantsresistant mutants (due to(due to
spontaneous mutation)spontaneous mutation) RifampicinRifampicin
 the possibility of bacilli to develop resistance tothe possibility of bacilli to develop resistance to
more than one drug is verymore than one drug is very low.low.ThereforeTherefore,,
treatment of two or more drugstreatment of two or more drugs reduces thereduces the
risk of developingrisk of developing drugdrug--resistanceresistance..
 Further, drugFurther, drug--combination therapy also serves tocombination therapy also serves to
reduce the incidence of relapse.reduce the incidence of relapse.
٢٢

23. Evolution of TB treatment
MonotherapyMonotherapy (Streptomycin)(Streptomycin)
22 drugsdrugs 19501950ss –– durationduration 1818--2424 monthsmonths
33 drugsdrugs 19601960ss –– durationduration 1212--1818 monthsmonths
33 drugs latedrugs late 19601960ss –– durationduration 99 monthsmonths
44 drugsdrugs 19701970ss –– durationduration 66 monthsmonths
MonotherapyMonotherapy (Streptomycin)(Streptomycin)
22 drugsdrugs 19501950ss –– durationduration 1818--2424 monthsmonths
33 drugsdrugs 19601960ss –– durationduration 1212--1818 monthsmonths
33 drugs latedrugs late 19601960ss –– durationduration 99 monthsmonths
44 drugsdrugs 19701970ss –– durationduration 66 monthsmonths

24. 22. How to kill the. How to kill the PersistersPersisters
(( i.e.i.e. semidormantsemidormant bacilli that metabolise slowly orbacilli that metabolise slowly or
intermittently.)intermittently.)
 It is believed that only during theseIt is believed that only during these spurts ofspurts of
activityactivity (last for about(last for about 22 minutes at a time) thatminutes at a time) that
drugs can kill these bugs.drugs can kill these bugs.
Time
MTb
Rapidly
multiplying
Slowly
multiplying
Dormant
A.spurt

25. Therefore, the continuation (Therefore, the continuation (22ndnd) phase is) phase is
directed at capturing these moments ofdirected at capturing these moments of
activity.activity.
 When sputum test results have become negative,When sputum test results have become negative,
usually withinusually within 22--66 monthsmonths, therapy should continue for, therapy should continue for
additionaladditional 44--66 months.(months.(TheThe 22ndnd phasephase))
Time
MTb
Rapidly
multiplying
Slowly
multiplying
Dormant
A.spurt

26. 0
10
20
30
40
50
60
70
80
90
100
95% Actively multiplying population
Intracellular
population Population with
spurts of metabolic
activity
Dormant
population
0
10
20
30
40
50
60
70
80
90
100
Isoniazid
Rifampicin
Streptomycin
Ethambutol
Rifampicin
Pyrazinamid
e
Isoniazid
Rifampicn
Not reached
by drugs
These 2 population are usually
killed within initial phase of
therapy
This population is
usually killed within the
2nd phase of therapy
Eradication
decrease
relapse &
resistance

27. 3. The regimen currently recommended
for the treatment of uncomplicated tuberculosis
6-Month regimen6-Month regimen
Isoniazid (INH) + rifampicin +
pyrazinamide + ethambutol or
streptomycin
Actively growing & IC-----4D
First 2 months
(Initial Phase)
Isoniazid + rifampicin 2D
Persisters Slowly & Spurt
Following 4 months
(Continuation Phase)

28. 4. The treatment of complicated tuberculosis
(e.g. relapse and treatment failure cases)
8-Month regimen
Isoniazid + rifampicin + pyrazinamide
+ ethambutol + streptomycin 5D
First 2 months
(Initial Phase)
Isoniazid + rifampicin + pyrazinamide
+ ethambutol + streptomycin 5D
First 2 months
(Initial Phase)
Isoniazid + rifampicin + pyrazinamide
+ ethambutol 4D
Further 1 or 2 Months
Isoniazid + rifampicin + ethambutol
3D
Five months
(Continuation Phase)

29. Adverse EffectsActionDrug
• Flu-like
• Hepatitis
• Thrombocytopenia
• Rashes
• Pink urine
Inhibits DNA dependent RNA
polymerase in bacteria ---
halting transcription.
5. kills actively growing bacilli
including the problematic
ones with only spurts of
metabolic activity
6. Resistance develops rapidly
if used on its own
-cidal
Rifampicin
Rifabutin Aids
Rifapentine
relapse
Inhibits DNA dependent RNA
polymerase in bacteria ---
halting transcription.
5. kills actively growing bacilli
including the problematic
ones with only spurts of
metabolic activity
6. Resistance develops rapidly
if used on its own
-cidal
• Nephrotoxicity
• Ototoxicity
• Neuromuscular
block
7. aminoglycosides (not
effective in acidic media) for
short period due to toxicity
Streptomycin

30. Adverse EffectsActionDrug
Isoniazid (INH)
Powerfully anti-TB; inhibits formation of mycolic
acid in bacterial cell wall=cidal
8. rapidly kills large numbers of actively
growing bacteria including those with
only occasional spurts of activity
• Insomnia
• Muscle twitching
• Peripheral neuropathy
• Hepatitis
Rifampicin
Rifabutin Aids
Rifapentine
relapse
Pyrazinamide
Isoniazid (INH)
Powerfully anti-TB; inhibits formation of mycolic
acid in bacterial cell wall=cidal
8. rapidly kills large numbers of actively
growing bacteria including those with
only occasional spurts of activity
• Insomnia
• Muscle twitching
• Peripheral neuropathy
• Hepatitis
Pyrazinamide
Ethambutol
Streptomycin

31. ActionDrug
Pyrazinamide
9. converted to the active pyrazinoic
acid effective uniquely in zones of
acute inflammation and against
quiescent bacilli within macrophages
Hepatotoxicity (10%)
Gouty attack
Isoniazid
(INH)
Rifampicin
Rifabutin Aids
Rifapentine relapse
Pyrazinamide
Pyrazinamide
9. converted to the active pyrazinoic
acid effective uniquely in zones of
acute inflammation and against
quiescent bacilli within macrophages
Hepatotoxicity (10%)
Gouty attack
Ethambutol
Streptomycin

32. Adverse EffectsActionDrug
Peripheral neuropathy
Color blindness
Pruritus
Joint pain
Abdominal pain
Confusion
Hallucination
Contraindicated in
pregnancy
Ethambutol
10.Concentrated in
tubercle bacilli, mode
of action not known.
11. Resistance develops
slowly.
-static
Isoniazid
(INH)
Rifampicin
Rifabutin Aids
Rifapentine relapse
Pyrazinamide
Peripheral neuropathy
Color blindness
Pruritus
Joint pain
Abdominal pain
Confusion
Hallucination
Contraindicated in
pregnancy
Ethambutol
10.Concentrated in
tubercle bacilli, mode
of action not known.
11. Resistance develops
slowly.
-static
Ethambutol
Streptomycin

33. So, Most modern regimens forSo, Most modern regimens for
the treatment of tuberculosisthe treatment of tuberculosis
includeinclude isoniazidisoniazid,, rifampicinrifampicin,,
andand pyrazinamidepyrazinamide,,
So, Most modern regimens forSo, Most modern regimens for
the treatment of tuberculosisthe treatment of tuberculosis
includeinclude isoniazidisoniazid,, rifampicinrifampicin,,
andand pyrazinamidepyrazinamide,,
٣٣

34. Isoniazid, pyrazinamide, and ethambutol are
considered to be specific antimycobacterial drugs.
Therefore, they are used in therapeutic trials for
diagnostic purposes.
Isoniazid is highly selective for mycobacteria ; the
drug can kill tubercle bacilli at concentrations 10,000
times lower than those needed to affect gram-positive
bacteria.
34
Isoniazid, pyrazinamide, and ethambutol are
considered to be specific antimycobacterial drugs.
Therefore, they are used in therapeutic trials for
diagnostic purposes.
Isoniazid is highly selective for mycobacteria ; the
drug can kill tubercle bacilli at concentrations 10,000
times lower than those needed to affect gram-positive
bacteria.

35. Ethambutol is a specific drug against
mycobacteria .Generally, it is used when resistance to
isoniazid and rifampicin is suspected.
Streptomycin has relatively low sterilising
activity, perhaps, because of its inability to penetrate
cells and not being effective against intracellular
bacilli.
35
Ethambutol is a specific drug against
mycobacteria .Generally, it is used when resistance to
isoniazid and rifampicin is suspected.
Streptomycin has relatively low sterilising
activity, perhaps, because of its inability to penetrate
cells and not being effective against intracellular
bacilli.

36. Postantibiotic Effect
After a culture of Mycobacterium tuberculosis had been exposed
to certain drugs for sometime, it took several days before growth
occurred.
(the “lag-period”, postantibiotic effect)
Therefore, 600 mg of rifampicin given once daily is
therapeutically superior to the same dose divided into two parts
administered at 12 hours interval.
practically all drugs should be given once daily (not divided
doses).
36
Postantibiotic Effect
After a culture of Mycobacterium tuberculosis had been exposed
to certain drugs for sometime, it took several days before growth
occurred.
(the “lag-period”, postantibiotic effect)
Therefore, 600 mg of rifampicin given once daily is
therapeutically superior to the same dose divided into two parts
administered at 12 hours interval.
practically all drugs should be given once daily (not divided
doses).

37. ANTILEPROSY DRUGS
•Leprosy (Hansen’s disease) is caused by Mycobacterium
leprae.
•Approximately 70%-in India.
• Bacilli - skin lesions or nasal discharges - enter susceptible
individuals via abraded skin or the respiratory tract.
37
ANTILEPROSY DRUGS
•Leprosy (Hansen’s disease) is caused by Mycobacterium
leprae.
•Approximately 70%-in India.
• Bacilli - skin lesions or nasal discharges - enter susceptible
individuals via abraded skin or the respiratory tract.

39. The World Health Organization recommends the triple-drug
regimen of dapsone, clofazimine, and rifampin for 6 to 24
months.
Dapsone (aminodiphenylsulfone) has been and remains a
mainstay of therapy.
39
The World Health Organization recommends the triple-drug
regimen of dapsone, clofazimine, and rifampin for 6 to 24
months.
Dapsone (aminodiphenylsulfone) has been and remains a
mainstay of therapy.