Pulmonary tuberculosis is caused by Mycobacterium tuberculosis, which commonly affects the lungs. The disease is characterized by a cough lasting over 3 weeks, production of sputum, fever, night sweats, and weight loss. Diagnosis involves sputum examination, chest x-rays, and the Mantoux skin test. Treatment involves a combination of antibiotics like isoniazid, rifampin, pyrazinamide, and ethambutol over a period of 6-9 months to prevent development of drug resistance. India has a high burden of tuberculosis with an estimated annual incidence of 1.96 million new cases.

1. PULMONARY TUBERCULOSIS
Presented By:
Anindya Banerjee
Pharmacovigilance Associate
Dept of Pharmacology
NRS Medical College, Kolkata

2. INTRODUCTION
 Tuberculosis is a chronic Infectious disease
• caused by M.tuberculosis/M.bovis
• mainly affecting the lung causing Pulmonary TB
• also affect other parts causing Extra Pulmonary TB
 Characterized by
•Cough lasting > 3 wks and not respond to usual antibiotic.
•Production of purulent, sometimes blood- stained sputum
•Evening rise of temp.
•Night sweats
•Weight loss

3. CHARECTERISTICS OF M. TUBERCULOSIS
 gram +ve bacilli
 Non motile, non sporing,&
noncapsulated
 Strict aerobes
 Branching filamentous forms ≈
fungal mycelium
=>MYCOBACTERIUM
 A.F.B => when stained by Carbol
Fuschin by
 Z-N Stain they resist
decolorisation by 25% H2S04
&Abs.alcohol
 Cell wall is lipid rich with mycolic
acid which is essential & unique
component

4. CAUSES:
The primary cause of TB, Mycobacterium tuberculosis , is a
small aerobic non-motile bacillus.
The M. tuberculosis complex includes four other TB-causing
mycobacteria: M. bovis, M. africanum, M. canetti and M.
microti. M. africanum is not widespread, but in parts of Africa it
is a significant cause of tuberculosis.
The high lipid content of this pathogen accounts for many of its
unique clinical characteristics.
 M. microti is mostly seen in immunodeficient people, although
it is possible that the prevalence of this pathogen has been
underestimated.

5. RISK FACTORS OF TUBERCULOSIS

6. Signs and symptoms:
When the disease becomes active, 75% of the
cases are pulmonary TB, that is, TB in the lungs.
 Symptoms include chest pain, coughing up
blood, and a productive, prolonged cough for
more than three weeks.
Systemic symptoms include
fever, chills, night sweats, appetite
loss, weight loss, pallor, and often a tendency
to fatigue very easily.
In the other 25% of active cases, the infection moves from the lungs, causing other
kinds of TB, collectively denoted extrapulmonary tuberculosis. This occurs more
commonly in immunosuppressed persons and young children.
Extrapulmonary infection sites include the pleura in tuberculosis pleurisy,
the central nervous system in meningitis, the lymphatic system in scrofula of the
neck, the genitourinary system in urogenital tuberculosis, and bones and joints
in Pott's disease of the spine.

8. Transmission of the disease
 Pulmonary tuberculosis is a disease of
respiratory transmission, Patients with the
active disease (bacilli) expel them into the air
by:
– coughing,
– sneezing,
– shouting,
– or any other way that will expel bacilli into
the air
 Transmission is dependent on closeness and
time of contact
 Once inhaled by a tuberculin free person, the
bacilli multiply 4 -6 weeks and spreads
throughout the body. The bacilli implant in
areas of high partial pressure of oxygen:
 lung
 renal cortex
 reticuloendothelial system

9. EPIDEMIOLOGY:
It is currently estimated that 1/2 of the world's population (3.1 billion) is
infected with Mycobacterium tuberculosis. Mycobacterium avium complex is
associated with AIDS related TB.
 The proportion of people who become sick with tuberculosis each year is
stable or falling worldwide but, because of population growth, the absolute
number of new cases is still increasing.
 In 2007 there were an estimated 13.7 million chronic active cases, 9.3 million
new cases, and 1.8 million deaths, mostly in developing countries.
The distribution of tuberculosis is not uniform across the globe; about 80% of
the population in many Asian and African countries test positive in tuberculin
tests, while only 5-10% of the US population test positive.

10. Most TB cases were in India and China
10 000 - 99 999
100 000 - 999 999
< 1 000
1 000 - 9 999
No estimate
Number of cases
1 000 000 or more
Asia
59%Africa
21%

11. Problem of TB in India
• Estimated incidence
– 1.96 million new cases annually
– 0.8 million new smear positive cases annually
– 75 new smear positive PTB cases/1lakh population per year
• Estimated prevalence of TB disease
– 3.8 million bacillary cases in 2000
– 1.7 million new smear positive cases in 2000
• Estimated mortality
– 330,000 deaths due to TB each year
– Over 1000 deaths a day
– 2 deaths every 3 minutes
Gopi P et al (TRC), IJMR, Sep 2005

12. Problem of TB in India (contd)
• Prevalence of TB infection
– 40% (~400m) infected with M. tuberculosis (with a 10% lifetime risk
of TB disease in the absence of HIV)
• Estimated Multi-drug resistant TB
– < 3% in new cases
– 12% in re-treatment cases
• TB-HIV
– ~2.31 million people living with HIV (PLWHA)
– 10-15% annual risk (60% lifetime risk) of developing active
TB disease in PLWHA
– Estimated ~ 5% of TB patients are HIV infected

13. India is the highest TB burden country accounting for more
than one-fifth of the global incidence
Indonesia
6%
Nigeria
5%
Other countries
20%
Other 13 HBCs
16% China
14%
South Africa
5%
Bangladesh
4%
Ethiopia
3%
Pakistan
3%
Phillipines
3%
India
21%
Source: WHO Geneva; WHO Report 2009: Global Tuberculosis Control; Surveillance, Planning and Financing
Global annual incidence = 9.4 million
India annual incidence = 1.96 million
India is 17th
among 22
High Burden Countries
(in terms of TB
incidence rate)

14. PATHOGENESIS OF TUBERCULOSIS
Pathogenesis in a previously unexposed
,immunocompetent person depends on the
development of anti-mycobacterial cell
mediated immunity,which confers resistance to
bacteria and development of hypersensitivity to
mycobacterial antigens.
Pathologic manifestation of tuberculosis like
caseating granuloma and cavitation are result
of hypersensitivity that develops in concert
with the protective host immune response.
Macrophages are the primary cells infected
by M.tuberculosis.

15. Diagnosis of Pulmonary TB
 Routine investigations- Hb, TLC,
DLC (lymphocytosis), ESR.
 Chest x-ray-
• Abnormalities often seen in apical
or posterior segments of upper lobe
or superior segments of lower lobe.
• May have unusual appearance in
HIV-positive persons.
• Cannot confirm diagnosis of TB.
15
Arrow points to cavity in
patient's right upper lobe.

16. TUBERCULIN (MONTOUX )TEST
The Mantoux skin test
consists of an intradermal
injection of 5 IU PPD is
extensor aspect of forearm
tuberculin.
The size of
induration is
measured 48–72
hours later.
Erythema (redness)
should not be
measured.
Mantoux test
injection site in a
subject without
chronic conditions or
in a high risk group
clinically diagnosed
as negative at 50
hours.

17. SPUTUM EXAMINATION – Sputum examination are essential to confirm TB
Best collected in morning before any meal.
Sputum examination on 3 days increase chances of detection.
Sputum can be collected from laryngeal swab or bronchial washing.
In small children, gastric lavage can be examined.
Smear should be prepared from thick dirty part of sputum & stained with Ziehl-Neelson
technique.
Culture - Use to confirm diagnosis of Tuberculosis.
Conventional cultures take up to 10 weeks.
Culture all specimens, even if smear report is negative.
Culture is done in Lowenstein Jansen media.
Susceptibility testing is essential.
Result in 4-14 days when liquid medium system is used.
For example- BACTEC can confirm TB growth within one week by indirectly
measuring TB bacilli growth in special bottles and medium.

18. Difficult to treat:
1. Most antibiotics are effective against rapidly growing organism in
contrast to M.tb slow growing
2. Mycobacterium Cell can be dormant, thus completely resistant to
many antibiotics or killed very slowly by few drugs
3. The lipid rich mycobacterium Cell wall is impermeable to many
drugs.
4. A substantial proportion are intracellular &chemotherapeutic agents
penetrate poorly
5. Mycobacterium =>develop resistance to any single drug
6. Caseation &fibrosis block the b.v. supplying necrotic area thus
penetration of antitubercular drug difficult

19. TREATING TB DISEASE
(GENERAL PRINCIPLES)
 Always treat with multiple drugs.
 Never add a single drug to a failing regimen.
 DOTS (Directly Observed Treatment Shortcourse) is given.
 Treatment course depends on the categories of the patient.
 Usually 6 months, sometimes 9 months.
 Four drugs for two months.
Isoniazid – Rifampicin – Ethambutol - Pyrazinamide
 Two drugs for four or seven months.
Isoniazid - Rifampicin
19

20. Classification of Antitubercular
Drugs
First line Drug(Essential AntiTB)
 High Anti TB effect
 Acceptable degree of toxicity
 Used routinely
- ISONIAZID(H)
-RIFAMPICIN(R)
-PYRAZINAMIDE(Z)
- ETHAMBUTOL(E)
- STREPTOMYCIN(S)

21. Contd.• SECOND LINE DRUG (RESERVE ANTI TB DRUG)
-low anti tb effect
- high toxicity
-or both
-used in special circumstances only
1. Fluroquinolone- Ciprofloxacin, Ofloxacin, Levofloxacin, Moxifloxacin
2. Amikacin
3. Capreomycin
4. Ethionamide
5. Para Amino salicylic Acid (PAS)
6. Cycloserine
7. Thiacetazone
Newer Drugs:
a) Linezolid
b) R-207910 (also known as TMC 2007)

22. ISONIAZID(INH)
Salient features:
1) Most active antitb drug
2)Important assets are
-potency
-infrequent toxicity
-low cost
3)Bactericidal for rapid growers
4)Useful for tb meningitis
5)Effective for both extra cellular & intracellular tb
6)If combined with other drug it has good
resistance
preventing action

23. Mechanism of Action
ISONIAZID
Kat G(catalase peroxidase
in mycobacteria)
Active INH
AcpM & Kas AcpM-Acyl Carrier protein
KasA( ßketoAcyl Carrier protein synthetase)
Block Mycolic Acid Synthesis

24. Pharmacokinetics
Absorption: complete orally. Oral dose=Parenteral dose
Distribution: penetrate all body tissue
Placenta
Meninges
Caseous tb lesion
Metabolism: In liver by N- Acetyltransferase, to acetylisoniazid. Generic
variation has been observed in its rate of N- Acetylation which is inherited as autosomal recessive trait.
• Indians are rapid acetylators while egyptians are slow acetylators.
• Excretion: 75-95% excreted in urine
-Dose adjustment is not required in Renal Failure
-INH & Acetyl Hydrazine are not bound to P.P, thus dialyzable
Contra Indication: - KNOWN HYPERSENSITIVITY
-ACUTE HEPATIC DISEASE

25. Drug interaction
• Inhibit metabolism of Warfarin,Diazepam,Disulfiram
• Abs.impaired by Al(OH)3
• PAS inhibits the metabolism of INH

26. Adverse Effect:-
I. Rash
II. Peripheral Neuropathy
III. Hepatitis
IV. Transient loss of Memory
V. Seizure
HEPATOTOXICITY
-Acetyl Hydrazine cause the damage
-↑in Serum Transaminase
-Can be fatal if not withdrawn promptly

27. Clinical Use
 Therapeutic: Essential component of all
AntiTB Regimen
 Prophylactic:
-Transmission to close contact
-Baby born to inf.mother
-Development of active TB in
immunodeficient individuals
Doses of INH
I. 5mg/kg/day
II. 10mg/kg/A.D
III. 10mg/kg/day –in serious infection
-If malabsorbtion is a problem
IV. Prophylactic: 5mg/kg/day

28. RIFAMPIN(R)
Semisynth. deri of Rifamycin B-from St.meditarranei
Bactericidal ,affect all subpopulation of
M.tb.acts best on Spurters &slow growing
Acts both extra &intracellularly
Good sterilising property &resistance preventing
action
Bactericidal efficacy ≈ INH
&>any other 1st
line drug
Analogue of RIFAMPIN isRIFABUTIN
obtained from Rifamycin S

29. Bactericidal Efficacy
Inhibits - Gm+ve
-Gm-ve
-Mycobact.inf
-M.tb,M.leprae,M.kansassi
Important ones are
-H.influenzae
-N.meningitis
-Legionella
-Brucella
-M.R.S.A

30. M.O.A Of Rifampicin
Normal synthesis of RNA from DNA by DNA dependent RNA polymerase (DDRP)
D.N.A
 DNA dependent R.N.A.polymerase
R.N.A

Protein Syn.

Cell multiplication
Rifampicin bind to β S.U of DDRP

Drug –Enz Complex

Suppression of chain initiation

31. Pharmacokinetics
Abs: -Well absorbed from g.i tract
-PAS interferes with abs.
-Food also interferes with abs.
Dist: -wide. Penetration to
•Cavities
•Meninges
•Caseous Mass
•Placenta
Rifampicin causes an orange red coloration of
body secretion due to various aspect of
Rifampin metabolism

32. P/K Contd.
Metabolism
Following abs. from G.I. Tract

Eliminated rapidly in the bile
&undergoes Enterohepatic Circulation

Rifampin is progressively
deacetylated

This metabolite is bactericidal
 T1/2 varies from 1.5-5 hrs
 EXCRETION: Urine-30%
Faeces 60-65%
Recycling through liver by excretion in bile, reabsorption from intestines
into portal circulation, passage back into liver, and re-excretion in bile.

33. Doses of Rifampin
Doses- 10mg/kg/day
10mg/kg/Alt.day
C/I –k/c/o history of h/s to Rifamycin
-Hepatic Dysfunction
Precaution –Careful monitoring of L.F.T.
-In elderly
- In alcoholics
-Pts. having hepatic disease

34. Side Effects:
1)Hepatitis
2)Exfoliative Dermatitis in H.I.V +ve
3)Fever, Thrombocytopenia, Haemolytic anemia
4)Flu like Syndrome
Adverse Effects:
Orange – Red Colour urine.

35. Drug Interactions of RIFAMPIN
Strongly induces CYTP450 isoforms
Oral Contraceptive Pill
Oral anticoagulant
Antiretroviral drugs –PI & NNRTI except EFAVIRENZ
Antifungal Drugs –Ketoconazole

36. USES OF RIFAMPIN
1)Mycobacterial infection
☻M.tb
☻M.leprae
☻Atypical mycobacteria
-M.kansassi
-M.intracellulare
-M.marinum

37. 2)Other indications
a)meningococcal meningitis-carrier state
600mg B.D for 2 days
b)H.influenzae meningitis –close contact
20mg/kg/dayfor 4days
c)Legionella infection -Along wiyh Erythromycin
d) Serious staphylococcal infection like
- osteomylitis
-prosthetic Valve Surgery
e)Brucellosis –Along with Doxycycline
f)MRSA
g)T/t of meningitis caused by highly penicillin resistant
strain

38. PYRAZINAMIDE(Z)
Synthetic analogue of Nicotinamide
Though weakly tuberculocidal

More active in acidic medium
Highly effective during 1st
2months
More effective against Slow Growing
Active both intra&extracellularly
Including Z in combination tharapy
-duration of t/t is ↓
-It has potent sterilising action

39. MOA Of Pyrazinamide
 Pyrazinamide
Mycobacterial Pyrazinamidase
Pyrazinoic Acid
Inhibits Mycolic Acid Synthesis
 Resistance due to mutation of gene pncA, A few
pyrazinamidase resistant strains with mutations in
the rpsA gene have also been identified.

40. Pharmacokinetics
 Absorption: Well absorbed from g.i.tract
 Distribution: good penetration to all body tissue
& CSF
 Metabolism: Pyrazinamide
Pyrazinoic Acid
5-OH pyrazinoic Acid
 T1/2  6-10hrs
 Dose: 25mg/kg/day once Daily
35mg/kg/day thrice in a week.

41. Adverse Effects:
1)Hepatotoxicity: Most hepatotoxic
 SGOT &SGPT
Serum Bilirubin
C/I-Not to be given with any degree of
hepatic dysfn
2)Inhibits the excren
of ureates

Hyperuracemia

Acute episodes of Gout
3)Joint pain ,Arthralgia

42. ETHAMBUTOL(E)
Tuberculostatic ,active against
M.tb
M.A.C
M.intracellularae
Rapid Growers are more susceptible
Hastens the rate of sputum conversion
Prevent the emergence of Resistant bacilli

43. M.O.A of Ethambutol
Ethambutol

Mycobact. Arabinosyl Transferase

Polymerisation reaction of
Arabinoglycan

Essential component of
Mycobacterial Cell wall
Ethambutol inhibits the enzyme Mycobacterial Arabinosyl
Transferase, which is required for polymerisation reaction of
Arabinoglycan

44. Pharmacokinetics
 Abssorption: Well absorbed from g.i.t.
 Distribution: Wide,penetrates the meninges
 Metabolism: Hepatic
 T1/2~ 4hrs
 Excretion :-unchanged in urine(3/4th
)
-Excreted by G.F& T.S
-Dose to be reduced in Renal failure
 C/I ; Cr. Clearance <50ml/min
Doses of Ethambutol : usual daily dose - 15mg/kg/day
30mg/kg/day can be given thrice in a
week orally.

45. Adverse Effects:
1)RETROBULBAR NEURITIS :causing
-Loss of Visual Acuity
- Red Green Color blindness
Early recognition &stoppage of drug-
visual toxicities is largely reversible
Contra-indication ;In children <6yrs
a) they are unable to report early.
b) may not permit the assessment of Vascular Acuity
& red green color blindness discrimination
2) Renal uric acid excretion
Hyperuricemia
3)Pruritus, Joint Pain

46. First-line Supplement Drug
 Aminoglycoside from Str.griseus
 1st
clinically active against Mycobact.
 Limitation of its use
i)dose related toxicity
ii)devlopment of resistant org.
iii)pt compliance is poor due to i.m
 Present status:
-Least used 1st
line A.T.D
-More active against extracellular bacilli
-Inactive against intracellular bacilii
STREPTOMYCIN(S)
1.Streptomycin
2.Rifabutin
3.Rifapentine

47. Mechanism of Action of Streptomycin
Streptomycin is a protein synthesis inhibitor. It binds to the small 16S
rRNA of the 30S subunit of the bacterial ribosome, interfering with the
binding of formyl-methionyl-tRNA to the 30S subunit.
 -Protein Syn . Is hampered
*Interferes with chain initiation
*Induce misreading of mRNA
* Incorporation of incorrect Amino Acid into peptide

Formation of Nonfunctional /toxic protein
*Cause break up of polysomes into monosomes
IRREVERSIBLE &LETHAL FOR CELL
This results in an unstable ribosomal-mRNA complex, leading to
a frameshift mutation and defective protein synthesis; leading to
cell death.

48. Pharmacokinetics
 Neither absorbed / destroyed in G.I.Tract.
 Absorption from inj site is rapid (30-60min)
 Distributed to Extracellular TB cavities.
 Not metabolized, Excreted unchanged in urine

49. Adverse Effects:
i)OTOTOXICITY-drugs get conc. In labrynthine fluid, both vestibular &
cochlear damage
ii)NEPHROTOXICITY
iii)Neuro Muscular PARALYSIS -Ach release,
sensitivity of post.syn. receptors.
iv)Sterile abscess at the inj. site
Contra Indication:
- Not to be given in pregnancy
-Avoid use with other ototoxic drug eg;High ceiling
diuretics,Minocycline,Cisplatin
-Avoid use of other nephrotoxic drug eg;Amphotericin B,
Vancomycin,Cyclosporin,Cisplatin
-Pts with renal disease.
-Cautious use with muscle relaxant.

50. Uses
 Sensitive to M.tb
Mycobacterium Avium Complex
M.kansassi
 It is as an important drug when inj. form is needed-
-especially with severe & life threatening
condition.
-TB meningitis
-Miliary TB
 Dose:15mg/kg/D
15mg/kg/A.D

52. Rationale behind Combination Therapy
To prevent emergence of resistant bacilli
Drugs like H & R act synergistically &
Z is more active during the inflammatory states
Duration of treatment is reduced
To act simultaneously with all subpopulation of
Mycobacterium tuberculosis

53.  Aminoglycosides: least effective and more toxic
Capreomycin - Viomycin – Kanamycin
Adverse effects:
 These drugs are: Nephrotoxic will cause
Proteinuria, Hematuria, Nitrogen metabolism,
and Electrolyte disturbances
However effect is reversible when drug is
stopped
 Capreomycin has replaced viomycin because of less toxic effects,
but all three drugs have the same effects.
Second line drugs:

54.  Can cause CNS disturbances
 Therapeutic States :
Cycloserine should be used when re-treatment is necessary
or when the micro-organism is resistant to the other drugs.
 It must be given in combination with other anti-tuberculosis
drugs.
 Mechanism of Action :
 An analog of D- alanine synthetase, will block bacterial
cell wall synthesis.
Cycloserine:

55.  cys absorbed orally, diffuses all over.
 About 1/3 of a dose is metabolised the rest is excreted
unchanged by kidney.
 Toxicity:
 Most common in the CNS: Headache, Tremor,
Vertigo, Confusion, Nervousness,
Pharmacokinetics:

56. These are first anti tubercular drugs.
It is a tuberculostatic drug.
Low efficacy drug.
Side effects:
hepatitis,
optic neuritis,
mental disturbences
impotence
Thioacetazone & Ethionamide:

57. PAS is a tuberculostatic and one of least active
drugs.
It inhibits denovo folate synthesis.
PAS is completely absorbed by oral route and
distributed all over .
T1/2 is 1hr.
Patient acceptability of PAS is poor.
Adverse effects ;
Rashes, fever, liver dysfunction
Para-amino salicylic acid:

58. Chemotherapy
DOTS (Directly Observed Treatment Shortcourse) :
To control tuberculosis requires:
 Effective, inexpensive, simple and standardised technology.
The success of the DOTS strategy depends on:
 Government commitment to a national tuberculosis
programme.
 Case detection –finding by smear microscopy examination
of TB susceptible in general health services.
 Regular uninterrupted supply of essential anti-TB drugs.
 Monitoring system for programme supervised and
evaluation.

59. Short Course Chemotherapy:
These are regimens of 6-9 month duration.
All regimens have an initial intensive phase
lasting 2-3 months to kill the TB bacilli and
afford symptomatic relief.
This is followed by continuation phase for 4-6
months so that relapse does not occur.

60. Type of patient Duration of treatment Regimen
Category-1
1.New sputum positive
2.Seriously ill, sputum
negative, Pulmonary
3.Seriously ill
Intensive
phase(2months)
Continuation
phase(4months)
INH+RMP+ETB+PZA
INH+RMP
Category-2
Retreatment group
1.Relapse
2.Treatment failure
Intensive
phase(3months)
Continuation
phase(5months)
INH+RMP+ETB+PZA
INH+RMP+ETB
Category-3
1.New smear negative
pulmonary
2.extrapulmonary
Intensive
phase(2months)
Continuation
phase(4months)
INH+RMP+PZA
INH+RMP
REGIMENS :

61.  Resistance to both Isoniazid and Rifampin and number of
other anti-TB drugs . MDR-TB has a more rapid course ,(some
die in 4-16 weeks).
 Treatment is difficult as second line drugs
 are less efficacious, less convenient, more expensive and
toxic.
 Therapy depends on drugs used in earlier regimen, dosage and
regularity with which they have been taken.
 In India>200,000patients have been treated under DOTS by
early 2001 with cure rate of 75-80%.
 In other countries 80-93%cure rates have been obtained.
Multiple Drug Resistance(MDR):

62. Extensively Drug Resistant TB (XDR TB) is a form of TB
caused by bacteria resistant to all the most effective Drug [i.e.,
MDR-TB plus resistance to any Fluroquinolone (FQ) and any
of the second line anti TB injectable drugs: Amikacin,
Kanamycin, Capreomycin
Extensively Drug Resistant TB (XDR- TB)

63. MDR/XDR Treatment Strategies: WHO
Three approaches to treatment:
 Standardized regimens
 Empiric regimens
 Individualized treatment regimens
(based on DST results)
The choice among these should be based on:
 Availability of second-line drugs
 Local drug-resistance patterns, and the history of use of
second-line drugs
 Drug susceptibility testing of first- and second-line drugs

64. Use any
available
One of
these
One of
these
First-line
drugs
Fluoroquinolones
Injectable
agents
Pyrazinamide
Ethambutol
Levofloxacin
Moxifloxacin
Ofloxacin
Amikacin
Capreomycin
Streptomycin
Kanamycin
Building a Regimen for MDR-TB
STEP 1
Begin with any
first-line agents
to which the
isolate is
susceptible
Add a
fluoroquinolone
and an
injectable drug
based on
susceptibilities
PLUS PLUS

65. Pick one or more of these
Oral second-line drugs
Cycloserine
Ethionamide
PAS
Building a Regimen for MDR-TB
STEP 2
If 4 drugs are
not identified in
Step 1:
Add second-line
drugs until you
have four to six
drugs to which
the isolate is
susceptible (and
preferably which
have not been
used to treat the
patient
previously)

66. Consider use of these
Third-line drugs
Clofazimine
Linezolid
Amoxicillin/
Clavulanate
Imipenem
Clarithromycin
STEP 3
Building a Regimen for MDR-TB
If there are
not four to six
drugs available
in the above
categories,
consider
third-line
drugs in
consultation
with an
expert.

67. Building a Regimen for XDR-TB
STEP 1
Begin with any
first-line agents
to which the
isolate is
susceptible
Add a
fluoroquinolon
e and an
injectable drug
based on
susceptibilities
Use any
available
One of
these
One of
these
First-line
drugs
Fluoroquinolones
Injectable
agents
Pyrazinamide
Ethambutol
Levofloxacin
Moxifloxacin
Ofloxacin
Amikacin ?
Capreomycin ?
Streptomycin ?
Kanamycin ?
Commonly not
susceptible
By definition
there is
fluoroquinolone
resistance
Select agent
based on history
and susceptibility
testing
PLUS PLUS

68. STEP 2
Building a Regimen for XDR-TB
Add second-
line drugs until
you have four
to six drugs to
which the
isolate is
susceptible
(and
preferably
which have
not been used
to treat the
patient
previously)
Pick one or more of these
Oral second-line drugs
Cycloserine
Ethionamide
PAS
With XDR-TB, often
all three of these agents
are necessary

69. STEP 3
Building a Regimen for XDR-TB
If there are
not four–six
drugs available
in the above
categories,
consider third-
line drugs in
consultation
with an
expert.
Consider use of these
Third-line drugs
Clofazimine
Linezolid
Amoxicillin/
Clavulanate
Imipenem
Clarithromycin

70. • Ensure laboratory services for hematology,
biochemistry and audiometry are available
• Establish a clinical and laboratory baseline before
starting the regimen
• Initiate treatment gradually when using drugs that
cause gastro-intestinal intolerance
• Ensure availability of ancillary drugs to manage
adverse effects
• Use DOT for all doses
Initiating Treatment: WHO

71. • Isolate until three consecutive sputum AFB smears
(or documented culture conversion) are negative
and there has been a good clinical response to
treatment
• Initiate MDR-TB treatment under close supervision
to provide patient education and monitoring and to
treat drug toxicity
• Tailor toxicity monitoring to specific drugs employed
• Seek consultation with an expert as soon as drug
resistance is known
MDR/XDR-TB: Management Principles

72. • Use daily patient-centered DOT throughout entire
treatment course
• Record drugs given, bacteriological results, chest
radiographic findings, and the occurrence of
toxicities
• Optimize management of underlying medical
conditions (example: diabetes) and nutritional
status
MDR/XDR-TB: Management Principles

73. MDR/XDR-TB: Monitoring
• Collect sputum specimens for smear and culture
periodically during treatment once culture negative
• Obtain end-of-treatment sputum specimen for
smear and culture
• Perform chest radiograph periodically during
treatment and at end of treatment
• Resources permitting, monitor minimum of two
years following treatment (quarterly during first
year, every six months during second year)

74. RNTCP

75. Evolution of TB Control in India
• 1950s-60s Important TB research at TRC and NTI
• 1962 National TB Programme (NTP)
• 1992 Programme Review
• only 30% of patients diagnosed;
• of these, only 30% treated successfully
• 1993 RNTCP pilot began
• 1998 RNTCP scale-up
• 2001 450 million population covered
• 2004 >80% of country covered
• 2006 Entire country covered by RNTCP

76. Objectives of RNTCP
• To achieve and maintain a cure rate of at least
85% among newly detected infectious (new
sputum smear positive) cases
• To achieve and maintain detection of at least
70% of such cases in the population

77. RNTCP Organization structure: State level
Health Minister
Health Secretary
MD NRHM Director Health
Services
Additional / Deputy / Joint
Director
(State TB Officer)
State TB Cell
Deputy STO, MO, Accountant,
IEC Officer, SA,
DEO, TB HIV Coordinator etc.,
State Training and Demonstration
Center (TB)
Director, IRL Microbiologist, MO,
Epidemiologist/statistician, IRL LTs etc.,

78. One/ 100,000
(50,000 in hilly/ difficult/
tribal area)
One/ 500,000
(250,000 in hilly/
difficult/ tribal area)
TB Health Visitors (TBHV),
DOT Provider
(MPW, NGO, PP, ASHA,
Community Volunteers)
Medical Officer, paramedical staff
And Laboratory Technician (20-50%)
Medical officer-TB Control,
Senior Treatment supervisor(STS),
Senior TB Laboratory Supervisor(STLS)
District Health Services
District TB Centre
Tuberculosis Unit
Microscopy Centre
DOT Centre
Nodal point for TB
control
Structure of RNTCP at district levels
Chief Medical Officer and
other supporting staff
District Administration District Magistrate/
District Collector
DTO, MO-DTC (15%), LT, DEO,
Driver, Urban TB Coordinators,
TBHVs, Communication Facilitators

79. Unique features of RNTCP
• District TB Control Society
• Modular training
• Patient wise boxes
• Sub-district level supervisory staff (STS, STLS)
for treatment & microscopy
• Robust reporting and recording system

80. 0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
110%
120%
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
Annualised New S+ve CDR Success rate
•Population projected from 2001 census
•Estimated no. of NSP cases - 75/100,000 population per year (based on recent ARTI report)
Annualized New Smear-Positive Case Detection Rate
and Treatment Success Rate in DOTS Areas, India, 2000-2009*

81. Impact of RNTCP
• Cure rate more than doubled compared with earlier NTP,
85% global target consistently achieved 2003 onwards
• Case detection rate is more than 70%
• Case fatality reduced from 29% to 4% in NSP cases, and
deaths due to TB from 500,000 to <330,000 a year
• Over 11 million patients initiated on DOTS, and over 2
million additional lives saved