Tuberculosis (TB) is a potentially fatal, contagious disease caused by Mycobacterium tuberculosis that mainly affects the lungs. It spreads through the air when people with active TB infection cough, sneeze or transmit saliva. Worldwide, TB kills about 2 million people annually. Diagnosis involves tuberculin skin testing or interferon-gamma release assays to check for exposure, followed by chest x-rays and testing of sputum or bronchoalveolar samples for evidence of M. tuberculosis if active disease is suspected.

1. BY : Dr. ZEEL NAIK

5.  Definition
 Causative agents
 Classification
 Spread of disease
 Epidemiology
 Signs and Symptoms
 Pathophysiology
 Precautions
 Diagnosis
 Treatment or Management
 MDR and XDR TB

7.  Tuberculosis (TB) is a potentially fatal
contagious disease that can affect
almost any part of the body but is mainly
an infection of the lungs.
Neo-latin word :
- Round nodule/Swelling
- Condition
“Tubercle”
“Osis”

8.  Worldwide, tuberculosis (TB) kills about 2 million people
each year, more than any other infectious organism.
 TB is caused by Mycobacterium tuberculosis, it presents
either as latent TB infection (LTBI) or as progressive active
disease.
 The latter typically causes progressive destruction of the
lungs, leading to death in most patients who do not receive
treatment.
 Currently, one-third of the world’s population is infected, and
drug resistance is increasing in many areas.

9. DEFINITION
 Tuberculosis, MTB, or TB (tubercle
bacillus) is a common and in many cases
lethal, infectious disease caused by
Mycobacterium tuberculosis.
 Tuberculosis mainly attacks the lungs but
can also affect other parts of the body.
 It is spread through the air when people
who have an active TB infection cough,
sneeze or otherwise transmit their saliva
through the air.

10. TB
 As of 2017, about two billion people worldwide are
infected with Mycobacterium tuberculosis, the causative
pathogen of tuberculosis disease, commonly known as
‘TB’.
 However, for the vast majority, (90-95%) of infected
individuals, the infection is contained by the immune
system and cannot multiply.
 In other words, the TB disease remains latent, or
dormant, as opposed to active, which usually causes
symptoms and can easily be transmitted to others.
 When the host’s immune system becomes compromised,
e.g. due to HIV or malnutrition and aging, TB can
reactivate, and become very serious, especially if the
infection spreads through the body.
 Moreover, people with active TB can easily infect 10-15
other people via close contact within a year.

12. Mycobacterium
Tuberculosis
 Mycobacteria are slender, rod-shaped, and
need high levels of oxygen to survive,
i.e.,“strict aerobes”.
 They possess a waxy cell wall that is capable
of retaining dyes even when exposed to
alcohol.
 Thus they are referred to as “acid-fast”,
appearing as bright- red colored rods when a
Ziehl–Neelsen stain is used.
 The wall also makes them incredibly hardy,
and allows them to resist weak disinfectants
and survive on dry surfaces for months.

14. Mycobacterium tuberculosis
Mycobacterium Bovis
Human
Animals

15. Other causative organisms
 Mycobacterium africanum
 Mycobacterium microti
 Mycobacterium leprae
 Mycobacterium avium
 Mycobacterium asiaticum
M. africanum
M. Bovis
M. Canetti
M. microti
M. tuberculosis complex

16. Anatomy of M.tuberculosis
 Discovered in 1882 by Robert Koch.

17. EPIDEMIOLOGY
 Tuberculosis is the 2nd most common
cause of death from infectious
disease(after those due to HIV/AIDS).
 TB is more common in developing
countries; about 80% of the population
in Asian and African countries test
positive in tuberculin tests, while only
5%-10% of the USA population test
positive.

18. ETIOLOGY
 TB spreads by breathing in air droplets
from a cough or sneeze of an infected
person.
 This is called primary TB.
 Most people who develop symptoms of
a TB infection first became infected in
the past.
 However in some cases, the disease
may become active within weeks after
the primary infection.

19. ETIOLOGY
 The following people are at high risk for
active TB:
 Elderly.
 Infants.
 People with weakened immune
systems, for example due to AIDS,
chemotherapy, diabetes , or certain
medications.

20. RISK OF TB INCREASES IF
PERSON :
 Are in frequent contact with people who
have TB.
 Have poor nutrition or malnourished.
 Lives in crowded or unsanitary living
conditions.
 The following factors may increase the rate
of TB infection in population:
 Increase in HIV infection.
 Increase in number of homeless
people(poor nutrition and environment).
 The appearance of drug-resistant strains.

21. PATHOPHYSIOLOGY
 M. tuberculosis is usually transmitted via inhalation, which is how they gain entry into the
lungs.
 Although, we breathe in all sorts of viruses and bacteria all the time, we have defenses
that take care of most of them.
 For one, air that we breathe in is turbulent in the upper airways, and drives most
bacteria against mucus which is then cleared pretty quickly.
 Ultimately, though, TB can avoid the mucus traps and make its way to the deep airways
and alveoli where we have macrophages which eat up foreign cells, digest, and destroy
them.
 With TB, they recognize foreign proteins on their cell surface, and phagocytize them, or
essentially package them into a space called a phagosome.
 With most cases, the macrophage then fuses the phagosome with a lysosome, which
has hydrolytic enzymes that can pretty much break down any biochemical molecule.
 TB’s tricky, though, and once inside the macrophage, they produce a protein that inhibits
this fusion, which allows the mycobacterium to survive.
 It doesn’t just survive, though, it proliferates, and creates a localized infection.
 At this point somebody has developed primary tuberculosis, which means that they
have signs of infection soon after being exposed to TB.

25. PATHOPHYSIOLOGY
 Even though it sounds bad, most people at this stage are actually
asymptomatic or maybe have a mild flu-like illness.
 About 3 weeks after initial infection, cell-mediated immunity kicks in, and
immune cells surround the site of TB infection, creating a granuloma,
essentially an attempt to wall off the bacteria and prevent it from
spreading.
 The tissue inside the middle dies as a result, a process referred to as
caseous necrosis, which means “cheese-like” necrosis, since the dead
tissue is soft, white, and looks a bit like cheese.
 This area is known as a “Ghon focus”.
 TB also gets to nearby hilar lymph nodes, either carried over by immune
cells through the lymph or by direct extension of the Ghon focus infection
and causes caseation there as well, and together, this caseating tissue
and associated lymph node make up the characteristic “Ghon complex”.
 Ghon complexes are usually subpleural and occur in the lower lobes of
the lungs.

27. PATHOPHYSIOLOGY
 The tissue that’s encapsulated by the granuloma undergoes
fibrosis, and often calcification, producing scar tissue that can be
seen on x-ray, this calcified ghon complex is called a “Ranke
complex”.
 In some cases, although a scar is leftover, the mycobacteria is
killed off by the immune system, and that’s the end of that.
 In other cases, even though they were walled off, they remain
viable, and are therefore still alive, but they’re just dormant.
 If and when a person’s immune system becomes compromised,
like with HIV infection, malnutrition or with aging, the Ghon focus
can become reactivated, and the infection can spread to either
one or both upper lobes of the lungs, it’s thought that this is
because oxygenation is greatest in these areas, and TB being an
aerobe, prefers areas of greater oxygenation.

29. PATHOPHYSIOLOGY
 Since they were previously exposed, the immune system’s memory T
cells quickly release cytokines to try and control the new outbreak, which
forms more areas of caseous necrosis, this time, though, it tends to
cavitate, or form cavities, which can allow the bacteria to disseminate, or
spread through airways and lymphatic channels to other parts of the
lungs, which can cause bronchopneumonia; but it can also spread via the
vascular system and infect almost every other tissue in the body, called
systemic miliary TB.
 When TB spreads to other tissues, it causes complications related to the
organ affected.
 Kidneys are commonly affected, resulting in sterile pyuria, or high levels
of white blood cells in the urine.
 It might also spread to the meninges of the brain, causing meningitis, the
lumbar vertebrae, causing Pott disease(tuberculous spondylitis), the
adrenal glands causing Addison’s disease(hypocortisolism), the liver
causing hepatitis, and the cervical lymph nodes causing lymphadenitis in
the neck, also known as scrofula(King’s Evil).

33. PATHOPHYSIOLOGY
 TB infection begins when the Mycobacteria
reaches the pulmonary alveoli, where they
invade and replicate within the endosomes of
alveolar macrophages.
 The Primary site of the infection in the lungs,
known as “GHON FOCUS”.
 Tuberculosis is classified as one of the
granulomatous inflammatory diseases.
 Macrophages, T Lymphocytes , B
Lymphocytes and fibroblasts are among the
cells that aggregate to form granulomas , with
lymphocytes surrounding the infected
macrophages.

34. PATHOPHYSIOLOGY
 The granuloma prevents dissemination
of the Mycobacteria and provides a local
environment for interaction of cells of the
immune system.
 Bacteria inside the granuloma can
become dormant, resulting in latent
infection.
 Another feature of the granulomas is the
development of abnormal cell death
(necrosis) in the center of tubercles.

35. PATHOPHYSIOLOGY
 If TB bacteria gain entry to the bloodstream
from an area of damaged tissue, they can
spread throughout the body and set up
many foci of infection, all appearing as tiny,
white tubercules in the tissues.
 This severe form of TB disease, most
common in young children and those with
HIV, is called systemic miliary TB.
 People with disseminated TB have a high
mortality rate even with treatment(about
30-40%)

36. Tuberculosis
Pulmonary TB
- Primary Disease
- Secondary Disease
Extra pulmonary
i. Lymph node TB
ii. Pleural TB
iii. TB of upper airways
iv. Skeletal TB
v. Genitourinary TB
vi. Miliary TB
vii. Pericardial TB
viii. Gastrointestinal TB
ix. Tuberculous Meningitis
x. Less common forms

37. EPIDEMIOLOGY
Asian : 59%
African : 26%
Eastern Mediterranean Region: 7.7%
The European Region : 4.3%
Region of the America : 3%

38. • Airborne

40.  The primary stage of TB usually doesn’t cause
symptoms.
 When symptoms of pulmonary TB occur, they may
include:
 Cough(usually cough up mucus)
 Hemoptysis
 Excessive sweating, especially at night.
 Fatigue
 Fever
 Unintentional weight loss.
 Breathing difficulty.
 Chest Pain
 Wheezing.

41. Severe Symptoms
 Persistent cough
 Chest pain
 Coughing with bloody sputum
 Shortness of breath
 Urine discoloration
 Cloudy & reddish urine

42. Based on types of TB

45. A. Pulmonary TB :-
1. Primary Tuberculosis :-
 The infection of an individual who has not been previously
infected or immunised is called Primary tuberculosis or Ghon’s
complex or childhood tuberculosis.
 Lesions forming after infection is peripheral and accompanied by
hilar which may not be detectable on chest radiography.
2. Secondary Tuberculosis :
The infection that individual who has been previously infected or
sensitized is called secondary or post primary or reinfection or
chronic tuberculosis.

46. B. Extra Pulmonary TB :-
• 20% of patients of TB Patient
• Affected sites in body are :-
1) Lymph node TB ( tuberculuous lymphadenitis):-
• Seen frequently in HIV infected patients.
• Symptoms :- Painless swelling of lymph nodes most commonly at
cervical and Supraclavical (Scrofula)
• Systemic systems are limited to HIV infected patients.
•
2) Pleural TB :-
Involvement of pleura is common in Primary TB
and results from penetration of tubercle bacilli into pleural
space.

47.  Involvement of larynx, pharynx and epiglottis.
 Symptoms :- Dysphagia, chronic productive cough
3) TB of Upper airways :-
4) Genitourinary TB :-
• 15% of all Extra pulmonary cases.
• Any part of the genitourinary tract get infected.
• Symptoms :- Urinary frequency, Dysuria, Hematuria.
5) Skeletal TB :-
• Involvement of weight bearing parts like spine, hip,
knee.
• Symptoms :- Pain in hip joints n knees, swelling of
knees, trauma.
6) Gastrointestinal TB :-
• Involvement of any part of GI Tract.
• Symptoms :- Abdominal pain, diarrhea, weight loss

48. 7) TB Meningitis & Tuberculoma :-
 5% of All Extra pulmonary TB
 Results from Hematogenous spread.
8) TB Pericardiatis :-
• 1- 8% of All Extra pulmonary TB cases.
• Spreads mainly in mediastinal or hilar nodes
or from lungs.
9) Miliary or disseminated TB :-
• Results from Hematogenous spread of Tubercle Bacilli.
• Spread is due to entry of infection into pulmonary vein
producing
lesions in different extra pulmonary sites.
10) Less common Extra Pulmonary TB
• Uveitis,
• Panophthalmitis,
• Painfull Hypersensitivity
related conjuctivitis.

52. DIAGNOSIS
 Testing for TB often starts with a purified protein derivative or PPD
intradermal skin test, sometimes known as a tuberculin skin test,
Mantoux test, or simply TB test.
 With this test, tuberculin is injected between layers of the dermis,
tuberculin is a component of the bacteria, and if a person has
previously been exposed to TB, the immune system reacts to the
tuberculin and produces a small, localized reaction within 48 to 72
hours; if the reaction creates a large enough area of induration (rather
than just redness), it’s considered to be a positive test.
 Positive tuberculin tests simply mean the patient’s been exposed at
some point to TB—it doesn’t differentiate between active and latent
disease.
 As an alternative to tuberculin skin tests, there are also interferon
gamma release assays (or IGRAs) which look for evidence in the blood
of previous exposure to TB proteins.
 Since this one’s a blood test, you don’t need to show up again to have
the test read like you do with the PPD.
 Also, the IGRA is more specific to TB rather than other types of
mycobacterial infections and is unlikely to be positive as a result of
having BCG vaccine in the past, a vaccine that protects against TB.

53. DIAGNOSIS
 And this is a pretty useful feature of IGRAs, since BCG
vaccine is given to many children around the world to
prevent disseminated TB.
 After doing a screening test with PPD or IGRA, anyone
with a positive result typically gets a chest Xray to look for
signs of active TB disease.
 In patients with symptoms like as fevers, night sweats,
weight loss, and coughing up blood, or hemoptysis, it’s
important to collect samples from either the sputum, or via
a bronchoalveolar lavage, which is where a bronchoscope
is inserted through the mouth or nose into the lungs, fluid
is squirted, and then the fluid is collected.
 These samples can get sent to the lab for staining,
culture, and PCR to look evidence of Mycobacterium
tuberculosis.

54. Tuberculin Skin Testing
 TB skin testing with the 5-TU strength of
brand purified protein derivative
(PPD),also known as the Mantoux test,is
the preferred method for skin testing.
 The product is injected into the skin (not
subcutaneously) with a fine (27-gauge)
needle and produces a small, raised,
blanched wheal to be read by an
experienced professional in 48 to 72
hours.

56. Additional Tests
 Morning sputum collections have the highest yield of
organisms.
 Daily sputum collections over three consecutive days
improve the yield of positive results.
 Sputum induction with aerosolized hypertonic saline may
produce a diagnostic sample in patients unable to
produce sputum.
 Bronchoscopy or aspiration of gastric fluid via a
nasogastrictube may be attempted in selected patients,
the latter being used more often in children.
 For patients with suspected extrapulmonary TB, samples
of draining fluid, biopsies of the infected site, or both may
be attempted.
 Blood cultures are positive occasionally, especially in
acquired immune deficiency syndrome (AIDS) patients
who have low CD4 counts.

57. 1.Bacteriological test:
a. Zeihl-Neelsen stain
b. Auramine stain(fluorescence microscopy)
2. Sputum culture test:
a. Lowenstein –Jensen(LJ) solid medium: 4-18
weeks
b. Liquid medium : 8-14 days
c. Agar medium : 7 to 14 days

58. 3.Radiography:
Chest X-Ray(CXR)

59. 5.Tuberculin skin test
(PPD)
 Injection of fluid into
the skin of the lower
arm.
 48-72 hours later –
checked for a
reaction.
 Diagnosis is based
on height of the skin.
1 dose = 0.1 ml contains 0.04µg
Tuberculin PPD.

60. Tuberculin test
interpretation

61. 1) Mask
2) BCG vaccine(Bacille Calmette – Guerin)
3) Regular medical follow up
4) Isolation of Patient
5) Ventilation
6) Natural sunlight
7) UV germicidal irradiation

63. BCG vaccine
 Bacille Calmette Guerin (BCG).
 First used in 1921.
 Only vaccine available today for protection against
tuberculosis.
 It is most effective in protecting children from the disease.

64. •Antituberculosis medications act mainly by preventing
the production of mycolic acid and the synthesis of this
cell wall.

66. TREATMENT

67. LATENT TB
 Treatment of latent TB infection typically involves
using a single drug for a prolonged period of time—
the most common approach is 300 mg daily
of isoniazid for 6-9 months in adults and adolescents
and 5 mg/kg for children.
 It’s important to stay ahead of the game and do
prophylaxis, which typically involves
taking isoniazid daily or twice a week, for six months.
 An alternative is rifampin(600mg) daily, for four
months.
 Pregnant women, alcoholics, and patients with poor
diets who are treated with INH should receive
pyridoxine(Vitamin B6), 10-50 mg daily, to reduce the
incidence of CNS effects to peripheral neuropathies.

68. ACTIVE TB
 Treatment of active TB disease is typically a combination
of antibiotics, which results in patients being non-
infectious to others usually within a few weeks.
 Until that point, though, patients can spread TB to others
and it’s typically adults with reactivated TB that are the
most infectious.
 As a result, patients are typically kept in negative
pressure rooms and visitors are asked to wear protective
N-95 masks that can’t filter out oil aerosols (N for “not
resistant to oil”) but can filter out at least 95% of other
aerosols (in this case TB).
 Even after patients are no longer contagious, they’re
typically kept on multiple medications for many months to
be sure the bacteria are destroyed usually with directly
observed therapy or DOT where somebody watches and
confirms that you’re taking the medication.

70. MDR-TB & XDR-TB
 Additionally, there’s an enormous worry
about new drug-resistant strains of TB that
are causing infections in various parts of
the world.
 You may hear of MDR-TB (multi-drug
resistant TB) or even the XDR-TB
(extensively drug resistant TB) which is
incredibly hard to treat because they don’t
die in the presence of our usual antibiotics
to treat TB such as isoniazid, rifampicin,
and fluoroquinolones.

72. GENERAL PRINCIPLES IN
TREATMENT OF TB
 Monotherapy can be used only for infected patients
who donot have active TB [latent TB infection (LTBI),
as shown by a positive skin test in the absence of
signs or symptoms of disease.
 Once active disease is present, a minimum of two
drugs and typically three or four drugs must be used
simultaneously from the outset of treatment.
 For most patients, the shortest duration of treatment
is 6 months, and 2 to 3 years of treatment may be
necessary for advanced cases of multidrug-resistant
TB (MDR-TB).
 Directly observed therapy(DOT) by a health care
worker is a cost-effective way to ensure completion
of treatment.

73. GENERAL PRINCIPLES IN
TREATMENT OF TB
 Patients with active TB should be
isolated to prevent spread of disease.
 Public Health Departments are
responsible for preventing the spread of
TB, finding where TB has already
spread using contact investigation.
 Surgery may be needed to remove
destroyed lung tissue, space –occupying
lesions , and some extra pulmonary
lesions.

74. ACTIVE TB
 The standard TB treatment regimen is
INH, Rifampin, Pyrazinamide and
ethambutol for 2 months followed by
INH and RIF for 4 months.

75. ISONIAZID(INH)
 Let’s start with isoniazid.
 It can be used on its own to treat latent infections and as
prophylaxis for people traveling to regions where tuberculosis is
common.
 Isoniazid can be administered orally or parenterally.
 In order to work, it’s first converted by a mycobacterial enzyme
called peroxidase, into its active metabolite, iproniazid.
 A mutation in the gene that codes for this enzyme helps the
bacteria develop resistance, because the mutated enzyme
won’t activate the medication.
 Iproniazid inactivates enzymes associated with mycolic acid
synthesis, and mycolic acid is needed to build bacterial cell
walls.
 It also inhibits mycobacterial peroxidase, preventing the
bacteria from metabolizing hydrogen peroxide, which
accumulates inside the cell causing serious damage.

76. ISONIAZID(INH)
 Side effects include rash, fever, and systemic lupus
erythematosus, called drug-induced SLE.
 It can also cause vitamin B6 deficiency, which leads to anemia
and neurological symptoms like dizziness, ataxia, or
encephalopathy, but the most common is peripheral
neuropathy.
 Fortunately, these side effects can be prevented with the
administration of pyridoxine, or vitamin B6.
 Pyridoxine is also useful as an antidote in case of overdose
with isoniazid, which can cause seizures, anion gap metabolic
acidosis, and coma.
 Last, but not least, patients who receive isoniazid should be
assessed monthly for symptoms of hepatitis and jaundice in
order to detect this serious potential side effect.
 If liver damage is present, the medication should be
discontinued right away.

80. RIFAMPIN
 Rifampin is the next medication.
 It can be administered orally or parenterally and acts by inhibiting
mycobacterial RNA polymerase, and therefore, the synthesis of RNA.
 A mutation in the gene that codes for this enzyme helps the bacteria
develop resistance.
 Since rifampin gets widely distributed throughout the body, it can get
into urine, saliva, tears, feces and sweat, which turns them orange.
 But, the most important side effect is hepatitis, which is more severe at
high doses.
 Luckily, it’s pretty uncommon, but elderly or alcoholic patients, or those
who already have liver disease, are at higher risk.
 Rifampin also causes other side effects such as rash, fever,
and gastrointestinal symptoms like abdominal pain, diarrhea, nausea,
and vomiting.
 Now, an important fact is that rifampin is a strong CYP450 enzyme
inducer, which means it increases the metabolism of many
medications, like ritonavir and other HIV antivirals.
 This can be problematic since these people with HIV are at a higher
risk of developing active tuberculosis.

82. ETHAMBUTOL
 Ethambutol is up next.
 This medication is administered orally.
 It exerts its effect by blocking arabinosyltransferase, which
synthesizes the arabinogalactan that’s used in the bacterial cell
wall.
 The main side effects of ethambutol is optic neuritis, which
decreases visual acuity and the ability to differentiate between
red and green.
 Due to this, regular vision checks are necessary while
taking ethambutol and the color blindness will resolve when the
treatment is discontinued.
 Since it’s difficult to do this in children under
five, ethambutol should not be given to them.
 Finally, this medication can decrease the renal excretion of uric
acid, raising its levels in the blood and could lead to gout.

84. PYRAZINAMIDE
 Next we have pyrazinamide.
 This medication inhibits mycobacterial fatty acid
synthase which is an enzyme that also participates in
the synthesis of mycolic acid.
 It’s administered orally.
 Like ethambutol, pyrazinamide also inhibits the
excretion of uric acid, almost always causing
hyperuricemia, which can cause acute episodes
of gout.
 Other side effects are arthralgias, anorexia, nausea,
and vomiting.
 But the most important is liver damage.
 Therefore, pyrazinamide should be avoided in
people with liver disease.

86. Streptomycin
 The last medication is streptomycin, which is
an aminoglycoside that acts on the 30s subunit of the
mycobacterial ribosome, thereby blocking protein
synthesis.
 It’s administered orally.
 Currently, it’s only used in combination with other
medications to treat miliary tuberculosis where the
bacteria is widely disseminated throughout the body, and
for TB meningitis.
 The side effects of streptomycin include rash and fever,
as well as other side effects caused by damage to the
VIII cranial nerve, which causes impaired hearing and
balance.
 Like with other aminoglycosides, nephrotoxicity is also a
problem with streptomycin.

89.  The treatment is different for latent and active infection.
 In fact, latent TB should only be treated when the patient is at risk of
developing the active infection.
 So, in all these cases, it’s important to stay ahead of the game and do
prophylaxis, which typically involves taking isoniazid daily or twice a week,
for six months.
 An alternative is rifampin daily, for four months.
 For active infection, on the other side, the treatment is a bit more complex.
 The main issue here is bacterial resistance. So to avoid it, it’s mandatory to
use a combination of antibiotics.
 Also, a directly observed therapy, or DOT, seems to be useful in order to
make sure the patient is taking their medications and to decrease the risk of
resistance.
 Therapy is done in two phases. The initial phase consists of daily doses
of isoniazid, rifampin, pyrazinamide, and ethambutol for two months.
 Then there’s the continuation phase, which consists only
of rifampin and isoniazid for four months.
 For HIV-positive patients, the only change that has to be made is to
replace rifampin for rifabutin during the whole therapy.
 It’s also important to keep in mind that pyridoxine should be given to
patients at risk of developing neuropathy due to isoniazid.

90. Drugs MOA Diagram
Isoniazid Inhibits mycolic acid synthesis.
RIFAMPICIN Blocks RNA synthesis by blocking
DNA dependent RNA polymerase
PYRAZINAMIDE •Bactericidal-slowly metabolizing
organism within acidic
environment of Phagocyte or
caseous granuloma.

91. Drugs MOA Diagram
ETHAMBUTOL •Bacteriostatic
•Inhibition of Arabinosyl
Transferase
STREPTOMYCIN •Inhibition of Protein
synthesis by disruption of
ribosomal function

92. ADRs and its Management

93. Treatment

94.  Intensive phase + continuation phase
 HREZ (2 months) + HRE (4 months)

95. DOTS - Directly observed treatment, short-course
 DOT means that a trained health care worker or other
designated individual provides the prescribed TB drugs and
watches the patient swallow every dose.

96.  TB caused by strains of Mycobacterium
tuberculosis that are resistant to at least
isoniazid and rifampicin, the most effective
anti- TB drug.
 Globally, 3.6% are estimated to have MDR-
TB.
 Almost 50% of MDR-TB cases worldwide
are estimated to occur in China and India.

97.  Extensively drug-resistant TB (XDR-TB) is a form
of TB caused by bacteria that are resistant to
isoniazid and rifampicin (i.e. MDR-TB) as well as
any fluoroquinolone and any of the second-line
anti-TB injectable drugs (amikacin, kanamycin or
capreomycin).

101. DRUG RESISTANCE
 If the organism is drug resistant, the aim
is to introduce 2 or more active agents
that the patient has not received
previously.
 With MDR-TB, no standard regimen can
be proposed.
 It is critical to avoid monotherapy.

102. DRUG RESISTANCE
 Drug resistance should be suspected in the following
situations:
 Patients who have received prior therapy for TB.
 Patients from geographic areas with a high
prevalence of resistant(southeast Asia).
 Patients who are homeless, IV drug abusers, and/or
infected with HIV.
 Patients who still have acid-fast bacilli positive
sputum smears after 2 months of therapy.
 Patients who still have positive cultures after 2-4
months of therapy.
 Patients who fails therapy or relapse after
retreatment.

103. SPECIAL POPULATION
 Tuberculosis meningitis and extra pulmonary
disease.
 In general , INH, Pyrazinamide, Ethionamide,
and cycloserine penetrate the CSF readily.
 Patients with TB meningitis are often treated
for longer periods(9-12 months).
 Extra pulmonary TB of the soft tissues can be
treated with conventional anti-TB drugs
regimen.
 TB of the bone is typically treated for 9
months, occasionally with surgical
debridement.

104. PREGNANT WOMEN
 The usual treatment of pregnant women is INH, RIF and
Ethambutol for 9 months.
 Women with TB should be cautioned against becoming
pregnant, as the disease poses a risk to the fetus as well as to
the mother.
 INH or ethambutol are relatively safe when used during
pregnancy.
 Supplementation with B vitamins is particularly important during
pregnancy.
 RIF has been rarely associated with birth defects.
 Ethionamide may be associated with premature delivery,
congential deformities , and DOWN’s syndrome when used
during pregnancy.
 Streptomycin has been associated with hearing impairment in
the newborn , including complete deafness.
 Cycloserine is not recommended during pregnancy.

105. RENAL FAILURE
 INH and RIF donot require dose
modifications in renal failure.
 Pyrazinamide and ethambutol being
nephrotoxic , typically require a
reduction in dosing frequency from daily
to 3 times weekly.

106. DOTS THERAPY
 DOTS stands for “ Directly Observed
Treatment, short course” and is a major plank
in the WHO global plan to stop TB.
 The DOTS strategy focuses on 5 main points
of action.
 These include government commitment to
control TB, diagnosis based on sputum smear
microscopy tests done on patients who
actively reports TB symptoms, DOTS
chemotherapy treatments, a definite supply of
drugs , and standardized reporting and
recording of cases and treatment outcomes.

107. DOTS THERAPY
 The WHO advises that all TB patients should have at
least the first 2 months of their therapy observed: this
means an independent observer watching patients
swallow their anti-TB therapy.
 The WHO extended the DOTS programme to include
the treatment of MDR-TB(called “DOTS-PLUS”).
 Implementation of DOTS-Plus requires the capacity
to perform drug-sensitivity testing and availability of
2nd line agents, in addition to all the requirements for
DOTS.
 DOTS-Plus is much more expensive than DOTS.

108. BCG(Bacillus Calmette- Guerin)
 It is a vaccine against tuberculosis that is prepared from a strain
of the attenuated(weakened) live bovine tuberculosis bacillus,
Mycobacterium bovis, that has lost its virulence in humans by
being specially sub cultured in an artificial medium for 13 years,
and also can be prepared from M.tuberculosis.
 At best, the BCG vaccine is 80% effective in preventing
tuberculosis for duration of 15 years.
 Except in neonates, a tuberculin skin test should always be
done before administering BCG.
 A reactive tuberculin skin test is a contraindication to BCG.
 BCG is given single intradermal injection at the insertion of the
deltoid.
 If BCG is given subcutaneously, then a local abscess may form
that can sometimes ulcerate, and may require treatment with
antibiotics.


109. Thank You!!!