Tuberculosis

ANTI-MYCOBACTERIALS

DIAGNOSIS OF TB
The recognition of an active TB case:
Symptomatic due to lesions caused by
Mycobacterium tuberculosis.
Confirmed by microbiologic studies to harbor
M.tuberculosis

The diagnosis of tuberculosis (TB) refers to the

recognition of an active TB case: the identification
of a patient who is symptomatic due to lesions
caused by Mycobacterium tuberculosis. A TB case is
a patient confirmed (by microbiologic studies) to
harbor the organism Mycobacterium tuberculosis.
Infrequently, a case of TB may also be one where
microbiologic work-up is negative but other data
support or suggest the presence of the organism.

The Gold Standard

TB Culture
with Drug Susceptibility Testing
Because of the increased sensitivity of TB culture to
detect TB cases compared to sputum microscopy
alone, international standards recommend that all
adults suspected to have pulmonary tuberculosis
should have TB culture in addition to sputum
microscopy where resources permit.

Classification of TB Cases
WHO Case Definitions:
Latent TB
Active TB
Pulmonary
Smear (-)
Smear (+)

Extra Pulmonary
Smear (-)
Smear (+)

Latent TB: TB infection but no evidence of the disease

A Clinically Active TB is classified as either Pulmonary
or Extrapulmonary, smear (-) or smear (+)

TB Symptomatic

Cough > 2weeks

Unexplained fever and chills
Night sweats
Weight loss
Anorexia
Chest pain
Fatigue and Body malaise

 When should one suspect that a patient may have

PTB?
In the Philippines, cough of two weeks or more should
make the physician and/or other healthcare workers
suspect the possibility of pulmonary tuberculosis.
Cough with or without the following: night sweats,
weight loss, anorexia, unexplained fever and chills,
chest pain, fatigue and body malaise, is suggestive of
TB.
A patient exhibiting cough of two weeks or more with
or without accompanying symptoms will be referred
to as a TB Symptomatic.

TB Symptomatic : work up

Sputum microscopy for AFB

Chest radiography (CXR)
Tuberculin Skin Testing (PPD)
Sputum TB culture and
Drug Susceptibility Testing
Blood or serum tests
Note: Other diagnostic modalities for TB
symptomatics with negative smears and cases of
Extrapulmonary TB shall not be discussed in the
interest of time and because these are beyond the
scope of the subject matter and therefore for further
discussion elsewhere.

Sputum microscopy for AFB

Preferably 3, at least 2
The most efficient way to ID TB cases
Easy to collect
Readily available, accessible, affordable, results
rapidly available
Correlates well with infectiousness

 The initial work-up of choice for a TB symptomatic is the sputum

microscopy for Acid Fast Bacilli. All patients who present with cough of
two weeks or more should preferably have three, but at the least two
sputum specimens sent for sputum microscopy for Acid Fast Bacilli (AFB).
Sputum microscopy is still the most efficient way of identifying cases of
tuberculosis.
Sputum collected first thing in the morning for three consecutive days is
recommended.
How should results of sputum microscopy be interpreted?
Results of sputum microscopy are interpreted and reported as follows:
SMEAR POSITIVE if at least two sputum specimens are AFB (+).
SMEAR NEGATIVE if none of the specimens are AFB (+).
DOUBTFUL When only one of the 3 sputum specimens is (+).
When results are doubtful, a second set of three must be collected
again.
If at least one of the second three is (+), the diagnosis is SMEAR
POSITIVE.
If all of the second three are (-), the diagnosis is SMEAR NEGATIVE.
Sputum smear for AFB is available, accessible, affordable, with results
rapidly available, correlates well with infectiousness.

TB Symptomatic : work up
Chest radiography (CXR)
Tuberculin Skin Testing (PPD)
Sputum TB culture and
Drug Susceptibility Testing
Blood or serum tests

 Chest radiographs are not routinely necessary in the management of a TB

symptomatic patient who is smear positive.A chest radiograph in smear
positive TB symptomatics may be helpful if other concomitant diseases or
life-threatening conditions are being considered.
The tuberculin skin testing (TST), more popularly known as PPD (for purified
protein derivative), will not add additional information if the patient is smear
(+). But:
TB symptomatic, smear (-) patients will benefit from Chest radiography, &
Sputum TB culture and Drug susceptibility testing.To further strengthen the
diagnosis.
In the Philippines where resources are limited and laboratory capability for
sputum culture is still being strengthened, sputum TB culture with DST is
primarily recommended for patients who are at risk for drug resistance
and should be done in the following smear positive patients:
o All cases of retreatment/ o All cases of treatment failure/o All other
cases of smear (+) patients suspected to have one or multi- drug resistant
TB (MDR-TB)
Certain blood or serum tests may be taken when specific risks for possible
adverse events during treatment are present

Classification of TB
based on
Location & Sputum Smear

Location
Pulmonary
TB

Smear

Definition of Terms

(+)

1. A patient w/ at least 2 sputum specimens

(+) for AFB, w/ or w/o CXR abnormalities
consistent with active TB or
2. A patient w/ 1 sputum specimen (+) for
AFB & w/ CXR abnormalities consistent
with active TB as determined by a
clinician, or
3. A patient w/ sputum specimen (+) for
AFB with sputum culture (+) for M. tb.

(-)

A patient with at least 3 sputum specimens () for AFB with CXR abnormalities consistent
with active TB, and there has been no
response to a course of antibiotics and/or
symptomatic medications, and the Medical
Officer decides treatment with anti-TB drugs.

Location
ExtraPulmonary
TB

Definition of Terms
1. A patient w/ at least 1 mycobacterial
smear / culture (+) from an extrapulmonary site (organs other than the
lungs: pleura, lymph nodes, genitourinary tract, skin, joints and bones,
meninges, intestines, peritoneum and
pericardium, among others), or
1. A patient with histiological and / or
clinical evidence consistent with active TB
and there is a decision by a Medical
Officer to treat the patient with anti-TB
drugs.

Categories of TB Cases according to

Previous Treatment Received by the
Patient
Once the diagnosis of active TB is made, a
case is also categorized according to
previous treatment received. Thus, cases
are either New, Relapse, Return to
treatment after default, Failures,
Transferred-in, and Others

Category

Definition

New

Patient who has never had tx for TB or

Patient who has taken anti-TB meds for <
four weeks.

Relapse

Patient declared cured of any form of TB

in the past by a physician after one full
course of anti-TB meds and now has
become sputum smear (+)

Return to
treatment
after default

Patient stops taking his medications for

two months or more and comes back to
the clinic smear (+).

Category

Definition

Failure

Patient while on tx, remained or became

smear (+) again at the 5th month of antiTB tx or later; or Patient smear (-) at the
start of treatment and becomes smear (+)
at the 2nd month.

Transfer-in

Patient whose mx was started from

another area and now transferred to a
new clinic

Chronic Case Patient who became or remained smear

(+) after completing fully a supervised retreatment regimen

Once the diagnosis of active TB is made, a case is also categorized according to

previous treatment received. Thus, cases are either New, Relapse, Return to
treatment after default, Failures, Transferred-in, and Others. This table
provides definitions of TB cases according to previous treatment received. This
categorization helps guide the health provider on the recommended treatment
regimens for that particular patient.

Treatment
Drug Therapy aims to:
Cure
Prevent death
Prevent relapse
Prevent drug resistance
Decrease transmission

 Drug therapy of TB aims to achieve the following

objectives:
Cure by rapidly eliminating most of the bacilli. Prevent
death from active TB or its late effects.
Prevent relapse of TB by eliminating the dormant bacilli.
Prevent the development of drug resistance by using a
combination of drugs. Decrease the transmission to others.
The need for multiple drugs and prolonged duration of
therapy = because naturally occurring drug resistant
mutants are present within large bacterial populations even
before chemotherapy is started. In addition, mycobacteria
replicate slowly, can remain dormant for prolonged periods
and can be eradicated only during replication.Finally, bacilli
live in several sites within the host, and each site contains
organisms with a different population size, metabolic
activity and replication rate.

Treatment
Therapeutic Principles
Treatment of disease must contain
multiple drugs to which organisms are
susceptible.
Drugs must be taken regularly.
Therapy must continue for a sufficient
length of time.

 Multiple drugs are given simultaneously: Since

mutant organisms naturally resistant to
multiple drugs are extremely rare, this
strategy decreases the likelihood of selecting
out drug-resistant organisms and prevents the
emergence of resistance.

Treatment
2 Phases of Treatment
Intensive Phase
kills actively replicating bacilli

Continuation Phase
kills slowly dividing bacilli
Intensive phase: initial, consisting of more than 2 drugs promotes
efficient killing of actively dividing organisms and leads to the rapid
reduction of large bacillary populations; provides relief of symptoms,
terminates transmission and prevents the emergence of drug resistance.
Continuation phase: uses fewer drugs, kills slowly or irregularly dividing
bacilli, sterilizes lesions, prevents relapse

Treatment Regimens

TB Patient To Be Given Tx

Drugs /TxDuration

New PTB smear (+) cases

2HRZE / 4HR
New seriously ill PTB smear (-) cases
w/ extensive parenchymal
involvement
New severely ill Extra-Pulmonary TB
cases

II

Failure cases
Relapse cases
Return after default smear(+)
Others smear (+)

III

New smear (-) but minimal PTB on 2HRZ / 4HR

CXR as confirmed by Medical officer
New Extra-Pulmonary TB (not
serious)

2HRZES/1HREZ/
5HRE

Take s of drugs used for Intensive and Continuation phases

For Regimens I & II For Patients >50kg BW: add 1 tab each INH 100mg, PZA
500mg, Ethambutol 400mg before initiation of treatment.
For Regimen III For Patients >50kg BW: add 1 tab each INH 100 mg, PZA
500mg before initiation of treatment.
Category IV (not present in the 2001 NTP manual: Chronic and multidrugresistant TB (smear positive after supervised retreatment). Multidrugresistant or individualized regimen per country protocol. Given if there is
resistance and/or decreased tolerance to 1st line drugs, Amikacin and
Quinolone are the only 2nd line drugs in Philippines

Outcomes of Treatment

Cure
Treatment Completed
Died
Treatment Failure
Defaulter Failure
Transfer Out

 Cure: sputum smear (+) patient who has completed tx and is sputum
smear (-) in the last month of tx and on at least one previous occasion.
Treatment completed: a patient who has completed tx but does not meet
the criteria to be classified as cure or failure. This group includes:
(1)a sputum smear-positive patient initially who has completed treatment
without follow-up sputum examinations during the treatment, or with only
one negative smear during the treatment, or without sputum in the last
month of treatment; and
(2)a sputum smear (-) patient who has completed treatment
Died - A patient who dies for any reason during the course of treatment
Failure: A patient who is smear(+)at five months or later during treatment
or a sputum smear (-) patient initially before starting tx and becomes
smear (+) during the treatment.
A defaulter is one whose treatment was interrupted for 2 consecutive
months or more
Transfer out: A patient who has been transferred to another facility with
proper referral/transfer slips for continuation of treatment.

Issues Unique to the Infant and

Child
with Tuberculosis

How and from whom do infants and

children acquire Tuberculosis?

A. playmates & classmates

B. yaya/driver/parents/grandparent
C. house pet
D. ingestion of cows milk

How?: airborne route/transmission

Childhood TB arises most often as a result of the inhalation of droplet nuclei
approximately 1-5 microns containing M.tuberculosis bacilli expectorated by a sputum
smear positive adult with pulmonary TB.
TB infected infants and postpubertal adolescents are at increased risk for progression
to TB disease and children aged less than 4 yrs are at increased risk for disseminated
disease.
From whom?: yaya/driver or parents/grandparent - by close contact with adults who
are TB(+)
TB is not a zoonotic disease so children cant get TB from their pets
Filipinos are not fond of drinking fresh milk(mycobacterium bovis), besides, most fresh
milk is pasteurized.

Spectrum of TB
TB exposure: child in close contact with a
source case
(-) Signs & symptoms presumptive of TB
(-) Tuberculin Skin Test (TST)
TB infection: child is found to have
(-) Signs & symptoms presumptive of TB
(+)Tuberculin Skin Test
(-) radiologic/laboratory evidence
suggestive of TB

Spectrum of TB
TB disease:
(+) signs & symptoms presumptive of TB
(+) Tuberculin Skin Test and/or
(+) radiologic/laboratory evidence suggestive
of TB

Diagnosis of TB in Children
GOLD STANDARD
a positive culture with or without
a positive AFB smear for
Mycobacterium tuberculosis

Why is the diagnosis of

Tuberculosis in a child so difficult?

the diagnosis of childhood

tuberculosis (TB) is especially
difficult compared to that of an
adult in the absence of a gold
standard in many cases because
of the following reasons:

Diagnosis of TB in Children
The occurrence of asymptomatic infection
(latent TB infection) and early disease in
childhood.
The poor bacteriologic yield.
The difficulty of collecting specimen in the
young.

 The occurrence of asymptomatic infection

(latent TB infection) and early disease in
childhood,
The poor bacteriologic yield brought about by
the paucibacillary character of TB in the young.
The difficulty of collecting specimen in the
young: i.e. children <10yrs of age may be unable
to properly expectorate their sputum, an
alternative would be gastric aspiration after
gastric lavage.

Diagnosis of TB in Children
Demonstration of acidfast bacilli on microscopy
and histologic changes on biopsy can only
provide presumptive diagnosis in the absence of
a positive culture.
Radiologic evidence is often equivocal: it
requires consensus among radiologists.
The Tuberculin Skin Test has logistic limitations
on top of high false negative findings even under
ideal settings.

 Demonstration of acid-fast bacilli on microscopy

and histologic changes on biopsy can only provide
presumptive diagnosis in the absence of a
positive culture.
Radiologic evidence is often equivocal: it requires
consensus among radiologists for a clear-cut set
of criteria.
The Tuberculin skin test has logistic limitations on
top of high false negative findings even under
ideal settings.

Diagnosis of TB in Children
In the absence of bacteriologic evidence,
a child is presumed to have active TB if
3 or more of the following criteria are
present:
Epidemiologic
Clinical
Immunologic
Radiologic
Laboratory

Epidemiologic
Exposure to an adult/adolescent with active
TB disease

Clinical: TB symptomatic
cough or wheezing of >2wks

unexplained fever of >2wks

loss of appetite, wt. loss, failure to gain wt.
failure to respond to 2wks of AB tx for LRTI
failure to regain previous state of health after 2
wks of viral infection or exanthema (measles)
fatigue, reduced playfulness, lethargy, loss of
normal energy
TB symptomatic: 3 or more of the following signs and
symptoms suggestive of TB

Immunologic
(+) Tuberculin Skin Test
>5mm induration
Hx: close contact with known or
suspected case of TB
Clinical findings suggestive of TB
Chest X-ray suggestive of TB
Immunocompromised condition
>10mm induration

2008 PPS Evidence Based Clinical Practice

Guidelines for Childhood TB recommendation
statement: After intradermal administration of
0.1ml of 5 TU PPD purified protein derivative, the
mantoux test is read at 48-72hours, regardless of
BCG status, an induration of >5 mm is considered
positive in the presence of any of the
following:history of close contact with a known or
suspected infectious case of TB, clinical findings
suggestive of TB, chest x-ray suggestive of TB,
immunocompromised condition. Otherwise, an
induration >10mm is considered positive.

Radiologic
No pathognomonic radiologic findings
Most suggestive of PTB:
hilar/paratracheal adenopathy
parenchymal changes

Laboratory
Laboratory findings suggestive of TB
Histologic
Cytologic
Biochemical
Immunologic
Molecular

Classification:
TB Disease in Children
Pulmonary TB
Latent Infection
Primary TB
Progressive Primary TB
Extra-Pulmonary TB

Latent Infection : infection associated with tuberculin hypersensitivity

and a positive tuberculin skin test but with no striking clinical or
roentgenographic manifestations. Occasionally, low grade fever is
found , usually by chance.
Primary TB: Infection among infants more frequently results in disease
with local progression and dissemination: the younger the patient, the
greater the risk of progressive disease until the age of 5 yrs. When
disease occurs it is usually the childhood type of pulmonary TB
referred to as Primary TB. A radiographic correlate is the
demonstration of the Ghon complex: the primary focus, lymphangitis,
regional lymphadenitis.
Progressive Primary disease: latent primary infection and primary
disease can progress into an area of advancing pneumonia. The
pulmonary focus enlarges and develops a large caseous center, instead
of resolving or calcifying. Persistent fever or cough, with malaise and
weight loss with lung findings suggestive of cavitation occur. Crepitant
rales and/or diminution of breath sounds over the affected area may
be appreciated.
Extrapulmonary Tuberculosis: TB of organs other than the lungs. Signs
and symptoms are referable to the site of lesion.

The First-Line

INH
Rifampicin
Pyrazinamide
Ethambutol
Streptomycin

Anti-TB Drugs

 First line drugs have superior efficacy and

acceptable toxicity
Second-line drugs haave less efficacy, greater
toxicity or both. These are used as alternatives
when there is either resistance, toxicity or
hypersensitivity to first-line drugs, in cases of
failure of clincal response to first line drugs and
when expert guidance is available.
Unfortunately, none of the secon-line drugs are
widely available locally.a
Except for ethambutol, all first-line drugs are
bactericidal agents.
The ATS, IDSA, and CDC no longer consider
streptomycin as a first-line drug

INH
MOA
Bactericidal for actively growing bacilli
Acts on extra/intracellular populations
Inhibit biosynthesis of mycolic acid (cell
wall component)
The INH prodrug is activated by KatG,
mycobacterial catalase peroxidase. Once
activated, forms a covalent complex that
blocks mycolic acid synthesis.

INH
Pharmacokinetics
Absorption Readily absorbed fr GIT
Distribution Diffuses to all body fluids
and tissues
CSF concn 20-100% of serum
Metabolism genetically determined
Rapid acetylators T/2 1hr; achieves
subtherapeutic levels if given once/wk
Slow acetylators T/2 3hrs

 Absroption is decreased by aluminum

hydroxide
Excreted in urine
Drug interactions may reduce the
metabolism of pheynytoin, carbamazepine
and ethosuximide
Routine monitoring of transaminases not
believed necessary for children
Protect drug from light.

INH
Adverse Reactions
Hepatotoxicity INH induced hepatitis
most frequent major toxic effect
d/c INH if (+) sx or if transaminases increase
>3.5 x upper limits of normal

Fever and rash hypersensitivity rxns

Peripheral neuropathy
due to increased pyridoxine excretion
Supplement 10mg B6 daily if with sz/malnut

Seizures in high doses

Optic neuritis, toxic psychosis

Rifampicin
Bactericidal / acts on extra and intracellular
bacillary populations
MOA: binds strongly to subunit of bacterial DNAdependent RNA polymerase inhibits RNA
synthesis.

Pharmacokinetics
Well absorbed orally, enterohepatic circulation
Well distributed in tissues, body fluids with
therapeutic levels in CSF

Rifampicin
Pharmacokinetics
Metabolism even deacetylated form
(metabolized form) has antibacterial activity
Excreted mainly through liver into bile and
urine (deacylated form)

Drug interactions:
Potentiate microsomal Cytochrome P450
mediated enzymatic activities causing increased
metabolism of digoxin, phenytoin,
chloramphenicol,coumadin, ketoconazole,
prednisone, theophyline

Rifampicin
Adverse Effects
GI intolerance may be severe
Produce reddish coloration of body fluids urine, tears, saliva
Cholestatic jaundice/hepatitis
Hypersensitivity: flushing, fever, pruritus,
flu-like sx
Increases risk of hepatotoxicity if used with
INH (adjust doses)

Rifampicin
Other clinical uses
Leprosy in combination with other drugs
For chemoprophylaxis- household contacts
of meningococcal and H.flu dis.
MRSA
In combination with Vancomycin or
Ceftriaxone for meningitis

Pyrazinamide
Weakly bactericidal but with potent sterilizing activity
within macrophages and areas of acute inflammation,
vs residual intracellular organisms that may cause
relapse.
MOA
Converted to active pyrazinoic acid (unknown drug
target and MOA)

Pharmacokinetics
Well absorbed from GIT
Widely distributed to body tissues and inflammed
meninges
T/2 8-11hrs

Pyrazinamide
Adverse Effects
Most hepatotoxic of all TB agents
GI sx
Photosensitivity and rash
Hyperuricemia due to decreased urate
excretion
Arthralgia, esp of shoulders
If patient is diabetic: monitor glucose levels
Protect from light.

Ethambutol
Bacteriostatic in macrophages, but with some
cidal action at higher doses.
Acts on extra and intracellular bacillary
populations, active vs bacilli in cavities.
MOA
Inhibitor of mycobacterial arabinosyl transferases
leading to inhibition of polymerization of
arabinoglycan, an essential component of the
mycobacterial cell wall.

Ethambutol
Pharmacokinetics
Well absorbed from the gut
CSF concn increases with inflammed
meninges = 4-64% of serum levels
50% of dose is excreted in the urine
unchanged
20% excreted in feces
Reduce dose by half if Cr clearance is
<10mL/min

Ethambutol
Adverse Effects
Retrobulbar neuritis
Reduced visual acuity
contraction of visual fields
green-red color blindness
Not usually seen at recommended doses
Hypersensitivity reactions rare
Should not be given to children <6yrs or where
visual acuity and color discrimination cannot be
monitored.

Streptomycin
Bactericidal aminoglycoside vs M.tb in vitro
but inactive vs intracellular bacilli limited
activity to suppression, activity limited to
extracellular bacteria.
MOA
Binds to 30S ribosomal subunit and
interferes with initiation of protein
synthesis by fixing the 30S-50S ribosomal
complex at the start codon (AUG) of
mRNA.

Streptomycin
Pharmacokinetics
Poorly absorbed orally
Must be given parenterally
Poor CSF penetration, unless meninges
inflammed
Elimination renal
reduce dose if with decreased UO or if (+)
casts/albumin in urine

Streptomycin
Adverse Effects
Ototoxicity
Nephrotoxicity
Vertigo and hearing loss most common
side effects
Sterile abscess
Lupoid reactions rare
Do not give with other nephrotoxic and
ototoxic drugs

Adverse Reactions
What are the recommendations in case the
patient develops these adverse drug
reactions?
GI intolerance
Mild skin reactions
Orange-red colored urine
Pain at the injection site
Burning sensation in the feet (periph neuropathy)
Arthralgia due to hyperuricemia
Flu-like sx

Side Effects

Drug
Responsible

GI intolerance Rifampicin

Mild skin
reactions

Any kind

Orange-red Rifampicin
colored urine

What to Do
Give
medication at
bedtime
Give antihistamines
Reassure the
patient

Side Effects

Drug
Responsible

What to Do

Burning
sensation
feet
Arthralgia
hyperuricemia
Flu-like sx

INH

Give vit B6

PZA

Give NSAID

Rifampicin

Give antipyretics

Side Effects

Drug
Responsible

What to Do

severe rash

Any kind esp

streptomycin

d/c anti TB
drugs, refer to
MD

hypersensitivity

Any kind esp

INH,Rifampicin
hepatitis
PZA
Impaired visual Ethambutol

Jaundice -

acuity/color
vision-optic

neuritis

d/c anti TB
refer, resume tx
if sx gone
d/c etham,
refer to ophtha

Side Effects

Drug
Responsible

What to Do

Hearing
impairmnt,
tinnitus CN8

Streptomycin

d/c anti-TB
drugs and refer
to MD

Oliguria/albumi Streptomycin
nuria
Rifampicin
Renal dis.
Psychosis and
convulsion

INH

Clinical Form

Intensive
Phase

TB Exposure
< 5 yrs
5 yrs

3H
to be modified based
on follow up TST
result

Latent TB
9H
PPD conversion
within past 1-2 yrs ()Cxray
Latent TB
9H
PPD(+) with stable
healed lesion
(-) previous Tx

Continuation
Phase

Clinical Form

Intensive
Phase

Latent TB
PPD(+),stable/healed
lesion, previous tx(+)
At risk for reactivation
due to
measles/pertussis
Latent TB
PPD(+),stable/healed
lesion, previous tx(+)
At risk for reactivation
due to
immunosuppression

1-2 H

H for the
duration
immunosuppression

Continuation
Phase

Clinical Form

Intensive
Phase

Continuation
Phase

Active TB disease
New, smear(-)
pulmonary TB

2HRZ

4HR or 6HE

Active TB disease
Less severe form
extrapulmonary TB

2HRZ

4HR or 6HE

Active TB disease
New, smear(+)
pulmonary TB

2HRZE(S)

4HR or 6HE

Clinical Form

Intensive
Phase

Continuation
Phase

Active TB Disease
New smear (-)
pulmonary TB
with extensive
parenchymal
involvement
Active TB Disease
Severe forms of
extrapulmonary TB
(other than TB
meningitis)

2HRZE(S)

4HR or 6HE

2HRZE(S)

4HR or 6HE

Clinical Form

Intensive
Phase

Continuation
Phase

Active TB Disease
TB Meningitis

2HRZS

4HR

Active TB Disease
Miliary TB
Bone & Joint TB

2HRZS

7-10HR

Active TB Disease
previously treated
smear(+)Pulmo TB,
Relapse tx after
interruption tx failure

2HRZES/
1HRZE

5HRE

TB & Pregnancy
TB in pregnancy should be treated
without delay.
H,R,Z,E have no known teratogenic
effects
2HRZE then 4HR
Pyridoxine 25mg/day
Streptomycin - contraindicated

 Tuberculosis in pregnancy should be treated without delay.

Untreated TB will cause more harm than adverse events associated
with treatment of pregnant women and babies. Infants born to
women with untreated TB have higher risks of having fetal growth
retardation, small for gestational age,
low APGAR scores, low birth weight and rarely congenital TB.
Isoniazid, rifampicin, pyrazinamide, and ethambutol have no known
teratogenic effects and are considered safe for pregnant patients with
TB. Although the safety of PZA is not yet well established, the WHO
recommends the use of PZA for 2 months.
The standard short- course chemotherapy consisting of an initial
phase using HRZE for two months followed by HR for four months
is recommended if the probability of TB is moderate to high.
Pregnant women taking isoniazid should be given pyridoxine
(Vitamin B6) at 25 mg/day because isoniazid may cause
demyelination in the patient and in the fetus.
Streptomycin may cause ototoxicity in fetuses and should not be
used in the treatment of pregnant patients with TB. [Grade B]

TB and Breastfeeding
Lactating women being treated for TB with the
first-line anti-TB drugs may continue to breastfeed.
The small concentrations of anti-TB drugs in breast
milk do not produce toxicity in nursing newborns.
Drugs in breast milk should not be considered as
an effective treatment for active TB or latent TB
infection in a nursing infant. Drug levels in breast
milk are not sufficient for Treatment of TB in the
infant.

Review
Mechanisms of Action of first line & second
line anti-TB drugs
Pharmacokinetics
Adverse Drug Reactions

 INH inhibits mycolic acid synthesis (cell wall synthesis)-Cidal

Rifampicin inhibits RNA synthesis by binding to RNA polymerase and
penetrates phagocytic cells Cidal
PZA Intracellular drug (macrophage) and works within the lysosome
MOA unknown Cidal/ not for longterm tx bec. Dormant bacilli resistant
to PZA
Ethambutol inhibits mycolic acid synthesis by inhibiting transferases
involved polymerization of cell wall components Static
Streptomycin inhibits protein synthesis
So INH/Ethambutol inhibit mycobacterial cell wall synthesis/ While
Rifampicin inhibits RNA synthesis/Streptomycin inhibitsProtein synthesis
PZA MOA unknown.
Adverse Drug Reactions: INH hepatitis, peripheral neuropathy, seizures
Rifampicin- orange color of body fluids, cholestatic jaundice
PZA most hepatotoxic, gout hyperuricemia
Ethambutol retrobulbar neuritis, difficult to administer to <6 years old
because visual acuity and color perception cannot be assessed
Streptomycin ototoxic and nephrotoxic