TREATMENT of TB in

ADULTS

by
Dr. Irfhan Ali Hyder Ali

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 LEARNING OBJECTIVES
• To update on treatment regimes &
modalities for PTB & EPTB

• To present evidence-based updates to

best suit TB management in Malaysia

• To emphasise on the importance of

proper treatment
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 INTRODUCTION
• Important to provide a standardised TB
regimen for all TB cases

• This section will cover all aspects of treatment:

– Pulmonary TB (PTB)
• New cases
• Relapse cases
– Extrapulmonary TB (EPTB)
– Standard regimes & duration

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 AIM OF TREATMENT
• Cure & reduce transmission

• Risk of developing TB is determined:

– infectiousness of index case
– smear positive PTB; PTB with cavities; laryngeal TB
– nature & duration of contact
– immune status of contact

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 EDUCATION
a. Nature of disease
b. Necessity of strict adherence with prolonged
treatment
c. Risks of defaulting treatment
d. Side effects of medication
e. Risks of transmission & need for respiratory
hygiene as well as cough/sneeze etiquette

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PULMONARY TUBERCULOSIS (PTB)
IN ADULTS
 NEW CASES
• 6-month regimen consisting of 2 months of
EHRZ (2EHRZ) followed by 4 months of HR
(4HR) is recommended for newly-diagnosed
PTB.

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 RECOMMENDED ANTITB DRUGS
RECOMMENDED DOSES

DRUG Daily 3X a week

Dose (range) Maximum in Dose (range) Maximum in
in mg/kg mg in mg/kg mg
body weight body weight

Isoniazid (H) 5 (4 - 6) 300 10 (8 - 12) 900

Rifampicin (R) 10 (8 - 12) 600 10 (8 - 12) 600
Pyrazinamide 25 (20 - 30) 2000 35 (30 – 40)* 3000*
(Z)
Ethambutol 15 (15 - 20) 1600 30 (25 – 35)* 2400*
(E)
Streptomycin 15 (12 - 18) 1000 15 (12 – 18)* 1500*
(S)
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 NEW CASES (cont.)
• Pyridoxine 10 - 50 mg daily needs to be added
if isoniazid is prescribed.
• *Daily treatment is the preferred regimen.
Adopted from WHO. Treatment of Tuberculosis Guidelines (4th Ed.), 2010

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 IMPORTANT POINTS
• Rifampicin
– should be used for the whole duration of treatment.
– NS difference in effectiveness & safety between rifampicin
& other antibiotics in the rifamycin group.
– whenever possible, rifampicin dosage should not be lower
than recommended dosage (10 - 12 mg/kg).
• Pyrazinamide beyond 2 months during the intensive
phase does not confer further advantage if the
organism is fully susceptible.
• Recurrence rate is low for both ethambutol-based
regimen & for streptomycin-based regimen.
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TREATMENT OF NEW CASES

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 PREVIOUSLY TREATED TB
• New cases who have taken treatment for
more than one month & are currently smear
or culture positive again (i.e. failure, relapse or
return after default)

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 DEFINITION
Previously treated Patient previously treated for TB including
relapse, failure & default cases .
Relapse A patient whose most recent treatment
outcome was “cured” or “treatment
completed”, & who is subsequently
diagnosed with bacteriologically positive TB
by sputum smear microscopy or culture.

Treatment after failure A patient who has received Category I

treatment for TB & in whom treatment has
failed.
Treatment after A patient who returns to treatment,
default bacteriologically positive by sputum smear
microscopy or culture, following
interruption of treatment for 2 or more
consecutive months.
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 PREVIOUSLY TREATED TB
• Recommend: retreatment regimen containing first-
line drugs 2HRZES/1HRZE/5HRE if country-specific
data show low or medium levels of MDR-TB in these
patients or if such data is not available.

• Drug sensitivity test (DST) must be done for patients.

When results become available, drug regimen should
be adjusted appropriately.

*This is WHO statement, no retrievable evidence

available.
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 TO START OR NOT?
• Interruption in intensive phase:
– If ≥14 days, to restart from beginning i.e. Day 1.
– If <14 days, to continue form last dose.

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 TO START OR NOT?
• Interruption in maintenance phase:
– If interruption occurs after patient receives 80% of total
planned doses, treatment may be stopped if sputum AFB
smear was negative at initial presentation. If sputum AFB
smear was positive, treatment should be continued to
achieve total number of doses.
– If total doses <80% & interruption lapse is ≥2 months,
restart treatment from beginning.
– If total doses is <80% & interruption lapse is <2 months,
continue treatment from date it stops to complete full
course.

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 TREATMENT OF
PREVIOUSLY TREATED TB

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 OPTIMAL DURATION
• Patients with sputum positive PTB should receive
antiTB drugs for a minimum duration of 6 months.

• Regimens with shorter duration of rifampicin are

associated with higher risk of failure, relapse &
acquired drug resistance.

• Even in patients with non-cavitary disease &

confirmed sputum culture, conversion at 2 months
fares poorer with a 4-month regimen compared to 6-
month regimen.
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OPTIMAL DURATION

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 MAINTENANCE PHASE
• In new patients with PTB, WHO recommends daily
dosing throughout the course of antiTB treatment.

• However, a daily intensive phase followed by thrice

weekly maintenance phase is an option provided that
each dose is directly observed & patient has
improved clinically.

• A maintenance phase with twice weekly dosing is not

recommended.

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 MAINTENANCE PHASE
• There is no difference in treatment failure, relapse &
acquired drug resistance rates between daily &
different intermittent dosing regimens in the
maintenance phase.1, 2, 3
Menzies D et al., PLoS Med, 2009
1

2Mwandumba HC et al., Cochrane, 2001

3Chang KC et al., Thorax, 2011

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MAINTENANCE PHASE

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 FIXED-DOSE COMBINATION
(FDC) IN MALAYSIA
• Forecox-Trac Film Coated Tab: isoniazid, rifampicin,
ethambutol & pyrazinamide
• Rimactazid 300 Sugar Coated Tab: isoniazid, & rifampicin
• Rimcure 3-FDC Film Coated Tab: isoniazid, rifampicin &
pyrazinamide
• Akurit-Z Tab: isoniazid, rifampin (rifampicin) & pyrazinamide
• Akurit Tab: isoniazid & rifampin (rifampicin)
• Akurit-Z Kid Dispersible Tab: isoniazid, rifampin (rifampicin) &
pyrazinamide
• Akurit-4: ethambutol, isoniazid, rifampin (rifampicin) &
pyrazinamide

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 FDC IN MOH
• 4-Drug combination: isoniazid 75 mg,
rifampicin 150 mg, pyrazinamide 400 mg &
ethambutol 275 mg tablet

• 3-Drug combination: isoniazid 75 mg,

rifampicin 150 mg & pyrazinamide 400 mg
tablet

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 RECOMMENDED DOSES
• 30 - 37 kg body weight: 2 tablets daily

• 38 - 54 kg body weight: 3 tablets daily

• 55 - 70 kg body weight: 4 tablets daily

• More than 70 kg body weight: 5 tablets daily

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 EFFECTIVENESS
• FDCs compared to separate-drug regimens
significantly reduce risk of non-compliance by
17% & consequently improve effectiveness of
therapy.1

• In term of bioavailability, FDCs are proven to

be bioequivalent to separate-drugs
formulations at the same dose levels.2
1 Bangalore S et al., Am J Med, 2007
2Agrawal S et al., Int J Pharm, 2002

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 OTHER ADVANTAGES
• Smaller number of tablets to be ingested may
also encourage patient adherence.

• Prescription errors are likely to be less

frequent for FDCs due to easy adjustment of
dosage according to patient weight.

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FDC

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 DIRECTLY OBSERVED
THERAPY (DOT)
• Direct observation of drug ingestion of the
DOTS component should not be the sole
emphasis in TB control programmes.

• It should not be a blanket approach; instead it

should be a process of negotiation & support,
incorporating patients’ characteristics &
choices.

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 DIRECTLY OBSERVED
THERAPY (DOT)
• Enhanced DOTS involving intensive contact
tracing & treating the contacts with TB can
reduce incidence of TB within a community
(p=0.04).1
1 Cavalcante SC et al., Int J Tuberc & Lung Dis. 2010

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DOT

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EXTRAPULMONARY TUBERCULOSIS
(EPTB) IN ADULTS
 DURATION OF EPTB TREATMENT -
NICE RECOMMENDATION1
• Meningeal TB – 2 months S/EHRZ+10HR*
• Peripheral lymph node TB – should normally
be stopped after 6 months
• Bone & joint TB – 6 months
• Pericardial TB – 6 months
1 National Collaborating Centre for Chronic Conditions and the Centre for Clinical Practice. Tuberculosis: clinical diagnosis and
management of tuberculosis, and measures for its prevention and control. 2011

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 DURATION OF EPTB TREATMENT -
WHO RECOMMENDATION1
• Regimen should contain 6 months of
rifampicin: 2HRZE/4HR*
• Duration of treatment for TB meningitis is 9 -
12 months &, bone & joint TB is 9 months
1 World Health Organization. Treatment of tuberculosis Guidelines. Fourth ed. 2010

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 MILIARY & DISSEMINATED TB

• There is no retrievable evidence on optimal

duration of treatment for disseminated TB &
miliary TB.

• There should be low threshold to suspect TB

meningitis in these groups of patients &
treatment duration should be prolonged
between 9 to 12 months.

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OPTIMAL DURATION OF
EPTB TREATMENT

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 CORTICOSTEROIDS IN EPTB

• Corticosteroid therapy may benefit patients

with some forms of EPTB. However literature
on corticosteroids in various form of EPTB is
scant.

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CORTICOSTEROIDS IN
EPTB TREATMENT

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 TB MENINGITIS
Severity Regime
Grade I Week 1: IV dexamethasone sodium phosphate 0.3
disease mg/kg/day
Week 2: 0.2 mg/kg/day
Week 3: Oral dexamethasone 0.1 mg/kg/day
Week 4: Oral dexamethasone a total of 3 mg/day,
decreasing by 1 mg each week

Grade II & III Week 1: IV dexamethasone sodium phosphate 0.4

disease mg/kg/day
Week 2: 0.3 mg/kg/day
Week 3: 0.2 mg/kg/day
Week 4: 0.1 mg/kg/day, then oral dexamethasone
for 4 weeks, decreasing by 1 mg each week

Prasad K et al., Cochrane, 2008

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TB PERICARDITIS

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 SURGERY IN PTB
• Diagnosis & obtaining tissue for culture & drug
sensitivity

• Management of TB complications

• Treatment of the disease itself where drug

therapy alone may be deemed insufficient to
achieve cure

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 SURGERY IN PTB
• While the advancement in surgical techniques
including video-assisted thoracoscopy
surgery/thoracotomy has reduced the surgical
mortality & morbidity, surgery for PTB is still
associated with significant complications due
to the presence of adhesions & scarring.

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 MAIN CHANGES IN CPG TB 2012

• Evidence-based
• Treatment after interruption explained in more detail
• Treatment regimes (maintenance) changed to daily
or 3X a week
• FDCs mentioned
• DOTS covered in more detail & done to suit
Malaysian context
• Duration of treatment for EPTB more concise
– Use of steroids recommended for TB meningitis &
pericarditis

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 TAKE HOME MESSAGES
• Adhere to standard regime

• Use correct doses & adequate duration

• Ensure compliance

• Treatment needs to be individualised

• Consult a doctor/physician with experience in

TB management when in doubt
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 THANK YOU

[email protected]

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