Treatment of tuberculosis

Zen Ahmad
Medical Faculty, Sriwijaya University
1882, ditemukan bakteri
penyebab (Mycobacterium
Tuberculosis) oleh Robert
Koch.

24 Maret diperingati sbg hari TB sedunia

Estimated burden of disease caused by TB,
2012 and 2016

460 000 kasus

ranking 4 dunia
1.020.000 kasus
Ranking 2 dunia

7.000.000 kasus 9.050.000 kasus

Rapid and accurate diagnosis is at the core
of the international strategy to control TB
Diagnosis of pulmonary TB

Clinical features

Smear sputum examination

CXR

Gene Expert

Other examinations (Elisa; PAP, others)

Clinical symptoms
Respiratory symptoms
 Cough  2 weeks (dry, sputum, haemoptysis)
 Breathlessness
 Chest pain

General symptoms
 Night sweats
 Fever
 Tiredness
 Loss of appetite, decrease of body weight
Tujuan pengobatan

• Menyembuhkan pasien TB
• Menurunkan angka kematian akibat TB
• Mencegah kekambuhan
• Menurunkan angka penularan
• Mencegah resisten obat
First line drugs
Essential OAT (WHO)

Recommended dose (Mg/Kg)

OAT Mechanism Everyday INTERMITENT
3X/week 2x/weeks
H Bactericidal 5 (4-6) 10 (8-12) 15 (13-17)
R Bactericidal 10 (8-12) 10 (8-12) 10 (8-12)
Z Bactericidal 25 (20-30) 35 (30-40) 50 (40-60)
S Bactericidal 15 (12-18) 15 (12-18) 15 (12-18)
E Bacteriostatik 15 (15-20) 30 (25-35) 45 (40-50)
• 37 studies were included
• Inappropriate treatment regimens in 67% of studies (the
percentage of patients receiving inappropriate regimens
varied between 0.4% and 100%)
• In 19 studies the quality of treatment regimen reporting
was low
Treatment guidelines
Guide of TB treatment

1. Minimally with 2 OAT

2. Short course regiments
3. Treatment divided in 2 phase
Initial phase: Bakterisidal
Continuous phase: Sterilizes and prevent of
relapse
4. Resistance test in old cases
5. Doses on body weight (range of BW)
The Basis for Multi-Drug therapy

High A INH (RMP,SM,E)

Continuous
growth PZA RMP
Speed of
B Acid C Spurts of
bacterial
growth inhibition metabolism

D
Dormant
Low
Mitchison, Tubercle 66:219-226
Mechanisms for treatment failure
and disease relapse
Number of
organisms

Bactericidal (Failure)

Sterilizing (Relapse)
Extracellular bacilli

Intracellular bacilli

Duration of therapy
Grading of activities of anti-tuberculosis drugs
Early Prevention
Drugs of resistance Sterilizing
bactericidal

Isoniazid ++++ +++ ++

Rifampisin ++ +++ ++++
Pirazinamid + + +++
Streptomicin ++ ++ ++
Etambutol ++ - +++ ++ +
ISTC, Standard 8

• All new cases should receive 1st line

treatment regimen
• The initial phase: 2 RHZE and the
continuation phase: 4 RH
• The doses of OAT should conform to
international recommendations
• FDC drugs may provide a more
convenient form of drug
administration
Regimen Berdasarkan Kategori (WHO / Depkes RI)
Kategori Kriteria penderita Regimen pengobatan

Fase awal Fase lanjutan

I  Kasus baru BTA (+) 2 RHZE (RHZS) 6 EH
 Kasus baru BTA (-) 2 RHZE (RHZS) 4 RH
Ro” (+) sakit berat 2 RHZE (RHZS)* 4 R3H3*
 Kasus TBEP berat

II Kasus BTA positif 2 RHZES / 1 RHZE 5 RHE

 Kambuh 2 RHZES / 1 RHZE* 5 R3H3E3*
 Gagal
 Putus berobat

III  Kasus baru BTA (-) 2 RHZ (E) 6 EH

 TBEP ringan 2 RHZ (E) 4 RH
2 RHZ* (E) 4 R3H3*
IV  Kasus kronik Obat-obat sekunder

* Yang diterapkan di Indonesia

Regimen berdasar kategori (WHO / Depkes RI)

Kategori Kriteria penderita Regimen pengobatan

Fase awal Fase lanjutan

I Kasus baru TB 2 RHZE (RHZS) 4 RH

2 RHZE (RHZS)* 4 R3H3*

II Kasus BTA positif 2 RHZES / 1 RHZE 5 RHE

 Kambuh 2 RHZES / 1 RHZE* 5 R3H3E3*
 Gagal
 Putus berobat

IV Kasus kronik Obat-obat sekunder (MDR)

* Yang diterapkan di Indonesia

Duration of rifampicin

 New patients with pulmonary tb should receive a

regimen containing 6 months of rifampicin
2HRZE/4HR

 The 2HRZE/6HE treatment regimen should be

phased out
Dosing frequency of TB treatment

 The optimal dosing frequency for new patients is daily

throughout the course of therapy

 In all patients with drug-susceptible pulmonary TB, the use

of thrice-weekly dosing is not recommended in both the
intensive and continuation phases of therapy, and daily
dosing remains the recommended dosing frequency

Guidelines for treatment of drug-susceptible tuberculosis and patient care;

WHO, 2017
Treatment extension

In new pulmonary TB patients treated with the

regimen containing rifampicin throughout treatment, if
a positive sputum smear is found at completion of the
intensive phase, the extension of the intensive phase
is not recommended
Initial regimen in countries with high
levels of isoniazid resistance

In populations with known or suspected high levels of

isoniazid resistance, new TB patients may receive
HRE as therapy in the continuation phase as an
acceptable alternative to HR
FDC

 The use of FDC tablets is recommended over

separate drug formulations in the treatment of
patients with drug-susceptible TB

Guidelines for treatment of drug-susceptible tuberculosis and patient

care; WHO, 2017
Fixed-dose combinations from the WHO Model
List of Essential Medicines
(revised April 2002)
Dosage schedules for adults(Cat 1)

Initial phase Continuation phase

Body weight (kg)
(2RHZE) (4RH,3x/weeks)
• 30 - 37 • 2 cap FDC • 2 cap FDC
• 38 - 54 • 3 cap FDC • 3 cap FDC
• 55 – 70 • 4 cap FDC • 4 cap FDC
• 71 and more • 5 cap FDC • 5 cap FDC
Fluoroquinolone-containing regimens

In patients with drugs-susceptible pulmonary TB,

4-month FQ containing regimens should not be used
and

the 6-month rifampicin-based regimenn 2RHZE/4RH

remains the recommended regimen

Guidelines for treatment of drug-susceptible tuberculosis and patient care;

WHO, 2017
Treatment of previously treated TB

 Specimens for culture and drug-susceptibility testing

should be obtained from all previously treated TB
patients at or before the start of treatment.
Drug-susceptibility testing should be performed for at
least isoniazid and rifampicin
 In settings where rapid molecular-based
drugsusceptibility testing is available, the results should
guide the choice of regimen
Treatment of previously treated TB

 In settings where rapid molecular-based

drugsusceptibility testing results are not routinely
available, TB patients whose treatment has failed or
other groups with high likelihood of MDRTB should be
started on an empirical MDR regimen
 In patients who require TB retreatment, the category II
regimen should no longer be prescribed and drug-
susceptibility testing should be conducted to inform the
choice of treatment regimen
Standard 11
• Assessment of the likelihood of drug resistance
− History of treatment
− Exposure to a possible source case having DR organisms
− Community prevalence of drug resistance
• Patients who remain AFB (+) at 3 months of treatment, fail,
defaulted, relapse and chronic cases should always be
assessed for possible drug resistance
• Culture and drug susceptibility testing should be
performed if drug resistance is considered
Standard 11
• For patients in whom drug resistance is considered to be
likely an Xpert MTB/RIF test should be the initial diagnostic
• If rifampicin resistance is detected, culture and testing for
susceptibility to INH, FQ and second-line injectable drugs
should be performed promptly
• Patient counseling and education, as well as treatment with
an empirical second-line regimen, should begin
immediately to minimize the potential for transmission
• Infection control measures appropriate to the setting should
be applied
Risk of resistance
Very high High Moderate and low
Failure of re- • Resistance • Failure in the Private Sector
treatment and Failures of • Remain Sm+ at 2-3 m. of the Cat. I
chronic TB Category I
• Relapses case
case • Exposure to
a known • Exposure in Institutions that have MDR-TB
MDR-TB out-breaks or a high MDR-TB prevalence
case • Residence in Areas with high MDR-TB
• History of using OAT drugs of Poor or
unknown Quality
• Treatment in programs that operate poorly
• Co-morbid associated with malabsorption
or rapid transit diarrhea
• HIV
Regimen saat ini

Kategori Kriteria penderita Regimen pengobatan

Fase awal Fase lanjutan

I Kasus baru TB 2 RHZE (RHZS) 4 RH

Kasus lama TB, tak MDR

IV Kasus MDR Obat-obat MDR

Standard 12
• Patients with MDR/XDR TB organisms should be treated with
specialized regimens containing 2nd line anti tuberculosis drugs
• The doses of anti TB drugs should conform to WHO recommend
• At least 5 drugs, PZA and 4 drugs to which the organisms are
known or presumed to be susceptible (including an injectable
agent) should be used in a 6–8 month intensive phase
• At least 3 drugs to which the organisms are known or presumed
to be susceptible, should be used in the continuation phase
• At least 18–24 months beyond culture conversion
• Consultation with a specialist experienced in treatment of patients
with MDR/XDR tuberculosis should be obtained
Drugs for tuberculosis
TB and HIV
 ARV medications should be started in all TB patients
living with HIV regardless of their CD4 cell count
 TB treatment should be initiated first, followed by ART as
soon as possible within the first 8 weeks of treatment
 HIV-positive TB patients with profound immunosuppres-
sion (e.g. CD4 cell counts less than 50 cells/mm3) should
receive ART within the first 2 weeks of initiating TB
treatment
Guidelines for treatment of drug-susceptible tuberculosis and patient care;
WHO, 2017
TB and HIV
 In patients with drug-susceptible pulmonary TB who are
living with HIV and receiving ARV therapy during TB
treatment, a 6-months standard treatment regimen is
recommended over an extended treatment for 8
months or longer

 The optimal dosing frequency is daily during the

intensive and continuation phase

Guidelines for treatment of drug-susceptible tuberculosis and patient care;

WHO, 2017
ISTC, Standard 14
• HIV testing and counseling should be recommended to all
patients with, or suspected of having, tuberculosis.
• Testing is of special importance as part of routine
management of all patients
• In areas with a high prevalence of HIV infection
• In patients with symptoms and/or signs of HIV-related conditions
• In patients with a history suggestive of high risk of HIV exposure
• In areas of high HIV prevalence integrated approaches to
prevention and treatment of both infections are
recommended
ISTC, Standard 15
• In persons with HIV infection and TB who have profound
immunosuppression (CD4 counts less than 50 cells/mm3),
ART should be initiated within 2 weeks of beginning
treatment for TB unless TB meningitis is present
• For all other patients with HIV and TB, regardless of CD4
counts, antiretroviral therapy should be initiated within 8
weeks of beginning treatment for TB
• Patients with TB and HIV infection should also receive
cotrimoxazole as prophylaxis for other infections
ISTC, Standard 16

Persons with HIV infection who, after careful

evaluation, do not have active tuberculosis should be
treated for presumed latent tuberculosis infection with
isoniazid for 6 months
The use of steroids

 In patients with tuberculous meningitis, an initial

adjuvant corticosteroid therapy with dexamethasone
or prednisolone tapered over 6-8 weeks should be
used
 In patients with tuberculous pericarditis, an initial
adjuvant corticosteroid therapy may be used

Guidelines for treatment of drug-susceptible tuberculosis and patient care;

WHO, 2017
Simpulan
 Rekomendasi OAT untuk kasus baru TB: 2HRZE/4HR
 Regimen mengandung quinolon tidak dianjurkan
 Pemakaian FDC direkomendasikan
 Pemakaian OAT setiap hari
 Pasien TB dengan HIV
 ART diberikan secpatnya (pada 8 minggu pertama)
 OAT cukup 6 bulan
 Steroid selama 6-8 minggu dipakai pada meningitis tb dan
pericarditis tb
 Pemberian OAT kategori 2 sudah ditinggalkan