DEFINISI

Multi-drug Resistant Tuberculosis (MDR-TB)

• As TB caused by organisms that are resistant
to Isoniazid and Rifampicin, two first-line anti
TB drugs, continues to threaten the progress
made in controlling the disease.

XDR-TB ( Extensively drug-resistant TB), defined as

MDR-TB that is resistant as well any one of the
fluoroquinolone and to at least one of the three
injectable second-line drugs ( amikacin, capreomycin
or kanamicyn).
 Definitions
MDR TB = Strains resistant to at least INH and RIF (most important
1st-line drugs)
XDR TB = MDR TB strains with additional resistance to any
fluoroquinolone and any of the 3 injectable second-line drugs
(amikacin, kanamycin, capreomycin)

TB with any
drug MDR TB XDR TDR
resistance
 Causes of drug resistant TB (DR-TB)
1. Microbiological perspective
Caused by genetic mutation that makes a drug ineffective
against the mutant bacilli.
2. Clinical & programmatic perspective
a. An adequate or poorly administered treatment regimen that
allows a drug-resistant strain to become the dominant strain in
a patient infected with TB.
b. On patient “noncompliance”:
- more often related to barriers to appropriate care, such as
the lack of diagnostic services, medications, transportation
within a TB control program, as well as the logistic and
financial constrains experienced by many patients and their
families.
In addition, physician errors have also been linked to
development of drug-resistant TB
 Faktor penyebab resistensi OAT terhadap kuman M TB
• Faktor Mikrobiologik
- Resisiten yang natural
- Resistensi yang didapat
- Amplifier effect
- Virulensi kuman
- Tertular galur kuman MDR
• Faktor Klinik
a. Penyelenggara kesehatan
- Keterlambatan diagnosis
- Terapi tidak mengikuti pedoman
- Penggunaan paduat OAT tidak adekuat
- Tidak ada pedoman/guideline
- Tidak ada/kurangnya pelatihan TB
- Tidak ada pemantauan pengobatan
- Fenmena addition syndrome : suatu obat yang ditambahkan pada
satu paduan yang telah gagal.
Bila kegagalan ini terjadi karena kuman TB telah resisten pada paduan
pertama maka “penambahan” 1 jenis obat tersebut akan menambah panjang
daftar obat yang resisten
- Organisasi program nasional TB yang kurang baik
b. Obat
 b. Obat
- Terapi TB perlu jangka waktu lama  6 bulan  membosankan
- Obat toksik  efek samping shg terapi gagal sampai selesai/komplit
- Obat tdk diserap dgn baik : rifampisin diminum pc, atau ada diare
- Kualitas obat kurang baik pada obat FDC  bioavibilitas rifampisin berkurang
- Regimen/dosis obat yang tidak tepat
- Harga obat tidak terjangkau
- Pengadaan obat terputus
c. Pasien
- PMO tidak ada / kurang baik
- Kurangnya informasi / penyuluhan
- Kurang dana untuk obat, pemeriksaan penunjang dll
- Efek samping obat
- Sarana dan prasarana transportasi sulit / tidak ada
- masalah sosial
- gangguan penyerapan obat
3. Faktor Program
3. Faktor Program
a. Tidak ada fasilitas untuk biakan dan uji kepekaan
b. Amplifier effect
c. Tidak ada program DOTS-PLUS
d. Program DOTS belum berjalan dengan baik
e. Memerlukan biaya yang besar

4. Faktor HIV/AIDS
a. Kemungkinan terjadi TB-MDR lebih besar
b. Gangguan penyerapan
c. Kemungkinan terjadi efek samping lebih besar

5. Faktor Kuman
Kuman M TB super strains
- Sangat virulen
- Daya tahan hidup lebih tinggi
- Berhubungan dengan TB-MDR
 Kriteria curiga MDR TB
di Indonesia

1. Pasien gagal dgn terapi kategori 2.

2. Pasien gagal dgn terapi kategori 1.
3. Pasien pernah mendapat terapi TB sebelumnya, termasuk
obat lini ke 2.
4. Pasien tidak terjadi konversi sputum 3 bulan setelah terapi
kategori 2.
5. Pasien tidak terjadi konversi sputum 3 bulan setelah terapi
kategori 1.
6. Kasus relaps.
7. Pasien kembali setelah putus berobat.
8. Pasien TB dengan riwayat kontak erat dengan pasien TB MDR
termasuk “health care workers”.

Bila salah satu kriteria ditemukan pada pasien, maka perlu dilakukan pemeriksaan kultur sputum dan tes
sensitiviti obat.
• As with most things in the medicine, prevention is
better than cure.
• In order to ensure that the patient is taking
medication correctly WHO now strongly advocate
the use of directly observed therapy (DOT).
The simple procedure means that the patient must
be seen to swallow their medication under the eye of
trained supervisor. This prevent drug resistance
emerging as it should ensure that monotherapy is
avoided
 General principles of designing a regime
•Regimens should be based on the history of drugs
taken by the patient.

•Drugs commonly used in the country and prevalence

of resistance to first line and second-line drugs should
be taken into consideration when designing a regimen.

•Regimens should consist of at least four drugs with

either certain, or almost certain, effectiveness. If the
evidence about the effectiveness of a certain drug is
unclear, the drug can be part of the regimen but it
should not be depended upon for success.
 General principles of designing a regime
•When possible, pyrazinamide, ethambutol and fluoroquinolones should be given
once per day as the high peaks attained in once-a-day dosing may be more
efficacious. Once-a-day dosing is permitted for other second-line drugs depending
on patient tolerance.

•The drug dosage should be determined by body weight.

•Treatment of adverse drug effects should be immediate and adequate in order to

minimize the risk of treatment interruptions and prevent increased morbidity and
mortality due to serious adverse effects

•An injectable agent (an aminoglycosideor capreomycin) is used for a minimum of

six months and at least four months past culture conversion

•The minimum length of treatment is 18 months after culture conversion

•Each dose is given as directly observed therapy (DOT) throughout the treatment.
 General principles of designing a regime
•DST of drugs with high reproducibility and reliability (and from a dependable
laboratory) should be used to guide therapy.

•It should be noted that the reliability and clinical value of DST of some first-line
and most of the second-line anti tuberculosis drugs have not been determined

•DST does not predict with 100% certainty the effectiveness or ineffectiveness of
a drug. DST of drugs such as ethambutol, streptomycin and Group 4 and 5 drugs
does not have high reproducibility and reliability

•Pyrazinamide can be used for the entire treatment if it is judged to be effective.

•Many DR-TB patients have chronically inflamed lungs, which theoretically

produce the acidic environment in which pyrazinamideis active. Alternatively, in
patients doing well, pyrazinamide can be stopped with the injectable phase if the
patient can continue with at least three certain, or almost certain, effective drugs.
Treatment of XDR TB
 Rational Classification of Anti-TB Drugs
All
Group 1: First Line Drugs, Oral(H,R,E,Z) Possible

Group 2: Quinolones: Of, Lf, Mox.,Gat 1

Group 3: Injectables: Sm, Km, Ak, Cm 1

Group 4: Other Second Line Drugs: Until

Et/Pth, Cs, PAS 4 New

Group 5: Reinforcement Drugs (poor) : Exceptional

If < 4
Am/Cl, Clof, Th, High dose INH, Linezolid

At least 4 New Drugs for a Good MDR-TB Treatment

 The step to prevent drug resistant TB
1. Take your treatments properly if you already have TB.
(most important thing)
2. Try your best to avoid patients that already have XDR-TB.
3. Acknowledge how XDR-TB/TB is spread.
4. Prevent non-drug-resistant TB if you got it before.
5. Contact your public health department if you notice
cases of TB are spreading.
6. Try not to go to other countries where TB is common.
7. Know the symptoms of “normal” TB.
8. Understand who are the people who are more open to
TB