tata laksana tb mdr dr. prayudi

8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi

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Management

Multidrug Resistance Tuberculosis

(MDR TB)PRAYUDI SANTOSO

Respirology and Critical Respiratory Division

Internal Medicine Department

Hasan Sadikin Hospital

Universitas Padjadjaran Medical School

Bandung Indonesia


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2

Outline

New definitions of DR TB and MDR Treatment

Outcome

Data on MDR and XDR - TB Current MDR-TB diagnosis

MDR-TB treatment Guideline Recommendation

PMDT implementation at Hasan Sadikin General

Hospital Bandung Indonesia


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3

Outline


Outcome






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Current TB Classification based on Drug Resistance

Monoresistance : resistance to one first line anti TB drug only

Polydrug resistance : resistance to more than one first line anti TB drug

(other than both isoniazid and rifampicin)

Multidrug resistance : resistance to at least both isoniazid and rifampicin

Extensive drug resistance : resistance to any fluoroquinolone and to at

least one of three second line injectable drugs (capreomycin, kanamycin

and amikacin), in addition to MDR

Rifampicin resistance: resistance to rifampicin detected using phenotypic

or genotypic methods with or without resistance to other anti TB drugs. It

includes any resistance to rifampicin, whether monoresistance, multidrugresistance, polydrug resistance or extensive drug resistance

Definition and Reporting Framework for TB WHO 2013 Revision


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5

Outline


Outcome






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MDR/XDR TB Epidemiology

630.000 MDR TB cases among 12 million TBpatients

Almost 60% of world TB cases are in India, China,

Russia and South Africa Highest proportion of MDR TB is in eastern

Europe and central Asia (9-32% of new cases and>50% of previously treated)

Globally 3.7% (2.1

5.2%) of new cases and 20%(13 -26%) of previously treated cases areestimated to have MDR TB

WHO global Tuberculosis report 2012

Stop TB Partnership, WHO The Global Plan to Stop TB 2011-2015


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MDR/XDR TB Epidemiology

Two-thirds of MDR TB cases are not enrolled

on treatment according to guideline

Treatment success low 5070%

Only 30 0f 107 countries reach target success

rate > 75%

Globally XDR TB has been identified in 84

countries

Proportion of XDR-TB in MDR-TB cases is 9%

WHO global Tuberculosis report 2012

Stop TB Partnership, WHO The Global Plan to Stop TB 2011-2015


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8

Causes of DR


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9

Causes of MDR

Patient mismanagement


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MDR TB In INDONESIA

DST Data Before PMDT Implementation

Second Line anti TB (FQ and Kanamycin) in the Market

this is likely to create XDR TB

Year LocationMDR TB

New Cases Prev Treated

2004 Kab. Timika Papua 2% -

2006 Prov. Central Java 1.9% 17.1%

2007 Kota Makassar 4.1% 19.2%

2009 Prov East Java 2% 9.7%

Source : Subdit TB MoH


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Result Indonesia PMDT 2009 and 2010 cohorts

Source : Register TB MDR Subdit TB MoH


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PMDT In Indonesia

Up to February 2013 :

- 4770 MDR TB suspect screened

- 1177 MDR TB patients

- 976 enrolled in treatment

Treatment success 71%

Up to November 2012 : 27 XDR TB diagnosed

Source : Register TB MDR Subdit TB MoH


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DRUG RESISTANCE

MECHANISM


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The development and spread of drug- and multidrug-resistant

tuberculosis.( WHO [2000]. Anti-tuberculosis drug resistance in the world )

WILD MTB STRAIN( contains a small number [ 106 ] of naturally drug-resistant

organisms arising through spontaneous mutations )

ACQUIRED DRUG RESISTANCE( mono, then MDR-TB )

SELECTION by monotherapy

( inadequate drug regimen or poor compliance )

PRIMARY DRUG RESISTANCE

( mono drug or MDR-TB )

TRANSMISSION due to diagnostic delay ,

over crowding and inadequate infection control

.


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Isoniazid ( H ) 1 x 10 5-10 6bacilli

Rifampicin ( R ) 1 x 10 7-10 8bacilli

Streptomycin ( S ) 1 x 105

-106

bacilli

Ethambutol ( E ) 1 x 10 5-10 6bacilli

Pyrazinamide ( Z ) 1 x 10 2-10 4 bacilli

Quinolones 1 x 10 5-10 6bacilli

Others 1 x 10 3-10 6bacilli

Frekuensi mutasi spontan resisten


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terdapat >10 8kuman TB

dalam kavitas

1 resistant ( R ) 100 resistant ( H )

100 resistant ( S)

100 resistant ( E )

0 resistant ( R + H )

0 resistant ( R + H + E )

Pada TB paru kasus BARU


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Z

RH

E

S S

S

cavitas = 10 8kuman

mekanisme terjadinya resistensi

: seleksi
http://localhost/var/www/apps/conversion/tmp/scratch_1/Selection%20Pressure.wmvhttp://localhost/var/www/apps/conversion/tmp/scratch_1/Selection%20Pressure.wmv


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Z

RH

E

S

S

S

cavitas = 10 8kuman

mekanisme terjadinya resistensi :

seleksi

SS

S

S

S

S

S

S

S

S

SS

S S


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Z

RH

E

S

S

S

cavitas = 10 8kuman

mekanisme terjadinya resistensi :

seleksi

SS

S

S

S

S

S

S

S

S

SS

S S

SR

SHSE

SZ

cavitas = 10 8kuman

S

S

SS

S


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Populasi campuran (sensitif dan resisten)Basil resisten thd INH

0 2 4 6 8 10 12 14 16 18 20 22 24

terjadinya strain resisten thd INH karenapengobatan tidak efektif (INH monoterapi)

pengobatan multi-

drug yang efektif

Minggu

Fall and Rise phenomenon


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Z

RH

E

S

R

H

Z

E

cavitas = 10 8kuman

cegah mekanisme seleksi :

terapi kombinasi

Terbunuh

semua
http://localhost/var/www/apps/conversion/tmp/scratch_1/Selection%20Pressure.wmvhttp://localhost/var/www/apps/conversion/tmp/scratch_1/Selection%20Pressure.wmvhttp://localhost/var/www/apps/conversion/tmp/scratch_1/Selection%20Pressure.wmvhttp://localhost/var/www/apps/conversion/tmp/scratch_1/Selection%20Pressure.wmvhttp://localhost/var/www/apps/conversion/tmp/scratch_1/Selection%20Pressure.wmv


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22

Outline


Outcome






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Kriteria Suspek TB MDR

(KLINIS)

1. Kasus kronik

2. Pasien TB tidak konversi pengobatan ulang (kategori 2)

3. Pasien TB yang pernah diobati, termasuk pemakaian OAT lini kedua(pengobatan Non DOTS)

4. Pasien TB gagal pengobatan dengan kategori 1

5. Pasien TB dengan hasil pemeriksaan dahak tetap positif setelahpemberian OAT sisipan (OAT kategori 1)

6. PasienTB kambuh

7. Pasien TB yang kembali setelah lalai/default(setelah pengobatankategori 1 dan atau kategori 2)

8. Suspek TB yang kontak eratdengan pasien TB-MDR, termasukpetugas kesehatan yang merawat pasien TB-MDR

9. Ko-infeksi TB-HIV yang tidak respons secara klinis terhadap

pengobatan TB


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GeneXpert


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With GeneXpert

Any person at high risk of MDR-TB could

undergo rapid testing

start an appropriate treatment immediately

while waiting for conventional culture and DST


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Sensitivity 94.4% and Specificity 98.3%


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Validity GeneXpert MTB/RIF in Detecting MDR-TB

at Hasan Sadikin Hospital Bandung

Proportion Method Media L-J

MDR TB (+) MDR TB (-) Total

PCRGeneXpert

MTB/RIF

RIF Resistant 36 3 39

RIF Sensitive 3 9 12

Total 39 12 51

Sensitivity: 92,3%; Specificity: 75,0%

Sirait N, Parwati I,Dewi SN, Suraya N 2013


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Outline


Outcome






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30

2000


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Indonesia ISTC 2008Obat dalam kurung = kesediaannya terbatas

PENGELOMPOKAN OAT WHO

Grup 1 -OAT oral lini pertama:isoniasid, rifampisin,etambutol, pirasinamid

Grup 2 -Obat suntik:streptomisin, kanamisin,amikasin, kapreomisin, (viomisin)

Grup 3 -Fluoroquinolon:ciprofloxasin, ofloxasin,levofloxasin, moxifloxasin, (gatifloxasin)

Grup 4 -Obat bakteriostatis oral:etionamid,cicloserin, para-aminosalicylic acid (prothionamid,

thioacetazon, terizidon) Grup 5 -Obat belum terbukti:clofasamin,

amoxicillin/klavulanat, claritromisin, linezolid


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Adults and adolescent


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Adults and adolescentDrug Weight class

Average

Daily dosage

3350

KG

5170 KG >70 KG (max dose)

Isonazid ( H)

(100, 300 mg)

46 mg/kg daily 200300 mg 300 mg 300 mg

Rifampicin (R)

(150, 300 mg)

10 -20 mg / kg daily 450600 mg 600 mg 600 mg

Ethambutol (E)

(400 mg)

25 mg / kg daily 8001200 mg 12001600 mg 16002000 mg

Pyrazinamide (Z)

(500 mg)

3040 mg/kg

daily

10001750 mg 1750 mg 20002500 mg

Streptomycin (S)

(1 g vial)

1520 mg/kg 500750 mg 1000 mg 1000 mg

Kanamycin (Km)

(1 g vial)

1520 mg/kg

daily

500750 mg 1000 mg 1000 mg

Capreomycin

(cm) (1 g vial)


Ofloxacyn (Ofx) Usual adult dose is 800 mg 800 mg 800 mg 8001000 mg

Levofloxacin (Lfx)

(250 mg, 500 mg)

Usual adult dose is 1000 mg 750 mg 7501000 mg 7501000 mg

Moxifloxacin(Mfx) (400 mg)

Usual adult dose is 400 mg 400 mg 400 mg 400 mg

Ethionamide

(Eto) (250 mg)

15 -20 mg/kg

daily

500 mg 750 mg 7501000 mg

Cycloserine (Cs)

(250 mg)

1520 mg/kg 500 mg 750 mg 7501000 mg

Terzidone 9Trd)

250 mg


PASER (4G sachets) 150MG/KG DAILY 8 g 8 g 8 -12 g


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Recommendation for MDR-TB Drug Regimen


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WHO 2011 update


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Step 1


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Step 3

Third line drugs

Imipenem Linezolid Macrolides

Amoxicillin/Clavulanate

Consider use of these

If there are not

4-6 drugs

available

consider 3rdline

in consult with

MDRTB experts

p

Use any

availableBegin with any

First line agents to

Which the isolate is

Susceptible

Add a

Fluoroquinolone

And an injectable

Drug based on

susceptibilities

Fluoroquinolones

Levofloxacin

Moxifloxacin

Injectable agents

Amikacin

Capreomycin

Streptomycin

Kanamycin

PLUSOne of

these

One of

these

First-line drugs

Pyrazinamide

Ethambutol

PLUS

Step 2 Pick one or more of these

Oral second line drugs

Cycloserine

Ethionamide

PAS

Add 2ndline drugs until

you have 4-6 drugs to

which isolate is

susceptible (which have

not been used previously)

BS


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Standardized PMDT Treatment Regimens

Z-Eto-Lfx-K-Cs/ Z-Eto-Lfx-Cs Kanamycin Resistance:

Change to Capreomycin

Fluoroquinolone Resistance: Add PAS

High dose Levofloxacine

Resistance to both Kanamycin and Fluoroquinolone:

Change to Capreomycin

add PAS

High dose Levofloxacine

Source : Indonesia MoH


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Outline


Outcome

Data on MDR and XDR - TB

Current MDR-TB diagnosis





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Struktur Organisasi Tim TB

RSHSDIREKTUR UTAMA

dr. H. Bayu Wahyudi, MPHM, Sp.OG

DIREKTUR MEDIK

dr. Rudi Kurniadi Kadarsyah, Sp.An, MM, M.Kes

KETUA

Arto Yuwono Soeroto, dr., SpPD-KP, FCCP

DEWAN KONSULTAN

SEKRETARIS

Iceu Dimas Kulsum, dr., SpPD

UNIT TB-HIVUNIT DOTS UNIT TB-MDR

Koordinator

Dedy Suyanto, dr.

Iceu Dimas Kulsum, dr., SpPD

Sasmayani Eko Winanti, dr., SpP

Diah Asri W, dr., SpA

Basti Andriyoko, dr., SpPKLeny Santani, dr., SpRad

PPDS

Koordinator

Rudi Wicaksana, dr., SpPD, KPTI

Medis RR Farmasi KIE

Rini Rahmawati, AMK

H. Darsito, AMK

Lies Ratnasari, SST

Dina

Ilham

Rina Yovita, dr., SpPD

Iceu D. Kulsum, dr., SpPD

Sasmayani E. Winanti, dr., SpP

Novita, dr.Intan Meilana, dr.

Mery Lestari, dr.

PPDS

Medis RR Farmasi KIE

Sigit, AMK

Dian HU, Skep, Ners.

Lies Ratnasari, SST

Nunung Nuraeni

Lia

Ega

Nirmala, dr.

Koordinator

Prayudi S, dr., SpPD-KP, M.Kes, FCCP

TAK

PPDS

Medis Paramedis RR Social Workers

Ii Sariningsih, AMK

Iis Nurhayati, AMKDedi Rahmadi, AMK

Lies Ratnasari SST

Dedi Rahmadi, AMK

TAK (Tim Ahli Klinik) Tim Multidisipliner

Arto Y. Soeroto, dr.,SpPD-KP, FCCP

Dr. Emmy HP, dr., SpPD-KP, KIC

Edi Sampurno, dr., SpP, MM

Yana Ahmad S, dr., SpPD-KPPrayudi S, dr., SpPD-KP, M.Kes, FCCP

Iceu D. Kulsum, dr., SpPD

Sasmayani E. Winanti, dr., SpPDedy Suyanto, dr.

Tri Wahyu, dr., SpBTKV

Dolvy Girawan, dr., SpPD-KGEH

Rudi Supriyadi, dr., SpPD-KGH

Nani Nathalia, dr., SpPD-KEMDIndra Wijaya, dr., SpPD

Leny Santari, dr., SpRad

Dominica, dr., SpMLucky, dr., SpKJ

Lina Lasminingrum, dr., SpTHT

Eppy Darmadi Ahmad, dr., SpOG(K)

Ahmad Rizal, dr., SpSBasti Andriyoko, dr., SpPK

Yunita Damopolii, dr., SpKK, M.Kes

KNCV

Lab. Kes. Propinsi

Farmasi

Yulia Setiawati, dra., Apt.

Ilham

Prof. Dr. Zulkarnain Dahlan, dr., SpPD-KP

Prof. Cissy B Kartasasmita, dr., SpA(K), PhD

Prof. Ida Parwati, dr., SpPKRista D. Soetikno, dr., SpRad(K)

Edi Sampurno, dr., SpP, MM


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MDR TB Unit Hasan Sadikin Hospital


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HASAN SADIKIN GENERAL HOSPITAL

Isolation Ward/ICU 25 beds for pulmonary TB

6 beds for MDR TB

4 beds for critical TB Patients (ICU)

Clinics 1 TB DOTS clinic

1 TB-HIV clinic

2 MDR clinics- 1 Pre conversion MDR TB patients

- 1 Post conversion MDR TB patients


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RAPAT TIM AHLI


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RAPAT TIM AHLI


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RUANG RAWAT TB-MDR


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POLI TB-MD


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POLI TB-MD


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POLI TB-MDR


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Mostly MDR TB patients are treated ambulatory from the beginning,unless

Psychiatric problems

Pneumonia, pneumothorax, lung abscess, pleural effusion

Severe liver disorder

Thyroid diseases

Renal insufficiency

Electrolyte imbalance

Severe malnourished

DM uncontrolled Malabsorbstion

Severe/ multiple comorbidities

No family support

(WHO 2011)

d k l l


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Hasan Sadikin Hospital Interim Result

(April 2012March 2013)

n Percentage

Screened (GeneXpert) 361 100

MDR TB 117 32.4

XDR TB 8 6.8

Treated 87 74.4

Conversion 26 33.4

Reversion 0 0

Died 12 15.7

Cure Data is not available yet

Treatment Completed Data is not available yet


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DST Result Jan 2012March 2013


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Expensive and

toxic drugs arenecessary


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Side Effect n Percentage

Nausea + vomiting 67 77

Dizziness 32 36.8

Arthralgia 21 24.1

Anorexia 12 13.8

Electrolyte imbalance 11 12.6

Anxietas + sleep disturbances 8 9.2

Tinnitus and hearing disturbances 6 6.9Peripheral neuropaty 5 5.7

Psychosis 5 5.7

Allergic reaction 4 4.6

Depression 3 3.4

Diarrhea 3 3.4

Visual disturbance 2 2.3

Erectile disfunction 2 2.3

hypothyroidism 2 2.3

Concentration disturbance 1 1.2

Global Policy: MDR TB and XDR TB


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Global Policy: MDR-TB and XDR-TB

1. Strengthen basic TB control, to preventM/XDR-TB

2. Scale-up programmatic management andcare of MDR-TB and XDR-TB

3. Strengthen laboratory services for adequate andtimely diagnosis of MDR-TB and XDR-TB

4. Ensure availability of quality drugs and theirrational use

5. Expand MDR-TB and XDR-TB surveillance

6. Introduce infection control, especially in high HIVprevalence settings

7. Mobilize urgently resources domestically andinternationally

8. Promote research and development into new

diagnostics, drugs and vaccines


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Studies (ongoing and future)

at Hasan Sadikin Hospital MDR TB Patients

Validity of GeneXpert

Risk Factors analysis for MDR TB development

Vitamin D in MDR TB patients

Cytokines in MDR TB patients

Gene Polymorphisms in MDR TB Patients


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Nobody wants me around..


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THANK YOU

tata laksana tb mdr dr. prayudi

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