Upload
dea
View
286
Download
0
Embed Size (px)
Citation preview
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
1/58
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
2/58
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
3/58
3
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
4/58
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
5/58
5
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
6/58
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
7/58
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
8/58
8
Causes of DR
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
9/58
9
Causes of MDR
Patient mismanagement
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
10/58
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
11/5811
Result Indonesia PMDT 2009 and 2010 cohorts
Source : Register TB MDR Subdit TB MoH
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
12/58
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
13/58
DRUG RESISTANCE
MECHANISM
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
14/58
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
.
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
15/58
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
16/58
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
17/58
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.wmv8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
18/58
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
http://localhost/var/www/apps/conversion/tmp/scratch_1/Selection%20Pressure.wmvhttp://localhost/var/www/apps/conversion/tmp/scratch_1/Selection%20Pressure.wmv8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
19/58
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
http://localhost/var/www/apps/conversion/tmp/scratch_1/Selection%20Pressure.wmvhttp://localhost/var/www/apps/conversion/tmp/scratch_1/Selection%20Pressure.wmv8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
20/58
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
21/58
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.wmv8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
22/58
22
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
23/58
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
24/58
GeneXpert
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
25/58
25
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
26/58
Sensitivity 94.4% and Specificity 98.3%
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
27/58
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
28/58
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
29/58
29
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
30/58
30
2000
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
31/58
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
32/58
Adults and adolescent
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
33/58
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)
1520 mg/kg daily 500750 mg 1000 mg 1000 mg
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
1520 mg/kg daily 500 mg 750 mg 7501000 mg
PASER (4G sachets) 150MG/KG DAILY 8 g 8 g 8 -12 g
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
34/58
34
Recommendation for MDR-TB Drug Regimen
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
35/58
WHO 2011 update
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
36/58
Step 1
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
37/58
37
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
38/58
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
39/58
39
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
40/58
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
41/58
MDR TB Unit Hasan Sadikin Hospital
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
42/58
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
43/58
RAPAT TIM AHLI
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
44/58
RAPAT TIM AHLI
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
45/58
RUANG RAWAT TB-MDR
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
46/58
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
47/58
POLI TB-MD
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
48/58
POLI TB-MD
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
49/58
POLI TB-MDR
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
50/58
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
51/58
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
52/58
DST Result Jan 2012March 2013
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
53/58
53
Expensive and
toxic drugs arenecessary
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
54/58
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
55/58
55
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
56/58
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
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
57/58
57
Nobody wants me around..
8/14/2019 Tata Laksana Tb Mdr Dr. Prayudi
58/58
THANK YOU