Penatalaksanaan

Tuberkulosis Resisten
Obat pada Anak
 Outline

Epidemiologi Tuberkulosis
Tipe Resistensi Obat pada Anak
Definisi
Diagnosis TB MDR pada anak.
Terapi TB MDR anak
Tatalaksana kontak TB MDR

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Epidemiologi
 Epidemiologi Tuberkulosis
Tuberkulosis (TB) : masalah kesehatan utama di dunia.
Tahun 2010 :sekitar 8,8 juta insiden kasus TB baru di
dunia.
Dari 12 juta prevalen kasus TB : sekitar 650.000 MDR.
Oktober 2011 : dilaporkan Extensively drug-resistant
TB
Lebih dari 50% strain MDR TB : Resistensi terhadap
ethambutol, pyrazinamid dan oxloxacin
Data TB MDR anak : ? (perkiraan jumlah TB anak
sekitar 10-20% kasus TB MDR dewasa)

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INT J TUBERC LUNG DIS e-publication ahead of print 8 May 2012 2012
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INT J TUBERC LUNG DIS e-publication ahead of print 8 May 2012 2012
Tipe Resistensi Anak
 Definisi
Monoresisten
Resisten terhadap isoniazid ATAU
rifampisin
Multidrug resisten (MDR)
Resisten terhadap isoniazid DAN
rifampisin
Extensively drug resisten (XDR)
MDR + resisten terhadap fluoroquinolon
dan salah satu obat injeksi lini kedua
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 Tipe Resistensi Pada Anak
Resistensi obat pada pasien TB : mutasi
genetik spontan pada genom MTB
Mutasi berhubungan dengan bacillary load
jaringan yang sakit.
Resistensi :
Regimen obat yang tidak adekuat
Tidak patuh pengobatan
TB MDR pada anak.
Transmisi kuman kebal obat dari kontak erat
Riwayat pengobatan sebelumnya
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Diagnosis MDR TB Anak
 Diagnosis TB MDR pada
anak.
Tidak ada obat baru maupun uji diagnostik
baru yang berhasil dikembangkan.
Diagnosis utama TB : kultur dan
pemeriksaan mikroskopis.
Kultur butuh waktu lama : keterlambatan
dalam diagnosis dan terapi.
Perlu alternatif uji diagnostik lain : nucleic
acid amplification test (NAATs)

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 Diagnosis TB MDR pada anak

Masalah diagnosis TB anak

Pausibasilar
Sulitnya memperoleh spesimen
Diagnosis TB MDR anak
Kejelian melihat gejala klinis dan
pemeriksaan penunjang

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 Kriteria tersangka MDR TB anak
1.Riwayat pengobatan dalam 6-12 bulan sebelumnya
2.Kontak erat dengan pasien yang telah diketahui MDR
3.Kontak erat dengan pasien yang meninggal karena TB, pengobatan TB gagal
atau yang tidak berobat teratur
4.Tidak menunjukkan perbaikan klinis setelah 2-3 bulan terapi TB lini pertama
(menetapnya gejala, hapusan BTA dan kultur tetap positif)

Ya Tidak

Penilaian klinis dan diagnostik TB Lanjutkan evaluasi untuk tersangka

MDR termasuk rapid test TB

Konfirmasi TB MDR Konfirmasi TB sensitif Tidak ada konfirmasi

Terapi MDR Terapi TB katagori anak

Petunjuk Juknis Managemen TB anak 2013 17

 Approach to diagnose TB in
children (WHO)
1. Careful history
a. includes history of TB contact
b. symptoms suggestive of TB
2. Clinical examination
includes growth assessment
3. Tuberculin skin test
4. Bacteriological confirmation whenever possible
5. Investigations relevant for suspected PTB or
suspected EPTB
6. HIV testing
World Health Organization 2014 18
 Approach to diagnose MDR TB
in children
1. Careful history
History of contact with MDR TB case is critical information
Consider in child failing first-line TB treatment despite
adherence
2. Clinical examination
3. Investigations relevant for suspected PTB or EPTB
Important to try to get samples for culture and DST
4. HIV testing
Failure to respond to TB treatment should consider HIV-related
lung disease that is not TB as well as the possibility of MDR TB
5. Bacteriological confirmation and drug susceptibility testing
whenever possible
Sputum (or other relevant samples e.g. lymph node aspiration)
should be collected in all children with suspected MDR TB for
culture with drug sensitivity testing (or LPA or Xpert MTB/RIF)
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 Practice points: diagnosis of MDR
TB in a child (WHO)

Confirmed DR TB is a laboratory diagnosis :

culture with DST or nucleic acid amplification
test (e.g. Xpert MTB/RIF)
Probable DR TB is diagnosed in a child with TB
and a recent close contact with DR TB
Suspected DR TB is when a child fails to improve
while adherent to first-line anti-TB treatment OR
if the adult source case is a treatment failure, a
retreatment case or recently died from TB

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Criteria for Suspected MDR-TB
History of previous treatment within the past 6-12 months
Close contact with a person known to have MDR-TB, including household and school contacts
Close contact with a person who has died from TB, failed TB treatment, or is non-adherent to TB
treatment
Failure to improve clinically after 2-3 months of first-line TB treatment, including persistence of
positive smears or cultures, persistence of symptoms, and failure to gain weight (radiological
improvement is frequently delayed)

Yes No Continue evaluation for

susceptible TB
Clinical assessment and MDR-TB
diagnostic work-up including sputum,
rapid tests, fluid sampling, biopsy

Results of diagnostic workup available No

Yes
Clinically stable without Clinically unstable with
concerning signs or concerning signs and
MDR-TB MDR-TB No diagnosis
symptoms symptoms present
confirmed confirmed confirmed

Await diagnosis and Consider empiric

Treatment First-line TB monitor closely MDR-TB therapy while
based on DST treatment awaiting diagnosis
The Sentinel Project on Pediatric
Drug-Resistent Tuberculosis dan USAID
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 Case Examples: Suspected MDR-TB in
a Child
Antonio is a 7-year-old boy with 3 weeks of fever,
cough, and a swollen right knee.
Antonios mother died last month. They say it was
from TB, but I do not know. She took her TB medication
every single day with the nurse watching her.
Has received all his recommended vaccinations.
On examination, pale and listless, 390C and his weight
is only 16 kg
He has cervical lymphadenopathy, right upper lobe
crackles on pulmonary exam, and examination of the
right knee shows a large effusion.

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 Case Examples: Suspected MDR-TB in
a Child
Concerned about the possibility of MDR-TB, given that his
mother died of TB while on first-line DOT.
Antonio is clinically stable with no immediate indication
to start empiric MDR-TB treatment.
He provides sputum for smear and culture, and a sample
of his knee fluid is sent to the lab for analysis as well.
All sample results are negative when his father brings
him back to the clinic with a temperature of 40.50C and
in respiratory distress.
Given his clinical instability and risk factors for MDR-TB,
you start him on an empiric MDR-TB regimen. MDR-TB is
never confirmed.

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 Key Points
A high index of clinical suspicion is needed for
timely diagnosis of MDR-TB in children.
Risk factors include a history of previous
treatment, failure to improve on first-line TB
treatment, known MDR-TB contact, contact with a
patient who died on TB treatment or failed TB
treatment.
Empiric treatment should be considered based on
the DST of the contact or based on DST results
from the childs own specimens (if available).
Early initiation of appropriate treatment is
essential to ensure good outcomes
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Diagnosis and management of MDR
TB in a child
(WHO)
Children with suspected MDR TB should
ideally be referred to a facility that can do
culture and drug susceptibility testing -
usually a tertiary facility
Hospitalisation is usually required for
treatment because it includes injectables
Follow-up and management of adverse events
should ideally be managed by experienced
paediatrician at tertiary level

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 Practice points: management
of MDR TB (WHO)
All children with suspected MDR TB should be
referred
Never add a single drug to a failing regimen
Treat according to DST results from child or from
likely source case (if results from child not available)
Give at least 3 drugs, preferably 4, to which patient
or adult source case is susceptible All treatment
daily and under direct observation
Caregivers need counselling and support regarding
adverse effects, treatment duration and adherence
Careful monitoring for clinical response and adverse
events
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Approach to treatment of MDR
TB in children (WHO)
1. Choice of treatment will be influenced by availability
of DST in child or contact, and drug resistance
surveillance in a particular setting
2. Minimum of 4 active drugs if extensive pulmonary or
disseminated disease
3. Start with first-line drugs to which DST results show
susceptibility (e.g. ethambutol, PZA)
4. Add an injectable (e.g. amikacin)
5. Add fluoroquinolone (e.g. levofloxacin or
moxifloxacin)
6. Duration 18 months limited evidence
7. Hospitalisation for 4-6 months for injectable
8. DOT by health worker
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 Terapi TB MDR anak
Prinsip dasar terapi TB MDR anak sama
dengan MDR TB dewasa.
Terapi sebaiknya berdasarkan hasil uji
kepekaan obat.
Ketika uji kepekaan obat tidak tersedia maka
terapi sebaiknya berdasarkan hasil uji
kepekaan obat sumber kasus.
Jika tidak ada hasil uji kepekaan obat dan
anak gagal terapi maka keputusan terapi
berdasarkan pola uji kepekaan obat strain
MDR di daerah yang bersangkutan.
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 Terapi TB MDR anak

Dosis yang tidak tersedia dalam formula pediatri

masalah under dosis atau over dosis
Anak tidak dapat mentoleransi cycloserine
(neuropsikiatri) dan ethionamide (diare dan
muntah).
Jumlah obat banyak ketidakpatuhan dan
putus obat.
Efek samping lebih besar pada anak-anak
monitor klinis dan laboratorium

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 Terapi TB MDR anak

Lama terapi TB MDR anak yang optimal juga

belum diketahui.
Rekomendasi WHO: lama terapi 18 bulan setelah
kultur negatif yang pertama, sedangkan untuk
XDR TB lama terapi 24 bulan setelah kultur
negatif yang pertama.
TB anak seringkali bersifat pausi baciller : lama
terapi disesuaikan lama terapi TB MDR dewasa.
Lama terapi fase intensif (ketika obat injeksi
digunakan) paling sedikit 6 bulan.

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Tabel . Obat yang digunakan dalam terapi TB
MDR anak.

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 Duration treatment : 6 - 34
months,
Duration follow-up : 12 -37
months.
The pooled estimate for
treatment success was 81,67%
(95% CI 72, 5490,80).
Died : 5,9% (95% CI 1,310,5)
Default : 6,2% (2,310,2)
Adverse event : 39,1% (28,7
49,4)
The most common adverse
events : nausea , vomiting.
Serious adverse events :
hearing loss, psychiatric eff
ects, and hypothyroidism.
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 CASE REPORT
N//13 yo admitted to ED
of Dr. Soetomo Hospital March 10th 2014

ANAMNESIS
Chief complaint : shortness of breathing and
longstanding cough

Decreased her appetite and she never

gained weight since last 2 years
 ...case report
October 24th 2012
October 24th 2012 was
diagnosed as pulmonary TB in
RSUD Jombang got intensive
phase FDC childood TB
Continue treatment at PHC
Simo Surabaya and show
improvement clinicaly
February 2014
Coughing, subfebrile,
wasting OAT from GP:
Rifampicin 300mg
INH 200mg
Ethambutol 500mg
May 8th 2013
10 March 2014
Completed her treatment
Condition worsening came to
lose apetite, bodyweight not
Dr. Soetomo Hospital ED
increased , and chest X-
Hospitalized in Pediatric Ward
raysno improvement
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 ...case report

Figure 1.Chest Xray examination after

completing anti-tuberculosis treatment in The
Puskesmas Simo
 ...case report

BIRTH AND SOCIAL HISTORY

IMMUNIZATION
Father had
HISTORY
diagnosed as
Born at a hospital pulmonary TB in
fullterm, BW2800g, January 2014, chest
BL49 cm, SC, didnt X-rays
spontaneously cry. miliaryTBantiTB
treatment.
Complete
Home village
immunization
crowded and
Breastfed18 minimal ventilation
months.
...case report

Fig.2 C Xrays of Her father and patients home village

...case report
PHYSICAL EXAMINATION

Alert BP 100/60 mm Hg, P 114 x/m, RR 36x/m,

temperature of 37.6 0C
Weakness of general condition
Heart was normal
Dim on percussion and decreased breath
sounds on left, wet crackles on both
Abdomen was flat and normal bowel sounds
Extremities was warm, dry, red and no edema
...case report
Nutritional
status
Bodyweight : 20kg
Height : 136,5cm
IBW : 32kg
% of IBW : 62%
...case report

AFB I,II : positive

TST : positive induration
20mm
DST : not yet revealed
Sputum culture : Streptococcus
acidonimus
Gene X-pert* : positive, rifampicin resistant
...case report
Chest X-ray

fibroinfiltrat on
both lung
Multiple cavitary in
the left lung field
Left lung field was
closed by
opacification
Tracheal deviation
to the left side.
...case report

MSCT
fibroinfiltrat on right
lung
Multiple bullae in the
left lung
Thickening of pleura
at upper right lung
and whole left lung
Retraction of trachea,
heart and major blood
vessels to the left
...case report

Based on :
Clinical manifestations
Laboratory examinations
Imaging (chest X-rays and MSCT)

Diagnosis :
Pulmonary MDR-TB + Destroyed Lung + Severe
malnutrition
Temperature Body
(o C) weight
(kg)
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T
BW
Patient 20
discharged
daily follow-up
at MDR clinic
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Labora
Laborator Hb 12.3 Hb 12.2 Hb 13.2
y result WBC 11100 WBC 13500 WBC
PLT 483000 PLT 588000 8050
ESR 120 PLT
419000
Microbiol 1st AFB 2nd AFB Sputum GeneXpert MTB
ogy stain(+) stain(+) culture: (+)
examinati TST S. Blood culture (-)
on induration Acidominim Sputum culture
20 mm us (-)
(Sensitive to
:
PCN G,
CAM,
OXA, LVF)

Therapy Intensive Intensive Intensive Planned for MDR MDR TB MDR TB

phase OAT + phase (HRZE phase TB treatment treatmen treatment 47
steroid: + steroid) (HRZE + KAN 1x350 mg t
Tatalaksana Kontak MDR
TB
 Management of child contact
of DR TB case (WHO)
Identification and symptomatic screening of all
contacts of DR TB cases is important
Symptomatic contacts require evaluation for
possible TB
Investigation of symptomatic contacts should
include sputum for culture and drug sensitivity
(or LPA or Xpert MTB/RIF)
Asymptomatic contacts need to be followed and
informed that prompt evaluation is required
should symptoms develop

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 Management of child contact
of DR TB case
There is very little evidence and no agreed consensus
on the use of or optimal regimen for preventive
therapy for asymptomatic contacts of drug resistant
TB cases
One approach is not to provide any preventive therapy
and opt for careful, regular follow-up informing the
contact about possible symptoms of TB and that
prompt evaluation is needed if symptoms develop
An alternative approach, especially for high-risk
contacts such as HIV-infected or young children, is to
choose a preventive therapy regimen that includes at
least two drugs to which the DR TB index case is
susceptible or nave and treat for at least 6 months
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The Sentinel Project on Pediatric
51
Drug-Resistent Tuberculosis dan USAID
 Case Example: Contact
Lelethu is a 2-year-old girl who is a known contact of
someone with MDR-TB.
The person with MDR-TB is her uncle who lives in the
same house as her but sleeps in a separate room.
He had been treated with first-line therapy for 5 months
before being diagnosed with MDR-TB and has been
coughing for months.
He has now been on MDR-TB treatment for 2 months and
is feeling much better. He is still getting injections daily
from the clinic.
Had 3+ sputum smear-positive microscopy, and his TB is
resistant to INH and RIF but susceptible to OFX, AMK and
THA.

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 Lelethu is very well , she is not coughing and has no fever or
sweating.
She seems to be growing very well along the 25th percentile.
Clinical examination is completely normal.
She should receive some MDR-TB preventive treatment. In a pilot
program in the Western Cape of South Africa, the program advises
giving INH at high dose (15-20mg/kg), EMB (20-25mg/kg), and OFX
(15-20mg) daily for 6 months.
The HIV test is negative.
Monitor every month to measure her weight, check how she is
getting on with the medications, and to ask if there are any
problems.
She takes her prophylactic medications for 6 months, and at the
twelfth month, she is still fit and well. Her weight and height have
increased.

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 Identitas
Nama : FP
Jenis kelamin: Perempuan
Tanggal lahir : 10 Oktober 2013
Alamat : Banyu urip wetan
Orangtua : Tn. N (alm, HIV+)
Ny. NA (HIV+ dan MDR TB)
Anak ke 3 dari 3 bersaudara
 17 Juli 3 Sept
10 Okt 13 Feb 14 22 Mei 14
Sept 13 14 14
13 (4 bln) (7 bln)
(9 bln) (11 bln)

Ayah By F lahir Ke Poli BB 7,9 BB 8 kg/

Respirologi anak BB 8,4
HIV + , SC ai kg/ 66 cm 69 cm
pro BCG kg/71 cm
29 BIHA Mtx test Klinis: baik
BB 5.8 kg/ 62 cm Cek HIV
Sept 13 BBL indurasi Lab: Hb 12/
Ro Thorax: timus 3
meningg 2700 g/49 13 mm Leuko 6700/
hipertropi metode
al cm Tx: KDT Tr 232.000/
Klinis anak baik hasil:
Ibu Tx: ARV anak (fase Hct 35/ LED
Ibu MDR TB non
hamil 9 profilaksis intensif) 5/ SGOT 42/
(resisten INH dan reaktif
bulan : ZDV, 1x1 tab SGPT 40/
Rif) mulai evaluasi
HIV + 3TC, NVP 2 mgg lagi BUN 15/ SK
terapi OAT 3 bln lagi
dan selama 6 BB > 8 kg 0,4 / Thorax
Mtx test OAT:
mulai mgg KDT 1x 2 : tdk ada
indurasi 0 mm KDT
ARV kmd tab proses
diberikan BCG anak fs
Cotrim spesifik
tidak ada reaksi lanjutan
profilaksis OAT: KDT
cepat BCG Pdx: 1x 2 tab
Anak fase
Mtx ulang 3 bln lg (bulan ke
lanjutan 1x 4)
Tx: INH 1x 20 2 tab
mg/kg/hari
 13 Feb 14 (4
10-10-13 17 Juli 14 (9
bln)
Lahir bln)
BB 5,8 kg/62
BB 2,7 kg/49 BB 8kg/69 cm
cm
cm 22 Mei 14 (7 3 Sept 14
bln) (11bln)
BB 7,9 kg/66 BB 8,4kg/71
cm cm
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