treatment tb
DESCRIPTION
tb, anakTRANSCRIPT
Treatment TB In Children
HMS Chandra KusumaPediatric Departement Of Fac. Med.
Brawijaya Univ.Saiful Anwar General Hospital
TB treatment outline•TB therapy•TB tracking•TB prophylaxis•TB prevention – BCG•Other aspects
Objectives of TB therapy• Rapid reduction of the bacilli number, to
cure the patient• ‘Sterilization’ to prevent relapses
to achieve two phases: Initial phase (2 months) – intensive, bacilli
eradication Maintenance phase (4 months / more) – ‘sterilizing’
effect, prevent relaps
• Prevention of acquired drug resistance,to achieve: principles of therapy
Ped TB therapy principles
Multi drug, NOT single drug (monotherapy) to prevent drug resistance risk of fall and rise phenomenon each TB drug has specific action to certain
TB bacilli population Long term, continue, uninterrupted
problem of adherence (compliance) The drug is taken daily and regularly
Smear +Culture +
Smear -Culture +
Smear -Culture -
108
107
106
105
104
103
102
101
100
Start of treatment(isoniazid alone)
Weeks of treatment0 3 6 9 12 15 18 WHO 78351
Sensitive organisms Resistant organisms
Nu
mb
er o
f b
acil
li p
er m
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f sp
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Toman K, Tuberculosis, WHO, 1979
The ‘fall and rise’ phenomenon
Hypothetical model of TB therapy
A
BC
Bacteridal activity & ‘sterilizing’ effect
0 1 2 3 4 5 6
Pop A = rapidly multiplying (cavity)
Pop B = slowly multiplying (acidic)
Pop C = sporadically multiplying (caseum)
Pop D = dormant, not multiplying
Months of therapy
D
TB bacilli populationLocation
cavity,extra cell
intra macrophag
e
caseous mass
TB population
A B CTB amount 107 - 109 105 - 106 103 – 104
metabolism & replication
active / rapidly
slowly sporadic / intermitte
nt acidity (pH) neutral /
baseacid neutral
most effective drug (consc’ly)
INH, RIF,ETB
PZA, RIF, INH RIF, INH
DrugsDaily dose
(mg/Kg/day) Adverse reactions2 Time/week
dose(mg/Kg/dose))
Isoniazid(INH)
5-15(300 mg))
Hepatitis, peripheral neuritis,hypersensitivity
15-40(900 mg))
Rifampicin(RIF)
10-15(600 mg))
Gastrointestinal upset,skin reaction, hepatitis, thrombocytopenia,
hepatic enzymes, including orangediscolouraution of secretions
10-20(600 mg)
Pyrazinamide(PZA)
15 - 40(2 g)
Hepatotoxicity, hyperuricamia,arthralgia, gastrointestinal upset
50-70(4 g)
Ethambutol(EMB)
15-25(2,5 g)
Optic neuritis, decreased visualacuity, decreased red-green colour
discrimination, hypersensitivity,gastrointestinal upset
50(2,5 g)
Streptomycin(SM)
15 - 40(1 g)
Ototoxicity nephrotoxicity25-40(1,5 g)
When INH and RIF are used concurrently, the daily doses of the drugs are reduced
National consensus of tuberculosis in children, 2001
Dosage of antituberculosis drug
TB therapy regimen 2 mo 6 mo 9 mo 12mo
INHRIFPZA
ETBSM
PREDDOT.S !
Corticosteroid
• Anti inflammation • prednison : oral, 1-2mg/kgBW/day, tid
2-4 weeks, tap off• Indications :
– Miliary TB– Meningitis TB– Pleuritis TB with effusion
Therapy problems (1)• The main : adherence / compliance• The factors :
– Long term treatment– Many drugs (tablets, powders, syrups)– Costly– Drug side effects– Initial improvement – misinterpreted by parents– Inconvenient health service– Socio-economic-cultural factors
• Lead to interrupted therapy or discontinuation drug resistance therapy failure
Therapy problems (2)• The other : monotherapy • the doctor factor:
– misuse of TB drug: other indications
• the patient factor:– too many drugs (tablets, powders, syrups)– limited fund– drug side effects
• Lead to mono-therapy drug resistance therapy failure
Therapy problems scheme
adherence
interrupted
discontinuation
patient
mono therapy
doctor
MDR TB
therapy failure
NTP failure
Therapy problem solutions
• DOTS : Directly Observe Treatment Short-course
• FDC : Fixed Dose Combination i.e. >2 drugs in one tablet / capsule in a fixed dose formulation
TB drugs & pharmaceutical formulation
Isoniazid (H)
Rifampicin (R)
Pyrazinamide (Z)
Ethambutol (E)
monosubstance
combi-packs
fixed dose comb
Combipack drugs two or more separate drugs put in one pack
FDC with IDAI formulation
fixed dose fixed dose combinationcombination
Fixed Dose Combination
FDC: >2 drugs in one tablet in a fixed dose formulation
• simple dosing• patient friendly, doctor friendly• increase adherence• reduce MDR• easier drug supplying• easier drug monitoring
FDC tablet formulation
WHO• H : 30 mg• R : 60 mg• Z : 150 mg
IDAI• H : 50 mg• R : 75 mg• Z : 150 mg
WHO FDC (H/R/Z:30/60/150 & H/R:30/60)
BW(kg)
Intensive, 2 mo(tablet)
Continuation, 4 mo(tablet)
<7 1 1
8-9 1,5 1,5
10-14 2 2
15-19 3 3
20-24 4 4
25-29 5 5
IDAI FDC (H/R/Z:50/75/150 & H/R:50/75)
BW (kg)
Intensive, 2 mo
(tablet)
Continuation, 4 mo(tablet)
5-9 1 1
10-19 2 2
20-33 4 4
Note: BW < 5kg should be referred and need tailored dosing
WHO vs IDAI fdc formulation• WHO:
– INH: 4-6 mg/kgBW– BW grouping: too many– not practical – hard to remember– a gap for BW 30-33 kg
• IDAI– INH: 5-10 mg/kgBW– simple BW grouping – more friendly both for doctor and patient
Therapy evaluation
•Clear improvement in clinical and supporting examination, especially in the first 2 month
•Main : clinical•supporting exam as
adjuvant
Therapy evaluation• Clinical improvement :
– Increased body weight – Increased appetite– Diminished / reduced symptoms (fever,
cough, etc)• Supporting examination :
– Chest X rays : 2 / 6 month (on indication)
– Blood : BSR – Tuberculin test : once positive, do not
needed to repeat !
Therapy failure
• Inadequate response, despite adequate therapy :– Review the diagnosis, not a TB case ?– Review other aspects : nutrition,
other disease– MDR – rarely in children
• Treatment discontinuation
TB treatment outline•TB therapy•TB tracking•TB prophylaxis•TB prevention – BCG•Other aspects
Transmission rate (Shaw ’54)
adultTB patient
AFB(+) AFB(-)culture(+)
culture(-)CXR (+)
65% 26% 17%
TB tracking
Child TBpatient
Adult TB patient
centri-petal
centri-fugal
TB tracking (case finding)
centripetal• trace the
source • adult people• close contact• by chest X ray
centrifugal• trace other
‘victims’• children• close contact• by tuberculin
TB treatment outline•TB therapy•TB tracking•TB prophylaxis•TB prevention – BCG•Other aspects
TB classification (ATS/CDC modified)
Class Contact Infection Disease Treatmen
t
0 - - - -
1 + - - proph I
2 + + - proph II?
3 + + + therapy
Primary prophylaxis• to prevent TB infection in TB Class 1
person• exposure (+), infection (-) tuberculin
negative• drug: INH 5 - 10 mg/kgBW/day• as long as contact take place, the source
should be treated• at least for 3 months• repeat TST:
– negative: success, stop INH– positive: fail, become TB Class 2 continue as
2nd proph
Secondary prophylaxis• to prevent TB disease in TB Class 2 person
(exposure (+), infection (+), disease (-)• and person with tuberculin conversion• certain high risk population
– under five, puberty– long term use of steroid– malignancy– certain infection: morbili, pertussis
• drug: INH 5 - 10 mg/kgBW/day• during the higher risk of TB disease
development: 6-12 month
TB treatment outline•TB therapy•TB tracking•TB prophylaxis•TB prevention – BCG•Other aspects
Prevention
• socio-economic improvement
• BCG immunization• chemoprophylaxis (1st & 2nd)• ‘therapy’
BCG immunization• mimicking the TB pathogenesis with
attenuated TB bacilli • without hematogenic spread and/or
without establishment of remote foci• CMI (+) DTH (+) TST (+) • older neonate (>2 month not vaccinated)
TST first• mass immunization : BCG without TST first• accelerated BCG reaction: help the
screening
TB treatment outline•TB therapy•TB tracking•TB prophylaxis•TB prevention – BCG•Other aspects
Other aspects
nutrition improvementprevent / search & treat other disease(s)
Thank you
FDC’s advantages NTP
success
MDR chanceprevent
monotherapy
FDC
simple manageme
nt
increase adherence
simple treatmen
t
single drug supply
WHO FDC dosage range (60/30/150)BW(kg)
Initial (2mo
)
Cont (4mo
)
Dosage range
<7 1 1 R:9-20mg,H:4-10mg,Z:21-50mg
8-9 1,5 1,5 R:8-9mg,H:5-5,6mg,Z:19-22mg
10-14 2 2 R:11-12mg,H:4,3-6mg,Z:21-30mg
15-19 3 3 R:9,4-12mg,H:4,3-6mg,Z:16-30mg
20-24 4 4 R:10-12mg,H:5-6mg,Z:25-30mg
25-29 5 5 R:10,3-12mg,H:5-6mg,Z:15-30mg
IDAI FDC dosage range (75/50/150)
BW (Kg)
Initial (2 mo)
Cont (4 mo)
Dosage range
5-9 1 1 R:8,3-15mgH:5-10 mgZ:15-30
10-19 2 2 R:7,9-15mgH:5-10mgZ:15-30mg
20-33 4 4 R:9-15mgH:6,7-10mgZ:18-30mg