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Treatment of TB in children
How many drugs?
Which drugs?
Duration of treatment?
Principles of antituberculosis
therapy
 Goal of treatment- to cure the child and to
prevent from relapse of the disease during
life-time
To reach the goal - theoretically eradication of
all mycobacterial populations
Principles of antituberculosis
therapy
Activities of antituberculosis drugs
 Bactericidal
 Sterilizing
 Prevention of drug resistance to companion
drugs.
Activities of antituberculosis drugs
 BACTERICIDAL ACTIVITY.
H> S> R> E> Z
 STERILIZING ACTIVITY.
R >Z> H> S> E
 PREVENTION OF DRUG RESISTANCE TO
COMPANION DRUGS.
H> R> E> S> Z.
Antituberculosis drugs
Grouping Drugs
Group 1
First line oral agents
isoniazid (H); rifampicin (R);
ethambutol (E);
pyrazinamide (Z);Rifabutin (Rfb)
Group 2
Injectable agents
kanamycin (Km); amikacin (Am);
capreomycin (Cm); streptomycin
(S)
Group 3
Fluoroquinolones
moxifloxacin (Mfx); levofloxacin
(Lfx);
ofloxacin (Ofx)
Antituberculosis drugs
Group 4
Oral bacteriostatic secondline
agents
ethionamide (Eto); prothionamide
(Pto);
cycloserine (Cs); terizidone (Trd);
paminosalicylic
acid (PAS
Group 5
Agents with unclear efficacy
(not recommended by WHO
for routine use in MDR-TB
patients
clofazimine (Cfz); linezolid (Lzd);
amoxicillin/clavulanate (Amx/Clv;
thioacetazone (Thz);
imipenem/cilastatin
(Ipm/Cln); high dose isoniazid
(high- dose
H); claritromycin (Clr
Antituberculosis drugs.
First-line oral agents
 Isoniazid (H) – backbone of TB chemotherapy
and treatment.
Bactericidal with the highest EBA
 Rifampicin (R) – bactericidal with high EBA and a
key sterilizing drug in short-course treatment
regimens of TB
 Pyrazinamide (Z) – high sterilizing agent.
Antituberculosis drugs
 Ethambutol (E) – bacteriostatic at low doses (15
mg/kg/day),
bactericidal at higher doses 25 mg/kg/day. The
primary role is
to prevent the emergence of drug resistance to
companion drugs
Treatment of tuberculosis in
children – special considerations.
 Malnourished children have higher rates of
hepatotoxicity
 Children with more advanced forms of disease
may experience more significant hepatotoxic
reactions than less severe children.
Recommended doses of first-line
anti-TB Drugs.
Drug Daily Dose and range
(mg/kg body weight)
Three times Dose and
range (mg/kg body
weight)
Izoniazid 5 (4-6) 10 (8-12)
Rifampicin 10 (8-12) 10 (8-12)
Pyrazinamide 25 (20-30) 35 (30-40)
Ethambutol children 20 (15-25)
adults 15 (15-20)
30 (25-35)
Streptomycin 15 (12-18) 15 (12-18)
Treatment of tuberculosis in
children – special considerations
Drug Daily dose and range
(mg/kg body weight)
Daily maximum (mg)
Isoniazid 10 (10-15) mg 300mg
*Rifampicin 15 (10-20) 600
Pyrazinamide 35(30-40) 2000
Treatment of tuberculosis in
children –
special considerations
 Recommended treatment regimens for children
in each TB diagnostic category. SHOW TABLE.
Recommended treatment
regimens for children
in each TB diagnostic category
 The use of streptomycin in children is mainly
reserved for the first 2 months of treatment of
TB meningitis
 Thioacetazone is no longer recommended as
part of first line-line regimen to treat TB
 Regimens without rifampicin during
continuation phase may be associated with
higher rate of treatment failure and relapse
CONT…..
 The dose of ethambutol 20 mg/kg/day (range 15-
25 mg/kg/day) is safe in children
Treatment of TB in children
1. The initial intensive multidrug phase
 Rapidly killing of the majority of viable
organisms
 Prevention of emergence of drug resistance
H > S > R > E > Z
2. Continuation phase
 Sterilization of tuberculosis lesions
 Prevention relapse
R > Z > H > S > E
Definitions
 MDR-TB:
MDR-TB is a laboratory diagnosis of resistance
mycobacterium tuberculosis to INH and Rifampicin
 XDR-TB:
Currently defined as MDR-TB with further
resistance to at least 3 of the 6 major classes
of 2d line drugs
Treatment of MDR-TB in children
 MDR-TB is a laboratory diagnosis
 Isolation of MT from child’s clinical
specimens is not available in most cases
 Early diagnosis relies on recognition of
potential drug resistance, based on the
contact history and/or response to treatment
When a possibility of drug resistance consider in
the management of a child??
 known adult source case with MDR-TB
 High prevalence of drug resistant TB in the
community in which child resides (without
known source case)
 An adult source case is treatment defaulter,
treatment failure, retreatment case or chronic case
with unknown drug susceptibility pattern
When a possibility of drug resistance consider in
the management of a child??
 Poor initial response to treatment
 TB relapses
 incomplete or incorrect treatment
Evidence regarding MDR-TB in children is
derived from reported case-series
1. All the treatment should be daily and
directly observed
2. Never add a single drug to a failing regimen
3. First line drugs to which the isolate is still
susceptible should be used
4. Use at least four drugs certain to be
effective
5. Add bactericidal drug as far as possible.
Treatment of MDR-TB in children
6. A fluoroquinolone and injectable should be
used if the isolate is susceptible to these
drugs
Injectable drug should be given for a
minimum of
6 months, or for at least 4 months after the
patient becomes and remains sputum
smear- or culture negative.
Treatment of MDR-TB in children
7. Thionamides, cycloserine / terizidone and PAS
can be added
8. Reserve drugs (clofazamine, claritromycin and
amoxicillin/clavulanate) with unproven efficacy
may sometimes be necessary to use for treatment
of extensively drug-resista.nt TB cases
9 .The optimal duration of treatment
depends extent of the disease,
anatomical location, response to
therapy, and the exact drug
susceptibility patterns, treatment
should be at least 12-18 months

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Treatment of childhood tb

  • 1.
  • 2. Treatment of TB in children How many drugs? Which drugs? Duration of treatment?
  • 3. Principles of antituberculosis therapy  Goal of treatment- to cure the child and to prevent from relapse of the disease during life-time To reach the goal - theoretically eradication of all mycobacterial populations
  • 4. Principles of antituberculosis therapy Activities of antituberculosis drugs  Bactericidal  Sterilizing  Prevention of drug resistance to companion drugs.
  • 5. Activities of antituberculosis drugs  BACTERICIDAL ACTIVITY. H> S> R> E> Z  STERILIZING ACTIVITY. R >Z> H> S> E  PREVENTION OF DRUG RESISTANCE TO COMPANION DRUGS. H> R> E> S> Z.
  • 6. Antituberculosis drugs Grouping Drugs Group 1 First line oral agents isoniazid (H); rifampicin (R); ethambutol (E); pyrazinamide (Z);Rifabutin (Rfb) Group 2 Injectable agents kanamycin (Km); amikacin (Am); capreomycin (Cm); streptomycin (S) Group 3 Fluoroquinolones moxifloxacin (Mfx); levofloxacin (Lfx); ofloxacin (Ofx)
  • 7. Antituberculosis drugs Group 4 Oral bacteriostatic secondline agents ethionamide (Eto); prothionamide (Pto); cycloserine (Cs); terizidone (Trd); paminosalicylic acid (PAS Group 5 Agents with unclear efficacy (not recommended by WHO for routine use in MDR-TB patients clofazimine (Cfz); linezolid (Lzd); amoxicillin/clavulanate (Amx/Clv; thioacetazone (Thz); imipenem/cilastatin (Ipm/Cln); high dose isoniazid (high- dose H); claritromycin (Clr
  • 8. Antituberculosis drugs. First-line oral agents  Isoniazid (H) – backbone of TB chemotherapy and treatment. Bactericidal with the highest EBA  Rifampicin (R) – bactericidal with high EBA and a key sterilizing drug in short-course treatment regimens of TB  Pyrazinamide (Z) – high sterilizing agent.
  • 9. Antituberculosis drugs  Ethambutol (E) – bacteriostatic at low doses (15 mg/kg/day), bactericidal at higher doses 25 mg/kg/day. The primary role is to prevent the emergence of drug resistance to companion drugs
  • 10. Treatment of tuberculosis in children – special considerations.  Malnourished children have higher rates of hepatotoxicity  Children with more advanced forms of disease may experience more significant hepatotoxic reactions than less severe children.
  • 11. Recommended doses of first-line anti-TB Drugs. Drug Daily Dose and range (mg/kg body weight) Three times Dose and range (mg/kg body weight) Izoniazid 5 (4-6) 10 (8-12) Rifampicin 10 (8-12) 10 (8-12) Pyrazinamide 25 (20-30) 35 (30-40) Ethambutol children 20 (15-25) adults 15 (15-20) 30 (25-35) Streptomycin 15 (12-18) 15 (12-18)
  • 12. Treatment of tuberculosis in children – special considerations Drug Daily dose and range (mg/kg body weight) Daily maximum (mg) Isoniazid 10 (10-15) mg 300mg *Rifampicin 15 (10-20) 600 Pyrazinamide 35(30-40) 2000
  • 13. Treatment of tuberculosis in children – special considerations
  • 14.
  • 15.
  • 16.
  • 17.  Recommended treatment regimens for children in each TB diagnostic category. SHOW TABLE.
  • 18. Recommended treatment regimens for children in each TB diagnostic category  The use of streptomycin in children is mainly reserved for the first 2 months of treatment of TB meningitis  Thioacetazone is no longer recommended as part of first line-line regimen to treat TB  Regimens without rifampicin during continuation phase may be associated with higher rate of treatment failure and relapse
  • 19. CONT…..  The dose of ethambutol 20 mg/kg/day (range 15- 25 mg/kg/day) is safe in children
  • 20. Treatment of TB in children 1. The initial intensive multidrug phase  Rapidly killing of the majority of viable organisms  Prevention of emergence of drug resistance H > S > R > E > Z 2. Continuation phase  Sterilization of tuberculosis lesions  Prevention relapse R > Z > H > S > E
  • 21. Definitions  MDR-TB: MDR-TB is a laboratory diagnosis of resistance mycobacterium tuberculosis to INH and Rifampicin  XDR-TB: Currently defined as MDR-TB with further resistance to at least 3 of the 6 major classes of 2d line drugs
  • 22. Treatment of MDR-TB in children  MDR-TB is a laboratory diagnosis  Isolation of MT from child’s clinical specimens is not available in most cases  Early diagnosis relies on recognition of potential drug resistance, based on the contact history and/or response to treatment
  • 23. When a possibility of drug resistance consider in the management of a child??  known adult source case with MDR-TB  High prevalence of drug resistant TB in the community in which child resides (without known source case)  An adult source case is treatment defaulter, treatment failure, retreatment case or chronic case with unknown drug susceptibility pattern
  • 24. When a possibility of drug resistance consider in the management of a child??  Poor initial response to treatment  TB relapses  incomplete or incorrect treatment
  • 25. Evidence regarding MDR-TB in children is derived from reported case-series 1. All the treatment should be daily and directly observed 2. Never add a single drug to a failing regimen 3. First line drugs to which the isolate is still susceptible should be used 4. Use at least four drugs certain to be effective 5. Add bactericidal drug as far as possible.
  • 26. Treatment of MDR-TB in children 6. A fluoroquinolone and injectable should be used if the isolate is susceptible to these drugs Injectable drug should be given for a minimum of 6 months, or for at least 4 months after the patient becomes and remains sputum smear- or culture negative.
  • 27. Treatment of MDR-TB in children 7. Thionamides, cycloserine / terizidone and PAS can be added 8. Reserve drugs (clofazamine, claritromycin and amoxicillin/clavulanate) with unproven efficacy may sometimes be necessary to use for treatment of extensively drug-resista.nt TB cases
  • 28. 9 .The optimal duration of treatment depends extent of the disease, anatomical location, response to therapy, and the exact drug susceptibility patterns, treatment should be at least 12-18 months