..

2557

.. 2557

.. 2557




2557
10,000

.. 2557. -- :
152
ISBN: 978-616-91609-1-5
1. (1) . (1)
. (1) (2) .
(2) . (2) . (2) . I. .


.. 2557

10

.. 2544-2551 (0-14 )
1-2

.. 2557

()


.. 2557

.. 2557

.. 2557

........................................................................................... 3
.. 2557.............................. 5
(Abbreviation)............................................................................... 8
......................................... 10
1 ....................... 13
2 ................................ 15
2.1 ................................................................................ 15
2.2 .... 22
3 ....................................................................... 29
3.1 ........................................................... 29
3.2 ........................ 31
3.3
.................................................................................. 43
3.4
................................................................................ 49
3.5 ............................................................ 51
3.6
..................................................................... 53


.. 2557

4 ....................................................................... 57
4.1 .................................................................... 58
4.2 .................................................................... 60
4.3 .................................................. 62
4.4 .......................................................................... 67
5 ..................................... 69
5.1 .................. 70
5.2 ...................................... 73
6 BCG .................................................................. 77
6.1 ................................................................... 77
6.2 ................ 81
7 ............................... 85
7.1 / ............................................ 85
7.2 ................................ 89
7.3 ................................................................... 95
7.4 ................................................................ 100
.......................................................................................102
.......................................................................................109
1 .................................... 109
2
Rapid Molecular Testing ..................................... 116
3 127
4 ........................................... 134
5 ....................................... 143


.. 2557

(Abbreviation)
AFB
AIDS
ART
Cs
CSF
CXR
DOT
DST
DR-TB
E, EMB
Eto
EPTB
FDC
FLDST
H, INH
HIV
INF
IGRA
Km
Lfx

Acid-fast bacilli
Acquired immunodeficiency syndrome
Antiretroviral therapy
D-cycloserine
Cerebrospinal fluid
Chest X-ray
Directly observed treatment
Drug susceptibility testing
Drug-resistant tuberculosis
Ethambutol
Ethionamide
Extrapulmonary tuberculosis
Fixed-dose combination
First-line drug susceptibility test
Isoniazid
Human immunodeficiency virus
Interferon
Interferon-gamma release assay
Kanamycin
Levofloxacin


.. 2557

MDR-TB
NNRTIs
NRTIs
NTM
NTP
LTBI
PAS
PIs
PMN
PTB
Rapid DST
R, RMP
SLDST
S, SM
SSC
TAD
TAF
TB
TB/HIV
TST
WHO
XDR-TB
Z, PZA

Multi-drug-resistant tuberculosis
Non-nucleoside reverse transcriptase inhibitors
Nucleoside reverse transcriptase inhibitors
Non-tuberculous mycobacterium
National tuberculosis control program
Latent tuberculosis infection
P-aminosalicylic acid
Protease Inhibitors
Polymorphonuclear cell
Pulmonary tuberculosis
Rapid drug susceptibility test
Rifampicin
Second-line drug susceptibility test
Streptomycin
Standard short-course (2HRZE/4HR)
Treatment after default
Treatment after failure
Tuberculosis
HIV-related TB
Tuberculin skin test
World Health Organization
Extensively drug-resistant tuberculosis
Pyrazinamide

2HRZE/ 4HR
Isoniazid + Rifampicin + Pyrazinamide + Ethambutol 2
Isoniazid + Rifampicin 4

10

.. 2557

(Strength of Recommendation and Quality
of Evidence)
(Strength of Recommendation)
++ (strongly recommend)

(Cost effective)

+ (recommend)

+/- (neither recommend nor

against)

- (against)


.. 2557

- - (strongly against)

(Quality of Evidence)
I
1) (systematic review)
(randomizecontrolled clinical trials)
2)
(well-designed, randomize-controlled, clinical
trial) 1

II
1) (systematic review)
(non-randomized, controlled, clinical trials)
2)
(well-designed, non-randomized, controlled
clinical trial)
3) (cohort)
(case control analytic
studies)
/

11

12

.. 2557

4) (multiple time series)

.. 2480

III
1) (descriptive studies)
2)

(fair-designed, controlled clinical trial)

IV
1)
(consensus)

2)
2

V
(Anecdotal report)


.. 2557

(WHO) .. 2554
490,000 / (470,000-510,000)
6 8.7 ( 13
)
.. 2544-2551
(0-14 ) 1-2

13

14

.. 2557

Mycobacteria Mycobacterium tuberculosis complex

Mycobacterium tuberculosis
Mycobacterium bovis
Mycobacterium africanum

(Acid fast bacilli) 2-4 micron

(Airborne Transmission) (Direct Contact)

(Index Case)


2


.. 2557

3
1.
2. / (TST)
Interferon gamma releasing assays (IGRAs)

20-30

15

16

.. 2557

1.

( 7 )
( )



( asthma bronchiolitis wheezing rhonchi)
wheezing

30-60


1. exudate (/
0.5) (Straw-colored)
2. 1,000-5,000/mm3

2.5 g/dL
3. AFB smear


.. 2557

Adenosine deaminase (ADA)
( cut-off 36-40 IU/L)

2. /
Tuberculin skin test Interferon gamma releasing
assays (IGRAs)

1. (index case) secondary TB (
) AFB
2.
2

2.1 1

2.2

3.

17

18

.. 2557

()

8

120 1

IGRAs
( ) 2

2


TST IGRAs

NTM

3.


( 8 ) ( 2
) (


.. 2557

)
(lateral)

()
1.
2.
(Gohns complex)
3. (calcification)
4. (miliary infiltration) 2-3

5. (cavity)
6. (lobar segmental atelectasis)

7. (effusion)
7 1-4
5-7

19

20

.. 2557

(++, IV)

(TST) IGRAs


.. 2557

(++, IV)
1. 3 AFB

2. ( 1)
TST ( 2)
( 4)

3. ( 1)
( 3)
TST IGRAs
/
AFB (
) 1-2

miliary infiltration

21

22

.. 2557

(Tuberculin skin test: TST)

(Hypersensitivity
reaction) mycobacterial antigen PPD (Purified Protein
derivative) (Latent tuberculosis
infection: LTBI)
(TB disease) TST
48-72

1) M. tuberculosis M.bovis
BCG Non-tuberculous mycobacterium (NTM)

2)

3)

1)
> 10 (
)
systemic steroid > 2 . / . /


.. 2557

20 . / 2
> 5
2) 5
isoniazid
(INH prophylactic treatment - IPT)

5-18 15
INH
10-14 INH
10 INH

PPD RT 23
24-48

1 1

23

24

.. 2557

(syringe) insulin syringe

50 IU 100 IU tuberculin syringe
0.1

( PPD 4)

(Interferon gamma releasing assays:

IGRAs)
Interferon gamma releasing assays (IGRAs)
interferon gamma
( M. tuberculosis)
M. tuberculosis
M. tuberculosis
BCG NTM M.kansasii, M.marinum, M.szulgal
IGRAs

12
4


.. 2557

1. 10
2-3
2. 10 5


nebulized 3-5% NSS (Induced sputum)
airborne transmission precaution
negative pressure room
gastric aspirate
3
50-70
nasopharyngeal aspirate
gastric aspirate

gastric aspirate
4-6 nasogastric tube
syringe 5, 10 20 2-5
sterile water 0.9% NaCl (NSS)
5-10
4% sodium bicarbonate

25

26

.. 2557

- AFB

AFB

3
AFB
15-20

-
Gold standard ( active TB disease)
(NTM)


AFB liquid media
solid media
2-6

AFB
(++, IV)


.. 2557

- (++, III)
PCR

AFB 96
AFB 66

- Xpert MTB/RIF

2 M. tuberculosis
rifampin ( rpoB gene)

Xpert MTB/RIF 74
rifampin


Xpert MTB/RIF

27

28

.. 2557


.. 2557

1.
4 (initial)
(standard short-course)

(initial phase)

(continuation phase)
2

29

30

.. 2557

()

2.

3.
6

4.
(Directly Observed Therapy;
DOT)

(+, IV)


.. 2557

nephrotic syndrome
aminoglycosides

1.
2HRZE/ 4HR (++, II)
2.
2HRZE/ 10HR (++, III)

(miliary tuberculosis)
50 lumbar puncture
12 (++, III)
3.
2HRZE/ 10HR (++,
III)
4.
6

(delay treatment response)
(continuation phase) 4 7-10
(++, II)

31

32

.. 2557

5.
2HRZES/ 1HRZE/
5HRE

6. intermittent regimen
(-, III)
1

Isoniazid
10-15 ././
( 300 .)

Rifampin
10-20 ././
( 600 .)

Pyrazinamide

Ethambutol

Streptomycin

30-40 ././
( 2 .)

15-20 ././
25 ././
( 1.2 )

20-40 ./.
( 1 )

Mild hepatic enzyme elevation,

hepatitis, peripheral neuritis,
hypersensitivity
Orange discoloration of secretions
or urine, staining of contact lenses,
vomiting, hepatitis, influenza-like
reaction, thrombocytopenia,
pruritus; oral contraceptives may
be ineffective
Hepatotoxic effects, hyperuricemia,
arthralgia, myalgia, GI upset
Optic neuritis (usually reversible),
decreased red-green color
discrimination, GI disturbance,
hypersensitivity
Auditory and vestibular toxic
effects, nephrotoxic effects, rash


.. 2557

1 ()

Amikacin

15-30 ./. (
1 )

Capreomycin 15-30 ./.

Cyclocerine 10-20 ././

( 1 )
2 *
Ethionamide 15-20 ././
( 1 )
2-3 *
Kanamycin
15-30 ./.
( 1 )

Levofloxacin <5
20 ././
2
> 5
10 ././
( 1 )
Ofloxacin
15-20 ././
( 800 .)

Auditory and vestibular toxic

effects, nephrotoxic effects
Auditory and vestibular toxic
effects, nephrotoxic effects
Psychosis, personality changes,
seizures, rash
GI disturbance, hepatotoxic effects,
hypersensitivity reactions,
hypothyroid
Auditory and vestibular toxic
effects, nephrotoxic effects

Theoretical effect on growing

cartilage, GI disturbances, rash,
headache, restlessness, confusion

Arthropathy, arthritis

33

34

.. 2557

1 ()

Moxifloxacin

Para-aminosalicylic acid
(PAS)

7.5-10 ././
Arthropathy, arthritis
( 400 .)

200-300 ././** GI disturbances, hypersensitivity,

( 10 )
hepatotoxic effects
2-4 **

*
** 150 ./. 8

streptomycin (First-line
drug) (+, II)
(INH, RF, PZA, EMB)
(daily
package) (fixed-dose drug combination; FDC)

(fixed-dose combination: FDC) HR,

HRZE


.. 2557

(+, II)



steroid
(-, II)
Immune Restoration
Syndrome paradoxical reaction


DOT 1

1.

2. (++, IV)
1.

35

36

.. 2557

1 (DOT)


.. 2557

2.
3. (intensive phase)
(continuation phase)
3. (++, II)
2



2

2
1.
2.
3. (drugto-drug / drug-to-food interaction)
4.
(immunocompromised host)

4+ 1+
5. NTM
6.
7.
2
1-2

37

38

.. 2557

(MDR-TB)
(MDR-TB)
isoniazid rifampicin MDRTB

(index case)

MDR-TB MDR-TB


4 (++, IV) first line
drug ( 1) 2, 3, 4,
5 (stepwise selection) (++, IV)
2 1 quinolone

1

2 MDR-TB kanamycin
amikacin

capreomycin


.. 2557

3 ofloxacin, levofloxacin
moxifloxacin ciprofloxacin

4
ethionamide protionamide
PAS cross-resistance
ethionamide PAS
hypothyroid cycloserine
18 ( 24
XDR-TB) intensive phase ()
6 (++, I) 4

intensive phase ( ) 3
(
) (+, III)
MDR-TB
MDR MDR-TB

.. 2555 >6Km5LfxEtoCs
1 PAS
>12LfxEtoCs PAS
(>6Km5LfxEtoCs (PAS)/ >12LfxEtoCs (PAS), Km5 Kanamycin 5 )

39


.. 2557

40

2 MDR-TB

1. First-line oral agents

2.

3.

4.

5.

Ethambutol (E)
Pyrazinamide (Z)
Rifabutin (Rfb)
Injectable agents
Kanamycin (Km)
Amikacin (Am)
Capreomycin (Cm)
Streptomycin (S)*
Fluoroquinolones
Ofloxacin (Ofx)
Levofloxacin (Lfx)
Moxifloxacin (Mfx)
Oral bacteriostatic
Para-aminosalicylic acid (PAS)
second-line agents
Ethionamide (Eto)
Protionamide (Pto)
Cycloserine (Cs)
Terizidone (Trd)
Agents with unclear role in
Clofazimine (Cfz)
treatment of drug resistant-TB Amoxicillin/Clavulanate (Amx/Clv)
Linezolid (Lzd)
Imipenem/Cilastatin (Ipm/Cln)
High-dose isoniazid (high-dose H)
Clarithromycin (Clr)
Thioacetazone (Thz)

* injectable agents


.. 2557

(++, III)

(Treatment after interruption)

()

1.
2.
3.

(+, III)



DOT

41

42

.. 2557

2
(Treatment after Interruption)


.. 2557

Rapid molecular testing

(index case)

1.

3 1
/ 2
3

(++, III)




maculopapular rash


systemic corticosteroid
prednisolone 1-2 //

43

44

.. 2557

- H R E Z
- 1/3 1/2
2-3

2. /




H, R Z bilirubin
AST/ALT rifampicin


.. 2557

AST/ALT
total bilirubin 1-2 1
(++, III)
AST/ALT
total bilirubin

(++,
III)


AST/ALT > 3 upper normal limit H, R
Z E, quinolone, streptomycin
AST/ALT < 3 upper normal limit
3

(++, III)
total bilirubin > 3 ./ AST/ALT
3 R
AST/ALT < 5 upper normal limit
1

45

46

.. 2557

AST/ALT > 5 upper normal limit H, R

Z E, quinolone streptomycin

re-challenge (++, II)

re-challenge fulminant hepatitis

AST/ALT < 2 total bilirubin

< 1.5 ./. re-challenge H, R
Z (++, II)
1
- re-challenge
7 7.2
AST/ALT total bilirubin 1
re-challenge AST/ALT total bilirubin

3. (Optic neuritis, Retrobulbar neuritis)

ethambutol
isoniazid
(dyschromatopsia --)
(central scotoma)


.. 2557

ethambutol

(visual acuity)
(+, III)

ethambutol
ethambutol 15 ././ 20 ./
./ (++, II)

isoniazid
isoniazid

47

48

.. 2557

3
(++, III)

(vertigo
nystagmus)

purpura

S
S

()

Z,R,H

H
R

aspirin, NSAIDs
paracetamol
pyridoxine 50-100
.

H, R, Z
E, H
R


.. 2557

Rifampicin



4
4
(A) (B)
(effect)
Isoniazid

Rifampicin

Alcohol, rifampicin
Aluminum salts
Carbamazepine,
phenytoin
Itraconazole,
ketoconazole
Oral hypoglycemic
Isoniazid
Itraconazole,
ketoconazole
Fluconazole
Caspofungin
Clarithromycin
Linezolid
TMP/SMX
Nevirapine

risk of hepatic injury

B,
, nystagmus, ataxia
B
B
INH toxic hydrazine
A, B
A
B
A, B
B
A
B

49

50

.. 2557

4 ()
(A) (B)
(effect)
Rifampicin

Pyrazinamide
Ethambutol

Amprenavir,
indinavir, ritonavir
Protease inhibitors
Cycosporine
Tacrolimus
Digoxin
Beta adrenergic
blockers
Oral anticoagulants
Oral contraceptives
Phenytoin
Theophylline
Isoniazid, rifampicin
Aluminum salts

A, B
A, B
B
B
B
B
Suboptimal anticoagulantion
B, spotting
B
B
risk of hepatotoxicity
A B


.. 2557

1.





2.

2.1
500 5
1 100
200 2

isoniazid

51


.. 2557

52

2.2 1

3.

3

rifampicin


.. 2557

(Organization of tuberculosis treatment unit, TB Clinic)

1.

2.
3.

4.

5.

6.

7.

(DOT)
8.

9.
10.

53

54

.. 2557

5
5

Congenital tuberculosis
AFB smear positive

-
(bronchoscopy, sputum induction,
aerosolized medication, suctioning,
endotracheal intubation)
cavity lesions, apical involvement,
miliary disease


.. 2557

( cavitation)

(cohort family) (++, II)
(surgical mask) (respiratory
hygiene/cough etiquette)
N 95 mask ( mask
) Fit test Fit check
(++, II)

Latent tuberculosis infection (LTBI)
(++, III)

1.
2.
3.
4.
5.
6.

( )
2.5 Pa
(leakage) 0.5 sq.ft

6-12 Air Change

anteroom (++, III)

55

56

.. 2557

High efficiency particulate air (HEPA) filters

(Ultraviolet, UVGI)
( remove inactivate )

(+, III)

natural ventilation



(HEPA, UVGI)
(++, III)


.. 2557

-

AFB
PCR TB (++, II)

57


.. 2557

58

-

-
AFB granuloma

-
gastric aspirate AFB PCR
TB (++, II)
-
(++,II)

(tuberculous lymphadenitis)

posterior anterior cervical chain supraclavicular fossa


(matted)
sinus tract


.. 2557

bronchiectasis

- needle biopsy
AFB

-
2HRZE/ 4HR
6
-
(++, II)
-

AFB (+, II)
AFB NTM

59

60

.. 2557

(+, II)
incision and drainage (- -, III)
- 6
( )

(Tuberculous osteomyelitis)

femur tibia sacroiliac



kyphosis

(cold abscess) (
)


.. 2557

()
(reactive new bone formation)

- (++, II)
-
PCR (++, II)
- MRI scans
(+, II)

- 2HRZE/10HR 12
(++, III)
-
sequestrated bony
fragments

(synovectomy) (+, II)

61

62

.. 2557

-
(++, II)
mechanical instability

- splint functional position active passive exercise
(++, I)

(TB meningitis) cerebral tuberculoma

(TB meningitis)



3
1 1-2


.. 2557

2 hypertonia
cranial nerve palsy
(hydrocephalus) (increase intracranial pressure)
(vasculitis)

3
hemiplegia paraplegia decerebrate posturing

1. 25
2. 10-500 /3
50

3. 40 ./.
0.5
4. (400-5,000 ./.)

AFB

63

64

.. 2557

2-6

PCR nucleic acid amplification
test (NAAT)
NAAT 71 95
multiplex PCR

(CT brain scan)

hydrocephalus, basal meningeal enhancement, periventricular lucency, infarction tuberculoma ( 12)
40-87
miliary pattern 12-20
miliary TB
50

(cerebral tuberculoma)
tuberculoma
frontal parietal

low high-density lobulated homogenous enhancement tubeculoma
tuberculoma


.. 2557

10-100 /3 50

-
(++, III) AFB (++, III)
(++, III)
- brain CT scan
(+, III)
- PCR nucleic acid amplification test (NAAT)
(+, II)
- adenosine deaminase (ADA)
interferon gamma release assays (IGRA)
(-, III)
-
(++, III)
-
(+, III)

65

66

.. 2557

- 4 2HRZE/10HR

Ethionamide Ethambutol
- prednisolone 2 //
4 // ( 60 /) 4
2
(++, I)

- cerebral tuberculoma spinal tuberculosis corticosteroid tuberculoma (paradoxical

reaction) (acute spinal cord compression) vertebral tuberculosis (+/-, IV)
- communicating hydrocephalus furosemide 1 //
acetazolamide 30-50 // (+, II)
(+, III)
- hydrocephalus

(ventriculo-peritoneal shunt)(+, III)
early decompression extra-dural lesions
(+ IV)


.. 2557

ileum ileocaecum



(ascites)

- exudates
- Serum-ascites albumin gradient (albumin concentration of
serum - albumin concentration of ascitic fluid) 1.1
-
- Adenosine deaminase (ADA)
( cut-off 36-40 IU/L)

- fibrinous strand ascites fluid, localized ascites (calcified lymph node)

- CT Abdomen peritoneal fluid peritoneal thickening omental mass

67

68

.. 2557

mesenteric para-aotic lymph nodes

adhesion stricture

- (++, II)
- CT abdominal imaging
(++, II)
- (+, II)
- (laparoscopy)
(biopsy)
AFB (+, II)

- 2HRZE/ 4-7HR (++, II)

-
fistula
(+, II)


.. 2557

(++, IV)
1

isoniazid
1

-
-
-

69

70

.. 2557


.. 2557

isoniazid 6-9
congenital tuberculosis

> 10 .
2 3 > 10 . 6 .
isoniazid 6-9

( 1) (+,III)

isoniazid Vitamin B6 (Pyridoxine) 0.2-0.5 mg/day

INH (+/-,III)

71

72

.. 2557

Rifampicin
Rifabutin

Isoniazid

B6
Pyrazinamide

Ethambutol
Ethionamide

Amikacin

0.5%
0.5%

10-20 mg/kg/day

0.75-2.3%

5-10 mg/kg/day

0.75-2.3%

20-30 mg/kg/day

15-20 mg/kg/day

( )
0.95-22.5%

Streptomycin

8-11%
Kanamycin
0.95-1.8%
2.3%
Quinolone

0.05-0.5%


.. 2557

3 (Contact Investigation and

Management) (++, IV)

73

74

.. 2557

16-17 49-58








isoniazid 3


6-9
(Latent
TB infection: LTBI) isoniazid 6
70-80 9 80-90
15

10-14


.. 2557

5-10
isoniazid 9
immunosuppression isoniazid
12

1.
5

(isoniazid)
2. isoniazid ( 10 / 300
)
6-9 9-12
CD4 2 (pyrazinamide+rifampin)


3. (MDR-TB)
(secondary chemoprophylaxis)
2

75

76

.. 2557


.. 2557

6
BCG

(BCG Vaccine) Mycobacterium bovis

Tokyo-172 (live attenuated vaccine) normal saline
2-8o.
2

(intradermal) 0.1 .

50

77

78

.. 2557

46-80
53

(++, IV)


(++,
II)

(++, IV)


(++, IV)
3-4
(++, IV)

(++, IV)


.. 2557

( 1)





(+, II)
6

6
(+, II)
6


(+/-, II)

1
1-2
(+, IV)

79


.. 2557

80

isoniazid / rifampicin


.. 2557

/
1.
2-6
2 95

supraclavicular

(+, I)

81

82

.. 2557

3 .
isoniazid / rifampicin 1-3
(aspirate) (+,I) (incision & drainage)

2. (BCG Osteitis)
0.2-72/100,000

M. tuberculosis complex


PZA
M. bovis PZA 12
(+, III)

3. (Disseminated BCG)
2 1
PZA


.. 2557

M. bovis pyrazinamide M. bovis

83

84

.. 2557


.. 2557

/
1.

-

2.

3.

85

86

.. 2557

4.


5. Rifampicin
NNRTIs (Nevirapine: NVP, Efavirenz: EFV) PIs
(Lopinavir/ritonavir: LPV/r)
PIs NNRTIs

gastric aspirate

isoniazid 9

1. CD4

2. CD4


.. 2557

2-8
Immune
Reconstitution Inflammatory Syndrome (
) CD4
CD4

- CD4 < 200 cells/ml < 15%

2
- CD4 200-350 cells/ml 15-25%

8
- CD4 > 350 cells/ml > 25%
CD4

rifampicin
NRTIs NNRTIs PIs

rifampicin NNRTsI PIs
1. NNRTIs EFV
( rifampicin) 3 EFV
NVP

87

88

.. 2557

2. NNRTIs
triple NRTIs AZT d4T + 3TC + ABC
rifampicin
NNRTsI PIs
ABC

3. PIs

3.1
rifampicin quinolones / aminoglycoside
PIs
3.2
rifampicin 2
rifampicin PIs PIs
rifampicin 2 ( rifampicin
) rifampicin
7-9

1. NNRTIs


.. 2557

NVP

2.
PIs PIs

2.1
PIs PIs
rifampicin 2 ()
rifampicin isoniazid ethambutol
7 quinolones ofloxacin levofloxacin
PIs

2.2
rifampicin quinolones
aminoglycoside PIs

isoniazid 0.6
rifampicin
2.7
0.023

89

90

.. 2557

1. acute hepatitis


isoniazid, rifampicin, pyrazinamide
ethambutol, aminoglycoside
quinolones ofloxacin, levofloxacin
(visual acuity)

2. chronic hepatitis B virus infection

isoniazid



HBeAg
3. chronic hepatitis C virus infection

5

14


.. 2557

4. (cirrhosis)
pyrazinamide aminoglycoside, quinolone
ethambutol rifampicin isoniazid
cirrhosis

( 2010)
1. cirrhosis
1. 4 2
isoniazid rifampicin 4
6
2. pyrazinamide
3 9

2. cirrhosis

1. 2

. isoniazid, rifampicin ethambutol 9

. isoniazid, rifampicin, ethambutol aminoglycoside

2 isoniazid rifampicin
6

91

92

.. 2557

2. 1
isoniazid, ethambutol aminoglycoside 2
isoniazid ethambutol 10
3.
cirrhosis hepato-renal syndrome, hepatic encephalopathy, ascites coagulopathy

. aminoglycoside ethambutol quinolone
18-24
. cirrhosis encephalopathy ethambutol fluoroquinolone,
cycloserine capreomycin aminoglycoside
18-24
chronic liver
disease Child-Turcotte-Pugh score
1 1-3
15
2


.. 2557

1 chronic liver disease

Child-Turcotte-Pugh score
Bilirubin, mg/dl (umol/l):
Score
<2 (<34)
2-3 (34-50)
>3 (>50)

1
2
3

Albumin (g/dL):
>3.5
3.5-2.8
<2.8

1
2
3

PT prolongation (INR):
<4 seconds (<1.7)
4-6 seconds (1.7-2.3)
>6 seconds (>2.3)

1
2
3

Ascites:
Absent
Slight
Moderate

1
2
3

Encephalopathy:
None
Grade 1-2
Grade 3-4

1
2
3

93

94

.. 2557

2 chronic liver
disease
Child-Turcotte- Liver
Treatment
Pugh score disease
<7
Stable

hepatotoxic 2
, pyrazinamide
8-10
Advanced

hepatotoxic 1 ; rifampicin
isoniazid; pyrazinamide
> 11
Very advanced hepatotoxic; streptomycin,
ethambutol, fluoroquinolones, amikacin,
kanamycin second-line
18-24

cirrhosis
1. AST / ALT 3
2. AST / ALT 5
3. bilirubin
bilirubin transaminase chronic liver disease rifampicin


.. 2557

isoniazid
isoniazid 50
rifampicin 150 3-4
pyrazinamide

AST
hepatotoxicity

isoniazid, rifampicin
pyrazinamide ethambutol, aminoglycoside
fluoroquinolone
CCr aminoglycoside
2HRZ/4HR

3

95


.. 2557

96

Recommen-
dation
GFR , HD,
PD, CRRT
Rifampicin

Isoniazid

Pyrazinamide

40 mg/kg/d
3
( 2 gm

>50 kg
1.5 gm
<50 kg)
dialysis

30%

half life
toxic
level

INH
neurotoxicity
psychosis
dialysis
INH Vitamin
B6

metabolite


.. 2557

3 ()

Recommen-
dation
GFR , HD,
PD, CRRT
Ethambutol

MDR TB

GFR 10-50
24-36
GFR <10
48
HD
dialysis
PD 48

CRRT 24-36

GFR <10

Quinolones
Moxifloxacin

GFR 10-50
50-75%
GFR <10
50%
HD
dialysis
Levofloxacin GFR <50
50%
GFR <20
50%
48
GFR <10
Ofloxacin

97

98

.. 2557

3 ()

Recommen-
dation
GFR , HD,
PD, CRRT
Thioamides
Prothionamide

HD 7.5-15 mg/kg/day
dialysis
250-500
mg/12 hrs
Streptomycin GFR 50-80 7.5 mg/
kg/dose 24 .
GFR 10-50 7.5 mg/
kg/dose 24-72

.
GFR <10 7.5 mg/kg/
dose 72-96 .
HD
dialysis
PD 20-40 mg/L/d
CRRT
24-72
Amikacin GFR >50
60-90%
GFR 10-50
30-70%

GFR <10
20-30%


.. 2557

3 ()

Recommen-
dation
GFR , HD,
PD, CRRT
Amikacin

HD
dialysis
PD 15-20 mg/L/d
CRRT
30-70%
12-15 mg/kg 3
dialysis

Capreomycin

MDR-TB
Cycloserine 250 mg/day
500 mg 3

Clofazimine 200-300 mg/day
MDR-TB

HD = Hemodialysis, PD = Peritoneal dialysis, CRRT = Continuous Renal

Replacement Therapy

99

100

.. 2557

(Congenital tuberculosis)

1. 1
2. primary complex
3.
4.

1.

2.
scattered infiltrates, bronchopneumonia, consolidation


.. 2557

3. CT scan abdomen periportal hypodensity

4. AFB
gastric aspirate endotracheal aspirate endotracheal
tube, spinal fluid, ear discharge
liver biopsy, lymph node biopsy, bone
marrow aspirate

5. polymerase chain reaction (PCR)

6. /
liver biopsy, lymph node biopsy

2-3
1. 2HRZAm/10HR

2. 2HRZE/4-10HR

101

102

.. 2557

1. WHO Global Tubercuolosis report 2012 :- WHO/HTM/TB/2012.6

2. Newton SM, Brent A,Anderson S,Whittaker E, Kappmann B, Pediatric
tuberculosis. Lancet Infect Dis 2008; 8: 498-510.
3. WHO. Guideline for national tuberculosis programme on the management of tuberculosis in children. Geneva. World Health Organization
2006.
4. Graham SM, Marais BJ, Gie RP. Clinical features and index of suspicious of tuberculosis in children. In: Schaaf HS, Zumla AI, eds. Tuberculosis: A Comprehensive Clinical Reference. St. Louis: Elsevier Inc. 2009:
154-63.
5. . (Pediatric Tuberculosis Diagnosis).
: , , ,
. .. 2553. :
. 2553: 32-68.
6. Fischer GB, Andrade CF, Lima JB. Pleural tuberculosis in children. Paediatr
Respir Rev. 2011; 12: 27-30.
7. McAdams HP, Erasmus J, Winter JA. Radiologic manifestations of pulmonary tuberculosis. Radiol Clin North Am. 1995; 33: 655-78.
8. Marais BJ, Gie RP, Schaaf HS, Starke JR, Hesseling AC, Donald PR, et
al. A proposed radiological classification of childhood intra-thoracic
tuberculosis. Pediatr Radiol. 2004; 34: 886-94.


.. 2557

9. Updated guidelines for using interferon gamma release assays to detect M. tuberculosis infection. MMWR 2010; 59: RR5 1-28.
10. Chang K, Lu W. Wang J, et al. Rapid and effective diagnosis of tuberculosis and rifampicin resistance with XpertMTB/RIF assay: a metaanalysis. J Infect 2012; 64: 580-8.
11. World Health Organization. Rapid advice: treatment of tuberculosis in
children 2010. http://whqlibdoc.who.int/publications/2010/9789241500
449_eng.pdf
12. World Health Organization. Treatment of tuberculosis guidelines. 4th ed.,
2010.
13. Shah I. Multidrug-resistant tuberculosis in children. The Pediatric infectious disease journal 2012 Sep; 31: 970-2.
14. American Academy of Pediatrics. Tuberculosis. In: Picekering LK, Baker
CJ, Kimberlin DW, Long SS, eds. Red Book: 2012 Report of the Committee on Infectious Diseases. Elk Grove Village, IL: American Academy
of Pediatrics; 2012: 736-59.
15. Gilbert DN, Moellering RC, Eliopoulos GM, Chambers HF, Saag MS.
The Stanford Guide to Antimicrobial Therapy 2012. 42nd Edition. 2012:
214-20.
16. . (MDR-TB) .
: , , , .
Update on Pediatric Infectious Diseases 2013, :
, 2556: 106-15.

103

104

.. 2557

17. CDC. Guidelines for environmental infection control in health-care facilities. Recommendations of CDC and the Healthcare Infection Control
Practices Advisory Committee (HICPAC). MMWR Recomm Rep. 2003;
52(RR-10): 1-42.
18. CDC. Guidelines for preventing the transmission of Mycobacterium
tuberculosis in health-care settings, 2005. MMWR Recomm Rep. 2005
Dec 30;54(RR-17): 1-141.
19. WHO. Epidemic-prone & pandemic - prone acute respiratory diseases:
Infection prevention & control in health care facilities 2007. http://
www.who.int/csr/resources/publication
20. Atkinson J, Chartier Y, Lcia Pessoa-Silva C, Jensen P, Li Y,Seto WH.
Natural Ventilation for Infection Control in Health-Care Settings 2009.
http://www.who.int/water_sanitation_health/publications/natural_ven
tilation/en/index.html
21. WHO policy on TB infection control in health-care facilities, congregate
settings and households. 2009. http://www.who.int/tb/publications/2009/
9789241598323/en/index.html
22. Patel VP, Desai TR, Chavda BG, Katira RM. Extemporaneous Dosage
form for oral liquids. Available at http://pharmacophorejournal.com/marchapril2011-article1.pdf. Accessed: August 13, 2011.
23. , , ,
. Pediatric Dose 3
. : , 2553.


.. 2557

24. , , .
Pediatric Extemporaneous Compounding
. :
, 2552.
25. American Academy of Pediatrics. Tuberculosis. In: Pickering LK, Baker
CJ, Kimberlin DW, Long SS, eds. Red Book: 2012 Report of the Committee on Infectious Diseases. Elk Grove Village, IL: American Academy
of Pediatrics; 2012:736-59.
26. Loto OM, Awowole I.Tuberculosis in pregnancy: a review.J Pregnancy.
2012;379271.
27. Mirium A, Prakash MJ. Tuberculosis in preganacy and in neonate. In:
Schaaf HS, Zumla AI, editors. Tuberculosis: A Comprehensive Clinical
Reference. St. Louis: Elsevier Inc.; 2009. p.572-580.
28. Skevaki CL, Kafetzis DA. Tuberculosis inneonates and infants: epidemiology, pathogenesis, clinical menifestations, diagnosis, and
management issues. Paediatr Drugs 2005; 7: 219-34.
29. Whittaker E, Kampmann B. Perinatal tuberculosis: new challenges in the
diagnosis and treatment of infants and newborn. Early Hum Dev 2008;
84: 795-9.
30. Brewer TF. Preventing tuberculosis with Bacillus Calmette-Gurein
vaccine: A meta-analysis of literature. Clin Infect Dis 2000; 31(suppl 3):
S64-7.

105

106

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31. Sirinavin S, Chotpitayasunondh T, Suwanjutha S, et al. Protective

efficacy of neonatal Bacillus Calmette-Guerin vaccination against
tuberculosis. Pediatr Infect Dis J 1991; 10: 359-65.
32. Hesseling AC, Cotton MF, Fordham von Reyn C, Graham SM, Gie RP,
Hussey GD. Consensus statement on the revised World Health Organization recommendations for BCG vaccination in HIV-infected infants.
Int J Tuberc Lung Dis 2008; 12: 1376-9.
33. Goraya JS, Virdi VJS. Treatment of BCG-lymphadenitis-a meta-analysis.
Pediatr Infect Dis J 2001; 20: 632-4.
34. Bernatowska EA, Wolska-Kusnierz B, Pac M, et al. Disseminated bacillus Calmette-Gurin infection and immunodeficiency. Emerg Infect Dis
2007; 13: 799-801.
35. Fujiwara PI, Clevenbergh P, Dlodlo RA. Management of adults living
with HIV/AIDS in low-income, high-burden settings, with special reference
to persons with tuberculosis. Int J Tuberc Lung Dis 2005; 9: 946-58.
36. Kwara A, Ramachandran G, Swaminathan S. Dose adjustment of the
non-nucleoside reverse transcriptase inhibitors during concurrent rifampicin-containing tuberculosis therapy: one size does not fit all. Expert
Opin Drug Metab Toxicol 2010; 6: 55-68.
37. Manosuthi W, Ruxrungtham K, Likanonsakul S, Prasithsirikul W, Inthong
Y, Phoorisri T, et al. Nevirapine levels after discontinuation of rifampicin
therapy and 60-week efficacy of nevirapine-based antiretroviral therapy
in HIV-infected patients with tuberculosis. Clin Infect Dis 2007; 44: 141-4.


.. 2557

38. Marais BJ, Rabie H, Cotton MF. TB and HIV in children - advances in
prevention and management. Paediatr Respir Rev 2011; 12(1): 39-45.
39. Mycobacterial infections. Guidelines for the prevention and treatment of
opportunistic infections among HIV-exposed and HIV-infected children.
MMWR 2009; 58: 19-25.
40. Schenker S, Martin RR, Hoyumpa AM. Antecedent liver disease and
drug toxicity. J Hepatol, 1999; 31: 1098-105.
41. Dhiman RK, Saraswat VA, Rajekar H, Reddy C, Chawla YK. A guide to
the management to tuberculosis in patients with chronic liver disease.
JCEH, 2012; 2: 260-70.
42. Guidelines for Treatment of Tuberculosis in patients with Renal disease.
Queensland Tuberculosis Control Centre. http://www.health.qld.gov.au/
ph/documents/qtbcc/32537.pdf.
43. Shing-Chi Lau, Patrick Pa-Shing Yeung, Niko Kei-Chiu Tse, et al. Drug
prescription in renal diseases. Practical paediatric nephrology 2005; 40:
348-57.
44. Kumar R, Gupta N, Sabharwal A. Congenital tuberculosis. Indian J Pediatr,
2005; 72: 631-3.

107

108

.. 2557


.. 2557

.. 2552 4

1.
2.
3.
4.

()

1.
1. 2. (
1)

(Pulmonary Tuberculosis: PTB)

(PTB SS+)
1

109


.. 2557

110

(
)

(
)

PTB, SS+
PTB, SS neg

PTB, SS not done

EPTB

(PTB SS neg)
1)
- 2 (
collected sputum 1 )
-
- ( Fluoroquinolone
)

2)
(M. tuberculosis )


.. 2557

(PTB SS not done)

(Extrapulmonary Tuberculosis: EPTB)

/

- (Mediastinal and/or hilar lymph nodes) (Pleural effusion)
-

2.



6

(New)

1

111

112

.. 2557

(Treatment after default)

Treatment after interruption
2
Direct smear Culture

(Relapse) recurrent
(True relapse) (Re-infection)


Direct smear Culture

(Treatment change after failure)

(New patient regimen) 5 (Remained positive) (Became positive)

2

(Transfer in)

(Other)


.. 2557

1



(Bacteriologically negative relapse) Relapse
Extrapulmonary TB)

113

114

.. 2557

AFB

< 1
> 2
(Default)

(New)

(Treatment After Default:

TAD Treatment After
Interruption)

Treatment success

(Relapse)

Treatment failed

(Treatment Change
After Failure: TAF)

(Transfer in)

(Other)


.. 2557

3.
3
3

(Cure)

(Treatment completed)

(
)

(Treatment success)

(Treatment failure)
()
5
DST
MDR-TB

(Died)

(Default)
/ 2

(Transfer out)

115

116

.. 2557

Diagnose: MTB
DST: RMP+INH
(Gene Xpert)
Diagnose: MTB
DST: RMP
Diagnose: MTB
DST: RMP+INH

LPA

RT-PCR

LPA

Diagnose: MTB

PCR

Diagnose: MTB
DST: RMP+INH

RT-PCR

Diagnose: MTB
DST: RMP+INH

LPA

()

Sputum,
Isolated
Culture

1,500

sputum

1,500

Sputum,
Isolated
Culture
Sputum,
Body Fluid,
Body Tissue
Sputum
Isolated
Culture
Sputum,
Isolated
Culture

1,500

600

1,500

1,500

.. 2557

Rapid Molecular Testing

()
()

putum,
olated
ulture

1,500

2-7

utum

1,500

1-2

1,500

2-7

600

3-5

putum,
olated
ulture
putum,
ody Fluid,
ody Tissue
putum
olated
ulture
putum,
olated
ulture

1,500

2-7

1,500

2-7

02-212-2279
207

02-5903567-69
Fax 02-5903574

02-580-1593

02-580-3423
1267

117

118

.. 2557

Diagnose: MTB
DST: RMP+INH

MAS-PCR,
RT-PCR,
LPA

DST: RMP+INH

RT-PCR

Diagnose: MTB
DST: RMP+INH

RT-PCR

(Gene Xpert)
Diagnose: MTB
DST: RMP

RT-PCR

Diagnose: MTB

RT-PCR

DST: RMP+INH

RT-PCR

()

Sputum,
or Culture

850

Sputum,
Body Fluid,
Body Tissue,
Isolated Culture
Sputum
Isolated
Culture
sputum
Sputum,
Body Fluid,
Body Tissue,
Isolated Culture,
Paraflim block
Sputum,
Body Fluid,
Body Tissue,
Isolated Culture,
Paraflim block

1,500

1,500

1,500

2,000

2,000


.. 2557

()

()

putum,
Culture

850

2-7

. /
02-419-8256-7
.

1,500

2-7

02-419-7062
02-419-7063

1,500

2-7

032-310-761-3

1,500

1-2

034-542 031
121

2,000

3-5

. .

02-201-1399

putum,
ody Fluid,
ody Tissue,
olated Culture
putum
olated
ulture

utum

putum,
ody Fluid,
ody Tissue,
olated Culture,
raflim block
putum,
ody Fluid,
ody Tissue,
olated Culture,
raflim block

2,000

2-7

119

120

.. 2557

10

12
(TB )

Diagnose: MTB
DST: RMP+INH
(Gene Xpert)
Diagnose: MTB
DST: RMP
Diagnose: MTB
DST: RMP+INH
(Gene Xpert)
Diagnose: MTB
DST: RMP
(Gene Xpert)
Diagnose: MTB
DST: RMP
(Gene Xpert)
Diagnose: MTB
DST: RMP

()

LPA

Sputum,
Isolated Culture

1,500

RT-PCR

sputum

1,500

RT-PCR

Sputum,
Isolated Culture

1,500

RT-PCR

sputum

1,500

RT-PCR

sputum

1,500

RT-PCR

sputum

1,500

.. 2557

()

()

putum,
olated Culture

1,500

2-7

utum

1,500

1-2

putum,
olated Culture

1,500

2-7

utum

1,500

utum

utum

045-255-836

1-2

053-140-772

1,500

1-2

073-212-332
116
Fax 073-211-727

1,500

1-2

076-361-234
1580

121


.. 2557

122

/
(Culture)

(NTRL)

()

.
1

2
3
4
5
6
7
8
9
10
11
12
13
14


.. 2557

15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35

/
2

.
3

123


.. 2557

124

36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57

/

5

8
9

10


.. 2557

58
59
60
61
62
63
64
65
66
67
68

11

12
( 12 )

IOM

69
70
71
72
73
74

: .. 2556

125

126

.. 2557


.. 2557

Isoniazid

Rifampicin

10 mg/ml 60 ml 50 mg/ml 60 ml
tab 100 mg
powder 3 g
6
type 2
type 4

21

30

Ethambutol

Pyrazinamide

50 mg/ml 64 ml
tab 400 mg
8
type 1

40 mg/ml 50 ml
tab 500 mg
4
type 1

30

30

127


.. 2557

128

(vehicle)
( 2) (simple syrup)
methylcellulose
carboxymethyl cellulose
1

Isoniazid suspension 10 mg/ml

Isoniazid tab 100 mg 6

Vehicle type 2

1.
2. geometric proportion

3.
4. 60 ml
5.

21

sorbitol


.. 2557

Rifampicin suspension50 mg/ml

Rifampicin

1.5

Vehicle type 4

1.
2. glycerin
(paste)
3. geometric proportion

4.
5. 30 ml
6.

30

Ethambutol suspension50 mg/ml

Ethambutol tab 400 mg

Vehicle type 1

1.

129


.. 2557

130

2. geometric proportion

3.
4. 64 ml
5.

30

Pyrazinamide suspension 40 mg/ml

Pyrazinamide tab 500 mg 4

Vehicle type 1

1.
2. geometric proportion

3.
4. 50 ml
5.

30


.. 2557

Vehicle type 1 Vehicle type 2 Vehicle type 4

CMC Mucilage
70% Sorbitol
Glycerol (Glycerin)
pH
Paraben concentration
Sodium benzoate
Purified water
Simple syrup qs to

14%
20%
pH 5-6
1%
5%
100%

14%
20%
5%
pH 5-6
1%
qs to 100%

pH 5-6
0.1 %
100%

30
1
2 isoniazid




Isoniazid 21
5 21 26
26

131

132

.. 2557

21


.. 2557

133

134

.. 2557

1. 13

2.
23 .2555

1.
a. (First Line Drugs)
b. (MDR-TB Drugs)
2.
a. (AFB, CXR)


.. 2557

b. (Sputum Culture)
c. (Drug Sensitivity Testing : DST)
d. Molecular assay
3.
4.

1. Molecular assay
1
a.
4
b.
Re-treatment : (Relapse), 2 (Treatment After Default )
On-treatment :
3
Pre-treatment :
(Household MDR-TB contact)
c. Molecular assay
(Smear positive)

135

136

.. 2557

1
.
.
2. S olid or liquid media 1
a. Molecular assay ( 1

Solid or liquid )
b.
c.


.. 2557

1
Molecular assay Solid / Liquid Culture
& DST

Re-treatment

On-treatment

( 3 )
Pre-treatment
(new case)
Household MDR-TB
contact

Re-treatment

On-treatment
( 3)
Pre-treatment (new case)
Household
MDR-TB contact, HIV

( On
treatment
)

- Re-treatment On-treatment
1b
- . Molecular
assay

137

138

.. 2557

- . Molecular assay

-
Molecular assay
. .

- 1
. .

.
2556

1.
.


SMART TB
. .

1) (First Line Drugs)

Isoniazid (H) 100 mg
Rifampicin (R) 300 mg


.. 2557

Rifampicin (R) 450 mg

Pyrazinamide (Z) 500 mg
Streptomycin (S)
Ethambutol (E) 400 mg
Ethambutol (E) 500 mg

2) (MDR-TB Drugs)

Ethionamide 250 mg
Kanamycin 1 gm injection
Ofloxacin 200 mg
Para-Amino Salicylic acid (PAS) 1gm
Cycloserine 250 mg

3) Fixed Dosed Combination (FDC)

2 FDC : Rifampicin 300 mg + INH 150 mg Rifampicin 150 mg + INH 100 mg
4 FDC : Rifampicin 150 mg + INH 75 mg + pyrazinamide 400 mg + Ethambutol 275 mg

(MDR-TB Drugs)
MDR-TB Treatment center

Ofloxacin

139


.. 2557

140

2.
2.1
(Capitation)
.
AFB 20 /
o CAT 1,2,3 3 3 samples
(Slide)
o CAT 4 6 3 samples (Slide)

100 /
o CAT 1,2,3 2
o CAT 4 5
CAT1 = 2 HRZE/4HR
CAT2 = 2 HRZES/1HRZE/5HRE
CAT3 = 2 HRZ/4HR
CAT4 = (MDR TB)

2.2 (Culture & DST)

. 1

200 / (Solid or
Liquid)


.. 2557

200 / (Solid or
Liquid)
Molecular assay 850 /

.
(Culture & DST) Liquid media
2555
31 2555

3.



.


.

4.

141

142

.. 2557

.


.

(
2556 /
2, 74-82)

02 2520161-4


02 211-1841 122


.. 2557

..
..
..
.
..

.() .

..

..

.


..
..

..

..

143


.. 2557

144

..

..
..
..
..
..

..

. .
. .
.


.. 2557

1 hyperaeration

145

146

.. 2557

2 Gohns complex

3 Calcification


.. 2557

4 Miliary infiltration

5 Fibronodular infiltration cavity 14

147

148

.. 2557

6 Segmental atelectasis

7 Effusion


.. 2557

8 body

9 body T5-T9 Cold abscess

TB spine

149

150

.. 2557

10.1
10.2 subcondral Tibia


.. 2557

11 Hydrocephalus basal meningeal enhancement

151

152

.. 2557

12 TST (transverse diameter)