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Topic Review

*
**

1.
2.

3.

(American Thoracic Society .. 2537)
(British Thoracic Society .. 2540)
(WHO Tuberculosis Unit .. 2540)
International Union Against Tuberculosis and Lung Disease
(IUATLD .. 2540)

100

**

106

(DNA)


Mycobacterium
tuberculosis Robert Koch
2425 0.5 3

(acid-fast
bacilli)


10









-
2




5 1
2
.. 2534 .. 2541
1,900
3 .. 2544

8.5 23

95



1-2

4

(multi-drug
resistance) ..
2535

.. 2536
4

12 179
1 1
6


.. 2534








2.53 .. 2539-2541

 19 4 - 2549

(gold)

6

50
2481 Rich Follis 7
(Johns Hopkins University)
(sulfanilamide)

Schatz Waksman streptomycin
.. 24878
Streptomyces griseus .. 2489 the
British Medical Research Council (BMRC)
streptomycin



92
streptomycin 3
9
Lehmann 10
(para-aminosalicylic acid, PAS)
PAS
4
.. 2491 streptomycin
PAS
4 11
streptomycin 10 PAS
.. 2495 Hoffman
LaRoche, ER. Squibb & Sons Bayer
isoniazid

107

isoniazid streptomycin
streptomycin PAS .
2498-2499 streptomycin 2.5,
PAS 2.6, isoniazid 1.3
2 24

Pyrazinamide (PZA) .. 2495

isoniazid Lederle Research
Laboratories .. 2503 rifampicin


18-24 6
12
Ethambutol (EMB) .. 2504

Madras



directly observed therapy (DOTS) ..
2501

(Food and Drug Administration, FDA)
isoniazid, pyrazinamide,
rifampicin, ethambutol, rifapentine, cycloserine,
ethionamide, capreomycin, PAS
streptomycin

rifabutin
aminoglycosides
(amikacin,
kanamycin), fluoroquinolones (ciprofloxacin,
moxifloxacin, levofloxacin) ( 1)

108

1.
First-line drugs

Second-line drugs

Isoniazid
Rifampin
Rifapentine
Rifabutin*
Ethambutol
Pyrazinamide
Streptomycin

Cycloserine
Ethionamide
Levofloxacin*
Moxifloxacin*
Gatifloxacin*
Para-aminosalicylic acid
Amikacin/kanamycin*
Capreomycin

* (Food and Drug Administration, FDA)

(shortcourse chemotherapy)
13
6 streptomycin isoniazid,
streptomycin, isoniazid rifampicin,
streptomycin, isoniazid pyrazinamide,
streptomycin, isoniazid and thioacetazone
18 isoniazid
thioacetazone 3
streptomycin, isoniazid rifampicin

314




(American Thoracic Society
.. 2537) (British Thoracic
Society .. 2540)
(WHO Tuberculosis

Unit .. 2540) International Union Against

Tuberculosis and Lung Disease (IUATLD ..
2540)





100
15,16,17,18
(isoniazid)

 19 4 - 2549
(isoniazid)
.. 2495

(mycolic acid) 19

( 1)

109

3-5
1 300
1-2

(acetylation)

1 20

110

(aminotranferases)
5
10-20

Black 21
114

35

10 50
2
14 .. 251522
2

1 23 Steele
24 ( 2) .. 2503-2523
0.6 Nolan
25 7 0.1-0.3
2.7
(rifampicin)
65
4.6
2.6

(cytochrome P 450)
(dilantin)

(aminotranferases) 3-5

2 24

0.2



(pyridoxine) 25

(Stevens Johnson
syndrome)

(antinuclear antibodies) 20
1

 19 4 - 2549

(monoamine)

(phenytoin)
(carbamazepine)

(rifamycins)

(rifampin) (rifabutin)
(rifapentine)

(RNA)
transcription ( subunit of RNA polymerase) ( 1)

10
1 600



( 6)
( 0.6)

0

111

2.7

1.1

2-3
(influenza) 0.40.7
1-2
8



3-6 Grosset
26
1200-1800
35-57
900
22-31 10
600


0.1

450 (cytochrome P 450)

(methadone)
(glucocorticoids)



(rifalazil, RLZ) (KRM1648
benzoxazinorifamycin)
27

112

40

(ethambutol)

(pyrazinamide)

(pyrazinamide)

(short-chain,
fatty-acid precursors) ( 1)
20-25 1



25-35
1


25
1
430 Yee 28 .. 2533
2542
(
6 4
3)

(ethambutol)




29
15-20 1

20

( 18
30 1
)
Leibold30


15 1

(Snellen chart)
(Ishihara tests)

 19 4 - 2549

113

(ethionamide)

(cycloserine)

(cycloserine)


(peptidoglycan) 10-15
1
1,000 500-750
2

50



Murray31 500
2 16%
500
3
(pyridoxine) 100-200

(ethionamide)

(mycolic acid) 1520 1
500-750 1-2



2

1-2


30 250500

114

(streptomycin)

15 1
10 1
59
5-7 2-4
2-3



streptomycin
100-120

(amikacin,
kanamycin, or capreomycin) ..
2490 32 2



kanamycin)

(amikacin

streptomycin

streptomycin
Black
33 amikacin
24

amikacin kanamycin
streptomycin

(capreomycin)
(capreomycin)

15 1
5-7
2-3 2-3

and

 19 4 - 2549





(para-aminosalicylic
acid)

(paraaminosalicylic acid)
812 2-3 34
7,492 38 ( 0.5)



1-3
(fluoroquinolones)

115

(fluoroquinolones)
(levofloxacin)
(moxifloxacin, MXF)
(gatifloxacin) 35

(MXF-RIF-PZA)

(INH-RIF-PZA)
(DNA)




500-1,000
400

16-20

( 0.51.8) (
0.5)
( 0.2-0.4)



80

50

(oxazolidinones)

116

50S (ribosomel 50S subunits)

5 23S (domain
V of the 23S rRNA)

(azole drugs)

Miconazole

(miconazole)
(clotrimizole)

450 (cytochrome P 450
homologs)
450

(mutation)

isoniazid streptomycin
1 106 1 108
1 105

1 1014 2

80

8-24





(
3)




(PPD-tuberculin skin test)
Mantoux

48-72

- 5

 19 4 - 2549
- 10


4
- 15

117

.. 2536-2537 14

58

3.
INH : isoniazid, RIF : rifampicin, PZA : pyrazinamide, EMB : ethambutol, SM : streptomycin, TB :
tuberculosis, CDC : Center for Diseases Control and Prevention

- Obtain bacteriologic confirmation and susceptibility testing for patients with TB or

suspected of having TB
- Place persons with suspected or confirmed smear-positive pulmonary or laryngeal TB in
respiratory isolation until noninfectious
- Begin treatment of patients with confirmed or suspected TB disease with 1 of the
following drug combinations, depending on local resistance patterns: INH, RIF, PZA, or
INH, RIF, PZA, EMB, or INH, RIF, PZA, SM
- Report each case of TB promptly to the local public health department
- Perform HIV testing for all patients with TB
- Treat patients with TB caused by a susceptible organism for 6 months, using an ATS/
CDC-approved regimen
- Reevaluate patients with TB who are smear positive at 3 months for possible nonadherence
or infection with drug-resistant bacilli
- Add >2 new antituberculosis agents when TB treatment failure is suspected
- Perform tuberculin skin testing on all patients with a history of >1 of the following: HIV
infection, injection drug use, homelessness, incarceration, or contact with a person with
pulmonary TB
- Administer treatment for latent TB infection to all persons with latent TB infection, unless
it can be documented that they received such treatment previously

118

4
3

2 2
(intensive phase) 4 4
(continuation or
maintenance phase) 2

6 (26
)

( 4-5) INH,
RIF, PZA, EMB 2
( 1) 2
2 6 ( 2)
3 ( 3)
The British
Medical Research Council (BMRC)

4




4-8

 19 4 - 2549

119

4.
1 : isoniazid, R : rifampicin, 2 : pyrazinamide, E : ethambutol, wk : week

Regimen
1

Drugs
IRZE

Initial phase
Interval and dose
7 days/wk for 56 doses
(8 weeks) or
5 days/wk for40 doses
(8 weeks)

Drugs
IR

IR
2

3
4

IRZE

IRZE
IRE

7 days/wk for 14 doses

IR
(2 weeks) then
twice weekly for 12 doses
(6 weeks) or
5 days/wk for 10 doses
(2 weeks) then
twice weekly for 12 doses
(6weeks)
3 times/wk for 24 doses IR
(8 weeks)
7 days/wk for 56 doses
IR
(8 weeks) or
5 days/wk for 40 doses
(8 weeks)
IR

Continuation phase
Interval and dose
7 days/wk for 126 doses
(18 weeks) or
5 days/wk for 90 doses
(18 weeks)
Twice weekly for 36 doses
(18 weeks)
Twice weekly for 36 doses
(18 weeks)

3 times/wk for 54 doses

(18 weeks)
7 days/wk for 217 doses
(31 weeks) or
5 days per week for 155 doses
(31 weeks)
Twice weekly for 62 doses
(31 weeks)

120

5.

Isoniazid
Rifampin
Pyrazinamide
Ethambutol
Streptomycin

5 ./. 300 .
10 ./. 600 .
15-30 ./. 2 .
15-25 ./.
15 ./. 1 .

15 ./. 900 .
10 ./. 600 .
50-70 ./. 4 .
50 ./.
25-30 ./. 1.5 .

15 ./. 900 .
10 ./. 600 .
50-70 ./. 3 .
25-30 ./.
25-30 ./. 1.5 .

(continuation or maintenance
phase) 2
4 (18 )
1 2
3
9
3
- (cavity)
2
-

90

6


12 ( 6)

 19 4 - 2549

121

6.

-
-
-
-*
-*
-
-
-

6
6-9
6
6
9-12
6
6
6

2




2

10-15
1
2
42

9-12
2 3-9 4-6

3-5

.. 2532
1

122

312
5
308

(
5.4 0.9 4
1.1 )
.. 2537-2540

(rifamate)
150 300
(rifater)
50 120
300
4

2




DOTs
(WHO)
International Union Against Tuberculosis and
Lung Disease (IUATLD)


7

DOTs

7. WHO
R : rifampicin, H : isoniazid, Z : pyrazinamide, E : ethambutol

Rifampicin + isoniazid +
pyrazinamide + ethambutol
Rifampicin + isoniazid + pyrazinamide
Isoniazid + ethambutol
Thioacetazone + isoniazid

R 150 mg + H 75 mg + Z 400 mg + E 275 mg

R 150 mg + H 75 mg + Z 400 mg
R 60 mg + H 30 mg + Z 150 mg (paediatric)
R 60 mg + H 30 mg (paediatric)
H 150 mg + E 400 mg
T 50 mg + H 100 mg
T 150 mg + H 300 mg

 19 4 - 2549

(bioavailability)

Dye 46
136
3.2



(isoniazid)
(rifampicin)

123

( 7)

( 8)



directly observed therapys (DOTs)
Weis
DOTs

.. 2537-2543 WHO48

124

7.
DOTs : directly observed therapy

-
- 3 1

- 4-6
- DOT
-
-
-
-
- 2
- M. bovis M. tuberculosis

 19 4 - 2549

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