1. Taiwan Guidelines for TB Diagnosis & Treatment 2013 8

2. I 2006 200572.5201253 27% 2004 200620082011 20133 3. II 2001 7 2004 2011 3 2012 4. III 2012 7 EMB INH INH Streptomycin AKuriT-4 ) AKuriT-3 18 5. IV 2013 6. i i - ii - 1. iii - 1. 2. 7-1 8 (mono- resistance) (poly-resistance) (Mono resistance) (Poly resistance) 8 Extensive drug-resistance, XDR Extensive drug resistance, XDR 8 isoniazidrifampin isoniazidrifampin MDR XDR-TB 8 (latent tuberculous infection) (preventive therapy) (latent tuberculosis infection) 9 // (http://www.cdc.gov.tw/) // (http://www2.cdc.gov.tw/lp.asp?ctNode=2415& CtUnit=1404&BaseDSD=7&mp=1) 9 (Relapse) (Treatment after failure) (Relapse) (Treatment after failure) Multidrug-resistant tuberculosis, MDR-TB 7. ii Multidrug-resistant tuberculosis, MDR-TB isoniazid rifampin isoniazid rifampin line probe assay Isoniazid Rifampicin 9- 10 (cured) (treatment completed) (failed) (Cured) (Treatment completed) (Failed) 14 4 5 21- 22 4.1 4 INH + RMP + PZA Rifater INH + RMP Rifinah INH + RMP + PZA Rifater INH + RMP Rifinah INH + RMP + PZA + EMB AKuriT-4 INH + RMP +EMB AKuriT-3 9 ethambutol isoniazid rifampin ethambutol ethambutol 10 rifampicinrifabutin 8. iii 27 4.3 4 28 4.4.3 1 2. 1 isoniazid 2.Isoniazid isoniazid critical concentration isoniazid 30 4.4.4 2 D. Rifampicin + ethambutol INH + PZA + FQ + TBN + KM 6 4 INH + PZA + FQ + TBN 18 G. Rifampicin + pyrazinamide INH + EMB + FQ + TBN + KM 6 4 INH + EMB + FQ + TBN 18 D.Rifampicin + ethambutol INH + PZA + FQ + TBN + KM 2 6 INH + PZA + FQ + TBN 18 G. Rifampicin + pyrazinamide INH + EMB + FQ + TBN + KM 2 6 INH + EMB + FQ + TBN 18 34 4.6.4 2 D. Rifampicin + ethambutol 9. iv D. Rifampicin + ethambutol INH + PZA + FQ + TBN + KM 6 4 INH + PZA + FQ + TBN 18 INH + PZA + FQ + TBN + KM 2 6 INH + PZA + FQ + TBN 18 35 4.6.4 2 H H. Isoniazid + ethambutol + pyrazinamide RMP + FQ + TBN + KM 2 RMP + FQ + TBN 9 Isoniazid isoniazid isoniazid 36 4.8.1Child AB Child AB Child 4-3 39 4.11.2 2. HIV 4.1 3 2 ; 3 2. 3 3. HIV 4.1 3 50 4-1 8 8. INH + EMB + PZARMP + FQ + TBN + KM 2RMP + FQ + TBN 9 10. v 55 4-3. Child-Pughs Classification 4-4. Grading of hepatic encephalopathy 57 5.1.2 4. BC HBsAg Anti-HCV AbAnti-HIV Ab 5. 248 CBCASTALT bilirubinuric acidBUNcreatinine BC 6.ethambutol ethambutol 4.BC BC HBsAg anti-HCV Ab anti-HIV Ab 5. 248CBC ASTALTbilirubinuric acidBUNcreatinineB C 6.ethambutol ethambutol 58 5.2.1 pyrazinamide (4) 13 mg/dL (5) pyrazinamide (4) 13 mg/dL (5)toxic epidermal necrolysisStevens-Johnson 11. vi Steven-Johnson syndrome syndrome 58 59 total bilirubin2 mg/dL total bilirubin3 mg/dL 61 RMPINHhemolytic anemiaagranulocytosisEMB PZA INHEMBPZA rifabutin RMPINHhemolytic anemiaagranulocytosisEMBPZA INHEMBPZA 63 78 7.Tan WC, Ong CK, Lo Kang SC, et al. Two years review of cutaneous adverse drug reaction from first line anti-tuberculous drugs. Med J Mlaysia 2007;;62:143-6. 8.Wang JY, Liu CH, Hu FC, et al. Risk factors of hepatitis during anti-tuberculous treatment and implications of hepatitis virus load. J Infect 2011;62:448-55. 69 6.1.3 Pyrazinamide (PZA) PZA PZA 13 mg/dL 12. vii 13 mg/dL PZA allopurinol PZA PZA PZABenzbromarone Urinorm 70 6.1.4 Ethambutol (EMB) : 139 EMB15 mg/kg 70- 71 6.1.5 AKuriT-4 (AKT-4) AKuriT-3 (AKT-3) 72 6.2.1 Streptomycin (SM) (1). 1515-20mg/kg 1000 mg 120 gm SM (1). 1515-20mg/kg 1000 mg 120 gm (MDR-TB) MDR-TB 72 6.2.1 Streptomycin (SM) SM:SM Streptomycin (1)loop diuretics (2)non-depolarizing muscle relaxants (3)amphotericin Bfoscarnetcidofovir 73 6.2.3Rifabutin (RFB) 3 (3) (3) Ccr95%)(2) 50%80% NAA NAA 3.3.6.3 NAA NAA NAA PCR NAA NAA NAA 3.3.6.4 2008 6 line probe assay rifampin isoniazid 41. 16 2010 3.3.7 2008 3.4 3.4.1 1. 2. 2008 41% 76% X X 3. NAA X NAA 3.4.2 3-1 2~3 X 1. X 2. X X (1). X2~3 42. 17 NAA(3-1) (fluoroquinolones aminoglycosides)1X X X (2). X 2~3 NAA(3-1) (fluoroquinolonesaminoglycosides)1 XX X (3). X 2~3 (2) 43. 18 3-1 ( 2~3 ) X 1 1 2 3 2~3 4 5 6 7 2 () 2 ) () () 3,4 2,3,4 6 5 ( fluoroquinolone aminoglycoside ) 1 7 44. 19 3-1(nucleic acid amplification test) 1. (Reasonable approach)1 2. (1) (2) 2 3. 3 (1) AFB(+) NAA(+) (2) AFB(+) NAA (-) (3) AFB(-) NAA(+) (4) AFB(-) NAA(-) 1. CDC 2009 (standard practice)(reasonable approach) 2. NAA 3. 4. AFB: acid-fast bacilli, NAA test: nucleic acid amplification test 45. 20 1. American Thoracic Society and the Centers for Disease Control and Prevention. Diagnostic standards and classification of tuberculosis in adults and children. Am J Respir Crit Care Med 2000;161: 1376-95. 2. Tuberculosis Coalition for Technical Assistance. International standards for tuberculosis care. 2nd edition, 2009. 3. Burrill J. Williams CJ. Bain G, et al. Tuberculosis: a radiologic review. RadioGraphics 2007; 27:125573. 4. Schaaf HS, Collins A, Bekker A, et al. Tuberculosis at extremes of age. Respirology 2010; 15: 747-63. 5. Andreu J, Cceres J, Pallisa E, et al. Radiological manifestations of pulmonary tuberculosis. Eur J Radiology 2004; 51: 13949. 6. Jeong YJ, Lee KS. Pulmonary tuberculosis: up-to-date imaging and management. AJR 2008; 191:83444. 7. Lee JJ, Chong PY, Lin CB, et al. High resolution chest CT in patients with pulmonary tuberculosis: characteristic findings before and after antituberculous therapy. Eur J Radiology 2008; 67: 1004. 8. Lee JJ, Suo J, Lin CB, et al. Comparative evaluation of the BACTEC MGIT960 system with solid medium for isolation of mycobacteria. Int J Tuberc Lung Dis 2003; 7: 569-74. 9. Palomino JC. Nonconventional and new methods in the diagnosis of tuberculosis: feasibility and applicability in the field. Eur Respir J 2005; 26: 33950. 10. Centers for Disease Control and Prevention. Controlling tuberculosis in the United States. Recommendations from the American Thoracic Society, CDC, and the Infectious Diseases Society of America. MMWR Morb Mortal Wkly Rep 2005; 54:No. RR-12. 11. Centers for Disease Control and Prevention. Updated guidelines for the use of nucleic acid amplification tests in the diagnosis of tuberculosis. MMWR Morb Mortal Wkly Rep 2009; 58:7-10. 46. 21 INHisoniazid RMPrifampicin PZApyrazinamide EMBethambutol FQ fluoroquinolone SMstreptomycin KMkanamycin TBNprothionamide PAS para-aminosalicylic acid CScycloserine cohort 5 4.1 4 INH + RMP + PZA + EMB 2 INH + RMP + EMB 4 1. 4-1 4-1 2. 30 3. 6-2 6-3 4. INH + RMP + PZA Rifater INH + RMP Rifinah INH + RMP + PZA + EMB AKuriT-4 INH + RMP +EMB 47. 22 AKuriT-3 5. 1 DOTDirectly Observed Treatment 6. 10 pyridoxinevitamin B6 HIV cycloserine isoniazid16-20 mg/kg/day 7. high-dose intermittent therapy, HDIT 8. Rifabutin rifampicin leukopenia2% rifampicincross resistance87% 3 8-1. HIV 9 8-2. rifampicin rifabutin 8-3.rifampicin Drug sensitivity test, DST rifabutin 9.ethambutolisoniazid rifampinethambutol ethambutol 10. rifampicinrifabutin 4.2 4 1. rifampicin rpoB gene mutation 2. Rifampicin 48. 23 3. Isoniazid isoniazid 4.2.1 4-2 1. INH + RMP + PZA + EMB + SM 2. rifampicin INH + PZA + EMB + FQ + TBN + KM 3. rifampicin INH + RMP + PZA + EMB 4. 4.4 5. 5-1. INH + RMP + PZA + EMB + SM 2 INH + RMP + PZA + EMB 1 INH + RMP + EMB 5 5-2. rifampicin INH + PZA + EMB + FQ + TBN + KM 6 4 INH + PZA + EMB + FQ + TBN 18 5-3. rifampicin INH + RMP + PZA + EMB 6-9 4.2.2 2 2 4 1. 49. 24 2. 3. 4. 4-3 1. INH + RMP + PZA + EMB + SM 2. rifampicin INH + PZA + EMB + FQ + TBN + PAS/CS + KM 3. rifampicin INH + RMP + PZA + EMB + SM 4. 4.4 5. 5-1. rifampicin INH + RMP + PZA + EMB + SM 2 INH + RMP + PZA + EMB 1 INH + RMP + EMB 5 5-2. rifampicin INH + PZA + EMB + FQ + TBN + PAS/CS + KM 6 4 INH + PZA + EMB + FQ + TBN + PAS/CS 18 4.2.3 1. 2. 2 3. 1. 4.2.3 4.4 2. 1 non-viable bacteria, NVB Non-tuberculous Mycobacteria, NTM 2 3 immune reconstruction inflammatory syndrome, IRIS 2-1. 50. 25 2-2. turnaround time 2-3. 2-4. 3. 3 empirical treatment 4-4 1. INH + RMP + PZA + EMB + FQ + TBN + CS + KM 2. rifampicin INH + RMP + PZA + EMB + SM 3. rifampicin INH + PZA + EMB + FQ + TBN + PAS/CS + KM 4. 4.4 5. 5-1. INH + RMP + PZA + EMB + FQ + TBN + CS + KM 6 4 INH + RMP + PZA + EMB + FQ + TBN + PAS/CS 18 5-2. rifampicin INH + PZA + EMB + FQ + TBN + PAS/CS + KM 6 4 INH + PZA + EMB + FQ + TBN + PAS/CS 18 5-3. rifampicin INH + RMP + PZA + EMB + SM 2 INH + RMP + PZA + EMB 1 INH + RMP + EMB 5 4.3 1. 51. 26 NTM rifampicin 2. 3. 4. NTM 5. 6. adherence DOT 1. cohort 2. 3. 52. 27 4. 5. 6. 7. DOT 8. 2 RMP 4.4 4.4.1 1. isoniazid rifampicin sensitivityspecificity 95%ethambutol streptomycin predictive value of resistance treatment after failureisoniazid rifampicin 90% 2. 34 53. 28 DOT 4.3 3. 3-1. 3-2. 3-3. 3-4. DOT 3-5. 5 4.4.2 INH + RMP + PZA 2 INH + RMP 4 4.4.3 1 A. Isoniazid 1. RMP + PZA + EMB INH 6-9 2. INH + RMP + PZA + EMB 2 INH + RMP + EMB 7 1. pyrazinamide 2 2. Isoniazid isoniazid critical concentration isoniazid B. Rifampicin INH + PZA + EMB 18 Ethambutol pyrazinamide 54. 29 C. Ethambutol INH + RMP + PZA 2 INH + RMP 4 D. Pyrazinamide INH + RMP 9 Pyrazinamide 4.4.4 2 2 1. 2. Central Reference Lab. 3. A. Isoniazid + rifampicin PZA + EMB + FQ + TBN + KM 6 4 PZA + EMB + FQ + TBN 18 B. Isoniazid + rifampicin + pyrazinamide/ethambutol FQ + TBN + PAS/CS + KM PZA/EMB 6 4 FQ + TBN + PAS/CS PZA/EMB 18 C. Isoniazid + ethambutol RMP + PZA + TBN + SM 2 RMP + PZA + TBN 55. 30 9 streptomycin D. Rifampicin + ethambutol INH + PZA + FQ + TBN + KM 2 6 INH + PZA + FQ + TBN 18 E. Pyrazinamide + ethambutol INH + RMP 9 F. Isoniazid + pyrazinamide RMP + EMB + SM 2 RMP + EMB 9 streptomycin G. Rifampicin + pyrazinamide INH + EMB + FQ + TBN + KM 2 6 INH + EMB + FQ + TBN 18 1. poly-resistant 2. fluoroquinolones levofloxacin moxifloxacin cycloserine pyridoxine 3. isoniazid/ethambutol/pyrazinamide 4. 56. 31 4-1. 4-2. 4 4-3. FEV1 0.8-1.0 L 4.5 1. 2. DOT 3. 1. 2. isoniazid 600 mg 3. 2 3 3-1. 3-2. bioavailability 3-3. absorption 4.6 1. 5 4.6 2. 4.6.34.6.4 4.6.14.6.2 4.6.34.6.4 3. rifampicin rifabutin 4. prothionamidepara-aminosalicylic acid 4.6.1 1 A. Isoniazid 57. 32 RMP + PZA + EMB 9 B. Rifampicin INH + PZA + EMB + SM 2 INH + PZA + EMB 18 streptomycin C. Ethambutol INH + RMP + PZA 6 D. Pyrazinamide INH + RMP + EMB 9 4.6.2 2 2 A. Isoniazid + rifampicin PZA + EMB + FQ + TBN + KM 6 4 PZA + EMB + FQ + TBN 18 B. Isoniazid + rifampicin + pyrazinamide/ethambutol FQ + TBN + PAS/CS + KM PZA/EMB 6 4 FQ + TBN + PAS/CS PZA/EMB 18 C. Isoniazid + ethambutol RMP + PZA + TBN + SM 2 RMP + PZA +TBN 9 58. 33 streptomycin D. Rifampicin + ethambutol INH + PZA + FQ + TBN + PAS/CS + KM 6 4 INH + PZA + FQ + TBN 18 E. Ethambutol + pyrazinamide INH + RMP + FQ + TBN + KM 2 INH + RMP + FQ + TBN 9 F. Isoniazid + pyrazinamide RMP + EMB + FQ + TBN + KM 2 RMP + EMB + FQ + TBN 9 G. Rifampicin + pyrazinamide INH + EMB + FQ + TBN + PAS/CS + KM 6 4 INH + EMB + FQ + TBN 18 4.6.3 1 A. Isoniazid RMP + PZA + EMB 6-9 B. Rifampicin INH + PZA + EMB 18 Ethambutol pyrazinamide 59. 34 C. Ethambutol INH + RMP + PZA 2 INH + RMP 4 D. Pyrazinamide INH + RMP 9 4.6.4 2 A. Isoniazid + rifampicin PZA + EMB + FQ + TBN + KM 6 4 PZA + EMB + FQ + TBN 18 B. Isoniazid + rifampicin + pyrazinamide/ethambutol FQ + TBN + PAS/CS + KM PZA/EMB 6 4 FQ + TBN + PAS/CS PZA/EMB 18 C. Isoniazid + ethambutol RMP + PZA + TBN + SM 2 RMP + PZA + TBN 9 D. Rifampicin + ethambutol INH + PZA + FQ + TBN + KM 2 6 INH + PZA + FQ + TBN 18 E. Ethambutol + pyrazinamide INH + RMP 9 F. Isoniazid + pyrazinamide RMP + EMB + SM 2 RMP + EMB 9 streptomycin 60. 35 G. Rifampicin + pyrazinamide INH + EMB + FQ + TBN + KM 2 6 INH + EMB + FQ + TBN 18 H. Isoniazid + ethambutol + pyrazinamide RMP + FQ + TBN + KM 2 RMP + FQ + TBN 9 Isoniazid isoniazid isoniazid 4.7 4.7.1 1. 2. rifampicin 50 g 3. 4.7.2 1. pyrazinamide isoniazid pyridoxine 2. trimester aminoglycosidesprothionamide 3. 4. 4.8 4.8 61. 36 1. isoniazidrifampicinpyrazinamide multi-drug resistance, MDR 2. EMB + FQ + SM 2-1. INH + RMP 4 2-2. 3 ethambutol streptomycin streptomycin 7% 2-3. Fluoroquinolones 2-4. Streptomycin 18 1 2-5. fluoroquinolones 3. 4. INH + RMP + EMB 5. 4.8.1 4-5 4.8.1 4.8.1 Child AB Child 4-3 streptomycin 1. 7-10 2 2. RMP + EMB + SM 7-10 3. 7-10 3-1. INH + RMP + EMB + SM 7-10 3-2. rifampincin 4. 3-1 INH + RMP + EMB + SM 62. 37 4-1. pyrazinamide streptomycin INH + RMP + EMB 4-2. isoniazid 5. 3-2 EMB + SM4-2 RMP + EMB + SM INH + EMB + SM3-2RMP + PZA + EMB + SM 4-2 7-10 6. 7-10 6-1. 3-2 INH + EMB + SM INH + PZA + EMB + SM4-2 RMP + PZA + EMB + SM streptomycin RMP + PZA + EMB 6-2. 3-2 INH + EMB + SM isoniazid 84-2 RMP + PZA + EMB + SM pyrazinamide 4.6.2 4.6.4isoniazid + pyrazinamide 7. 6-1 INH + PZA + EMB + SM 3-2 7-1. 4.6.1 4.6.3rifampicin 7-2. 4.6.2 4.6.4rifampicin + pyrazinamide 8. 6-2 EMB + SM 23 pyrazinamide 8-1. 4.6.2 4.6.4 isoniazid + rifampicin 8-2. 4.6.2 4.6.4isoniazid + rifampicin + pyrazinamide 9. 7 4.8.2 Child C Child C INH + RMP + EMB EMB + FQ + TBN/PAS + CS + KM 4.9 63. 38 Ccr < 30 ml/minute 4.9.1 A. 1. Isoniazidrifampicin isoniazid pyridoxine 2. Ethambutol pyrazinamide 3 3. B. 1. Cycloserineaminoglycosideslevofloxacin ethambutol 2. Prothionamidepara-aminosalicylic acidmoxifloxacin 3. 4.10 4.10.1 4.10.2 transamin 4.10.3 2 1. 2. 4.11 4.11.1 1. 2. 3. 4. 4-1. 1 1 64. 39 4-2. 1 4-3. 4.11.2 1. 2 4.1 3 6 2. 3. HIV 4.1 3 65. 40 1. World Health Organization. Treatment of Tuberculosis: Guidelines -- 4th ed. World Health Organization ;WHO/HTM/TB/2009.420 2. Management of Tubeculosis. A Guide to the Essentials of Good Practice, 6th ed. International Union Against Tuberculosis and Lung Disease, Paris 2010. 3. American Thoracic Society, Centers for Disease Control and Prevention, Infectious Disease Society of America. Treatment of tuberculosis. Am J Respir Crit Care Med 2003;167:603-62. 4. World Health Organization. Treatment of Tuberculosis: Guidelines for the programmatic management of drug-resistant tuberculosis emergency update 2008. World Health Organization ;WHO/HTM/TB/2008.402 5. Chiang C-Y, Schaaf HS. Management of drug-resistant tuberculosis. Int J Tuberc Lung Dis 2010; 14: 672-82. 6. Caminero A, Sotgiu G, Zumla A, et al. Best drug treatment for multidrug-resistant and extensively drug-resistant tuberculosis. Lancet Infect Dis 2010;10: 6219. 7. Kim SJ. Drug-susceptibility testing in tuberculosis: methods and reliability of results. Eur Respir J 2005; 25: 5649. 66. 41 4-1 1 1 1 2 3 4 5 2 (4.2.2) (4.1) 1 (4.2.1) 4.3 4.4 (4.2.2) 1 (4.1) 3 2 (4.2.3) (4.2.3) 3 2 67. 42 4-2 1INH + RMP + PZA + EMB + SM 2 INH + RMP + PZA + EMB 1 INH + RMP + EMB 5 2INH + PZA + EMB + FQ + TBN + KM 6 4 INH + PZA + EMB + FQ + TBN 18 3INH + RMP + PZA + EMB 6-9 RMP 4.4 RMP 1 RMP 3 2 4.4 4.11 4.11 4.4 4.11 68. 43 4-3 1INH + RMP + PZA + EMB + SM 2 INH + RMP + PZA + EMB 1 INH + RMP + EMB 5 2INH + PZA + EMB + FQ + TBN + PAS/CS + KM 6 4 INH + PZA + EMB + FQ + TBN + PAS/CS 18 3INH + RMP + PZA + EMB + SM 2 INH + RMP + PZA + EMB 1 INH + RMP + EMB 5 RMP 4-4 RMP 1 RMP 3 2 4.4 4.11 2 4.11 4.11 4.4 4 1. 2. 3. 4. 69. 44 4-4 1INH + RMP + PZA + EMB + FQ + TBN +CS + KM 64INH + RMP + PZA + EMB + FQ + TBN +CS 18 2INH + PZA + EMB + FQ + TBN + PAS/CS + KM 6 4 INH + PZA + EMB + FQ + TBN + PAS/CS 18 3INH + RMP + PZA + EMB + SM 2 INH + RMP + PZA + EMB 1 INH + RMP + EMB 5 RMP 4-4 RMP 1 RMP 3 2 4.4 4.11 4.11 4.4 4.11 70. 45 4-5 Child C EMB+FQ+ TBN/PAS+ CS+KM baseline 5-7 RMP+EMB+SM 7-10 INH+RMP+EMB+SM 7-10 EMB+SM 5-7 5-7 INH+EMB+SM 7-10 INH+ RMP+ EMB1 9 1 2 3-1 3-2 4-1 5 INH+RMP +EMB INH+ RMP+EMB 71. 46 1INH + RMP + EMB 9 2RMP + PZA + EMB 9 3RMP + EMB + FQ + TBN + KM 2 RMP + EMB + FQ + TBN 9 4INH + PZA + EMB + SM 2 INH + PZA + EMB 18 5 INH + EMB + FQ + TBN + PAS/CS + KM 6 4INH + EMB + FQ + TBN 18 6PZA + EMB + FQ + TBN + KM 6 4 PZA + EMB + FQ + TBN 18 7EMB + FQ + TBN + PAS/CS + KM 6 4 EMB + FQ + TBN + PAS/CS 18 4.8.1 4.6.3/4.6.4 4.11 E-1 RMP+EMB+SM 5-7 RMP+PZA+EMB+SM 7-10 RMP+PZA+EMB2 9 E-1 PZA 4.6.2 INH+PZA 3 EMB+SM 5-7 INH+PZA+EMB+SM 7-10 4.6.2 RMP+PZA 5 4.6.2 RMP 4 5-7 PZA+EMB+SM 7-10 4.6.2 INH+RMP+PZA 7 4.6.2 INH+RMP 6 E-1 E-1 4-2 5 6-1 6-2 6-1 6-2 7-1 7-2 8 8-1 8-2 72. 47 4-1 INH + RMP + PZA + EMB 2 INH + RMP + EMB 4 1. INH + RMP + PZA + EMB + SM 2 INH+ RMP + PZA + EMB 1 INH + RMP + EMB 5 2. RMP INH + PZA + EMB + FQ + TBN + KM 6 4 INH + PZA + EMB + FQ + TBN 18 3. RMP INH + RMP + PZA + EMB 6-9 4. (2 ) 1. INH + RMP + PZA + EMB + SM 2 INH + RMP + PZA + EMB 1 INH + RMP + EMB 5 2. RMP INH + PZA + EMB + FQ + TBN + PAS/CS + KM 6 4 INH + PZA + EMB + FQ + TBN + PAS/CS 18 3. RMP INH + RMP + PZA + EMB + SM 2 INH + RMP + PZA + EMB 1 INH + RMP + EMB 5 4. 1. INH + RMP + PZA + EMB + FQ + TBN + CS + KM 6 4 INH + RMP + PZA + EMB + FQ + TBN + CS 18 2. RMP INH + PZA + EMB + FQ + TBN + PAS/CS + KM 6 4 INH + PZA + EMB + FQ + TBN + PAS/CS 18 3. RMP INH + RMP + PZA + EMB + SM 2 INH + RMP + PZA + EMB 1 INH + RMP + EMB 5 4. 73. 48 INH + RMP + PZA 2 INH + RMP 4 1 1. INHRMP + PZA + EMB INH 6-9 INH + RMP + PZA + EMB 2 INH + RMP + EMB 7 2. RMPINH + PZA + EMB 18 3. EMBINH + RMP + PZA 2 INH + RMP 4 4. PZAINH + RMP 9 2 1. INH + RMPPZA + EMB + FQ + TBN + KM 6 4 PZA + EMB + FQ + TBN 18 2. INH + RMP + PZA/EMBFQ + TBN + PAS/CS + KM PZA/EMB 6 4 FQ + TBN + PAS/CS PZA/EMB 18 3. INH + EMBRMP + PZA + TBN + SM 2 RMP + PZA + TBN 9 4. RMP + EMBINH + PZA + FQ + TBN + KM 6 4 INH + PZA + FQ+ TBN 18 5. PZA + EMBINH + RMP 9 6. INH + PZARMP + EMB + SM 2 RMP + EMB 9 7. RMP + PZAINH + EMB + FQ + TBN + KM 6 4 INH + EMB + FQ + TBN 18 74. 49 1 1 1. INHRMP + PZA + EMB 9 2. RMPINH + PZA + EMB + SM 2 INH + PZA + EMB 18 3. EMBINH + RMP + PZA 6 4. PZAINH + RMP + EMB 9 2 1. INH + RMPPZA + EMB + FQ + TBN + KM 6 4 PZA + EMB + FQ + TBN 18 2. INH + RMP + PZA/EMBFQ + TBN + PAS/CS + KM PZA/EMB 6 4 FQ + TBN + PAS/CS PZA/EMB 18 3. INH + EMBRMP + PZA + TBN + SM 2 RMP + PZA + TBN 9 4. RMP + EMBINH + PZA + FQ + TBN + PAS/CS + KM 6 4 INH + PZA + FQ + TBN 18 5. EMB + PZAINH + RMP + FQ + TBN + KM 2 INH + RMP + FQ + TBN 9 6. INH + PZARMP + EMB + FQ + TBN + KM 2 RMP + EMB + FQ + TBN 9 7. RMP + PZAINH + EMB + FQ + TBN + PAS/CS + KM 6 4 INH + EMB + FQ + TBN 18 75. 50 2 1 1. INHRMP + PZA + EMB 6-9 2. RMPINH + PZA + EMB 18 3. EMBINH + RMP + PZA 2 INH + RMP 4 4. PZAINH + RMP 9 2 1. INH + RMPPZA + EMB + FQ + TBN + KM 6 4 PZA + EMB + FQ + TBN 18 2. INH + RMP + PZA/EMBFQ + TBN + PAS/CS + KM PZA/EMB 6 4 FQ + TBN + PAS/CS PZA/EMB 18 3. INH + EMBRMP + PZA + TBN + SM 2 RMP + PZA + TBN 9 4. RMP + EMBINH + PZA + FQ + TBN + KM 6 4 INH + PZA + FQ + TBN 18 5. EMB + PZAINH + RMP 9 6. INH + PZARMP + EMB + SM 2 RMP + EMB 9 7. RMP + PZAINH + EMB + FQ + TBN + KM 6 4 INH + EMB + FQ + TBN 18 8. INH + EMB + PZARMP + FQ + TBN + KM 2 RMP + FQ + TBN 9 76. 51 4-1. 1. 2 2. 4.4 3 3. 6 4 4. 1 5 4.1 5. 4.2.1 10 6. 3 * 4.2.3 7 7. 4.2.2 8 8. 1 9 4.1 9. 4.2.1 10 10. 3 * 4.2.34.2.2 * 3 4 5 2 77. 52 4-2. R: INH 1 2010 1 7 2010 3 4 2009 /12 /28 R: INH, EMB RMP INH + RMP + PZA + EMB DOT DOT 1. :2009 /12 /282. :2009 /12 /283. :2009 /12 /28 4. :2010 /2 /3 5. :2010 /2 /3 6. :2010 /2 /3 7. : 8. : 9. : 10.: 11.: 12.: 1. :2009 /12 /282. :2009 /12 /283. :2009 /12 /28 4. :2010 /2 /3 5. :2010 /2 /3 6. :2010 /2 /3 7. : 8. : 9. : 10.: 11.: 12.: 2 2010 3 5 2010 4 1 2009 /12 /28 R: INH, EMB RMP INH + RMP + EMB DOT DOT 1. :2010 /3 /5 2. :2010 /3 /5 3. : 4. : 5. : 6. : 7. : 8. : 9. : 10.: 11.: 12.: 1. :2010 /3 /5 2. :2010 /3 /5 3. : 4. : 5. : 6. : 7. : 8. : 9. : 10.: 11.: 12.: 78. 53 3 2010 4 2 2010 5 27 2009 /12 /28 R: INH, EMB RMP INH + RMP + PZA + EMB + SM DOT DOT 1. :2010 /4 /5 2. :2010 /4 /5 3. : 2010/ 4/ 29 4. :2010 /4 /29 5.: 6.: 7. : 8. : 9. : 10.: 11.: 12.: 1. :2010 /4 /5 2. :2010 /4 /5 3. : 2010/ 4/ 29 4. :2010 /4 /29 5.: 6.: 7. : 8. : 9. : 10.: 11.: 12.: 4 2010 5 28 2010 6 10 2009 /12 /28 R: INH, EMB RMP INH + RMP + PZA + EMB + MFX + TBN + PAS + KM DOT DOT 1. :2010 /5 /31 2. :2010 /5 /31 3. : 4. : 5. : 6. : 7. : 8. : 9. : 10.: 11.: 12.: 1. :2010 /5 /31 2. :2010 /5 /31 3. : 4. : 5. : 6. : 7. : 8. : 9. : 10.: 11.: 12.: 79. 54 5 2010 6 11 2010 / 5 /31 R: INH, RMP, EMB RMP 2010 / 5 /31; INH + PZA + EMB + MFX + TBN + PAS + KM DOT DOT 1. :2010 /7 /12 2. :2010 /7 /12 3. : 2010/ 8/9 4. :2010 /8 /9 5. : :2010 /10 /4 6. : :2010 /10 /4 7. : 2010 /11 /1 8. : 2010 /11 /1 9. : 10.: 11.: 12.: 1. :2010 /7 /12 2. :2010 /7 /12 3. : 2010/ 8/9 4. :2010 /8 /9 5. : :2010 /10 /4 6. : :2010 /10/4 7. : 2010 /11 /1 8. : 2010 /11 /1 9. : 10.: 11.: 12.: RMP DOT DOT 1. : 2. : 3. : 4. : 5. : 6. : 7. : 8. : 9. : 10.: 11.: 12.: 1. : 2. : 3. : 4. : 5. : 6. : 7. : 8. : 9. : 10.: 11.: 12.: 80. 55 4-3. Child-Pughs Classification Factors Units 1 2 3 Serum bilirubin mg/dL 3.0 Serum albumin g/dL >3.5 2.8-3.5 6 INR 2.3 Ascites None Easily Poorly controlled controlled Hepatic encephalopathy None Grade 1,2 Grade 3,4 Child-Pughs Classification: A (a score of 5-6); B (7-9); C (10 or above) 4-4. Grading of hepatic encephalopathy Grade 1 - Trivial lack of awareness; euphoria or anxiety; shortened attention span; impaired performance of addition or subtraction Grade 2 - Lethargy or apathy; minimal disorientation for time or place; subtle personality change; inappropriate behaviour Grade 3 - Somnolence to semistupor, but responsive to verbal stimuli; confusion; gross disorientation Grade 4 - Coma (unresponsive to verbal or noxious stimuli) 81. 56 5.1 5.1.1 95% adherence 5.1.2 1. DOT (1) (2) (3) 2. X 3. X12 82. 57 X 4. BC BC HBsAganti-HCV Ab anti-HIV Ab 5. 248 CBCASTALTbilirubinuric acidBUNcreatinine BC 6. ethambutol ethambutol 7. aminoglycosidestreptomycin 5.1.3 5.2 5.2.1 1. (1) AST/ALTAST/ALT (2) (3) Flu-like syndromeAST/ALT (4) 13 mg/dL 2. 83. 58 (1) Primperan (2) (3) NSAID (4) pyridoxine 3. pyrazinamide rechallenge (1) AST/ALTAST/ALT (2) (3) creatinine0.5 mg/dL (4) 13 mg/dL (5) toxic epidermal necrolysis Stevens-Johnson syndrome (6) (7) 5.2.2 1. 2. 84. 59 INHRMP INHRMP 1. INHearly bactericidal activity 2. RMPINH 1. N-acetyltransferase 2slow acetylator (1) A. total bilirubin 3 mg/dL B. (2) A. INHRMPPZA Fluroquinolone B. BC BCB C. r-GT D. (3) A. 1-2 B. SMKMEMBfluoroquinolone fluoroquinolone 85. 60 SMKMfluoroquinolone Fluoroquinolone fluoroquinoloneSMKM SMSMKMMDR-TB SMKM INHRMPPZA 5-1 INHRMPPZA C. B PTbilirubin > 2 mg/dL B 2. acneurticaria maculopapular rashexfoliative dermatitiserythema multiforme Stevens-Johnsontoxic epidermal necrolysis (1) (2) A. B. C. INHRMPEMBPZA de-sensitization5-2 prednisolone 10 - 15 mg 3. dyschromatopsiacentral scotoma 86. 61 (1) EMB15 20 mg/kg1 2%EMB INHrifabutinethionamideclofazimine linezolid (2) A. EMB B. 4. (1) PZA INHRMP (2) 5. rifabutinRMPINH hemolytic anemiaagranulocytosisEMBPZA INHEMBPZA 6. PZA tuberculous arthritisautoimmune arthropathy 13 mg/dL 13 mg/dLPZA allopurinol 7. INHRMPdrug feverRMP 8. SM 5.2.3 87. 62 5.3 X 88. 63 1. World Health Organization. Treatment of Tuberculosis: Guidelines for National Programmes, 4th ed. World Health Organization Document 2009;WHO/HTM/TB/2009.420. 2. American Thoracic Society, CDC, and Infectious Diseases Society of America. Treatment of Tuberculosis. MMWR 2003;52:RR-11 3. Ormerod LP, Horsfield N. Frequency and type of reactions to antituberculosis drugs: observations in routine treatment. Tuber Lung Dis 1996;77:37-42. 4. Steele MA, Burk RF, DesPrez RM. Toxic hepatitis with isoniazid and rifampin: a meta-analysis. Chest 1991;99:465-71. 5. Saukkonen JJ, Cohn, DL, Jasmer RM, et al. An Official ATS Statement: Hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med 2006;174:935-52. 6. Donald P, Dermot M, Maritz S, et al. Ethambutol efficacy and toxicity. World Health Organization Document 2006;WHO/HTM/TB/2006.365. 7. Tan WC, Ong CK, Lo Kang SC, et al. Two years review of cutaneous adverse drug reaction from first line anti-tuberculous drugs. Med J Mlaysia 2007;;62:143-6. 8. Wang JY, Liu CH, Hu FC, et al. Risk factors of hepatitis during anti-tuberculous treatment and implications of hepatitis virus load. J Infect 2011;62:448-55. 89. 64 5-1 () a 0 - - + 1 INH 100 mg/day 2 INH 200 mg/day 3~5 INH full dose + 6 +RMP 150 mg/day 7 +RMP 300 mg/day 8~10 +RMP full dose + 11 +PZA 250 mg/day 12 +PZA 500 mg/day 13 +PZA full dose + a ALTAST total bilirubin EMB INHRMP PZA 90. 65 5-2 () 0 - - 1 INH 50 mg/day 2 INH 100 mg/day 3 INH 300 mg/day 4 +RMP 150 mg/day 5 +RMP 300 mg/day 6 +RMP full dose 7 +EMB 200 mg/day 8 +EMB 400 mg/day 9 +EMB full dose 10 +PZA 250 mg/day 11 +PZA 500 mg/day 12 +PZA full dose 91. 66 5-1 1. 7) 8) 9) 3 mg/dL 2. SMKM + FQN + EMB 1-2 5-1 92. 67 () ( 6-1) isoniazid rifampicin (1)Isoniazid (INH)Rifampicin (RMP)Ethambutol (EMB)Pyrazinamide (PZA) (2)Cycloserine (CS)a Prothionamide (TBN)a Para-aminosalicyclic acid (PAS) Ethionamide (ETH)b Kanamycin (KM)a ; Amikacin (AMK)a ; Capreomycin (CM)b ; Streptomycin (SM)a 6.1 ( 6-2) 6.1.1 Isoniazid (INH) 1. INH early bactericidal activity 2. (1). 54-6mg/kg300 mg (2). (3). (4). 3. (1). 10-20%(transaminase) 0.1-0.15% 350.3%35-491.2%50-642.3% (2). 5 mg/kgINHpyridoxal phosphate apotryptophanasepyridoxine pyridoxine pyridoxine (vitamin B6) 93. 68 (3). (4). (Lupus-like syndrome); 1% (5). Stevens-Johnson syndrome 4. (6-4) INHINH phenytoincarbamazepinephenytoin carbamazepine 6.1.2 Rifampicin (RMP) 1. RMPrifamycinRNA-polymerase early bactericidal activityRMP 12-25% RMP 600 mg10g/mL 2-4 2. (1). 108-12mg/kg600 mg (2). (3). (4). 3. (1). RMPRMP (2). 10 mg/kg (3). RMPINH (transaminase) 4. (6-4) (1). RMP RMPRMP estrogen50g (2). coumadin 94. 69 / RMP (3). rifamycin (immune reconstitution inflammatory syndrome IRIS)(paradoxical reaction) (4). 6.1.3 Pyrazinamide (PZA) 1. PZAnicotinamide(analogs)INH RMP(pH5.5) (sterilizing activity) PZA 2Mycobacterium bovis 2. (1). 2515-30mg/kg 2000 mg 1000 mg (40-55 kg )1500 mg (56-75 kg)2000 mg ( 76 kg) (2). (3). (4). 3 3. (1). 2-20%(3 gm/day) 25 mg/kg5%INHRMP (2). PZA 13 mg/dLPZA PZAPZA BenzbromaroneUrinorm (3). (salicylates)NSAIDs (4). (5). 4. PZA 95. 70 6.1.4 Ethambutol (EMB) 1. EMB CNSEMB INHEMB RMP 2. (1). 1515-20mg/kg 800 mg ( 40~55 kg)1200 mg (56~75 kg)1600 mg (76~90 kg) 1600 mg (2). (3). (4). 3 3. (1). (Retrobulbar neuritis)EMB 15 mg/kg 1% (central scotoma) (2). 4. EMB(antacids) 6.1.5 (6-2) 1. AKuriT-4 (AKT-4) : (1). INH 75 mgRMP 150 mgPZA 400 mgEMB 275 mg (2). 30-37Kg238-54Kg355-70Kg 96. 71 471Kg5 (3). 5AKT-430 AKT-4 (4). AKT-4PZA 1. Rifater ( RFT ) (1). INH 80 mgRMP 120 mgPZA 250 mg (2). (3). 5RFT40RFT (4). RFTPZA 2. AKuriT-3 (AKT-3) : (1). INH 75 mgRMP 150 mgEMB 275 mg (2). 30-37Kg238-54Kg355-70Kg 4 71Kg5 (3). 5AKT-330 AKT-3 1. Rifinah (RFN) (1). [RFN300]INH 150 mgRMP 300 mg (2). [RFN150]INH 100 mgRMP 150 mg (3). 50 [RFN300] 50 [RFN150] (4). 6.2 ( 6-3) 6.2.1 Streptomycin (SM) 1. SM SM 97. 72 2. (1). 1515-20mg/kg1000 mg 120 gm(MDR-TB) MDR-TB (2). 6050 kg10 mg/kg 500-750 mg (3). (4). (5). 2-31512-18 mg/kg 3. (1). (2). ototoxity (3). (4). 120 gm 4. (1). loop diuretics (2). non-depolarizing muscle relaxants (3). amphotericin Bfoscarnetcidofovir 6.2.2 Levofloxacin(LFX)/Moxifloxacin(MFX) 1. fluoroquinolone DNA gyraseRMPINH aminoglycoside 2. (1).LFX500~1000 mg/day750 mg/dayMFX400 mg/day (2). (3). 98. 73 (4).Ccr < 30 mL/minuteLFX3750~1000 mg/day MFX 3. (phototoxicity)(QT interval prolongation) 4. (1).class Ia quinidineprocainamide class III amiodaronesotalol (2).(antacids)sucralfate (3).Fluoroquinolones 6.2.3 Rifabutin (RFB) 1. RFBrifamycinRFB(RNA) (DNA) RMP M. tuberculosisM. kansasiiM. marinumM. xenopiM. haemophilumM. avium complexRMPRMPRFB 65~10 INH 31-OH RFB25-deacetyl RFB 1218 2. (1).5 mg/kg(300 mg)RFB10 mg/kg( 600 mg)RMP (2). (3). Ccr LFX > OFX 3. gatifloxacin (dysglycemia) (Group 4) (bacteriostatic) ethionamide (ETH)b protionamide (TBN)a cycloserine (CS)a terizidone (TRD)c p-aminosalicylic acid (PAS)a 105. 80 (Group 5) Clofazimine (CFZ)c linezolid (LZD) amoxicillin/clavulanate (AMX/CLV) thioacetazone (THZ) Imipenem/cilastatin (IPM/CLN) high-dose isoniazidd clarithromycin (CLR) 1. WHO MDR-TB 2. 3. (G1-G4) 4. Guidelines for the programmatic management of drug-resistant tuberculosis: emergency update 2008. Geneva, World Health Organization, 2008 (WHO/HTM/TB/2008.402). a. b. c. MDR-TB d. INH 16-20 mg/Kg/day 106. 81 6-2 () / mg/Kg() Max () 50Kg 50Kg isoniazidINH / 54-6 Max: 300 mg 100 mg/tab 2-3 100 mg/tab 3 rifampinRMP / 108-12 Max: 600 mg 150 mg/tab 3 300 mg/tab 2 pyrazinamidePZA 2515-30 Max: 2000 mg 40~55 kg: 500 mg/tab 2 56~75 kg: 500 mg/tab 3 76 kg: 500 mg/tab 4 ethambutolEMB 1515-20 Max:1600 mg 40~55 kg: 400 mg/tab 2 56~75 kg: 400 mg/tab 3 76 kg: 400 mg/tab 4 () 50 Kg 50 Kg Rifinah150 (RFN) (RMP 150 mg + INH 100 mg) Rifinah1503 --- Rifinah300 (RMP 300 mg + INH 150 mg) --- Rifinah3002 Rifater (RFT) (RMP 120 mg + INH 80 mg +PZA 250 mg) 1. 10 kg 1 5 2. RFT AKuriT-4 (AKT-4) (RMP 150 mg + INH 75 mg + PZA 400 mg + EMB 275 mg) 1. 30-37Kg 2 38-54Kg 3 50Kg 4 55-70Kg 4 71Kg 5 2. 5 30 AKT AKuriT-3 (AKT-3) (RMP 150 mg + INH 75 mg + EMB 275 mg) 107. 82 6-3 () () / streptomycinSM / 15 mg/kg15-20 6 > 6 (1) (2) (3) (4) (5) X (6) 2-3 15 mm 6 6 () 127. 102 8.4 8.4.1 1. 2. 8.4.2 8.4.3 8.4.4 1. 2. 8.5 (Treatment of latent tuberculosis infection)(8-1~8-3) 8.5.1 8.5.2 X 8.5.3 8.5.4 isoniazid 8.5.5 isoniazidisoniazid 10 mg/kg (300 mg)9(270) 8.5.6 9(270) 8.5.7 isoniazid + rifampin + pyrazinamide 2isoniazid + rifampin 3 isoniazid 8.5.8 XX 6X 8.5.9 1. isoniazid 2. 3. aspartate aminotransferase (AST)alanine aminotransferase (ALT)bilirubin 4. isoniazidASTALT ASTALT 128. 103 8.6 8.6.1 3-4 8.6.2 isoniazidrifampinpyrazinamideprothionamide ethambutolstreptomycinstreptomycinamikacin 8.6.3 ethambutol4 8.6.4 levofloxacinmoxifloxacinfluoroquinolone 8.6.5 isoniazid 8.6.6 isoniazid pyridoxine 8.6.7 () 6* INH + RIF + PZA + EMB 2 ** INH + RIF 4 9 INF + RIF INF + RIF 9-12 INH + RIF + PZA + EMB 2 ** INH + RIF 7-10 12 INH + RIF + PZA + levofloxacin moxifloxacin aminoglycoside prothionamide2 INH + RIF10 18-24 3-6 ( levofloxacin moxifloxacin)# 9-12 INH + RIF + PZA + EMB 2 ** INH + RIF + EMB 7-10 ** INHisoniazidRIFrifampinPZApyrazinamideEMBethambutol * ** EMB PZA (miliary TB) 129. 104 # 8.6.8 () isoniazid 10-15 mg/kg (300 mg) rifampin 10-20 mg/kg (600 mg) pyrazinamide 30-40 mg/kg (2 gm) ethambutol 15-25mg/kg (1.6 gm) streptomycin 20-40 mg/kg IM (1 gm) amikacin 15-30 mg/kg kanamycin 15-30 mg/kg IM (1 gm) prothionamide 15-20 mg/kg bid-tid (1 gm) cycloserine 10-20 mg/kg (1 gm) para-aminosalicylic acid (PAS) 150 mg/kg bid-qid (12 gm) Levofloxacin 7.5 -10 mg/kg qd (1 gm)* , Moxifloxacin 7.5-10 mg/kg (400 mg) , 8.6.9 8.6.10 ASTALT 1. 2. 3. 6 4. 5. () 8.6.11 1. 2. 3. 1-2 mg/kg/day prednisolone6-8 8.7 8.7.1 93-9 9 130. 105 8.7.2 X (8-2, 8-3) 1. 2. 3. 8-1, 8-2 8.7.3 8.8 8.8.1 X 8.8.2 (congenital tuberculosis) 8.7.1 8.8.3 X 2 8.8.4 X 1. 2006 5 13 () 2. 2012 4 18 () 131. 106 1. Voss LM. Management of tuberculosis in children. J Paediatr Child Health 2000; 36:530-6. 2. Isaacs D, Mellis CM. Tuberculosis in children in Australia: strategies for control. Med J Aust 1998; 168: 121-4. 3. Anonymous. BCG vaccine. WHO position paper. Wkly Epidemiol Rec 2004;79:27-38. 4. American Academy of Pediatrics: 2003 Red Book: Report of the Committee on Infectious Diseases. 26th ed. Elk Grove Village, IL: American Academy of Pediatrics, 2003. 5. Anonymous. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Care Med 2000;161 (Suppl.):S221-47. 6. World Health Organization.Guidance for national tuberculosis programmes on the management of tuberculosis in children.2006, Geneva. WHO/HTM/ TB/2006.371 7. Ena1 J, Valls V. Short-course therapy with rifampin plus isoniazid, compared with standard therapy with isoniazid, for latent tuberculosis infection: a meta-analysis. Clin Infect Dis 2005; 40:6706. 8. Anonymous. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. Recommendations of CDC, the Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation. MMWR 2000;49(RR10):1-128. 9. World Health Organization.Treatment of tuberculosis in children.2010, Geneva. WHO/HTM/ TB/2010.13. 132. 107 ( 1)TST ( 2) X X AP + Left lateral PA+ Left lateralAP view, 13 Left lateral TST