多重抗藥性肺結核的診斷與治療

多重抗藥性肺結核的診斷與治療 98 年結核病個案管理專員教育一般訓練講師群

結核菌發生抗藥性突變菌株的機率藥名抗藥機率 Rifampin 10-8 Isoniazid, Streptomycin, Ethambutol, 10-6 Kanamycin, Para-AminoSalicylate Ethionamide, Enviomycin, 10-3 Cycloserine, Capreomycin, Viomycin, Thiacetazone Shimao T. Tubercle 1988;68(supp):5-15.

抗藥性結核菌如何發生 R H INH+RMP+PZA 合併藥物治療無菌 Z H R Z INH 單一治療 INH 抗藥 RMP 抗藥 PZA 抗藥無抗藥 H H H H H H H H H H H H INH 抗藥性結核菌

抗藥性結核菌如何發生 ( 續 ) H H H H H H R HZ H H H H H H H H 分裂突變 INH 抗藥 INH+RMP 抗藥 INH+PZA 抗藥 H H H H H H H H H H H H H H R HZ H INH + RMP 單一治療 INH+RMP 多重抗藥性結核菌 H R H R H R H R H R H R H H R R H R H R H R H R H R

治療在結核桿菌病人的效果混合族群 ( 感受性和抗藥性的 ) INH 抗藥性桿菌不夠有效的治療例如 (INH 單一處方 ), 造成 INH 抗藥性菌株之崛起 Log cfu 多種有效藥物治療 0 2 4 6 8 10 12 14 16 18 20 22 24 Weeks

MDR-TB and XDR-TB 多重抗藥與廣泛 ( 超級 ) 抗藥結核菌 Multidrug-resistant TB Resistance to at least both INH and RMP Extensively (Extremely) Drugresistant TB Resistance to at least both INH and RMP (MDR-TB) in addition to resistance to any fluoroquinolone, and to at least one of three injectable 2nd-line anti-tb drugs (capreomycin, kanamycin and amikacin) 多重抗藥結核菌同時對 INH 和 RMP 有抗藥性廣泛 ( 超級 ) 抗藥結核菌除了對 INH 和 RMP 抗藥之外, 也對任一種 FQ 和任一種針劑的二線藥也同時具有抗藥性 WHO. XDR-TB Extensively Drug-resistant TB. Nov, 2006

Acquired and primary resistance 獲得性抗藥與原發性抗藥 Acquired drug resistance Emergence of resistance to a formerly active drug during or after therapy Primary drug resistance Presence of resistance in a previously untreated case 獲得性抗藥原來沒有抗藥性, 在治療期間或治療之後, 細菌產生抗藥性 ( 在台灣約佔 MDR-TB 7 成比例 ) 原發性抗藥未曾治療過, 細菌即已有抗藥性 ( 即受到抗藥性細菌的感染, 約佔 3 成 )

WHO/HTM/TB 2008.394 AntiTB drug resistance in the world Report #4, 2008

Nation year Drug Overall FQN resistance FQN R to all sensitive strain FQN R to MDR strain Reference Phillipine 1989-1994 Ofloxacin 7.2% 0 24.0% Int J Tuber Lung Dise 2001 ciprofloxacin 6.0% 1.0% 10.3% 1995-2000 Ofloxacin 35.3% 24.4% 51.4% Ciprofloxacin 26.8% 17.4% 51.4% USA Canada 1995-2001 Ciprofloxacin 1.8% 0.3% 4.1% Clini Infect Dis 2005 Korea oloxacin 1.1%(nonretreat) 4.1%(retreatme nt case) Int J Tuberc Lung Dis 2007 Taiwan KVGH 1995-1997 Ofloxacin, 6.3% 7.7% J Antimicro ciprofloxacin, Chemothe 2005 1998-2003 Levofloxacin 0-4.3% 20% Taiwan TUVH 2004-2005 Ofloxacin, ciprofloxacin, Levofloxacin, Moxifloxacin 3.3% 19% J Antimicro Chemothe 2007

台灣結核病患數分布估算 (2007) 通報 : 結核病 17,997 確診 : 14,480 確診 : 查痰陽性 11,150 確診 : 塗片陽性 6,081 確診 ( 管理中 ): 多重抗藥 411 In 2007, there were 14,480 confirmed TB cases and the incidence was 63.2/105 persons 確診 ( 管理中 ): 慢開結核 25

Drug resistance patterns in Taiwan, 1960 2004 Drug resistance (%)+ Hospital* No. strains Study period INH EMB RMP SM Any MDR *Primary drug resistance A 162 1960-1962 13.4 - - 11.7 22.2 - B 154 1962 8.4 - - 7.8 14.3 - B 557 1971-1972 22.6 - - 15.4 30.8 - B 1,914 1979-1982 8.4 0.1 0 9.2 17.9 - B 1,924 1984-1988 6.8 0.4 0.2 5.0 9.9 - B 1,935 1990-1995 9.2 0.7 1.5 5.7 12.3 1.2 B 249 1996 12.0 0.8 2.0 4.8 16.1 1.6 C 254 1996-1999 4.7 5.9 5.9 11.0 22.0 1.6 D 456 2001-2002 14.9 2.6 3.3 11.4 20.6 2.4 E 190 2001-2002 11.1 5.8 2.1 5.3 16.8 2.1 F 611 2002-2004 6.8 0.8 1.8 6.2 12.8 1.8

Drug resistance patterns in Taiwan, 1960 2004 Drug resistance (%)+ Hospital* No. strains Study period INH EMB RMP SM Any MDR Acquired drug resistance B 200 1996 63.0 28.5 46.5 21.5 67.0 46.0 C 199 1996-1999 25.6 11.1 32.2 17.1 49.2 15.1 B 183 2000-2001 37.7 10.9 25.1 17.5 42.6 24.6 D 57 2001-2002 31.6 15.8 17.5 19.3 36.8 15.8 E 62 2001-2002 54.8 33.9 45.2 17.7 64.5 45.2 F 324 2002-2004 50.9 12.6 44.4 17.9 55.8 42.2 Combined drug resistance G 942 1982-1986 20.4 15.3 8.8 9.8 27.8 8.1 A 651 1990-1992 14.7 10.3 10.6 11.2 22.6 8.3 G 884 1992-1996 20.9 12.8 11.8 9.1 28.9 10.1 B 1,091 1996 31.5 11.4 18.2 11.9 35.5 17.3 C 453 1996-1999 13.9 8.2 17.4 13.7 34.0 7.5 H 693 1996-2000 35.9 15.7 13.4 28.6 52.4 11.4 I 1,411 1998-2002 19.0 15.7 6.1 10.0 30.5 5.1 D 513 2001-2002 16.8 4.1 4.9 12.3 22.4 3.9 E 252 2001-2002 21.8 12.7 12.7 8.3 28.6 12.8 F 935 2002-2004 22.2 5.2 16.5 10.2 27.6 15.8

Second-line drug resistance pattern in different group in Chest Hospital in 2001-2006 ALL SENSITIV NON-MDR MDR Drug resistance No % No % No % TOTAL 1338 71.00% 309 16.00% 227 12.00% KM 4 0.30% 30 9.71% 45 19.82% TBN 0 0.00% 22 7.12% 34 14.98% PAS 5 0.37% 40 12.94% 53 23.35% OFLO 21 1.57% 40 12.94% 80 35.24%

MDR group : HR resistance % Second-line drug resistance pattern in different group in Chest Hospital in 2001-2006 40 35 30 25 20 15 10 5 0 35.24 23.35 19.82 14.98 12.94 12.94 9.71 7.12 0.3 0 0.37 1.57 KM TBN PAS OFLO all sensitive Non-MDR MDR All sensitive group : HRE SM all sensitive Non-MDR group : at least one of HER SM resistance exclude HR resistance

Extensively Drug Resistant TB in Taiwan Study population : 215 MDR isolates( 研檢在 2004-2005 取得之菌株 ) Drug resistant Patterns of 2nd-line Drugs Ofloxacin: 42.8% (92/215) Kanamycin: 16.3% (35/215) Ethionamide: 15.8% (34/215) PAS: 26.0% (56/215) XDR-TB in 2004, 116 MDR isolates tested: 10.3% (12/116) in 2005, 99 MDR isolates tested: 10.1% (10/99) Taiwan Surveillance of Drug Resistance in Tuberculosis (TSDRTB), 2003-5

抗結核化學治療處方錯誤藥物劑量不足或數目不足在治療失敗時, 僅加上一種新的藥物, 形成只有單一藥物治療 WHO. Guidelines for the management of drug-resistant tuberculosis, 1997

WHO_HTM_TB_2006.361_Guidelines for the programmatic management of drug-resistant tuberculosis

Drug Susceptibility Test agar proportional method First-line drug Middlebrook 7H10 agar plate Isoniazid 0.2 μg/ml Isoniazid 1.0μg/mL Rifampin 1.0μg/mL Streptomycin 2.0μg/mL Streptomycin 10.0 μg/ml Ethambutol 5.0μg/mL Ethambutol 10.0 μg/ml Second-line drug Middlebrook 7H11 agar-base Capreomycin 10.0μg/mL Ethionamide 10.0μg/mL Kanamycin 6.0 and 12 μg/ml Ofloxacin 2.0μg/mL p-aminosalicylic acid 8.0μg/mL Rifabutin 0.5μg/Ml Levofloxacin(1ug/ml), Moxifloxacin ( 0.5ug/ml)

GenoType MTBDRplus

Performance of MTBDRplus assay Study site Year Author Sample Germany 2007 South Africa Hillemann D. et al. cultures/ sputum Accuracy for MDR(%) >90 2008 Barnard M. et al. sputum 98.8 Denmark 2008 Vijdea R. et al. cultures >93 Caribbean 2008 Akpaka P.E. et al. cultures/ sputum 29.4 Spain 2008 Lacoma M. et al. cultures 75

MDR-TB isolate rechecking program Strain receiving inactivation Reporting Non-MTBC Molecular Diagnosis * 1. real time PCR 2. Genotype MTBC 3. PCR-RFLP 4. Sequencing Molecular Diagnosis of Drug Resistance profile 1. Genotype MTBDR-plus 2. Drug-resistant genes sequencing 3. multiplex PCR Reporting MTBC MDRTB Non-MDRTB Second-line DST Subculture (liquid/solid media) First-line DST MDRTB Genotyping Reporting Strain banking

Evaluation study Study Period May, 2007 to April, 2008 Sample 242 MDR confirmed M. tuberculosis isolates 30 all susceptible M. tuberculosis isolates Methods Reference : Agar proportion method or MGIT Molecular: Primary: Genotype MTBDRplus Secondary: DNA Sequencing

Drug resistance detection 100 Sensitivity 90 (%) 80 95.5 97.9 81.8 93.4 78.5 91.3 GT MTBDRplus Sequencing 70 60 RIF only INH only MDR Drug resistance

Anti-tuberculosis drug available in Taiwan Grading DRUG Group-1 First-line Isoniazid, Rifampicin, Ethambutol, Pyrazynamide Group 2- injectable agents Streptomycin, Kanamycin, Amikacin, capreomycin Group 3 Fluoroquinolones Ciprofloxacin, OFloxacin, Levofloxacin, Moxifloxacin Group 4- bacteriostatic second-line agents Ethionamide, Cycloserine, p- aminosalicyclic acid(pas), terizidone Group-5 ATTwith unclear efficacy Amoxicillin/Clavulanate, Clarithromycin, Linezolid, clofazimine

區域醫療團隊合作醫院台北區台北市立萬芳醫院團隊聯絡人 : 余明治醫師 02-29307930#52958 台北市立萬芳醫院台北市立聯合醫院和平院區衛生署台北醫院馬偕醫院疾病管制局公佈 96 年 MDR 結核病醫療照護團隊名單北區中區衛生署桃園醫院團隊聯絡人 : 林美宏個管師 03-3699721#2457 衛生署彰化醫院團隊聯絡人 : 黃尹文醫師衛生署桃園醫院及新屋分院衛生署新竹醫院衛生署竹東醫院衛生署台中醫院衛生署彰化醫院衛生署南投醫院衛生署苗栗醫院衛生署草屯療養院衛生署豐原醫院台中榮民總醫院中山醫藥大學附設醫院中國醫藥大學附設醫院南區高高屏區衛生署胸腔病院團隊聯絡人 : 簡順添主任 06-2705911#3266 衛生署胸腔病院成功大學醫學院附設醫院衛生署台南醫院嘉義灣橋榮民醫院衛生署旗山醫院衛生署屏東醫院衛生署嘉義醫院高雄榮民總醫院高雄市立民生醫院東區防癆協會團隊聯絡人 : 李仁智主任 03-8561825#2118 慈濟醫院門諾醫院台東馬偕醫院衛生署花蓮醫院衛生署台東醫院鳳林榮民醫院

MDR-TB 醫療照護計畫之治療策略個案確診 : 臨床病程,, CXR, TB 培養和鑑定 ID Chest CT 和病理報告排除 NTM 感染藥物敏感性試驗 (DST) : 區域參考實驗室報告 HR 抗藥 MDR-TB 治療委員會確認個案由 CDC 參考實驗室 ( 昆陽 ) 再次確認 : Mycobacterium tuberculosis complex 菌株確認 Genotype MTBDRplus 快速複驗 RIF/INH 抗藥基因定序第一線藥物敏感性試驗複驗

Treatment strategies for MDR-TB Guidelines for the programmatic management of drug-resistant tuberculosis (WHO/HTM/TB/2006. 361) Editors-in chief Michael Rich Peter Cegielski Ernesto Jaramillo Kitty Lambregts

MDR Tuberculosis Predictors of Success and Failure Success Failure Use of pyrazinamide Previous therapy any/or ethambutol, if Number of drugs resistant susceptible Presence of cavitation Use of fluoroquinolone Low BMI Use of > 5 drugs HIV infection Sputum conversion by2 Poor adherence months Positive cultures at 2-3 Surgical resection months

Recommended treatment strategies for MDR-TB

經驗性處方 (Empirical treatment) 處方決定前必須評估以前之抗結核藥物治療史第一線藥物之抗藥型式 HER, SM, sometimes ofloxacin 胸腔病院 : HER, SM, Ethionamide, PAS, ofloxacin 接觸史 : 指標個案的抗藥型式台灣的初始抗藥之比率 (Primary drug resistance rate)

決定治療處方先經驗處方 (Empirical treatment), 再根據藥敏試驗決定個別處方 (Individualized treatment) 大部分的 MDR-TB 個案治療已知 HER, SM 是否抗藥根據胸腔病院統計, 在 HR 有效的病人, 其二線藥抗藥的比例極低所有 MDR-TB 個案, 均須送二線藥敏根據二線藥敏再調整處方

如何選擇藥物 Regimen selection 根據過去治療史至少四種確定有效或極可能有效的藥物全程均應有四種藥物 ( 包括 intensive phase and continuous phase) 如果藥物有限, 或因副作用無法使用, 在維持期 (continuous phase ) 至少須有 3 種藥如果 DST 未知, 或藥物有效性存疑, 或疾病為兩側廣泛而嚴重, 則須 4 種藥以上根據體重調整劑量須每天給藥第一線藥如 PZA, EMB 和 fluoroquinolones 可一天一次為執行 DOTS-PLUS, 二線藥儘量一天兩次打針藥物 : 至少每個星期 5 次

如何選擇藥物 Regimen selection 針劑 ( streptomycin / kanamycin/ amikacin ) 至少使用 6 個月如果痰抹片仍陽性, 且無副作用產生, 可延長至痰陰轉選擇一新的 Fluoroquinolones (levofloxacin or Moxifloxacin ) 即使 DST 為 ofloxacin 抗藥如果 ofloxacin 抗藥, 建議使用 moxifloxacin 每次劑量均須執行 DOT 給藥建議 PZA 全程使用除非病人無法使用或證實無效 PZA 通常不計算在有效藥之內使用藥物紀錄卡

Building a Treatment Regimen Step 1 Group1 Group2 Group3 Ethambutol Streptomycin Ofloxacin Pyrazinamide Kanamycin Levofloxacin Amikacin Moxifloxacin Capreomycin Gatifloxacin Step 2 Group4 Ethionamide Protionamide Cycloserine Terizidone Thioacetazone P-aminosalicylic acid Step 3 Group5 Clofazimine Imipemen Amoxacillin/Clavulanate Macrolides linezolid

建立多重抗藥性結核病的處方第一步開始用任何有效的第一線藥物根據藥物感受性試驗加入 fluoroquinolone 和一個注射的藥物 Use any available First-line drugs Pyrazinamide Ethambutol One of these PLUS PLUS Fluoroquinolones Levofloxacin Moxifloxacin Ofloxacin Ciprofloxacin One of these Injectable agents Amikacin Capreomycin Streptomycin Kanamycin

建立多重抗藥性結核病的處方第二步如果第一步仍未達到四個有效藥物 : 加入第二線藥物直到有四個到六個對此菌株是有效的藥物 ( 並且最好是之前此病人沒有使用過的 ) Pick one or more of these Oral second-line drugs Cycloserine Ethionamide PAS

建立多重抗藥性結核病的處方第三步如果第二步仍然未達到四個到六個有效的藥物, 要考慮照會專家後加上第三線的藥物 Consider use of these Clofazimine Linezolid Amoxicillin/ Clavulanate Third-line drugs Imipenem Clarithromyci n

治療時間 Duration of Treatment 至少痰培養陰轉後 18 個月如果收入 MDR-TB 醫療照護計畫, 計畫時間為 2 年

Treatment Regimens for MDR-TB Pattern of Drug Resistance Suggested Regimens Mininum duration of Rx Comments INH, RIF (± SM) PZA, EMB, FQN, injectable, ± another 2nd -line drug 18-24 beyond culture conversion INH, RIF (± SM),and EMB or PZA FQN, EMB pr PZA, injectable, Plus 2 other 2nd -line drugs 24 beyond culture conversion consider surgery INH, RIF, EMB, PZA( ± SM) FQN, injectable, 3 other 2nd-line drugs 25 beyond culture conversion consider surgery INH, RIF,EMB, PZA, FQN 3 2nd -line drugs, injectable, plus consider 3rd-line drug 26 beyond culture conversion consider surgery INH, RIF,EMB, PZA, injectables FQN, 3 2nd -line drugs, plus consider 3rd-line drug 27 beyond culture conversion surgery if possible INH, RIF,EMB, PZA, FQN, injectables At least 5 2nd and 3rd-line drugs At least 24 beyond culture conversion surgery if possible

住院治療 Hospitalization 如果 MDR-TB 有傳染性, 建議在臺灣人口密集的狀況下, 住院 1~2 個月, 可減少傳播機會根據秘魯研究, 後續社區治療, 執行 DOTS- PLUS, 治療效果與住院治療效果一樣, 此時應衛教 MDR-TB 病患空氣傳染之防護, 除了就醫需要時, 亦應減少外出

新個案住院原則因未治療之傳染性較強, 建議住院治療加強衛教, 找出變成 MDR-TB 的原因, 個別處理藥物副作用, 調整副作用評估開刀可能 ( 尤其治療 3~8 個月後培養仍未陰轉者 ) 不合作, 強制住院

衛教 Education 病人及家屬衛教找出一線藥治療失敗的原因確定順從性不佳的原因營養治療副作用處理

出院通常住院 1 至 2 個月痰陰轉 : TB 培養陰轉 : 較好 AFB 抹片陰轉 : 可接受處方已完成且病人可接受, 並確定服藥順從性病人同意接受社區或居家 DOTS-PLUS

多重抗藥結核病患者治療過程的追蹤多重抗藥結核病患者開始治療前需要詳細的詢問病史, 並作理學檢查, 需要施行胸部 X 光檢查和痰檢驗, 治療開始後要定期追蹤, 注意病人是否有進步是否有副作用如有副作用, 須小心調整藥物

1. 每個月至少要到門診由臨床醫師評估壹次醫生必須詳問病人的症狀是否有改善是否有副作用出現 2. 每個月量體重 3. 每個月皆需送痰做耐酸菌塗片檢查及結核菌培養直到痰陰轉痰陰轉後改為每兩月送痰直到治療結束痰陰轉是最重要的評估因素 4. 藥物敏感試驗在進入治療前須確定患者有多重抗藥治療後如果痰培養持續陽性可以每 3 至 6 月再做藥物敏感試驗 5. 胸部 X 光片 : 每參個月照一次病人臨床症狀如果有惡化, 可提前照胸部 X 光片注意事項

6. 腎功能 : 每隔壹至參個月驗一次肝腎功能 7. 病人如接受 Aminoglycocide 的注射時須每個月驗腎功能 8. HIV 檢驗 - 進入治療時須驗壹次, 以後視狀況而驗 9. 懷孕檢驗 - 生產年齡的女性進入治療時須驗壹次, 以後視狀況而驗注意事項 ( 續 ) 10. 視力檢查 - 病人如服用 EMB, 須每個月驗壹次 11. 關懷員須每天送藥到患者手上必須訓練關懷員了解治療的副作用, 如果有任何副作用發生須盡快通知醫護人員

Sputum Culture Conversion in MDR-TB, Patients, Latvia Of patients with initial sputum conversion within 60 days of treatment, 86% had a good outcome vs 51% who did not achieve conversion (p<0.001) Holtz, T. H. et. al. Ann intern Med 2006;144:650-659

100.0 95.0 90.0 85.0 80.0 75.0 70.0 65.0 60.0 55.0 50.0 MDR 結核病醫療照護團隊的痰培養累計陰轉率 ( 共 228 人, 追蹤達 425 天整 ) p1 p2 p3 p4 p5 p6 p7 p8 p9 p10 p11 p12 新病人復發初次治療失敗再治治療失敗

手術治療 Surgical intervention 如果病人有內科治療失敗之可能, 或治癒後複發機會高者, 須考慮外科治療開刀原則 Criteria for surgery 侷限病灶, 可切除開完刀後有足夠肺功能有足夠藥物可使用內科治療已 3 至 4 個月何人須考慮開刀 Candidate for surgery 壁厚之開洞, 大的開洞內科治療 3 至 6 個月, 痰側未陰轉開刀前評估 Pre-operative survey 電腦斷層 CT 肺功能 Lung function test 術後照護 Post-operative care 仍須服藥 12-24 個月

Outcomes of Surgery in Patients with MDR-TB Reference Country Years N Operative Mortality Post-op Mortality Mortality Culture Conversion Sung S. Korea 1994-98 27 0 0 25.9% 82% Park S. Korea 1995-99 49 0-16% 94% Kir Turkey 1993-05 79 2.5% - 5% 95% Shiraishi Japan 2000-02 30 0 3% 23% 100% Li China 1990-05 188 0.5% 3.2% 13.9% 99% Takeda Japan 1998-03 35 2.9% - 14.3% - Pomerantz USA 17 years 172 3.3% 6.8% 12% 99%

藥物供應 Drug management 所有的二線藥物由疾病管制局供應 ( 除了第五類藥物中的 Augmentin Clartithromycin Linezolid) 二線藥物申請, 須經審查委員審查

二線抗結核藥物申請流程 ( 一般醫院 ) 申請醫院檢附完整資料不同意同意, 每日上午 10 點前傳真胸腔病院疾病管制局分局疾病管制局分局署立胸腔病院寄發抗結核二線藥物 TEL:06-2705826 FAX:06-2705280 二線抗結核藥物委員審核同意或不同意補件醫院回覆單

MDR 醫療團隊申請免費抗結核二線藥流程 MDR 合作醫院依團隊規定時間表格提出抗結核二線藥物申請 MDR 醫療團隊組成之審核小組進行審核醫院有放置抗結核二線藥醫院未放置抗結核二線藥回覆申請醫院回覆申請醫院同時由 MDR 核心醫院寄送藥品予申請醫院申請醫院依審核結果直接給藥申請醫院依審核結果給藥

DOTS-PLUS 病人每個 MDR-TB 病人均須接受 DOTS-PLUS 治療以病人為中心之 DOTS-PLUS 病人為中心 : 在家, 工作場所, 在學校, 醫院, 藥局, 咖啡廳, 病人補助 Incentive for patient 交通費 Transit fee 營養費 Nutrition fee : 門診及住院免費

DOTS-PLUS 觀察員, 關懷員至少一天兩次, 最好每個劑量關懷員, 醫院個管師與公衛系統 ( 衛生局, 衛生所, 公衛護士 ) 須緊密結合, 共同照護病人

Evidence of feasibility and effectiveness of DOTS- Plus: Treatment outcomes in some DOTS-Plus sites 100% 8 10 12 80% 21 28 14 8 4 Failed 12 12 15 60% Defaulted 12 Died 40% 76 59 61 Cured 20% 48 0% April 2005 WHO/STB/THD Estonia Peru Philippines Russia-Tomsk

Outcomes of MDR-TB Therapy, Resistance to < 5 Drugs Reference Country Years Median Drug-R Patient N Cure/ Complete Died Default Failed Chiang Taiwan 1992-96 3 299 153 (51) 29 (9) 87 (29) 28 (9) Leimane Latvia 2000 4 204 135 (66) 14 (7) 26 (13) 29 (14) Burgos USA 1982-00 3 37 32 (94) 0 1 (3) 1 (3) Palmero Argentin a 1996-99 4 141 64 (45) 27 (19) 28 (20) 7 (5) Park Korea 1997-99 4 83 63 (76) - 20 (24) 11 (13) Tahaoglu Turkey 1992-99 4 158 121 (77) 7 (4) 17 (11) 13 (8) Adapted from Caminero JA. Int J Tuberc Lung Dis 2006;10:829

Outcomes of MDR-TB Therapy, Resistance 5 Drugs Reference Countr y Years Median Drug-R Patient N Cure/ Complete Died Default Failed Mitnick Peru 1996-99 6 75 55 (73) 5 (7) 14 (19) 1 (1) Geerlings Nether. 1985-98 6 39 32 (82) 6 (14) - 1 (2.5) Narita USA 1994-97 5 81 46 (57) 26 (32) 9 (11) - Chan USA 1984-98 6 139 71 (75) 16 (11) 21 (15) 31 (15) Adapted from Caminero JA. Int J Tuberc Lung Dis 2006;10:829

Comprehensive Treatment of Extensively Drug- Resistant Tuberculosis

Treatment Outcome of MDR-TB at CDCB, 1992-1994 Outcomes No.(225) % Successful treatment 121 53.8 Unfavorable responses 34 15.1 Died of TB 37 16.4 Died of non-tb 4 1.8 Defaulters 29 12.9

MDR-TB Treated with Ofloxacin Ofloxacin (+)* n=66, (%) Ofloxacin (-)* n=126, (%) Successful Tx 47 (71.2) 74 (58.7) Tx failure 19 (28.8) 52 (41.3) Unfavorable response 10 (15.2) 24 (19.1) Death due to TB 9 (13.6) 28 (22.2) *P=0.08 between regimens with and without ofloxacin

Treatment Outcomes of Initial and Acquired MDR-TB Initial MDR-TB* n =27 (%) Acquired MDR-TB* n= 165 (%) Successful Tx 22 (81.5) 99 (60.0) Tx failure 5 (18.5) 66 (40.0) Unfavorable response 4 (14.8) 30 (18.2) Death due to TB 1 (3.7) 36 (21.8) * p=0.032 between initial and acquired MDR-TB

容易發生副作用的危險因子年老營養不良懷孕酗酒肝腎功能異常愛滋病糖尿病過敏體質不規則用藥除抗結核藥物外還需使用其他藥物

MDR-TB 病人出現的副作用

結核藥物常見之副作用藥物副作用皮膚症狀肝炎胃腸症狀週邊神經病變關節病變腎病變血液病變視力異常聽覺前庭功能異常臨床表徵搔癢皮疹皮膚潮紅色素沉著水泡胃口變差噁心嘔吐黃疸倦怠胃口變差噁心嘔吐上腹部痛麻木針刺感燒灼痛或手足軟弱無力痛風 SLE 樣病變血尿高尿素血症急性腎衰竭白血球偏低血小板低視力模糊紅綠色盲聽力變差暈眩耳鳴常見藥物 RMP, EMB, INH, 較少見於 PZA, RBT INH, RMP, PZA, TBN 較少見於 EMB, RBT RMP, PZA, RFB,TBN,PAS INH, EMB PZA, INH RMP, SM, KM, Capreomycin INH, RMP, PZA, EMB, RBT EMB SM, KM, Capreomycin

各種副作用的可能原因和處理方法

常用的輔助藥品

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多重抗藥性肺結核的 診斷與治療

多重抗藥性肺結核的診斷與治療