20080416 ntuh 2-treatment of tuberculosis new.ppt [...
TRANSCRIPT
Treatment of Tuberculosis 2結核病的治療 (二)結核病的治療 (二)
陸 坤 泰陸 坤 泰
C t tContentsHi t f t b l i t t t• History of tuberculosis treatment
• Anti-TB agentsg• Principles of anti-TB chemotherapy• Initial treatment• Initial treatment• Retreatment• Treating drug resistant tuberculosis• Monitoring during therapy• Monitoring during therapy• Treatment for special groups
RetreatmentRetreatment
再治療再治療
Recommended Treatment Regimens for TB Diagnostic Category Ⅱ
• TB Patients• TB PatientsPreviously treated sputum smear-(+) PTB：relapse；- relapse；
- treatment after interruption (default)；- treatment failuretreatment failure (drug sensitivity test before prescription, proven MDR-TB use category IV)p g y )
• Initial phase (Daily or 3 times weekly) 2 HRZES / 1 HRZE2 HRZES / 1 HRZE
• Continuation phase (Daily or 3 times weekly)5 HRE WHO Guidelines 20035 HRE WHO Guidelines 2003
Prevalence of ResistanceRetreated Patients (n=183)
Treatment failure (n=33)Relpase (n=93)Treatment after default (n=57)Total (retreated patients n=183)
70
80Total (retreated patients, n=183)
with
la
tes
40
50
60
tient
s nt
iso l
20
30
40
% o
f pat
esis
ta
0
10
INH RIF EMB SM Any one MDR
% re
ydrug
Chiang CY et al. J Formos Med Assoc 2004
小心抗藥就在你身邊
復發病人的治療復發病人的治療
曾接受一個完整療程之結核藥物治療並經診療醫師宣告治癒而再次痰塗片或培養陽性的病人
復發病人治療的時機復發病人治療的時機
• 兩套痰耐酸菌塗片(+), 且臨床懷疑肺結核( ),復發的病人;
• 痰結核菌培養(+) 且臨床懷疑肺結核復發病人;• 痰結核菌培養(+), 且臨床懷疑肺結核復發病人; 組織病理學/組織培養證實之肺外結核復發病人;注意事項注意事項:復發肺結核病人應有細菌學之診斷依據, 診療醫師 如懷疑結核病人復發 在開藥治療前，應盡一切可能查痰或安排相關檢查;病人復發, 在開藥治療前，應盡一切可能查痰或安排相關檢查; 不應針對僅胸部Ⅹ光惡化但痰陰性的結核病人啟用再治處方。
Prevalence of ResistanceRelapse (N = 93)
• Prevalence of resistance to any drug, 33.3%
40
%
single any
%
29
16 1203040 single any
10.8
0 04.3
12.9
4.3
16.112.9
1020
0 00
INH RMP EMB SM MDR
Chiang CY et al. J Formos Med Assoc 2004
請不要只想怎麼開藥
失落再治病人失落再治病人
中斷治療2個月以上而再次痰塗片或培養陽性的新病人或再治病人
藥物已不是舞台的重心藥物已不是舞台的重心
如何處理失落再治病人？
• 診療醫師在治療失落再治的病人時，應先• 診療醫師在治療失落再治的病人時，應先確認造成病人失落的原因是否已經排除，若未排除而勉強繼續用藥 將造成更嚴重若未排除而勉強繼續用藥，將造成更嚴重的抗藥性菌株，對公共衛生絕對有害無利。
Prevalence of Resistance Treatment Default (N = 57)
Pre alence of resistance to an dr g 42 1%• Prevalence of resistance to any drug 42.1%
35.140 single any
19.3 17 5 19.320
30
%% 12.377
17.5
10
20%%
0 00
INH RMP EMB SM MDRINH RMP EMB SM MDRChiang CY et al. J Formos Med Assoc 2004
失落再治病人的處理
中斷時間在兩個月以內或痰(-)者
• 追蹤病人
( )
• 解決造成中斷治療的問題
• 加強驗痰繼續原處方治療並補足中斷期間加強驗痰繼續原處方治療並補足中斷期間
失落病人:中斷時間超過兩個月且痰(+)
•追蹤病人、解決造成中斷治療的問題
失落病人:中斷時間超過兩個月且痰( )
2HERZ+SM/1HERZ/5HER
避免產生更多的抗藥避免產生更多的抗藥而不是治療多重抗藥結核而不是治療多重抗藥結核
2HERZS / 1HERZ / 5HERAn 8 month regimen for relapse return after interruptionAn 8-month regimen for relapse, return after interruption and treatment failure我們強烈建議不要輕易使用fluoroquinolone類的‧我們強烈建議不要輕易使用fluoroquinolone類的藥物治療再治病人，應將之保留於治療多重抗藥結核病人。不要因為怕針劑(streptomycin)的麻煩結核病人。不要因為怕針劑(streptomycin)的麻煩而輕易使用如INH + RMP + EMB + PZA + FQN這樣的處方治療再治病人。這樣的處方治療再治病人。
要有處理多重抗藥的能力
失敗再治病人失敗再治病人
前次治療失敗後重啟再次治療之病人前次治療失敗後重啟再次治療之病人治療4個月後痰結核菌培養(+)、或治療5個月後痰抗酸菌塗片(+)、或治療前痰陰性、治療2個月後變成痰塗片或痰培養(+)的新病人。
失敗再治病人治療的時機失敗再治病人治療的時機
• 治療四個月後痰結核菌培養(+)；
• 治療五個月後痰耐酸菌塗片 ；
治療前痰細菌學( ) 治療二個月
(+)
• 治療前痰細菌學(-) 、治療二個月後變成痰細菌學(+)者。
失敗再治病人治療的時機失敗再治病人治療的時機1
• 失敗再治病人的判定以痰細菌學檢查為唯一依據，只有胸部Ⅹ光惡化但查痰(-)的病人，只有胸部Ⅹ光惡化但查痰( )的病人不列為失敗再治病人。
診療醫師應盡一切可能驗痰• 診療醫師應盡一切可能驗痰，藉以取得細菌學惡化的證據，也可以此菌株提供寶貴的藥敏試驗，作為後續治療的指引。作為後續治療的指引
失敗再治病人治療的時機失敗再治病人治療的時機2
• 在未取得細菌學證據前，不應把病人列為失敗再治病人不應把病人列為失敗再治病人，輕易啟用再治處方。臨床懷疑病人治療失敗時，一定要先 確定其服藥的順服度。一定要先 確定其服藥的順服度
• 如果病人是因不按規服藥，導致持續痰細菌學(+)或細菌學惡化導致持續痰細菌學(+)或細菌學惡化，應優先解決其順服度的問題，而不是輕易另加新藥。
Prevalence of ResistanceTreatment Failure (N = 33)
• Prevalence of drug resistance to any drug 69.7%
66 7 69.7 66 780 single any66.7 69.7
36.4
66.7
40
60
%%
0 3 0 0
36.421.2
20
40%%
0 3 0 00
INH RMP EMB SM MDR
Chiang CY et al. J Formos Med Assoc 2004
避免產生更多的抗藥避免產生更多的抗藥治好治療反應較慢的病人治好治療反應較慢的病人（不是治療多重抗藥結核）（不是治療多重抗藥結核）
2HERZS / 1HERZ / 5HERAn 8-month regimen for relapse, return after interruption and treatment failure
Treating Drug ResistantTreating Drug Resistant TUBERCULOSIS
In designing a regimen,do not
i t k d iaim to keep drugs in reservereserve.
WHO. Guidelines for the management of drug-resistant tuberculosis, 1997
藥物選擇基本原則藥物選擇基本原則多重抗藥性結核、2種以上一線抗藥、2種以上一線副作用
• 依藥敏試驗結果選擇至少3 種以上證實有效的藥物，或未曾服用過的藥物。
• 保護的藥物：RMP、FQN• 保護的藥物：RMP、FQN
• 不含RMP的處方，儘量在治療前6 個月使用針劑
• 不含RMP的處方，須治療18 個月以上.......
什麼時候要用到第二線結核藥物？第二線結核藥物？
• 藥物感受性試驗結果發現抗藥性菌株，INH/RMP/EMB 3藥物中任2種以上抗藥的病人。
• 已知藥敏試驗的結核病人因藥物副作用，致上述3藥物無法使用任2種以上藥物：3藥物無法使用任2種以上藥物：
藥敏試驗結果為全敏感，或抗藥藥物恰好都是副作用藥物。此時副作用藥物視同抗藥藥物處理此時副作用藥物視同抗藥藥物處理。
藥敏試驗之抗藥藥物不全然是副作用藥物。此時副作用藥物加抗藥藥物共同處理藥物加抗藥藥物共同處理。
單一藥物抗藥單一藥物抗藥含已知藥敏試驗的藥物副作用病人
開始治療時已知其細菌為抗藥性菌株:
含已知藥敏試驗的藥物副作用病人
開始治療時已知其細菌為抗藥性菌株:治療時藥敏情形不明, 已開始用藥, 治療途中藥敏試驗報告出爐治療途中藥敏試驗報告出爐，才發現為抗藥性菌株。治療時發生單一藥物副作用治療時發生單一藥物副作用，先依單一藥物副作用建議的處方治療。後來藥敏試驗報告發現一線藥物均有效後來藥敏試驗報告發現一線藥物均有效或恰好僅副作用藥物抗藥；此時副作用藥物視同抗藥物處理。
結核病其他治療方式1結核病其他治療方式1single drug resistance
• PZA: 9HRE - INH + RIF + EMB 每日一次口服，治療9個月
• RIF: 18 HEZ±Q／HEQ - INH + PZA + EMB ± FQN 治療18個月，PZA至少2個月。
• INH: 6-9*ERZ - 全程採 RIF + PZA + EMB 每日一次口服，*2月痰培養(+) 個案治療9個月 其他個案治療6個月*2月痰培養(+) 個案治療9個月、其他個案治療6個月。
• EMB: 2HRZ+4HR 或9HR INH + RIF + PZA 每日一次口服，2個月後改INH + RIF- INH + RIF + PZA 每日一次口服，2個月後改INH + RIF
4個月 。
• 二種以上一線藥物抗藥: 使用二線藥。請參考多重抗藥段二種以上一線藥物抗藥: 使用二線藥 請參考多重抗藥段
結核病其他治療方式2
more drugs resistance
• INH + RMP:
more drugs resistance
• INH + RMP:EMB + PZA + FQN + TBN + SM 至少6個月, 或EMB + PZA + FQN + TBN 12 18個月EMB + PZA + FQN + TBN 12-18個月
• INH + RMP + EMB/PZA/SM:FQN + TBN + PAS/CS + KM/AM，加EMB/PZA中可用者至少6個月，再FQN + TBN + PAS/CS，加EMB/PZA中可用者12-18個月
• INH + EMB: RMP + PZA + FQN 9個月• INH + EMB: RMP + PZA + FQN 9個月
結核病其他治療方式3結核病其他治療方式3
more drugs resistance
• RMP + EMB:INH + PZA + FQN + SM 6個月或INH + PZA + FQN + SM 6個月或INH + PZA + FQN 12個月EMB + PZA:EMB + PZA:INH + RMP 9個月
INH + PZA:INH + PZA:RMP + EMB + FQN 9個月RMP + PZA:RMP + PZA: INH + EMB + FQN + SM 6個月或INH + EMB + FQN 12個月INH + EMB + FQN 12個月
結核病其他治療方式4single drug intolerance
• PZA: 9HRE9- INH + RIF + EMB 每日一次口服，治療9個月
• RIF: 6HEZ+SM then 6HEZ每日一次口服 每週五次針劑- INH + PZA + EMB 每日一次口服、每週五次針劑，
治療6個月後停止針劑，再繼續治療6個月。• INH: 6 9*ERZ• INH: 6-9 ERZ
- 全程採 RIF + PZA + EMB 每日一次口服，*2月痰培養(+) 個案治療9個月、其他個案治療6個月。( )
• EMB: 6HRZ +SM - INH + RIF + PZA 每日一次口服合併針劑，治療6個月二種以上一線藥物副作用 加強驗痰 暫不用藥• 二種以上一線藥物副作用: 加強驗痰，暫不用藥取得藥敏試驗結果後，副作用藥物併同抗藥性藥物依前段抗藥性結核建議調整處方。前段抗藥性結核建議調整處方。
萬不得已的治療方式5more drugs intolerance
限痰(+)且重症之病人
• INH + RMP: EMB + PZA + FQN + TBN + PAS/CS + SMEMB + PZA + FQN + TBN + PAS/CS + SM
• INH + RMP + EMB/PZA/SM: FQN + TBN + PAS/CS + KM/AMK，加 EMB/PZA中可用者FQN TBN PAS/CS KM/AMK 加 EMB/PZA中可用者
• INH + EMB: RMP + PZA + FQN + TBN + SM• RMP + EMB: INH + PZA + FQN + TBN + SM• RMP + EMB: INH + PZA + FQN + TBN + SM• EMB + PZA: INH + RMP + FQN + TBN + SM
INH PZA RMP EMB FQN TBN SM• INH + PZA: RMP + EMB + FQN + TBN + SM• RMP + PZA: INH + EMB + FQN + TBN + PAS/CS + SM
其他應注意事項其他應注意事項1
• 多重抗藥病人大半因未能規則服藥所致，啟用二線藥物治療前應先確定造成病人啟用二線藥物治療前應先確定造成病人未能按規治療的原因已經解決，以免產生更多藥物抗藥的結核菌株多藥物抗藥的結核菌株。
• 多重抗藥病人的前後藥敏試驗可能會變動，判讀必須非常審慎。應定期驗痰，追蹤藥敏試驗結果，根據系列應定期驗痰 追蹤藥敏試驗結果 根據系列報告，綜合研判最適合病人的治療方式。
其他應注意事項其他應注意事項2
• 治療多重抗藥病人時，全程使用PZA有治療意義，惟應格外注意高血清尿酸、有治療意義，惟應格外注意高血清尿酸、肝炎等副作用。
• 臨床懷疑多重抗藥，但無藥敏試驗報告的病人，建議加強驗痰，俟取得藥敏試驗病人 建議加強驗痰 俟取得藥敏試驗報告後再選用適當的二線藥物，如非治療不可，建議先使用8個月再治處方。不可，建議先使用8個月再治處方。
M it i T t tMonitoring TreatmentA. Treatment response / Treatment failure
Sputum examination clinical status CXRSputum examination, clinical status, CXRB. Toxicity
Mi i t l ti th● Minor intolerance- continue therapy,symptomatic treatment, antihistamin
● Hepatitis - LFT, stop all drugs, rechallenge● Hypersensitivity-desensitization● Drug interaction
C. AdherenceC. Adherence
抗結核藥物的毒性抗結核藥物的毒性
• 影響中樞神經：INH, T1314, EMB• 高尿酸症：PZA EMB• 高尿酸症：PZA, EMB• 視神經炎：EMB, INH, SM, T1314維他命B6缺乏 INH T1314 DCS• 維他命B6缺乏：INH, T1314, DCS
• 癩皮病：INH, T1314,• 末梢神經變性症：INH, T1314, DCS, SM• 體液/組織變色：RMP RBT CFZ• 體液/組織變色：RMP, RBT, CFZ• 腎毒性/耳毒性：SM, CPM
Drug Hepatitis – meta-analysisg p y
Total person-months INH: 12128; RIF: 10428; EMB: 5009;
Ormerod LP, et al. Tuberc Lung Dis 1996;77:37-42.
pPZA: 1448; SM: 353
抗結核藥物之間的交互作用抗結核藥物之間的交互作用
INH RMP：增加肝毒性• INH-RMP：增加肝毒性
• INH-PAS：增加INH血中濃度
•RMP-PAS：減少RMP之吸收
•RMP-CFZ：減少RMP之吸收•RMP-CFZ：減少RMP之吸收
• T1314-INH：增加中樞神經毒性
增加中樞神經毒性• T1314-DCS：增加中樞神經毒性
•EMB-T1314：增加視神經炎增加視神經炎
•SM-T1314：增加視神經炎
DCS INH：增加中樞神經毒性•DCS-INH：增加中樞神經毒性
併用Rifampicin時會減少本身效果之藥物併用Rifampicin時會減少本身效果之藥物
• Acetaminophen• Anticoagulant, oral
• Diltiazem• Estrogenes
• Benzodiazepines• Ciprofloxacin
• Fluconazole• Haloperidol
• Chloramphenicol• Clofibrate
• Niefedipine• Propanolol
• Contraceptives, oral• Corticosteroids
• Qunidine• Sulfonylureas
• Cycloserine• Digitalis
• Theophyllines• Verapamil
Effect of Simultaneous oral administration of PAS(0.2 g/kg) 0n serum concentration of RMP (0.2 mg/kg) in 30 patients
Time(h)
RMP(μg/mL)mean + SD
RMP(μg/mL)mean + SD
Significancep
without PAS with PAS2 6.06 + 0.62 2.91 + 0.33 < 0.001
4 5.64 + 0.41 2.96 + 0.25 < 0.001
6 4.36 + 0.39 2.45 + 0.20 < 0.001
8 2.98 + 0.33 1.77 + 0.23 < 0.01
Digoxin-Rifampin Interactiong p
• SDC and daily doses of digoxin and RMP are showing for patient EP form December 1981 to December 1982for patient EP form December 1981 to December 1982
Gault H et al. Clin Pharmocol Ther 1984;35:750-4
Warfarin-Rifampin InteractionRifampin markedly decreased the
p
decreased the plasma level of warfarin andwarfarin and markedly increased the one-stage prothrombin activityO’Reilly RAAnn Intern Med1975;83:505-8;
Warfarin-Rifampin InteractionWarfarin Rifampin Interaction
The rifampin caused the plasma concentration of warfarin to fall to zer 0 and the 0ne-stage prothrombin activity toprothrombin activity to 100% of normal (Chronic daily Therapy)(Chronic daily Therapy)
O’Reilly RAAnn Intern Med1975;83:505 81975;83:505-8
結核病人治療中應追蹤事項結核病人治療中應追蹤事項 1
服藥順服度病人是否依約定期回診；主動為病人預約下次
回診時間，提高病人回診動機。未依約回診追蹤
的病人為不合作服藥的高危險群，建議與公共衛的病人為不合作服藥的高危險群，建議與公共衛
生單位連絡，及早因應。
隨時拿出藥物樣品 詢問病人服藥顆數及服藥時隨時拿出藥物樣品，詢問病人服藥顆數及服藥時
間能正確回答的病人，未必代表規則服藥；但無
法正確回答的病人，應格外注意其服藥順服度的
問題。
結核病人治療中應追蹤事項2結核病人治療中應追蹤事項2
服藥順服度服藥順服度詢問病人尿液顏色大多數在服藥初期會有尿液變紅
的現象的現象。
為能確實掌握病人服藥順服度，宜鼓勵病人(尤其
是痰塗片 病人 接受 觀察用藥 不建議是痰塗片(+) 病人)接受DOT，觀察用藥，不建議
開立慢性病連續處方箋。
驗痰(至少第0、2、5月及完治時)痰(+) 病人最好每月追蹤驗痰直至陰轉為止；痰( ) 病人最好每月追蹤驗痰直至陰轉為止；
病人於完治時，應再安排驗痰，至少應符合世界衛生
組織滿2個月、第5個月及完治時各二套驗痰的標準。組織滿2個月、第5個月及完治時各二套驗痰的標準。
結核病人治療中應追蹤事項結核病人治療中應追蹤事項3
‧血液生化檢查 (第0、2、4、8週)使用藥物前應安排血液及生化檢查，建議項目如下：使用藥物前應安排血液及生化檢查，建議項目如下：
CBC、AST/ALT、Bilirubin、Uric Acid、BUN/Cre。使用藥物後的第2 4 8週建議追蹤上項檢查 其他使用藥物後的第2、4、8週建議追蹤上項檢查，其他
可視病情需要，另外增加檢查。使用SM / KM / AM病人應特別注意追蹤腎功能 聽力 及平衡能力病人應特別注意追蹤腎功能、聽力、及平衡能力。
視力、辨色力檢查 (每月)( )使用EMB病人，應按月檢查視力及辨色力。
結核病人治療中應追蹤事項4
‧胸部 X光檢查(新病人及再治病人：第0、1、2月及完治時；(新病人及再治病人 第0 1 2月及完治時；
多重抗藥病人：每6個月)所有肺結核新病人及再治病人，建議在治療前所有肺結核新病人及再治病人，建議在治療前
及治療中第1、2個月及完治時追蹤胸部X光；
至於多重抗藥病人則建議每6個月追蹤胸部X光至於多重抗藥病人則建議每6個月追蹤胸部X光。
治療完成的條件治療完成的條件• 正確處方規則服藥
• 痰塗片 肺結核
• 足夠的治療時間
(+)• 痰塗片 肺結核病人於治療過程中至少一次痰塗片 且最後一個月之治療時痰塗片
(+)(-)
( )一個月之治療時痰塗片 。
• 痰塗片(-)肺結核
(-)
初始痰塗片 但後續無法驗痰新案*病人於治療過程中系列追蹤胸部X光病灶曾經進
(+)
步、或維持穩定不惡化。
* 此類病人應儘可能採痰，避免只以胸部X光決定停藥。
治療的完成與完治後追蹤治療的完成與完治後追蹤正確處方、規則服藥、足夠的治療時間
• X光具空洞，且二月痰培養陽性病人？
正確處方、規則服藥、足夠的治療時間
X光具空洞 且二月痰培養陽性病人？美ATS.CDC/IDSA建議延長治療，但因台灣並未採用每週二次的高劑量間歇性療法，不建議比照辦理。
• 下列病人可延長治療時間3個月併有糖尿病、矽肺症、結核瘤 (tuberculoma)開洞未癒合的病人 可考慮延長治療 至 個月的病人，可考慮延長治療3至6個月。
• 完治後追蹤
完成治療後的結核病人，建議於完治後的第一年每半年追蹤一次，此後每年追蹤一次。追蹤時，應安排胸部X光檢查 並盡可能驗痰檢查，並盡可能驗痰。
Anti TB Therapy in Special SituationsAnti-TB Therapy in Special Situations
• 1. Pregnancy• 2. Breast feedings2. Breast feedings• 3. Oral contraception
4 Li di d• 4. Liver disorders• 5. Established chronic disease• 6. Acute hepatitis• 7 Renal failure• 7. Renal failure• 8. HIV infection
WHO Guidelines 2003WHO Guidelines 2003
Anti-TB Therapy in Special Situationspy pPregnancy
• A woman should be asked whether she is pregnant before she starts TB regimen
• Most anti-TB drugs are safe for use in pregnancy• Treatment of choice: RIF-INH with/without EMBTreatment of choice: RIF INH with/without EMB• SM should not used during pregnancy because
of ototoxicity to the fetusof ototoxicity to the fetus • PZA been not recommended in USA but
recommended by IUAT WHOrecommended by IUAT, WHO• Second-line drugs: only aminoglycosides have
i iteratogenicity
Pregnancy Outcome Among Women Receiving Anti-TB Therapy and in a Normal Population
S S ill bi h P M lf dDrug
Spontaneousabortion
%
Still-birth
%
Prematurebirth%
Malformedinfants
%% % % %
INH 0.34 0.61 1.83 1.09EMB 0 16 0 78 4 08 2 19EMB 0.16 0.78 4.08 2.19RMP 1.67 2.15 0.48 3.35SM 0 97 0 0 16 91SM 0.97 0 0 16.91Normal
l ti6.8 2.2 7.1 1.4 – 2.0
2 3 13 8population 2.3 – 13.8
Snider et al Am Rev Respir Dis 1980; 122:65-79Snider et al Am Rev Respir Dis 1980; 122:65 79
Anti TB Drugs in PregnancyAnti-TB Drugs in Pregnancy
Appropriate for use
UseIf needed
Not foruse
Isoniazid Pyrazinamide EthionamideRifampicin Ethambutol AminoglycosidesRifampicin Ethambutol Aminoglycosides
Cycloserine
CapreomycinFl i lFluoroquinolone
Barber PG et al 1995 in Lutwick LI ed “Tuberculosis”Barber PG et al 1995, in Lutwick LI ed Tuberculosis
Outcome of Pregnancy in patients withactive Pulmonary TB
Variable Maurya & Sapre* Schaeffer et al**
Study period 1989-1992 1933-1951 1952-1972N=172 N=596 N=1059
Pregnancy outcomeNormal delivery 87 61.6 64.5Forceps delivery 0 27.6 28.7B h 0 4 5 2 7Breech 0 4.5 2.7Cesarean section 13 6.3 4.1Elective 9 ND NDElective 9 ND NDEmergency 4 ND ND
* J Obstet Gynecol India 1975 **Obstet Gynecolo 1975
Anti-TB Therapy in Special SituationsAnti TB Therapy in Special SituationsBreastfeeding 1
• A breastfeeding woman with TB should receive a full course of TB treatmentreceive a full course of TB treatment
• Timely and properly applied therapy is the best way to prevent transmission of TBB to her babyy
• All anti-TB drugs are compatible with breastfeeding: a woman taking them canbreastfeeding: a woman taking them can safely continue to breastfeed
Anti-TB Therapy in Special SituationsAnti-TB Therapy in Special SituationsBreastfeeding 2
• Mothers and baby should stay together and• Mothers and baby should stay together and the baby continue to be breastfed in normal wayway
• The baby should be given prophylactic INH for at least 3 months be ond the time thefor at least 3 months beyond the time the mother is considered to be non-infectious
• BCG vaccination of the new born should be postponed until the end of INH prophylaxis y
Anti-TB Therapy in Special SituationsAnti TB Therapy in Special SituationsOral Contraception
• Rifampicin interacts with contraceptive medicationswith a risk of decreased protective efficacy against t a s o dec eased p otect e e cacy aga stpregnancy
• A woman receiving oral contraception may choose• A woman receiving oral contraception may choosebetween 2 options while receiving rifampicin:
following consultation with a clinician an oralfollowing consultation with a clinician, an oralcontraceptive pill containing a higher dose of
t (50 ) b t kestrogen (50 μg) may be taken, oranother form of contraception may be used
女性特別議題
生育年齡女性
女性特別議題
‧生育年齡女性儘可能月經來時照胸部Ⅹ光避孕藥容易失效 建議改用其他避孕方法避孕藥容易失效，建議改用其他避孕方法或使用高量劑型(50μg)。
‧孕婦、授乳不須人工流產，如用INH，宜併用B6。不須人工流產，如用INH，宜併用B6。不得使用SM/KM/AMK，可能造成胎兒先天耳聾。避免使用TBN/FQN，PZA雖具爭議性但建議使用。避免使用TBN/FQN PZA雖具爭議性但建議使用如非照Ｘ光不可，必須對腹部作適當的保護。接受抗結核藥物治療的母親可以授母乳。接受抗結核藥物治療的母親可以授母乳
Anti-TB Therapy in Special Situations Di b t M llit 1Diabetes Mellitus 1
• Before the introduction of anti-TB therapy,yTB caused significant mortality in diabetics
• With effective chemotherapy, diabetics withTB fare as well as non-diabetics
• Therapy of TB is the same as for non-diabetics• Pyridoxin should be given
Anti-TB Therapy in Special Situations Diabetes Mellitus 2Diabetes Mellitus 2
• All patients should be carefully monitoredfor neuropathy and hepatic disease
• Higher relapse rates among diabetics ,( particularly in poorly controlled ), solonger course of therapy may be indicated
• A higher incidence of MDR-TB among diabetics( Baskar 1997, New York City )
Silicosis and Pulmonary TuberculosisSilicosis and Pulmonary Tuberculosis
• Silicosis often occurs with or is complicated by TB infectionTB infection
• Coexistent of silicosis and tuberculosis: 65-75%P d i t i l t f th l l b• Predominant involvement of the lower lobe
• Advanced silicosis had a greater incidence of active TB
• Free silica: enhancing effect upon TBFree silica: enhancing effect upon TB• Progressive massive fibrosis = to a form of TB
Sili TB d t b diffi lt t t lx
• SilicoTB appeared to be difficult to control
S SAnti-TB Therapy in Special Situations Silicosis 1
• Higher rates of tuberculosis for silicotic patients th h t th ldthroughout the world
• Impairment of macrophage function affects the ability of macrophages to inhibit the growth of TBBability of macrophages to inhibit the growth of TBB
• Longer therapeutic regimens with the same drugs as for nonsilicotic patients are necessary due toas for nonsilicotic patients are necessary due to the lower penetration of the drugs in silicotic nodules
• The standard 6-month short course therapy is inadequate
Anti-TB Therapy in Special SituationsAnti-TB Therapy in Special Situations Silicosis 2
• Hong-kong study ( Am Rev Respi Dis 1991:143:262)Bacteriologic relapses g p6-month therapy: 22%, 8-month therapy: 7%
• In the silicotic patients the sterilizing phase must be prolonged and patients should be treated for at least 9prolonged and patients should be treated for at least 9 months
• If pyrazinamide is not included in the regimen, therapy with INH and RMP must be prolonged for a minimum ofwith INH and RMP must be prolonged for a minimum of 12 months
• Retreatment regimens must also be prolonged as much g p gas 12 months and the follow-up for these patients should also be prolonged for 5 years
• Preventive chemoprophylaxis with INH has been• Preventive chemoprophylaxis with INH has been considered
Anti-TB Therapy in Special SituationsAnti TB Therapy in Special SituationsRenal Failure
• INH, RMP and PZA are either eliminated almost entirely by biliary excretion or metabolized in to y y ynontoxic compounds
• They can be given in normal dosage to patients i h l f ilwith renal failure
• Patients with severe renal failure should receive vitamin B6 with INH to prevent peripheral neuropathyvitamin B6 with INH to prevent peripheral neuropathy
• SM and EMB are excreted by the kidney. Where facilities are available to monitor renal functionWhere facilities are available to monitor renal function closely, SM and EMB may be given in reduced doses
• The safest regimen: 2 HRZ/4HR• The safest regimen: 2 HRZ/4HR
Anti-TB Agents Requiring Dose Modification inAnti TB Agents Requiring Dose Modification in Renal or Hepatic Insufficiency
Drug Renal Hepatic Drug Renal Hepatic gfailure
pfailure
gfailure
pfailure
Amikacin + - Kanamycin + -Capreomycin + - Ofloxacin + -Cycloserine + - PAS + +Ethambutol + - Pyrazinamide + +Ethionamide - + Rifampicin - +pIsoniazid + + Streptomycin + -
Barber PG et al 1995. In Lutwick ed “Tuberculosis”
Anti-TB Therapy in Special SituationsAnti-TB Therapy in Special SituationsRenal Failure (CCr < 30 – Dialysis)
‧一線結核藥物：INH 及RMP不須改變劑量 腎衰竭時宜加用B6－INH、及RMP不須改變劑量，腎衰竭時宜加用B6。
－EMB、PZA依一般劑量每週投與三次(較不建議依CCr調整劑量)；洗腎病患時，在透析後投藥(但CCr調整劑量)；洗腎病患時，在透析後投藥(但Quinolone可HD前給)。
二線結核藥物：二線結核藥物－Quinolone比照EMB、PZA調整投藥頻率。－TBN/PAS不經由腎臟代謝，不必調整投藥頻率。
C l i 比照EMB PZA調整投藥頻率－Cycloserine比照EMB、PZA調整投藥頻率。－ SM, KM, Amikacin, Capreomycin比照EMB 、PZA
調整投藥頻率。調整投藥頻率。
其他治療議題
發燒的處理
其他治療議題 1
‧發燒的處理 37-80%
－low grade到high spiking、幾天到幾個月都有可能。o g ade到 g sp g 幾天到幾個月都有可能－只要診斷確定，可併用Acetaminophen。
34%一週內退燒，64%二週內退燒，發燒時間Median 10天(1天～109天)
咯血的處理‧咯血的處理－心理建設最重要，請病人不要panic、bed rest，p讓血自然流出氣道。
－止咳是最重要的治療方式。－注意Vital Sign、Fluid/Blood component的補充。－可使用Transamin。
其他治療議題
使用類固醇避免後遺症
其他治療議題 2
‧使用類固醇避免後遺症
在診斷確定，無抗藥性之虞時，下列病人可考慮使用類固醇，以避免嚴重後遺症：可考慮使用類固醇 以避免嚴重後遺症－結核性腦膜炎－結核性心包膜炎(須早期使用)結核性心包膜炎(須早期使用)－氣管內結核 (2003 ATS guideline並未提及)
下列TB已不建議使用類固醇：－結核性肋膜炎(2003 ATS guideline不建議)( g )
Causes of Inadequate Anti TB Treatment 1Causes of Inadequate Anti-TB Treatment 1HEALTH.CARE PROVIDERS
INADEQUATE REGIMENSINADEQUATE REGIMENS
• Inadequate guidelines• Noncompliance with guidelines • Absence of guidelines• Absence of guidelines• Poor training
No monitoring of treatment• No monitoring of treatment • Poorly organized or funded
TB control program
WHO Guidelines for the programmatic management of drug-resistant tuberculosis 2006
Causes of Inadequate Anti-TB Treatment 2DRUGS INADEQUATE SUPPLY/QUALITY
• Poor quality• Unavailability of certain drugs• Unavailability of certain drugs
(stock-outs or delivery disruption) • Poor storage conditions • Wrong dose or combinationg
Causes of Inadequate Anti TB Treatment 3Causes of Inadequate Anti-TB Treatment 3PATIENTS INADEQUATE DRUG INTAKE
• Poor adherence ( or poor DOT) • Lack of information• Lack of information • Lack of money
(no treatment available free of charge)(no treatment available free of charge) • Lack of transportation • Adverse effects• Adverse effects• Social barriers
M l b ti• Malabsorption• Substance dependent disorders
Thank You !Thank You !
第二線抗結核藥物第二線抗結核藥物
L fl i (C it)• Levofloxacin (Cravit)• Moxifloxacin (Avelox)• Streptomycin (SM) • Kanamycin (KM)y ( )• Amikacin (AMK)• Rifabutin (RBT)Rifabutin (RBT)• Prothionamide (T1321)• Ethionamide (T1314) Selman Abraham Waksman • Ethionamide (T1314)• Para-Aminosalicylate (PAS)• Cycloserine (CS)
(1888-1973)
1952 Nobel Prize
• Cycloserine (CS)
Levofloxacin (Cravit)Levofloxacin (Cravit)
• Bactericidal against M. tuberculosis.• MIC for M. tuberculosis
0.25-0.5 μg/mL; • Usual dose:Usual dose:
• Levofloxacin 500-1000 mg/d (10mg/kg/d)• Toxicity:• Toxicity:
• GI disturbance 0.5-1.8%• Neurological effects: dizziness insomnia 0 5%• Neurological effects: dizziness, insomnia 0.5%• Cutaneous reactions: 0.2-0.4%
AminoglycosidesAminoglycosidesB t i id l• Bactericidal
• Usual dose:Amikacin (AMK)
• 15 mg/kg/d i.m. for 3mthen 15 mg/kg 3x/wk for 3m
T i it• Toxicity• Renal toxicity• Ototoxicity• Ototoxicity
• hearing loss • vestibular dysfunction Kanamycin (KM)• vestibular dysfunction
• Rash• Neurotoxicity
y ( )
yStreptomycin (SM)
Ethionamide (T1314, ETA)
• 2-ethylthioisonicotinamideB t i id l ff t t• Bactericidal effect：strong
• MIC: 0.6-2.5 μg/mLT i ff t GI di t b ( t lli t t )• Toxic effect: GI disturbance (metallic taste)
difficult to control DM,i h l thperipheral neuropathy,
tender gynecomastia, impotencef ki h• Allergic manifestations: skin rashes,
purpura, stomatitis• Precaution：liver function test
P i l il t (PAS)Para-aminosalysilate (PAS)
• Bacteriostatic• MIC: 1 8 g/mL• MIC: 1-8 μg/mL• Usual dose: 200 mg/kg daily (8-12 g daily)• Toxicity
• Hepatotoxicity: 0.3%Hepatotoxicity: 0.3%• GI disturbance: 11%• Malabsorption syndrome• Malabsorption syndrome• Hypothyroidism
Coag lopath• Coagulopathy
d- Cycloserine（DCS)d Cycloserine（DCS)• An antibiotics, isolated from S. orchidaceous,
and other selected species of Streptomyces• Tuberculostatic effect: weakube cu ostat c e ect ea• MIC: 5-20 μg/mL• Dosage: 250 mg bid for 2 wks then• Dosage: 250 mg bid for 2 wks, then
250 mg tid or qid• Toxic effect: Psychosis convulsion somnolence• Toxic effect: Psychosis , convulsion, somnolence,
headache, tremor, hyperreflexia• Allergic manifestations：fever skin rashes• Allergic manifestations：fever, skin rashes• Precautions：not used in patients with a prior history
of renal impairement epilepsy or mental instabilityof renal impairement, epilepsy or mental instability
Kanamycin (KM)Kanamycin (KM)• An antibiotis, isolated from S. kanamyceticus• Bactericidal effect: middle, MIC: 1-8 μg/mL• Dose： 1 gm bid, twice weakly, org y
1 gm qd, 5 times weekly• Toxic effect：vestibular damage, cochlearToxic effect vestibular damage, cochlear
damage, renal injury, curare-like effect,paresthesias restlessness headache painparesthesias, restlessness, headache, painand persistent nodules at injection site
• Allergic manifestations： eosinophilia fever• Allergic manifestations： eosinophilia, fever,shin rash, pururitus, anaphylaxis (rare)
&• Precautions：audiogram, BUN & urinalysis
Capreomycin (CPM)A tibi ti i l t d f S l• An antibiotics isolated from S. capreolus
• Bactericidal effect： middle• Dose： 15 mg/kg/d, usually 1 gm/d
for 60 days then 1 gm twice weeklyfor 60 days then 1 gm twice weekly• Toxic effect： renal injury, vestibular damage,
hl dcochlear damage• Allergic manifestations：eosinophilia,
shin rash, fever, anaphylaxis• Precautions：urinalysis, BUN, audiogramPrecautions urinalysis, BUN, audiogram
Huber GL Tuberculosis: In Remington JS Klein JO (eds):Huber GL Tuberculosis: In Remington JS, Klein JO (eds): Infectious Diseases of the Fetus and Newborn Infant 1983, p576
Mean plasma quinidine concentrations in the 4 subjects who received oral quinidine, 6 mg/kg, before(control) and after oral q , g g, ( )RMP 500 mg/d for 7 days
Arbitrary Grading for Renal Function
G G SGrade GFR(mL/min)
Serum creatinin(Approx) μmol/L
Mild 20 - 50 150 - 300M d t 10 20 300 700Moderate 10 - 20 300 - 700
Severe < 10 > 700