Microsoft PowerPoint NTUH 2-Treatment of Tuberculosis new.ppt [相容模式]

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1 Treatment of Tuberculosis 2 結核病的治療 ( 二 ) 陸坤泰

2 Contents t History of tuberculosis treatmentt t Anti-TB agents Principles of anti-tb chemotherapy Initial treatment Retreatment Treating drug resistant tuberculosis Monitoring during therapy Treatment for special groups

3 Retreatment 再治療

4 Recommended Treatment Regimens for TB Diagnostic Category Ⅱ TB Patients Previously treated sputum smear-(+) PTB: - relapse; - treatment after interruption (default); - treatment failure (drug sensitivity test before prescription, proven MDR-TB use category IV) Initial phase (Daily or 3 times weekly) 2 HRZES / 1 HRZE Continuation phase (Daily or 3 times weekly) 5 HRE WHO Guidelines 2003

5 Prevalence of Resistance Retreated Patients (n=183) with lates tients nt isol % of pat re esista Treatment failure (n=33) Relpase (n=93) Treatment after default (n=57) Total (retreated patients, n=183) INH RIF EMB SM Any one MDR drug Chiang CY et al. J Formos Med Assoc 2004

6 小心抗藥就在你身邊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

7 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 ; 組織病理學 / 組織培養證實之肺外結核復發病人 ; 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 ; 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

8 Prevalence of Resistance Relapse (N = 93) Prevalence of resistance to any drug, 33.3% % % 40 single any INH RMP EMB SM MDR Chiang CY et al. J Formos Med Assoc 2004

9 請不要只想怎麼開藥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

10 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, 將造成更嚴重的抗藥性菌株, 對公共衛生絕對有害無利

11 Prevalence of Resistance Treatment Default (N = 57) Prevalence of resistance to any drug 42.1% % %% single any 30 % INH RMP EMB SM MDR Chiang CY et al. J Formos Med Assoc 2004

12 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 2HERZ+SM/1HERZ/5HER

13 避免產生更多的抗藥而不是治療多重抗藥結核 2HERZS / 1HERZ / 5HER An 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) 的麻煩而輕易使用如 INH + RMP + EMB + PZA + FQN 這樣的處方治療再治病人

14 要有處理多重抗藥的能力失敗再治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

15 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 (-) 治療二個月後變成痰細菌學 (+) 者

16 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, 不列為失敗再治病人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

17 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, 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, 應優先解決其順服度的問題, 而不是輕易另加新藥

18 Prevalence of Resistance Treatment Failure (N = 33) Prevalence of drug resistance to any drug 69.7% %% 80 single any INH RMP EMB SM MDR Chiang CY et al. J Formos Med Assoc 2004

19 避免產生更多的抗藥治好治療反應較慢的病人 ( 不是治療多重抗藥結核 ) 2HERZS / 1HERZ / 5HER An 8-month regimen for relapse, return after interruption and treatment failure

20 Treating Drug Resistant TUBERCULOSIS In designing a regimen, do not aim to keep drugs in reserve. WHO. Guidelines for the management of drug-resistant tuberculosis, 1997

21 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 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...

22 什麼時候要用到第二線結核藥物? 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 : 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

23 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 : 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, 才發現為抗藥性菌株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

24 結核病其他治療方式 1 single 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 EMB: 2HRZ+4HR 或 9HR - 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

25 結核病其他治療方式 2 INH + RMP: more drugs resistance EMB + PZA + FQN + TBN + SM 至少 6 個月, 或 EMB + PZA + FQN + TBN 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 中可用者個月 INH + EMB: RMP + PZA + FQN 9 個月

26 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 12 個月 EMB + PZA: INH + RMP 9 個月 INH + PZA: RMP + EMB + FQN 9 個月 RMP + PZA: INH + EMB + FQN + SM 6 個月或 INH + EMB + FQN 12 個月

27 結核病其他治療方式 4 single drug intolerance PZA: 9HRE - INH + RIF + EMB 每日一次口服, 治療 9 個月 RIF: 6HEZ+SM then 6HEZ - INH + PZA + EMB 每日一次口服每週五次針劑每週五次針劑, 治療 6 個月後停止針劑, 再繼續治療 6 個月 INH: 6-9*ERZ - 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

28 萬不得已的治療方式 5 more drugs intolerance 限痰 (+) 且重症之病人 INH + RMP: EMB + PZA + FQN + TBN + PAS/CS + SM INH + RMP + EMB/PZA/SM: 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 EMB + PZA: INH + RMP + FQN + TBN + SM INH + PZA: RMP + EMB + FQN + TBN + SM RMP + PZA: INH + EMB + FQN + TBN + PAS/CS + SM

29 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, 根據系列報告, 綜合研判最適合病人的治療方式

30 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

31 Monitoring Treatment A. Treatment response / Treatment failure Sputum examination, clinical status, CXR B. Toxicity Minor intolerance- continue therapy, symptomatic treatment, antihistamin Hepatitis - LFT, stop all drugs, rechallenge Hypersensitivity-desensitization Drug interaction C. Adherence

32 抗結核藥物的毒性影響中樞神經 :INH, T1314, EMB 高尿酸症 :PZA, EMB 視神經炎 :EMB, INH, SM, T1314 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

33 Drug Hepatitis meta-analysis Total person-months INH: 12128; RIF: 10428; EMB: 5009; PZA: 1448; SM: 353 Ormerod LP, et al. Tuberc Lung Dis 1996;77:37-42.

34 抗結核藥物之間的交互作用 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 T1314-INH: 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 SM-T1314: 增加視神經炎 DCS-INH: 增加中樞神經毒性

35 併用 Rifampicin 時會減少本身效果之藥物 Acetaminophen Anticoagulant, oral Benzodiazepines Ciprofloxacin Chloramphenicol Clofibrate Contraceptives, oral Corticosteroids Cycloserine Digitalis Diltiazem Estrogenes Fluconazole Haloperidol Niefedipine Propanolol Qunidine Sulfonylureas Theophyllines Verapamil

36 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 Significance p without PAS with PAS < < < < 0.01

37 Digoxin-Rifampin Interaction SDC and daily doses of digoxin and RMP are showing for patient EP form December 1981 to December 1982 Gault H et al. Clin Pharmocol Ther 1984;35:750-4

38 Warfarin-Rifampin Interaction Rifampin markedly decreased the plasma level of warfarin and markedly increased the one-stage prothrombin activity O Reilly RA Ann Intern Med 1975;83:505-8;

39 Warfarin-Rifampin Interaction The rifampin caused the plasma concentration of warfarin to fall to zer 0 and the 0ne-stage prothrombin activity to 100% of normal (Chronic daily Therapy) O Reilly RA Ann Intern Med 1975;83:505-88

40 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

41 結核病人治療中應追蹤事項 2 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 DOT, 觀察用藥, 不建議開立慢性病連續處方箋驗痰 ( 至少第月及完治時 ) 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

42 結核病人治療中應追蹤事項 3 血液生化檢查 ( 第週 ) 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

43 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

44 治療完成的條件痰塗片 (+) 肺結核正確處方規則服藥足夠的治療時間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 (-) 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

45 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? 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 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

46 Anti-TB Therapy in Special Situations 1. Pregnancy 2. Breast feedings 3. Oral contraception 4. Liver disordersd 5. Established chronic disease 6. Acute hepatitis 7. Renal failure 8. HIV infection WHO Guidelines 2003

47 Anti-TB Therapy in Special Situations Pregnancy 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-INHINH with/without EMB SM should not used during pregnancy because of ototoxicity to the fetus PZA been not recommended in USA but recommended by IUAT, WHO Second-line drugs: only aminoglycosides have teratogenicity i

48 Pregnancy Outcome Among Women Receiving Anti-TB Therapy and in a Normal Population Drug Spontaneous Still-birth Premature Malformed abortion birth infants % % % % INH EMB RMP SM Normal population Snider et al Am Rev Respir Dis 1980; 122:65-79

49 Anti-TB Drugs in Pregnancy Appropriate for use Use If needed Not for use Isoniazid Pyrazinamide Ethionamide Rifampicin Ethambutol Aminoglycosides Cycloserine Capreomycin Fluoroquinolone l Barber PG et al 1995, in Lutwick LI ed Tuberculosis

50 Outcome of Pregnancy in patients with active Pulmonary TB Variable Maurya & Sapre* Schaeffer et al** Study period N=172 N=596 N=1059 Pregnancy outcome Normal delivery Forceps delivery Breech Cesarean section Elective 9 ND ND Emergency 4 ND ND * J Obstet Gynecol India 1975 **Obstet Gynecolo 1975

51 Anti-TB Therapy in Special Situations Breastfeeding 1 A breastfeeding woman with TB should receive a full course of TB treatment Timely and properly applied therapy is the best way to prevent transmission of TBB to her baby All anti-tb drugs are compatible with breastfeeding: a woman taking them can safely continue to breastfeed

52 Anti-TB Therapy in Special Situations Breastfeeding 2 Mothers and baby should stay together and the baby continue to be breastfed in normal way The baby should be given prophylactic INH for 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

53 Anti-TB Therapy in Special Situations Oral Contraception Rifampicin interacts with contraceptive medications with a risk of decreased eased protective e efficacy against pregnancy A woman receiving oral contraception may choose between 2 options while receiving rifampicin: following consultation with a clinician, an oral contraceptive pill containing a higher dose of estrogen (50 μg) ) may be taken, or another form of contraception may be used

54 生育年齡女性女性特別議題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

55 Anti-TB Therapy in Special Situations Diabetes Mellitus 1 Before the introduction of anti-tb therapy, y TB caused significant mortality in diabetics With effective chemotherapy, diabetics with TB fare as well as non-diabetics Therapy of TB is the same as for non-diabetics Pyridoxin should be given

56 Anti-TB Therapy in Special Situations Diabetes Mellitus 2 All patients should be carefully monitored for neuropathy and hepatic disease Higher relapse rates among diabetics, ( particularly in poorly controlled ), so longer course of therapy may be indicated A higher incidence of MDR-TB among diabetics ( Baskar 1997, New York City )

57 Silicosis and Pulmonary Tuberculosis Silicosis often occurs with or is complicated by TB infection Coexistent of silicosis and tuberculosis: 65-75% Predominant involvement of the lower lobe Advanced silicosis had a greater incidence of active TB Free silica: enhancing effect upon TB Progressive massive fibrosis x= to a form of TB SilicoTB appeared to be difficult to control

58 Anti-TB Therapy in Special Situations Silicosis 1 Higher rates of tuberculosis for silicotic patients throughout h t the world Impairment of macrophage function affects the ability of macrophages to inhibit the growth of TBB Longer therapeutic regimens with the same drugs as 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

59 Anti-TB Therapy in Special Situations Silicosis 2 Hong-kong study ( Am Rev Respi Dis 1991:143:262) Bacteriologic relapses 6-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 9 months If pyrazinamide is not included in the regimen, therapy with INH and RMP must be prolonged for a minimum of 12 months Retreatment regimens must also be prolonged as much as 12 months and the follow-up for these patients should also be prolonged for 5 years Preventive chemoprophylaxis with INH has been considered

60 Anti-TB Therapy in Special Situations Renal Failure INH, RMP and PZA are either eliminated almost entirely by biliary excretion or metabolized in to nontoxic compounds They can be given in normal dosage to patients with ihrenal lfailure Patients with severe renal failure should receive vitamin B6 with INH to prevent peripheral neuropathy SM and EMB are excreted by the kidney. Where facilities are available to monitor renal function closely, SM and EMB may be given in reduced doses The safest regimen: 2 HRZ/4HR

61 Anti-TB Agents Requiring Dose Modification in Renal or Hepatic Insufficiency Drug Renal Hepatic Drug Renal Hepatic failure failure failure failure Amikacin + - Kanamycin + - Capreomycin + - Ofloxacin + - Cycloserine + - PAS + + Ethambutol + - Pyrazinamide + + Ethionamide - + Rifampicin - + Isoniazid + + Streptomycin + - Barber PG et al In Lutwick ed Tuberculosis

62 Anti-TB Therapy in Special Situations Renal 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 -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 Quinolone 可 HD 前給 ) 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 -Cycloserine C l i 比照 EMB PZA 調整投藥頻率 - SM, KM, Amikacin, Capreomycin 比照 EMB PZA 調整投藥頻率

63 其他治療議題 1 發燒的處理 37-80% -low o grade 到 high spiking 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 - 心理建設最重要, 請病人不要 panic bed rest, 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

64 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 : - 結核性腦膜炎 - 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 )

65 Causes of Inadequate Anti-TB Treatment 1 HEALTH.CARE PROVIDERS INADEQUATE REGIMENS Inadequate guidelines Noncompliance with guidelines Absence of guidelines Poor training No monitoring of treatment Poorly organized or funded TB control program WHO Guidelines for the programmatic management of drug-resistant tuberculosis 2006

66 Causes of Inadequate Anti-TB Treatment 2 DRUGS INADEQUATE SUPPLY/QUALITY Poor quality Unavailability of certain drugs (stock-outs or delivery disruption) Poor storage conditions Wrong dose or combination

67 Causes of Inadequate Anti-TB Treatment 3 PATIENTS INADEQUATE DRUG INTAKE Poor adherence ( or poor DOT) Lack of information Lack of money (no treatment available free of charge) Lack of transportation Adverse effects Social barriers Malabsorption Substance dependent disorders

68 Thank You!

69 第二線抗結核藥物 Levofloxacin (Cravit) Moxifloxacin (Avelox) Streptomycin (SM) Kanamycin (KM) Amikacin (AMK) Rifabutin (RBT) Prothionamide (T1321) Ethionamide (T1314) Para-Aminosalicylate (PAS) Cycloserine (CS) Selman Abraham Waksman ( ) 1952 Nobel Prize

70 Levofloxacin (Cravit) Bactericidal against M. tuberculosis. MIC for M. tuberculosis μg/ml; Usual dose: Levofloxacin mg/d (10mg/kg/d) Toxicity: GI disturbance % Neurological effects: dizziness, insomnia 0.5% Cutaneous reactions: %

71 Aminoglycosides Bactericidal id Usual dose: 15 mg/kg/d i.m. for 3m then 15 mg/kg 3x/wk for 3m Toxicity it Renal toxicity Ototoxicity hearing loss vestibular dysfunction Rash Neurotoxicity Streptomycin (SM) Amikacin (AMK) Kanamycin (KM)

Ethionamide (T1314, ETA) 2-ethylthioisonicotinamide Bactericidal id effect:strong t MIC: 0.6-2.

72 Ethionamide (T1314, ETA) 2-ethylthioisonicotinamide Bactericidal id effect:strong t MIC: μg/ml Toxic effect: GI disturbance (metallic taste) t difficult to control DM, peripheral neuropathy, tender gynecomastia, impotence Allergic manifestations: skin rashes, purpura, stomatitis Precaution:liver function test

73 Para-aminosalysilate il (PAS) Bacteriostatic MIC: 1-8 μg/ml Usual dose: 200 mg/kg daily (8-12 g daily) Toxicity Hepatotoxicity: 0.3% GI disturbance: 11% Malabsorption syndrome Hypothyroidism Coag lopath Coagulopathy

74 d- Cycloserine(DCS) An antibiotics, isolated from S. orchidaceous and other selected species of Streptomyces Tuberculostatic c effect: ect weak MIC: 5-20 μg/ml Dosage: 250 mg bid for 2 wks, then 250 mg tid or qid Toxic effect: Psychosis, convulsion, somnolence, headache, tremor, hyperreflexia Allergic manifestations:fever, skin rashes Precautions:not used in patients with a prior history of renal impairement, epilepsy or mental instability

75 Kanamycin (KM) An antibiotis, isolated from S. kanamyceticus Bactericidal effect: middle, MIC: 1-8 μg/ml Dose: 1 gm bid, twice weakly, or 1 gm qd, 5 times weekly Toxic effect:vestibular damage, cochlear damage, renal injury, curare-like effect, paresthesias, restlessness, headache, pain and persistent nodules at injection site Allergic manifestations: eosinophilia, fever, shin rash, pururitus, anaphylaxis (rare) Precautions:audiogram, BUN & urinalysis

76 Capreomycin (CPM) 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 weekly Toxic effect: renal injury, vestibular damage, cochlear damage Allergic manifestations:eosinophilia, shin rash, fever, anaphylaxis Precautions:urinalysis, urinalysis, BUN, audiogram

77 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

78 Mean plasma quinidine concentrations in the 4 subjects who received oral quinidine, 6 mg/kg, g, before(control) and after oral RMP 500 mg/d for 7 days

79 Arbitrary Grading for Renal Function Grade GFR Serum creatinin (ml/min) (Approx) μmol/l Mild Moderate Severe < 10 > 700

期有使用 PZA, 含 Rifampin 之短期治療達到合理的成功率目前最常使用的組合為六個月的短程治療方案, 即加強期使用 INH RMP EMB 及 PZA 治療二個月, 持續期停用 PZA, 再治

期有使用 PZA, 含 Rifampin 之短期治療達到合理的成功率目前最常使用的組合為六個月的短程治療方案, 即加強期使用 INH RMP EMB 及 PZA 治療二個月, 持續期停用 PZA, 再治第二章結核病的治療及副作用處理 2002 年 8 月 1 日研訂 2009 年 2 月 19 日第 3 次修訂壹前言卡介苗即使普遍接種, 也無法透過群體免疫力預防感染的蔓延, 故儘早發現最具傳染性的病患, 儘早使用藥物治療降低其傳染性, 避免細菌的