索任 簡歷 內科專科醫師 職業醫學專科醫師 胸腔暨重症醫學專科醫師 結核病專科醫師 1979 台灣大學 醫學院 醫學系 現任 曾任 1979 台灣大學 醫學院 醫學系 現任 2005/5 - 中華民國防癆協會第一胸腔病防治所醫師 2006/1- 行政院衛生署傳染病防治諮詢委員會結核病防治組召集人 2006/7- 馬偕醫院胸腔內科顧問醫師 2005/5- 行政院衛生署桃園醫院胸腔內科顧問醫師 2002- 中華民國職業病醫學會理事 1994- 台灣結核病醫學會理事 曾任 2002/7 – 2005/3 行政院衛生署桃園醫院內科師一級主治醫師 2002/2 – 2002/7 行政院衛生署胸腔病院副院長代理院長 2001/8 – 2002/1 行政院衛生署慢性病防治局副局長代理局長 1999/7 – 2001/8 行政院衛生署慢性病防治局副局長 1997/1 – 1999/6 台北縣慢性病防治所醫師 1989/3 – 1997/1 台灣省慢性病防治局技正兼主任 1984/4 – 1989/3 台灣省防癆局技正兼主任 1983/7 – 1984/4 台灣省防癆局主治醫師 1979/7 – 1983/7 台灣省防癆局(台大醫院代訓)住院醫師及總住院醫師

結核病診治實務 社團法人中華民國防癆協會 第一胸腔病防治所 http://www.tb.org.tw 索 任 醫 師 索 任 醫 師 http://solo8388.myweb.hinet.net solo@tstb.org 結核病醫學會 http://www.tstb.org

結核病防治 化學治療 結核病的傳染期 = 病人延遲 +醫師延遲 +病人治療管理不當 傳染 transmission 傳染性 結核病 非傳染性 Prophylactic treatment 預防性 治療 化學治療 卡介苗 接種 病人延誤 醫師延誤 傳染 transmission 死亡 接觸 Source: Interventions for Tuberculosis Control and Elimination, IUATLD 2002 Preventive therapy Doctor’s delay Patient’s delay Infectious TB Non-Infectious TB Latent TB infection Exposure BCG vaccination Death Chemotherapy 結核病的傳染期 = 病人延遲 +醫師延遲 +病人治療管理不當 結核病防治 巫XX 47M 910529 治療管理不當 巫XX 50M 940909 結核潛伏感染 陳XX 52F 830411 陳XX 50F 810327

肺結核的延誤診治 Delayed diagnosis of pulmonary TB 中位數 範圍 病人延遲: 7天 (1-28天) 醫療機構延遲: 23天 (5-51天) 總延遲： 44天 (18-92天) 台南縣全縣, 台南市及 高雄縣的13鄉鎮 江振源：台南地區歸因於病人與醫療機構之結核病診斷與治療之延遲之時間及因素分析研究. 2003 衛生署疾病管制局九十二年度科技研究發展計畫 Chiang CY et al. Int J Tuberc Lung Dis. 2005; Sep;9(9):1006-12.

結核病診治指引

病例討論 1 Productive cough off and on since Jan, 2006 溫 X X 41 F (BD:1965/1/10) 病例討論 1 2006/4/21 Productive cough off and on since Jan, 2006 Presented to hospital on 2006/4/21, CXR taken. What is your decision at this moment?

溫 X X 41 F (BD:1965/1/10) 病例討論 1 2006/09/15 Productive cough persisted, easily fatigue, and became dyspneic for 2weeks. Visit 台東慢防所 on 2006/9/15. No fever. Wt loss+ 41kg (Apr)  36kg (Sep) What is your decision?

誰是結核病人?

診斷結核病 病史 理學檢查 結核菌素皮膚試驗 胸部X光檢查 結核菌學檢查 病理學檢查 其他: PCR, 血清學檢查

現病史 全身性症狀：如倦怠、體重減輕、發燒、 夜間盜汗等。 呼吸道症狀：如長期（三週以上）咳嗽、喀痰；咯血、呼吸短促、胸痛等。 其他系統症狀：如合併喉結核時可能會喉痛聲音嘶啞；合併結核性腦膜炎時可能會頭痛昏迷；合併腸結核時可能會腹痛腹瀉等。 肺結核病人初發病時往往沒有明顯 或特異性的症狀，且症狀經過緩慢 ，時好時壞，具有傳染性的肺結核 病人則常有反復咳嗽喀痰等症狀。

病史 過去史 肺結核病好發因素：糖尿病？粉塵史？胃切除？服用成分不明中藥或類固醇藥物？腎衰竭？其他疾病？老年？男性？…… 過去結核病史及詳細治療經過，有沒有可能是抗藥性病人？ 懷孕？過敏史？ 家族史接觸史 結核病接觸史？原住民？醫護人員是否曾長期與抗藥性病人接觸？

診斷結核病 病史 理學檢查 結核菌素皮膚試驗 胸部X光檢查 結核菌學檢查 病理學檢查 其他: PCR, 血清學檢查

如何檢查結核菌感染 結核菌素測驗 (不夠精準的檢查) 結核菌素 tuberculin (Koch,1890) Mantoux test (1907) 干擾 – 宿主的抵抗力, 卡介苗或其他非結核分枝桿菌(NTM)感染, 測驗技術和判讀經驗 台灣早年結核病盛行率高，50年前的20歲以上成人已有80%的結核菌素皮膚試驗陽性（表示已感染）。

診斷結核病 病史 理學檢查 結核菌素皮膚試驗 胸部X光檢查 結核菌學檢查 病理學檢查 其他: PCR, 血清學檢查

怎樣檢查肺結核病？ 胸部X光 驗痰: 塗片顯微鏡檢及結核菌培養(連續3套痰間隔8-24小時) 胸部Ｘ光檢查 驗痰

那些人須要檢查肺結核病？ 因症就診 咳嗽 3 週以上 定期檢查-高危險群 新近感染者(結核菌素測驗反應陽轉) 肺部疑纖維化肺結核病灶但未曾接受治療 HIV感染者 糖尿病人 腎衰竭長期洗腎者 長期服用免疫抑制劑者 年長者……等

Standards for Diagnosis Standard 1 All persons with otherwise explained productive cough lasting 2-3 weeks or more should be evaluated for tuberculosis

ISTC: The providers role International Standard of TB Care ISTC: The providers role All providers who undertake evaluation and treatment of patients with TB must recognize that, not only are they delivering care to an individual, they are assuming an important public health function.

Standards for Diagnosis Standard 2 All patients (adults, adolescents, and children who are capable of producing sputum) suspected of having pulmonary tuberculosis should have at least 2, and preferably 3, sputum specimens obtained for microscopic examination. When possible, at least one early morning specimen should be obtained.

Standards for Diagnosis Standard 3 For all patients (adults, adolescents, and children) suspected of having extrapulmonary tuberculosis, appropriate specimens from the suspected sites of involvement should be obtained for microscopy and, where facilities and resources are available, for culture and histopathological examination.

Standards for Diagnosis Standard 4 All persons with chest radiographic findings suggestive of tuberculosis should have sputum specimens submitted for microbiological examination.

肺結核的胸部Χ光特徵 好發部位: 肺上葉(Upper Lobe) 的頂小葉(Apical Segment) 及後小葉(Posterior Segment), 肺下葉 (Lower Lobe) 的上小葉(Superior Segment). 散在性及多發性病灶, 常同時發生在不同的肺葉, 也常兩側肺同時有結核病灶. 新鮮病灶常呈不規則及不均勻的斑駁狀肺實變陰影 常同時存在不同程度的陳舊性纖維化陰影 常有空洞形成

Far advnaced cavitary TB 1991-6-4 1992-5-24

TB TB 何時了 – Delayed diagnosis

TB TB 何時了

How reliable is chest radiography No radiographic picture (or pattern) is absolutely typical of tuberculosis Chest radiography can be very helpful in localizing abnormalities in the lung. To establish the tuberculous etiology of an abnormality, further examination is necessary, and only bacteriology can provide the final proof.

痰結核菌檢查 耐酸菌鏡檢 結核菌培養 菌種鑑定 藥物敏感性試驗 直接抹片 離心濃縮 Solid media: Liquid media Lewenstein-Jensen (LJ) Media, 7H10, 7H11 agar selective media Liquid media MGIT 960: 7H9 Bactec 460TB: 7H12 菌種鑑定 藥物敏感性試驗

Mycobacterium tuberculosis Robert Koch (1843-1910) 1905 Nobel Prize M. kansasii 非結核分支桿菌 痰塗片陽性的結核病人具有高度傳染性 Fluorescent stain 結核分支桿菌 Mycobacterium tuberculosis Sputum smear acid-fast (Kinyong) stain

164名病人422次M.tb培養陽性的痰檢體。 直接塗片陽性者 131 (31.0%) 離心濃縮塗片陽性 231 (54.7%) Comparison of Direct and Concentrated Sputum Smear for Detection of M. tb 164名病人422次M.tb培養陽性的痰檢體。 直接塗片陽性者 131 (31.0%) 離心濃縮塗片陽性 231 (54.7%) 許等. 胸腔醫學 2006;21:附冊P.156

Mycobacterium tuberculosis 結核菌在適合的環境下約20-24小時分裂1次 7H10 Agar MGIT960 Lewenstein-Jensen (LJ) Media 痰塗陰培陽的病人，傳染性不到塗陽病人的 1/3

Delayed diagnosis of TB 3 2001-8-20 2 2000-11-13 1 2000-10-16

Delayed diagnosis of TB 84-12-9 5 Delayed diagnosis of TB 83-4-11 4 80-12-3 1 82-1-29 3 81-3-27 2

Standards for Diagnosis Standard 5 The diagnosis of sputum smear-negative pulmonary tuberculosis should be based on the following criteria: At least 3 negative sputum smears (including at least one early morning specimen); Chest radiography findings consistent with tuberculosis; and Lack of response to a trial of broad-spectrum antimicrobial agents. (NOTE: Because the fluoroquinolones are active anainst M.tuberculosis, they should be avoided.) For such patients, if facilities for culture are available, sputum cultures should be obtained. In persons with known or suspected HIV infection, the diagnostic evaluation should be expedited.

疑似肺結核病患之診斷步驟 疾病管制局: 結核病診治指引, 2006 第二版

疑肺結核診斷實例 – 蔡XX/39F 蔡 X X 39 F Cough and lumpy throat off and on for 2-3months Fever – Wt loss – CXR PA and RL 95/6/14

結核病診斷實例 – 黃張XX/67F 黃 X X 映 1939/11/24 F Cough with sputum and rhinorrhea 2wk Fever (-) Wt loss (-) FH of TB (-) PH of DM (-)

結核病診斷實例 – 黃張XX/67F 2 處置 痰液塗片耐酸菌鏡檢及結核菌培養 X 3套 Amoxicillin 500mg tid X 7d FU CXR 1wk later 調舊片比較 結果 痰3次AFB(-) 1週後X光略惡化 痰培養中

3 結核病診斷實例 – 黃張XX/67F 95/05/03 黃XXX 95/05/10 黃XXX

4 結核病診斷實例 – 黃張XX/67F 臨床診斷塗片陰性肺結核 11/29 開始標準抗結核治療 95/05/10

TB TB 何時了 – Delayed diagnosis 2006/2/24 2004/9/27 2006/2/10

病例定義 結核病疑似個案（Tuberculosis suspects） 結核病例（A case of tuberculosis） 任何人有可疑結核病的症狀或徵象，特別是長期咳嗽。 結核病例（A case of tuberculosis） 細菌學證實，或經臨床醫師診斷的結核病人。 註：任何接受結核病治療的病人都應記錄。不完整的試驗性治療不可作為診斷方法。 確診結核病例（A definite tuberculosis case） 結核分枝桿菌（Mycobacterium tuberculosis complex）培養陽性的結核病人。 （在培養無法常規作到的國家，兩次痰塗片耐酸菌[AFB] 陽性的結核病人也認定為「確診」病例）。 WHO. Treatement of tuberculosis, 3nd ed. 2003. WHO/CDS/TB 2003.313

病例定義 痰塗片陽性肺結核 至少兩次顯微鏡檢痰塗片陽性；或 至少一次顯微鏡檢痰塗片陽性、且經醫師判定胸部X光之病灶符合肺結核之變化、決定施予一完整療程之抗結核治療；或 至少一次顯微鏡檢痰塗片陽性且該檢體結核分枝桿菌培養陽性。 WHO. Treatement of tuberculosis, 3nd ed. 2003. WHO/CDS/TB 2003.313

病例定義 痰塗片陰性肺結核 定義一： 定義二： 至少三套痰檢體顯微鏡檢痰塗片檢查皆為陰性；且 胸部X光之病灶符合活動性肺結核之變化，且 臨床上對一週之廣效抗生素治療無反應；且 醫師決定施予一完整療程之抗結核治療。 定義二： 顯微鏡檢痰塗片陰性但痰培養陽性之病人 WHO. Treatement of tuberculosis, 3nd ed. 2003. WHO/CDS/TB 2003.313

病例討論 1 Productive cough off and on since Jan, 2006 溫 X X 41 F (BD:1965/1/10) 病例討論 1 2006/4/21 Productive cough off and on since Jan, 2006 Presented to hospital on 2006/4/21, CXR taken. What is your decision at this moment?

溫 X X 41 F (BD:1965/1/10) 病例討論 1 2006/09/15 Productive cough persisted, easily fatigue, and became dyspneic for 2weeks. Visit 台東慢防所 on 2006/9/15. No fever. Wt loss+ 41kg (Apr)  36kg (Sep) What is your decision?

Standards for Treatment Treatment for TB is not only a matter of individual health, it is also a matter of public health. All providers must have the knowledge to prescribe a standard treatment regimen and the means to assess adherence to ensure that treatment is completed.

Standards for Treatment Standard 7 Any practitioner treating a patient for tuberculosis is assuming an important public health responsibility. To fulfill this responsibility the practitioner must not only prescribe an appropriate regimen but, also, be capable of assessing the adherence of the patient to the regimen and addressing poor adherence when it occurs. By so doing, the provider will be able to ensure adherence to the regimen until treatment is completed. 決定開始治療，應於 1 週內向當地衛生局作傳染病通報。

區分為初治或再治病人 新病人 (New case)：不曾接受過抗結核藥治療或曾接受少於四週抗結核藥治療之病人。 -1 新病人 (New case)：不曾接受過抗結核藥治療或曾接受少於四週抗結核藥治療之病人。 再治病人(Retreatment case) 復發 (Relapse)：曾接受一個完整療程之抗結核藥治療並經醫師宣告治癒而再次痰塗片或培養陽性之病人。 失落再治 (Treatment after default)：中斷治療兩個月以上而再次痰塗片或培養陽性之病人。 失敗再治 (Treatment after failure)：治療五個月後依然痰塗片或培養陽性的病人，或者治療前痰陰性、治療二個月後變成痰塗片或培養陽性的病人。 疾病管制局: 結核病診治指引, 2006 第二版

Drug Resistance of MTB for each Treatment Category in Taiwan Chiang CY,et al. Formos Med Assoc, 2004. * Jen-Jyh Lee et al, Tzu Chi Med J, 2003.

區分為初治或再治病人 其他病人(Other)：在監督下接受完整之再治處方治療後依然痰塗片或培養陽性之病人，或使用二線藥物之多重抗藥病人。 -2 其他病人(Other)：在監督下接受完整之再治處方治療後依然痰塗片或培養陽性之病人，或使用二線藥物之多重抗藥病人。 多重抗藥病人（Multidrug-resistant tuberculosis, MDR-TB）：藥敏試驗顯示至少對Isoniazid及Rifampin抗藥。 慢性病人（Chronic case）：在監督下接受完整之二線藥物治療後依然痰細菌學陽性的病人；或對大多數一線、二線藥物抗藥，致無法選用足夠有效藥物治療的結核病人；或因嚴重藥物副作用無法接受治療的病人。 疾病管制局: 結核病診治指引, 2006 第二版

MDR-TB and XDR-TB Multidrug-resistant TB Resistance to at least both INH and RMP Extensively Drug-resistant 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) WHO. XDR-TB – Extensively Drug-resistant TB. Nov, 2006

Standards for Treatment Standard 8 -1 All patients (including those with HIV infection) who have not been treated previously should receive an internationally accepted first-line treatment regimen using drugs of known bioavailability. The initial phase should consist of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol. The preferred continuation phase consists of isoniazid and rifampicin given for four months. Isoniazid and ethambutol given for six months is an alternative continuation phase regimen that may be used when adherence cannot be assessed, but it is associated with a higher rate of failure and relapse, especially in patients with HIV infection.

Standards for Treatment Standard 8 -2 The doses of antituberculosis drugs used should conform to international recommendations. Fixed-dose combinations of two (isoniazid and rifampicin), three (isoniazid, rifampicin, and pyrazinamide), and four (isoniazid, rifampicin, pyrazinamide, and ethambutol) drugs are highly recommended, especially when medication ingestion is not observed.

結核病標準初次治療 標準治療 2HRZE/4HRE 每日一次口服 前 2 個月 INH+RMP+PZA+EMB 如證實無 INH 或 RMP 抗藥, 則考慮停用 EMB 標準治療 2HRZE/4HRE 每日一次口服 前 2 個月 INH+RMP+PZA+EMB 後 4 個月 INH+RMP+EMB 成人劑量 Isoniazid (INH) 5mg/kg/d Rifampin (RMP) 10mg/kg/d Pyrazinamide (PZA) 25mg/kg/d Ethambutol (EMB) 15mg/kg/d 適用初治新案 (new case)：不曾接受過抗結核藥治療或曾接受少於 4 週抗結核藥治療之病人。

肺結核標準初次治療 治療藥物組合 2HRZE/4HRE 若證實INH及RMP無抗藥性，即考慮停用EMB RFT (INH+RMP+PZA) + EMB for 2 months then RFN (INH+RMP) + EMB for 4 months 強烈建議以固定複方製劑RFT取代INH+ RMP+PZA單方組合；固定複方製劑RFN 取代INH+RMP單方組合 若證實INH及RMP無抗藥性，即考慮停用EMB

抗結核藥物劑量及常見副作用 疾病管制局: 結核病診治指引, 2006 第二版 藥物 給藥方式 劑量 (mg/kg) (最大劑量) 每日 每週三次 兒童b 成人 兒童 單方藥物 毒性 Isoniazid 肝、神經、皮膚敏感 口服或肌肉注射 10-15 (300 mg) 5 (300 mg) － 15 (900 mg) Rifampin 肝、血液、腹部症候、皮膚敏感 口服或靜脈注射 10-20 (600 mg) 10 (600 mg) Pyrazinamide 肝、高尿酸 口服 1000 mg (≤ 45 kg) 1500 mg (46~75 kg) 2000 mg (≥ 76 kg) 50-70 (3 gm) Ethambutol 視神經炎 15-20 25-30 Streptomycin 耳、腎 肌肉或靜脈注射 20-40 (1 gm) 15 (1 gm) 25-30 (1.5 gm) 疾病管制局: 結核病診治指引, 2006 第二版

抗結核藥物劑量及常見副作用 疾病管制局: 結核病診治指引, 2006 第二版 給藥方式 藥物 劑量 (mg/kg) (最大劑量) 複方藥物 Rifinah-150 (Rifampin 150 mg + Isoniazid 100 mg) 口服 體重小於50 kg:【Rifinah-150】3錠 Rifinah-300 (Rifampin 300 mg + Isoniazid 150 mg) 體重大於50 kg:【Rifinah-300】2錠 Rifater (Isoniazid 80mg + Rifampin 120mg + Pyrazinamide 250mg) 成人依體重每增加10 kg，加服1 錠，每日最多5錠。 疾病管制局: 結核病診治指引, 2006 第二版

Standards for Treatment Standard 9 -1 To foster and assess adherence, a patient-centered approach to administration of drug treatment, based on the patient’s needs and mutual respect between the patient and the provider, should be developed for all patients. Supervision and support should be gender-sensitive and age-specific and should draw on the full range of recommended interventions and available support services, including patient counseling and education.

Standards for Treatment Standard 9 -2 A central element of the patient-centered strategy is the use of measures to assess and promote adherence to the treatment regimen and to address poor adherence when it occurs. These measures should be tailored to the individual patient’s circumstances and be mutually acceptable to the patient and the provider. Such measures may include direct observation of medication ingestion (directly observed therapy—DOT) by a treatment supporter who is acceptable and accountable to the patient and to the health system.

送藥到手 服藥入口 嚥下再走 TB

Standards for Treatment Standard 10 All patients should be monitored for response to therapy, best judged in patients with pulmonary tuberculosis by follow-up sputum microscopy (two specimens) at least at the time of completion of the initial phase of treatment (two months), at five months, and at the end of treatment. Patients who have positive smears during the fifth month of treatment should be considered as treatment failures and have therapy modified appropriately. (See Standards 14 and 15.) In patients with extrapulmonary tuberculosis and in children, the response to treatment is best assessed clinically. Follow-up radiographic examinations are usually unnecessary and may be misleading.

治療效果評估 門診評估症狀及病人服藥順從性： 結核菌檢查 治療第1個月至少應回診2次，以後每月至少1次。 痰抹片耐酸菌鏡檢及結核菌培養： 每個月至少檢查1次，直到連續2個月培養陰性； 治療滿6個月時再檢查1次。 菌種鑑定： 每次培養陽性均應作菌種鑑定。 藥物敏感性試驗: 第1次培養陽性的菌株， 治療滿3個月後仍培養陽性的菌株。 疾病管制局: 結核病診治指引, 2006 第二版

治療效果評估 -3 胸部X光檢查： 至少在治療滿2個月，及治療滿6個月時作胸部X光檢查。

完成治療 痰陰 (塗片及培養) 症狀改善 胸部X光改善 服藥期滿

副作用評估 門診症狀評估：治療第1個月至少應回診2次，以後每月至少1次。 治療前 視力及辨色力 血液生化學檢查 -1 門診症狀評估：治療第1個月至少應回診2次，以後每月至少1次。 治療前 視力及辨色力 血液生化學檢查 GOT、GPT、T-bil、Cr、BUN、Glucose、UA 血球計數及白血球分類

副作用評估 治療期間 視力及辨色力：使用EMB期間至少每月1次。 GOT、GPT、T-bil、UA 其他：依門診症狀評估作適當的檢查。 -2 治療期間 視力及辨色力：使用EMB期間至少每月1次。 GOT、GPT、T-bil、UA 治療滿1-2週 (第1次回診) 滿1個月 滿2個月 滿3個月 其他：依門診症狀評估作適當的檢查。

Standards for Treatment Standard 11 A written record of all medications given, bacteriologic response, andadverse reactions should be maintained for all patients.

李 X X 50M 初治 日 期 92/9/13 10 /11 11 /8 12 /6 93/1/3 1 /31 2 /26 3 /25 4/ 22 5 /20 6 /17 天數 28 INH 0.3 V 完治 EMB 1 RMP 0.45 體重 ? X光 7/19 12/6 1/31 4/22 6/17 抹片 (-) 2x (-) 培養 MTB 2x DST (S) HERS

Standards for Treatment Standard 12 In areas with a high prevalence of HIV infection in the general population and where tuberculosis and HIV infection are likely to co-exist, HIV counseling and testing is indicated for all tuberculosis patients as part of their routine management. In areas with lower prevalence rates of HIV, HIV counseling and testing is indicated for tuberculosis patients with symptoms and/or signs of HIV-related conditions and in tuberculosis patients having a history suggestive of high risk of HIV exposure.

Standards for Treatment Standard 13 All patients with tuberculosis and HIV infection should be evaluated to determine if antiretroviral therapy is indicated during the course of treatment for tuberculosis. Appropriate arrangements for access to antiretroviral drugs should be made for patients who meet indications for treatment. Given the complexity of co-administration of antituberculosis treatment and antiretroviral therapy, consultation with a physician who is expert in this area is recommended before initiation of concurrent treatment for tuberculosis and HIV infection, regardless of which disease appeared first. However, initiation of treatment for tuberculosis should not be delayed. Patients with tuberculosis and HIV infection should also receive cotrimoxazole as prophylaxis for other infections.

Standards for Treatment Standard 14 An assessment of the likelihood of drug resistance, based on history of prior treatment, exposure to a possible source case having drug-resistant organisms, and the community prevalence of drug resistance, should be obtained for all patients. Patients who fail treatment and chronic cases should always be assessed for possible drug resistance. For patients in whom drug resistance is considered to be likely, culture and drug susceptibility testing for isoniazid, rifampicin, and ethambutol should be performed promptly.

Drug Resistance of MTB for each Treatment Category in Taiwan Chiang CY,et al. Formos Med Assoc, 2004. * Jen-Jyh Lee et al, Tzu Chi Med J, 2003.

Standards for Treatment Standard 15 Patients with tuberculosis caused by drug-resistant (especially multipledrug resistant [MDR]) organisms should be treated with specialized regimens containing second-line antituberculosis drugs. At least four drugs to which the organisms are known or presumed to be susceptible should be used, and treatment should be given for at least 18 months. Patientcentered measures are required to ensure adherence. Consultation with a provider experienced in treatment of patients with MDR tuberculosis should be obtained.

Second-line Anti-tuberculosis Drugs Levofloxacin (Cravit) Moxifloxacin (Avelox) Streptomycin (SM) Kanamycin (KM) Amikacin (AMK) Rifabutin (RBT) Prothionamide (T1321, TBN) Ethiomide (T1314) Para-AminoSalicylate (PAS) Cycloserine (CS) Selman Abraham Waksman (1888-1973) 1952 Nobel Prize

抗結核藥物劑量及常見副作用 疾病管制局: 結核病診治指引, 2006 第二版 藥物 給藥方式 每日劑量 (最大劑量) 副作用 Capreomycin 肌肉或靜脈注射 15-30 mg/kg (1 gm) 聽力、平衡功能損害、腎毒性 Kanamycin Amikacin 聽力、平衡功能損害、腎毒性、頭暈、藥物濃度不穩定 Prothionamide 口服 15-20 mg/kg (1 gm) 胃腸不適、肝毒性、過敏反應、金屬味 Para-aminosalicylic acid (PAS) 150 mg/kg (16 gm) 胃腸不適、肝毒性、過敏反應、鈉滯留 Cycloserine 精神異常、抽慉、憂鬱症、頭痛、皮疹、藥物交互作用 疾病管制局: 結核病診治指引, 2006 第二版

抗結核藥物劑量及常見副作用 藥物 給藥方式 每日劑量 (最大劑量) 副作用 Levofloxacin 口服 500~1000 mg 胃腸不適、頭暈、過敏反應、頭痛、躁動不安、藥物交互作用 Moxifloxacin 400 mg Rifabutin 5mg/kg(最高劑量300 mg) 肝、血液、腹部症候、皮膚敏感、眼葡萄膜炎(uveitis) 疾病管制局: 結核病診治指引, 2006 第二版

肺結核再次治療：治療失敗 應照會有經驗的結核科、胸腔科或感染科醫師 藥敏試驗結果不明時，繼續原治療藥物，並加LVX(MOXI)+IA+T1321+PAS (三種以上從未用過的藥)； 藥敏試驗結果明朗後，依藥敏試驗結果和過去用藥史，選定有效的藥物組合及決定治療期間。

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

肺結核再次治療：中斷與復發 應照會有經驗的結核科、胸腔科或感染科醫師 藥敏試驗結果不明時 RFT (INH+RMP+PZA) +EMB + SM for 2 months, then RFT (INH+RMP+PZA) +EMB for 2 months, then RFN (INH + RMP) + EMB for 5 months 藥敏試驗結果明朗後，依藥敏試驗結果和過去用藥史，選定有效的藥物組合及決定治療期間 (表二) 。 依以下優先次序選定有效的藥物組合 第1優先：藥敏試驗有效且從未用過的藥。 第2優先：藥敏試驗有效，以前曾使用未超過4週。 第3優先：藥敏試驗有效，以前曾使用超過4週，但使用時合併有其他2種以上藥敏試驗有效的藥同時使用。 以上優先次序相同者，依以下優先次序選藥： RMPINHLVX(MOXI)SMKMAMKPZAEMBT1321PASCS

抗藥性結核病的治療 前1-2個月住院隔離治療 出院須通知衛生所，並預約門診 門診至少每月1次 每月追蹤痰塗片及培養 每3月追蹤胸部X光 對所選用的治療藥物沒有明顯副作用 連續3次痰塗片陰性或 臨床及X光進步 出院須通知衛生所，並預約門診 門診至少每月1次 每月追蹤痰塗片及培養 (住院初期可每2週驗3套) 每3月追蹤胸部X光

Benchmarks in TB epidemiology 發生率 (/100,000) >1,000 TB epidemic (結核病疫區) >100 High risk for TB (結核病高負擔地區) <10 Low risk for TB (結核病低負擔地區) <1 TB program enter elimination phase (結核病防治進入結核病根除期) < 0.1 TB can be said eliminated (結核病根除) 結核病流行指標 Enarson DA. TB as a global public health problem. In: Kaufmann SHE. Mycobateria and TB, 2003

Thank you for your attention

TB TB 何時了 潛伏感染  發病 HS 抗藥 治療中 HS 抗藥 大兒子 67-11-11 M 95-2-23 “5” M+C+ 大女兒 69-4-3 F 82-3-13 “5” M+C+ ST N/A 82-12 完治 小女兒 71-3-19 F 88-6-28 “3” M+C+ HS 抗藥 89-4 完治 父 39-10-15 M 75-4-7 “5” M+C+ HS 抗藥 76-10 完治

TB TB 何時了 – 診斷延遲 95/01/12 94/02/23

Standards for Diagnosis Standard 6 The diagnosis of intrathoracic (i.e., pulmonary, pleural, and mediastinal or hilar lymph node) tuberculosis in symptomatic children with negative sputum smears should be based on the finding of chest radiographic abnormalities consistent with tuberculosis and either a history of exposure to an infectious case or evidence of tuberculosis infection (positive tuberculin skin test or interferon gamma release assay). For such patients, if facilities for culture are available, sputum specimens should be obtained (by expectoration, gastric washings, or induced sputum) for culture.

International Standards for Tuberculosis Care The purpose of the International Standards for Tuberculosis Care (ISTC), developed by the Tuberculosis Coalition for Technical Assistance (TBCTA), is to describe a widely accepted level of care that all practitioners, public and private, should seek to achieve in managing patients who have, or are suspected of having, tuberculosis.

International Standards for Tuberculosis Care The Standards are intended to facilitate the effective engagement of all care providers in delivering high-quality care for patients of all ages, including those with sputum smear-positive, sputum smear-negative, and extra pulmonary tuberculosis, tuberculosis caused by drug-resistant Mycobacterium tuberculosis complex (M.tuberculosis) organisms, and tuberculosis combined with human immunodeficiency virus (HIV) infection.