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
簡歷
索任
 現任




2005/5 2006/120021994-
社團法人中華民國防癆協會第一胸腔病防治所所長
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
中華民國職業病醫學會理事
台灣結核病醫學會理事
 曾任









2002/7 – 2005/3
2002/2 – 2002/7
2001/8 – 2002/1
1999/7 – 2001/8
1997/1 – 1999/6
1989/3 – 1997/1
1984/4 – 1989/3
1983/7 – 1984/4
1979/7 – 1983/7
行政院衛生署桃園醫院內科師一級主治醫師
行政院衛生署胸腔病院代理院長
行政院衛生署慢性病防治局代理局長
行政院衛生署慢性病防治局副局長
台北縣慢性病防治所醫師
台灣省慢性病防治局技正兼主任
台灣省防癆局技正兼主任
台灣省防癆局主治醫師
台灣省防癆局住院醫師及總住院醫師
1979
台灣大學
醫學院
醫學系
Tuberculosis and diseases
caused by nontuberculosis
mycobacteria in Taiwan:
Clinical aspect
社團法人
中華民國防癆協會
第一胸腔病防治所
索 任 醫 師
solo@tstb.org
http://www.tb.org.tw
台北市民權西路104號2樓
The Genus Mycobacterium
 Gram-positive, acid-fast, non-spore-forming,
straight or slightly curved rods (0.2~0.6 
1.0~10m) coccobacillary, filamentous,
branched
 Pigment in dark or after exposure to light
 Aerobic or microaerophilic
 Subdivision: rapid growers, slow growers
 Large amounts of lipid in cell walls: mycolic
acids
 Typical species: Mycobacterium tuberculosis
Classification of mycobacterial species
commonly cause human disease
Mycobacterium tuberculosis complex
M. leprae
Slowly growing mycobacteria
Photochromogens (Runyon group I)
Scotochromogens (Runyon group II)
Nonchromogens (Runyon group III)
Rapidly growing mycobacteria
(Runyon group IV)
Mycobacterium tuberculosis complex





M. tuberculosis
M. bovis
M. africanum
M. microti
M. canetti
M. tb
M. kansasii
結核病 –
被遺忘了的瘟疫
Tuberculosis
1992
傳染源
Latent infection vs. disease
感染
發病
感染：會呼吸的人都是結核病的易感宿主
發病：新近感染及免疫力減弱為主要危險因子
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
怎樣檢查肺結核病？
胸部Ｘ光檢查
驗痰
TB TB 何時了
潛伏感染  發病
大女兒 69-4-3 F
大兒子 67-11-11 M
82-3-13 “5” M+C+
父 39-10-15 M
75-4-7 “5” M+C+
HS 抗藥
76-10 完治
95-2-23 “5” M+
ST N/A
小女兒 71-3-19 F
82-12 完治
88-6-28 “3” M+C+
HS 抗藥
89-4 完治
結核病
Class I
Exposure
Class II
Class III
Disease
Infectious
83-4-11
Latent TB Infection
Non Infectious
81-3-27
Death
TB TB 何時了 – 診斷延遲
93/10/12
94/11/30
TB TB 何時了 – 診斷延遲
94/02/23
95/01/12
TB TB 何時了 – 不規則治療
910529
940909
傳染 transmission
化學治療
Chemotherapy
結核病防治
結核病的傳染期 = 病人延遲 +
醫師延遲 +病人治療管理不當
Prophylactic
treatment
預防性
治療
Preventive
醫師延誤
病人延誤
Doctor’s delay
Patient’s delay
therapy
傳染性
結核病
接觸
Exposure
結核潛伏
感染
Subclinical
infection
Infectious TB
死亡
非傳染性
結核病
Non-Infectious
TB
BCG
vaccination
卡介苗
Source: Interventions for Tuberculosis
Control and Elimination, IUATLD 2002
Death
結核病防治
三個基本動作
盡早找出結核病人
盡速治癒每個找出來的病人
不讓結核菌產生抗藥性
結核菌持續挑釁
衛生體系重組 (Health reform)
抗藥性結核菌
HIV/AIDS
貧窮
Mycobacteria other than
M. tuberculosis and M. leprae
Nontuberculous mycobacteria (NTM)
Mycobacteria other than tuberculosis
(MOTT)
Environmental mycobacteria
Opportunistic mycobacteria
Atypical mycobacteria
Anonymous mycobacteria
Unclassified mycobacteria
NTM of Clinical Significance
Runyon classification and major species
I. Photochromogens
 M. kansasii, M. marinum, M. simiae, M. asiaticum
II. Scotochromogens
 M. gordonae, M. scrofulaceum, M. szulgai, M. flavescens
III. Nonchromogens
 MAC (M. avium, M. intracellulare), M. terrae complex, M.
ulcerans, M. xenopi, M. malmoense, M. haemophilum, M.
genavense, M. gastri, M. celatum
IV. Rapid growers
 M. fortuitum, M. chelonae, M. abscessus, M. phlei, M. vaccae
I. Photochromogen
M. marimun
M. kansasii
II. Scotochromogen
M. gordonae
M. szulgai
M. scrofulaceum
III. Nonchromogen
M. intracellulare
M. avium
M. xenopi
IV. Rapid grower
M. chelonae
M. abscessus
M. fortuitum
Historical Perspective
and Epidemiology of the NTM (I)
Organism
First human Source (s)
case
Animal
reservoir (s)
Rapid growers
MAC
1930s
1943
Soil, water
Soil, water
M. ulcerans
M. marinum
M. scrofulaceum
M. kansasii
M. xenopi
M. simiae
1948
1951
1950s
1953
1965
1965
Unknown
Salt, fresh water
Lake, river water
Water
Hot water tank, taps
Water (rare)
Cats, cattle, dogs…
Birds, cats, swine
dogs, horses
Cats
Fish
Cattle, swine
Cattle, deer, swine
Cats, cattle, swine
Monkeys
Emerging Infections I, 1998
Geographic Distribution
Organism
Distribution
M. malmoense, M. xenopi
Coal-mining regions,
northern Europe
Japan, Australia
Southwestern US, Israel,
Cuba
Africa, Australia,
southeast Asia
Southern, central US
New York City
M. shimoidei
M. simiae
M. ulcerans
M. kansasii
M. haemophilum
Epidemiology of NTM
Environmental Sources
 Most NTM have been recovered from water and soil
Mycobacteria
Sources of infection
MAC, M. kansasii
Tap water; airborne
M. marinum
Salt, fresh water, fish tanks, swimming pool
M. xenopi
Hot water; hospital heating tank (43-45oC)
M. simiae
Tap water
M. genavense
Dogs, pet bird (psittacine birds)
Rapid growers
Tap or distilled water, dialysate; nosocomial
 Environmental sources of infection are likely:
 M. ulcerans, M. haemophilum, M. szulgai, M. celatum, M.
genavense, M. conspicumm
The most important nontuberculous
mycobacteria
Harrisons principles of internal medicine, 15th ed.
-1
The most important nontuberculous
mycobacteria
Harrisons principles of internal medicine, 15th ed.
-2
Principal Types of Mycobacterial Disease
in Man and the Causative Agents (1)
Disease
Usual
Uncommon
Tuberculosis
M. tuberculosis
M. bovis
M. africanum
Leprosy
M. leprae
Lymphadenopathy
M. avium complex
M. scrofulaceum
Many other species
Post-traumatic
abscesses
M. Chelonae
M. fortuitum
M. terrae
M. flavescense
Swimming pool
granuloma
M. marinum
Buruli ulcer
M. ulcerans
Other skin lesions
M. haemophilum
M. kansasii
M. shinshuenses
Principal Types of Mycobacterial Disease
in Man and the Causative Agents (2)
Disease
Usual
Uncommon
Opportunistic pulmonary
disease
M. avium complex
M. kansasii
M. xenopi
M. malmoenses
M. scrofulaceum
M. asiaticum
M. celatum
M. gordonae
M. simiae
M. Szulgai
M. chelonae
M. fortuitum
HIV-associated
M. avium complex
M. genavense
Non-HIV-associated
M. avium complex
M. chelonae
Disseminated Disease
Diseases Caused by
Nontuberculous Mycobacteria
 Most disease: in immunosuppressed patients
 Source of infection: environment
 Person-to-person transmission: not proved
 Culture contamination: environmental
saprophytes
 Colonization without producing overt disease
 Assessing clinical significance of isolates
 Clinical syndromes
NTM infection of the lung in HIV- patients
often occur in the context of preexisting
lung disease, especially:
chronic obstructive pulmonary disease (COPD),
bronchiectasis,
pneumoconiosis,
cystic fibrosis, and
previous tuberculosis
AJRCCM 1997; 156:S1-S19.
Diagnosis of NTM pulmonary disease
Clinical criteria
 Compatible signs/symptoms (cough, fatigue
most common; fever, weight loss, hemoptysis,
dyspnea) with documented deterioration in
clinical status of underlying disease,
and
 Reasonable exclusion of other diseases (eg. TB,
cancer, histoplasmosis) or adequate treatment
of other conditions with deterioration in clinical
signs/symptoms
AJRCCM 1997; 156:S1-S19.
Diagnosis of NTM pulmonary disease
Radiographic Criteria
 Chest X-ray
Evidence of progression if baseline film > 1 year old
Infiltrates with or without nodules (persistent  2 months
or progressive)
Cavitation
Multiple nodules as a solitary finding
 HRCT
Multiple small nodules
Multifocal bronchiectasis with or without small lung
nodules
AJRCCM 1997; 156:S1-S19.
Diagnosis of NTM pulmonary disease
Bacteriologic Criteria
 At least 3 sputum/bronchial wash speciemens within previous year
 Three positive cultures with negative AFB smears, or
 Two positive cultures and one positive AFB smear,
OR
 Single available bronchial wash and inability to obtain sputum
sample
 Positive culture with 2+, 3+, or 4+ growth, or
 Positive culture with 2+, 3+, or 4+ AFB smear
OR
 Tissue biopsy, any of following
 Any growth from bronchopulmonary tissue biopsy
 Granuloma and/or AFB on lung biopsy with at least one positive
cultures from sputum or bronchial wash
 Any growth from usually sterile extrapulmonary
AJRCCM 1997; 156:S1-S19.
Diagnosis of NTM pulmonary disease
 To conclusively diagnose NTM pulmonary
disease, all three criteria – clinical, radiographic,
and bacteriologic – must be satisfied
 Culture positive with 1+ growth is sufficient if
HIV-positive with CD4<200 (excluding MAC) and
in patients with general severe immune
suppression, leukemia, lymphoma, organ
transplantation, or other immunosuppressive
therapy
AJRCCM 1997; 156:S1-S19.
Diagnosis of NTM pulmonary disease
Comment
The criteria fit best with
M. avium complex
M. abscessus
M. kansasii
At least three respiratory samples should
be evaluated
Other reasonable causes should be
excluded
Expert consultation
AJRCCM 1997; 156:S1-S19.
M. kansasii pneumonia
a
b
c
Chest radiographs of a patient with severe emphysema and
bilateral upper lobe disease caused by Mycobacterium kansasii.
(a) Before treatment. (b) After 9 months of antimycobacterial
treatment. (c) 2 months after the end of treatment.
M. avium complex pneumonia
 54 year-old woman
 Fever, cough, weight
loss, neck LAP
 VATS-AFB (+)
 Blood, pleural fluid (+)
for M. avium complex
MAC pneumonia
(MACxIII, sputum)
MAC pneumonia
46/M, AML, M2, post C/T; Pulmonary M. avium Infection
Plus PCP; (CIP+EMB+RIF+Baktar)
8/03/2002
18/03/2002
(4017766)
AIDS,
MAC
28/F, cystic bronchiectasis
M. abscessus
M. Chelonae
64 year-old woman
Destructive lung
M. chelonae
Clarithromycin
+ ciprofloxacin
Persistent infection
Disseminated MAC infection
MAC tenosynovitis
75/M, CRI, herb
Fever, right hand
lesion for 2 weeks
WBC, 6300;
CRP, 1.33
Tenosynovitis
EMB+CIP+CLA
MAC lymphadenitis
45 year-old female
Productive cough for 3 weeks
Neck LAP
P. marneffei pneumonia
MAC lymphadenitis
M. marinum infection
(Fish-tank granuloma)
 A red-violet,
verrucous plaque on
the dorsum of the
thumb of a fish-tank
hobbyist arose at the
site of an abrasion.
Harrisons principles of internal medicine, 15th ed.
M. Marinum infection
M. ulcerans infection
(Buruli ulcer)
 A huge ulcer with a
clean base and
undermined margins
extends into the
adipose tissue of a
Ugandian child.
Harrisons principles of internal medicine, 15th ed.
M. flavescens
NTM skin infection
M. marinum
M. kansasii skin infection
38 year-old female,
SLE
Recurrent
M. chelonae infection
 Edema, erythematous
nodules, scars on the
lower legs of an 83year-old female, who
was taking oral
glucocoricoids
chronically for asthma.
Harrisons principles of internal medicine, 15th ed.
M. chelonae
NTM skin infection
M. absxessus
M. kansasii
Clinically Significant NTM Disease
NTUH, 1992-1996
Infection
Pulmonary
No.
10
Etiologies
MAC (3), M. fortuitum (2), M. abscessus (1)
M. chelonae (1), M. gordonae (1)
Soft tissue &
osteomyelitis
16
M. abscessus (4), M. fortuitum (2), M. marinum (2)
M. chelonae (1), M. gordonae (1),
M. haemophilum (1), M. kansasii (1)
Disseminated
5
MAC (3), M. chelonae (1), M. scrofulaceum (1)
Keratitis &
conjunctivitis
7
M. abscessus (2), M. fortuitum (2), M. chelonae
(2), M. xenopi (1)
Peritonitis
1
MAC (1)
Shih JY et al J Formos Med Assoc 1997
Thanks for attention
M. kansasii pneumonia
30 F
NTM infection of the lung in HIV- patients
 Cavitary disease in the upper lung zones, similar to pulmonary
tuberculosis, is seen in approximately 90 percent of patients with M.
kansasii infection and perhaps 50 percent of those with
Mycobacterium avium complex (MAC) infection.
 The cavities caused by these organisms tend to have thinner walls
and less surrounding parenchymal opacity than those caused by M.
tuberculosis
 Approximately 50 percent of patients with MAC lung disease have
radiographic abnormalities characterized by nodules associated with
bronchiectasis or nodular/bronchiectatic disease.
 The nodules and bronchiectasis are usually present within the same
lobe and occur most frequently in the right middle lobe and lingula
NTM Disease
Treatment Regimen Recommendations
Mycobacteria
Established
Suggested
M. scrofulaceum
M. malmoense,
M. simiae (lung) RIF, ETH, INH, STM (AMIK) CLAR (AZI), CIP, CLOF
MAC (disseminated)
CLAR (AZI), ETH
CLOF, RIFB, RIF, CIP, AMK
M. kansasii, M. szulgai
RIF, INH, ETH
STM, CIP, CLAR
M. xenopi
RIF, INH, ETH
STM
M. marinum
ETH, RIF, DOX, TMP-SMX STM, CIP
M. haemophilum
–
RIF, CFOX, DOX, TMP-SMX
M. fortuitum
AMIK, CIP, SULF
CLOF, CLAR, CFOX, DOX,
IPM
M. abscessus
AMIK
CLOF, CLAR, CLOX
M. chelonae
TOB (AMIK)
CLOF, CLAR, DOX
Manual of Clinical Microbiology 1999
MAC Pulmonary Diseases
Treatment
 Clarithromycin (500 mg bid) or azithromycin (250 mg
gd)
 Rifampin (600 mg qd) or rifabutin (300 mg qd)
 Ethambutol (25 mg/kg for 2 m, then 15 mg/kg)
 Streptomycin (2-3 times/week for first 8 weeks)
Duration: culture (-) on therapy for one year
Disseminated M. avium Complex Disease
Treatment
1. Clarithromycin (500 mg bid) or azithromycin (250500 mg gd)
2. Ethambutol (25 mg/kg for 2 m, then 15 mg/kg)
3. Rifabutin (300 mg qd) or rifampin (600 mg qd)
(Clofazimine, ciprofloxacin, amikacin, streptomycin)
Duration: 1+2+3 life long
M. kansasii Pulmonary Disease
Treatment
 Isoniazid (300 mg qd)
 Rifampin (600 mg qd)
 Ethambutol (25 mg/kg for 2 m, then 15 mg/kg)
 Clarithromycin or rifabutin (substituted for rifampin)
in AIDS patients with protease inhibitors
Duration: 18 months with > 12 month culture (-)
Antibiotic Treatment
Rapidly Growing Mycobacteria
Bacteria
M. abscessus
Parenteral
Amikacin, Imipenem
Clarithromycin,
Oral
Quinolones,
Sulfonamides
M. chelonae
Amikacin (tobramycin), Clarithromycin
Imipenem
M. fortuitum
Amikacin, Cefoxitin
Clarithromycin
M. smegmatis Amikacin, Imipenem
Doxycycline,
Quinolones,
Sulfonamides
Guay DRP Ann Pharmacother 1996
Antibiotic Treatment
Rapidly Growing Mycobacteria (III)
 Pulmonary disease
Organism
Treatment
M. fortuitum Cefoxitin + amikacin (4-8 weeks)
sulfamethoxazole + doxycycline +
ciprofloxacin (ofloxacin)
M. abscessus
Cefoxitin + amikacin + macrolides
(4-6 weeks) surgical excision
macrolides (6-12 months)
Clinical Syndromes
of NTM Disease
 Chronic pulmonary disease
 Lymphadenitis
 Localized skin, soft tissue, and skeletal infection
 Infection of bursae, joints, tendon sheaths, and
bones
 Disseminated disease in patients without AIDS
 Disseminated disease in patients with AIDS
 Other infections
Harrisons principles of internal medicine, 15th ed.
NTM Pulmonary Disease
Immune Suppression
Local
Alcoholism
Bronchiectasis
Cyanotic heart disease
Cystic fibrosis
Prior mycobacterial
disease
Pulmonary fibrosis
Smoking/COPD
None
General
Leukemia
Lymphoma
Organ transplantation
Immunosuppressive
therapy
HIV (+), CD4 count <200