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有效期間：民國 101年10月01日 至 101年10月31日 止

    Case Discussion
< Report of a Case>

　　A 77-year-old male patient, with a 10-year history of diabetes mellitus, was admitted because of acute onset of fever, chills, diarrhea and non-productive cough after returning from a cruise tour 4 days later. He was admitted to the emergency service at this hospital because of altered mental status. At the emergency service, the temperature was 39.5°C, the blood pressure 116/58 mmHg, the pulse rate 128 beats per minute, and the respiration rate 36 breaths per minute. Chest auscultation revealed crackles at the right upper and left lower lung fields. There were no lymphadenopathies, skin rashes, throat exudates, cardiac murmurs, peritoneal signs or legs edema. Neurological examination revealed that he was poorly oriented to persons, place, and time. There was no neck stiffness, meningeal signs, or focal neurological signs. The tendon reflex was normal. Lumbar puncture was performed and the results did not show pleocytosis. He was admitted to the intensive care unit for acute respiratory distress and confusion status. Endotracheal intubation was performed.

　　His family reported that the diabetes mellitus had been well controlled with diet and metformin. He was a retired senior high school teacher and had a habit of smoking for several decades. There was no history of recent operation, hospitalization, animal contact or family clustering of similar cases.

The results of laboratory studies were as follows.

1. CBC and differential count:
WBC
/μl

RBC
M/μl

Hb
g/dl

Plt
K/μl

Hct
%

MCV
fL

Band
%

Neutro
%

Baso
%

Eos
%

Mon
%

Lym
%

17300

4.07

15.4

178

41.4

89.4

6

78

1

2

3

10

2. Biochemistry:
A/G
g/dl

ALP
U/L

AST
U/L

ALT
U/L

r-GT
U/L

BUN
mg/dL

Cre
mg/dL

Na
mmol/L

K
mmol/L

Cl
mmol/L

3.7/3.4

225

87

124

45

54.8

1.73

125

4.3

102

Ca
mmol/L

P
mmol/L

Mg
mmol/L

Glu
mg/dL

LDH
U/L

TG
mg/dL

T-CHO
mg/dL

UA
mg/dL

BilT/D mg/dL

2.02

3.5

0.94

139

463

174

223

7.6

1.4/0.8

3. ABG (non-rebreather mask, FiO2 100%)
pH

PCO2
(mmHg)

PO2
(mmHg)

HCO3-
(mEq/L)

B.E
(mEq/L)

7.41

18

72.9

11.3

-11.0

4. Sputum routine
Microscopy of an expectorated sputum specimen disclosed PMNs, 50-75/low power fields (LPF), few epithelial cells (<10/LPF), and no pathogens by Gram's stain.

5. CSF study
Open Pressure
(mmH2O)

WBC

Lymphocyte

Neutrophil

Glucose
(mg/dL)

Protein
(mg/dL)

101

4

4

0

58

40

6. Chest X ray
CXR revealed alveolar infiltrates in the left lower and right upper lobes.

< 說明>

　 退伍軍人症是由退伍軍人桿菌(Legionella)引起的傳染病。此病名由來，源於1976年在美國召開的退伍軍人大會時，退伍軍人桿菌曾引致肺炎爆發而命名。退伍軍人桿菌可在多種的環境中存在，尤其適合在攝氏20 – 45度的溫水中生長。它可存活在不同的水源環境裏，如水缸、冷熱水系統、冷卻水塔、按摩池、噴水池和家居呼吸道醫療器材等。退伍軍人菌可於環境中(包括：水及泥土)存活數個月，且能持續維持其致病性；其中水環境是退伍軍人菌天然生長處，也是感染的主要來源；其傳播途徑則以飛沫(droplet)直接吸入為主，尤其經由噴霧狀之水氣(aerosol)，其來源包括：冷卻水塔、呼吸治療器械、淋浴等。此外，傷口直接接觸污染之水，亦會造成感染。退伍軍人症並不會透過人與人之間的接觸而傳播。退伍軍人症大部分發生於免疫機能異常之病人，包括：年長者(50歲以上)、具有嚴重潛在疾病如糖尿病、慢性心肺疾病、抽菸、酒癮、接受器官移植及使用免疫抑制藥物等病患。非典型肺炎為退伍軍人症主要之臨床表現，而病人之症狀差異極大，從輕微咳嗽、發燒至呼吸衰竭、多器官衰竭等。潛伏期約2至10天。主要病徵包括發燒、乾咳、呼吸困難、疲倦、頭痛、肌肉疼痛、腹痛和腹瀉。病情嚴重時可出現神經系統病徵（如精神錯亂）和呼吸衰竭，並引致死亡。在疾病早期，病人常表現出一些非特異性之症狀，包括：發燒(常高於攝氏40度)、疲倦、肌肉疼痛、頭痛等。病人通常表現乾咳、相對性心搏過慢、腹瀉、神智不清等；部份受退伍軍人桿菌感染的患者，可能只會出現短暫和自行減退的發熱病徵，這類非肺炎性的情況稱為「龐蒂亞克熱」（ Pontiac fever ）。實驗室常規檢查以低鈉血症及肝功能異常為退伍軍人症最常見之檢驗異常情形。胸部Ｘ光並無特異性的表現，可以是局部性浸潤、腫瘤樣、結節狀、單或雙側性侵犯、開洞甚至肋膜積水等，不易由胸部Ｘ光來驟下診斷。退伍軍人桿菌不易染色，為革蘭氏染色陰性桿菌，退伍軍人菌培養需要特殊的培養皿，培養時需要半胱胺酸（ cysteine ）及其他營養素。因此不易執行。血清學及尿液之抗原抗體檢查經常使用來確定診斷。到目前為止共發現 14 種嗜肺性退伍軍人桿菌（ Legionella pneumophila ）的血清型，其中以血清型第一型最常引起退伍軍人病。實驗室確定診斷包括：(1)由肺組織、呼吸道分泌物、胸膜液、血液或其他正常無菌的部位，分離出退伍軍人桿菌。(2)直接免疫螢光抗體試驗，在肺組織、呼吸道分泌物或胸膜液檢驗出嗜肺性退伍軍人桿菌（L. pneumophila）。(3)以間接免疫螢光抗體試驗檢測血清抗體效價，恢復期（4至12週）比發病初期效價有四倍以上增加，且≧128倍。(4)以酵素連結免疫分析法或放射免疫分析法檢驗出尿中有嗜肺性退伍軍人桿菌血清型第一型（ L. pneumophila serogroup Ⅰ）之抗原。退伍軍人病患者之死亡率可高達 15 ％，治療延誤往往大大地增加其死亡率，尤其對於罹患嚴重之社區性或院內肺炎，其死亡率更可高達80％，所以臨床醫師務必將此病列入考慮並給予經驗療法。常用治療藥物包括紅黴素類(macrolides)、(口奎)諾酮類(fluoroquinolones)、四環黴素類(tetracyclines)、磺胺類(trimethoprim/sulfamethoxazole)等。預防退伍軍人症之預防，包括：將水加熱至攝氏70-80度、置放銅銀離子化器械、加氯消毒等，定期清洗水塔一年至少兩次。目前並沒有預防退伍軍人症的疫苗。

< 參考資料 >

  1. 衛生署疾病管制局：傳染病介紹 - 退伍軍人症。http://www.cdc.gov.tw/professional/disease.aspx?treeid=beac9c103df952c4&nowtreeid=6b7f57aafde15f54. (accessed on July 31, 2012)
  2. Longo DL, Fauci AS, Kasper DL, et al. (eds). Chapter 147. Legionella Infections. Harrison's Online Harrison's Principles of Internal Medicine, 18th edition. 2012
  3. van Duin D. Diagnostic challenges and opportunities in older adults with infectious diseases. Clin Infect Dis. 2012;54(7):973-8.
  4. Carratala J, Garcia-Vidal C. An update on Legionella. Curr Opin Infect Dis 2010;23(2):152-7.
  5. Stout JE, Yu VL. Legionellosis. N Engl J Med 1997;337(10):682-7.

繼續教育考題
1.
(C)		 Which is the most possible causative pathogen for this patient with severe community-acquired pneumonia?
A Streptococcus pneumoniae
BHaemophilus influenzae
CLegionella pneumophila
DStaphylococcus aureus
2.
(C)		 Which of the following investigations is most helpful in identifying the etiology of pneumonia in this case?
ASputum acid-fast stain
B Blood culture
CUrinary antigen test
DNasal swab for isolation
3.
(A)		 Which of the following is not a risk factor of acquiring the causative pathogen in this case?
ANo previous pneumococcal vaccination
BSmoking with chronic pulmonary disease
CDiabetes mellitus
DChronic renal disease
4.
(C)		 Which of the following is the most important transmission route of the causative pathogen in this case?
AAir-borne transmission from diseased human
BContact transmission from healthcare workers
CAerosol inhalation from water environment
DBlood transfusion or needle sharing from diseased human
5.
(D)		 Which of the following is not a poor prognostic factor of pneumonia in this case?
AElderly (>65 years)
BSeptic shock with acute renal failure
CMultiple lobar pneumonia with hypoxia
DNumerous PMNs (50-75/LPF) in the sputum specimens
6.
(B)		 Which of the following antimicrobial agents is not active for the causative pathogen in this case?
A Erythromycin
BCeftriaxone
CLevofloxacin
DDoxycycline

答案解說
    1. ( C ) 本病患為嚴重社區性肺炎，病患有乾咳、呼吸困難、腸胃症狀(腹痛和腹瀉)、意識不清等非典型肺炎之臨床表現，另外本病患之旅遊史與水接觸以及初步實驗室檢查(包括痰液革蘭氏染色未見明顯致病原、白血球增多、低鈉血症及肝腎功能異常)亦為退伍軍人症常見之檢驗表現。
    2. ( C )退伍軍人桿菌雖然為革蘭氏染色陰性桿菌，但不易在一般的染色中可看到；另外，退伍軍人菌培養時需要半胱胺酸（cysteine）及其他營養素，因此需以需要特殊的培養皿(Buffered charcoal yeast extract (BCYE) agar)執行，一般的血液培養皿無法生長。血清及尿液之抗原抗體檢查是目前最常使用來確定退伍軍人症診斷的檢驗。
    3. (A )退伍軍人症發生之高危險族群為：年長者(50歲以上)、有潛在慢性疾病(如糖尿病、慢性心肺疾病、腎臟病)、抽菸、酒癮、接受器官移植及使用免疫抑制藥物等病患，未接受肺炎球菌疫苗並非本疾病之危險因子，目前並無退伍軍人症疫苗可預防。
    4. ( C )退伍軍人桿菌可在多種的環境中存在，尤其適合在攝氏20 – 45度的溫水中生長。退伍軍人菌可於環境中(包括：水及泥土)存活數個月，且能持續維持其致病性；其中水環境是退伍軍人菌天然生長處，也是感染的主要來源；其傳播途徑則以含有病原菌之環境飛沫(droplet)直接吸入為主，尤其經由噴霧狀之水氣(aerosol)，其來源包括：冷卻水塔、呼吸治療器械、淋浴等。退伍軍人症並不會透過人與人之間的接觸而傳播。
    5. ( D )退伍軍人症病人之肺炎症狀與進展差異極大，從輕微咳嗽、發燒至呼吸衰竭、多器官衰竭等皆有可能。根據研究顯示：年齡越大、有嚴重慢性系統性疾病(糖尿病、慢性肺部疾病、腎臟病、惡性腫瘤、接受免疫抑制劑治療或器官移植)、初期病情越嚴重（如缺氧、休克、多發性肺葉浸潤）等皆是預後不良之危險因子。而痰液中白血球數目與疾病嚴重度並無直接關係。
    6. ( B )常用治療退伍軍人症藥物包括：紅黴素類(macrolides如erythromycin)、(口奎)諾酮類(fluoroquinolones如levofloxacin)、四環黴素類(tetracyclines如doxycycline)、磺胺類(trimethoprim/sulfamethoxazole)等。而盤尼西林類(penicillins)及頭孢子素類(cephalosporins)對退伍軍人菌感染並無治療效果。

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