<Brief
History>
This 73-year-old woman is a case of hypertension and
ovarian cancer diagnosed in Dec 2004, status post debulking
surgery and 5 times of the chemotherapy with chemotherapy
(Taxol + Carboplatin). The latest chemotherapy was performed
at gynecology ward on April 2, 2005 and she was discharged on
April 13. There was no obvious side effect of the chemotherapy
before this admission. She denied travel or animal exposure
before this admission.
However, bilateral leg weakness developed since April 26
2005, followed by fever at night 2 days later. She was brought
to ER where a urine examination showed hematuria and pyuria.
Her consciousness was lethargy on arrival. Urosepsis was
diagnosed and cefotiam was given. Her fever persisted and her
conscious level deteriorated since April 29. Neck stiffness
was also noted later at ER. For suspected intra-pelvic
infection and CNS infection, antibiotic was switched to 3rd
generation cephalosporin since April 29. Brain CT without
contrast enhancement on April 30 showed no obvious abnormality
without space occupying lesion. Lumbar puncture was suggested
but the family hesitated. She was then admitted to our ward on
May2.
<Physical
Examination>
On physical examinations, the body temperature was 37.0℃,
blood pressure 140/60 mmHg, pulse rate 120 /min, and the
respiratory rate 22 /min. Her consciousness was E3V2M4. The
conjunctivae were not pale and sclerae were not icteric. Light
reflex of the pupils was sluggish but symmetric. The neck was
stiffness and there was no lymphadenopathy or jugular vein
engorgement. The chest was symmetrically expanded with clear
breath sound.The heart beats were regular. No heart murmur was
audible. The abdomen was flat and soft on palpation. There was
no tenderness or rebound tenderness. The extremities were free
movable and there was no cyanosis, clubbing or pitting edema.
The peripheral pulse was palpable.
<Laboratory
Data>
1.
CBC/DC
WBC K/uL |
RBC M/uL |
Hb G/dL |
Hct % |
MCV fL |
PLT K/uL |
6370 |
3.0 |
9.4 |
27.4 |
91.3 |
51 |
Band % |
Seg % |
Eos % |
Baso % |
Mono % |
Lym % |
25 |
70 |
0 |
0 |
1 |
3 | 2.
Biochemistry Study
BUN mg/dL |
Cre mg/dL |
Na mmol/L |
K mmol/L |
Ca mmol/L |
Alb g/dL
|
TP g/dL |
23.1 |
0.9 |
123 |
4.3 |
2.29 |
3.06 |
5.6 |
T-Bil mg/dL |
AST U/L |
ALT U/L |
ALP U/L |
GGT U/L |
NH3 μmmol/L |
CRP mg/dL |
1.50 |
19 |
19 |
273 |
104 |
7 |
22 | <Course and Treatment>
After a
thorough discussion with her family, they agreed CSF study and
lumbar puncture was performed on May 2. CSF study revealed
white cell count: 300 /μl with differential count:
lymphocyte/neutrophil: 45/55, total protein: 344 mg/dL,
glucose: 184 mg/dL, and LDH: 1188 IU/L. Her conscious
deteriorated to comatose so acyclovir was added for suspected
viral encephalitis. Respiratory distress developed though
chest roentgenogram showed no opacity. Blood gas did not show
respiratory acidosis or hypoxemia. She was then intubated for
impending respiratory failure. Gram-positive bacilli was found
by Gram stain of CSF culture on May 4. Ampicillin with
gentamicin were given and acyclovir was discontinued.
Following CSF study on May 4 showed pleocytosis up to 600/μl
with persistent high protein level. Seizure attacks and
intermittent myoclonus developed. Listeria monocytogenes
finally isolated from CSF culture. Ampicillin and gentamicin
was instituted for three weeks. Low grade fever and CRP waned
gradually. Her consciousness became complete clear 3 weeks
later and she was extubated smoothly thereafter.
<討論>
本案例為一腫瘤病人,發生腦膜腦炎,因為家屬遲疑腦脊髓液穿刺,起初只用一般治療腦膜炎針對肺炎雙球菌以及格藍氏陰性桿菌之第三代頭包芽素(third-generation
cephalosporin)治療,且腦脊髓穿刺結果為主要淋巴球為主之白血球增生,原本只懷疑為病毒,但其腦脊髓液蛋白質又很高,又比較像結核菌,黴菌性腦膜炎或經治療後之細菌性腦膜炎。直到培養出來才知道是對所有頭包芽素沒有效之李斯特菌感染。李斯特菌感染表現主要以腦膜炎,菌血症,以及腸胃炎為主。因為工作因素較常接觸動物者比如獸醫,屠宰業,畜牧業等屬於高危險群。正常人雖也有可能得病,但特別容易患有李斯特菌感染症的情況是孕婦及免疫力不全之病人,例如腫瘤患者、酗酒、使用類固醇者,以及新生兒或老人等。李斯特菌的主要傳染途徑是遭受污染的牛奶,或是牛的排泄物污染水源或食物所致。若牛奶未經徹底消毒,則製成的乳製品便可能會帶有致病菌。冷藏的乳製品及冰品若於製造過程中消毒不完全,就可能會帶有這個細菌。
李斯特菌感染中樞神經系統時,比起一般的細菌性腦膜炎,有以下不同點:病程有時較亞急性,較容易有抽搐發生,頸部比較少僵硬,腦脊髓液的格蘭氏抹片發現細菌之陽性比率較低,而腦脊髓液主要是以淋巴球為主之白血球增生,有時與結核性腦膜炎難區分。要注意的是雖然只有1/3之
Listeria monocytogenes,在腦脊髓液格蘭氏染色中可看到細菌,比起一般的60%
90%少,但格蘭氏染色抹片仍是腦膜炎病人應該執行的檢驗,因為其快速簡便且特異性很高。不管是培養或初步染色,在腦脊髓液中,一但發現格蘭氏陽性桿菌(Gram
positive bacilli),除非是污染菌(diphtheroids),比如 Bacillus,
Lactobacillus ,或Corynebacterium,就應考慮有高致病力的Listeria
monocytogenes,要趕緊調整抗生素用藥。
在2004年美國感染症醫學會腦膜炎的經驗療法中建議,大於50歲者,因為考慮S.
pneumoniae, N. meningitidis, L. monocytogenes, aerobic
gram-negative bacilli等細菌的感染,所以建議Vancomycin加上 ampicillin
以及第三代頭包芽素( third-generation
cephalosporin)是作為第一線經驗療法,屬於A-III的建議等級。在台灣的腦膜炎主要是以克雷白氏桿菌以及肺炎雙球菌為最多,李斯特菌比國外略少,但在台灣的腦膜炎菌種分佈研究,也約佔3-10%不等,可見此菌在台灣是的確存在的。因此遇到腦膜炎病人,詢問動物接觸病史,或飲食內容,以及找出免疫差的高危險群病人是很重要的。若確定為Listeria
monocytogenes感染,建議使用ampicillin(每天12g)(或penicillin)
加上Gentamicin(每天每公斤5mg)治療3週,有時免疫力差的病人,或是有腦膿瘍的病人治療時間會更久。若有過敏,可考慮用Trimethoprim-sulfamethoxazole或
meropenem 替代。
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