惡性梗阻性黃疸患者膽道分離細(xì)菌藥敏與感染的相關(guān)因素分析

楊清慧 李文濤

(復(fù)旦大學(xué)上海醫(yī)學(xué)院腫瘤學(xué)系-復(fù)旦大學(xué)附屬腫瘤醫(yī)院介入科 上海 200032)

惡性梗阻性黃疸患者膽道分離細(xì)菌藥敏與感染的相關(guān)因素分析

楊清慧 李文濤△

(復(fù)旦大學(xué)上海醫(yī)學(xué)院腫瘤學(xué)系-復(fù)旦大學(xué)附屬腫瘤醫(yī)院介入科 上海 200032)

目的 分析惡性梗阻性黃疸(malignant obstructive jaundice,MOJ)患者膽汁致病菌分布及藥物敏感情況,探討梗阻類型、腹部手術(shù)史、梗阻程度及時(shí)間等因素與致病菌感染的相關(guān)性。方法 選取2015年1月至2016年3月在我院就診的93例MOJ患者資料行回顧性分析,所有病例行經(jīng)皮肝穿膽汁引流術(shù)(pertutaneous transhepatic biliary drainage,PTBD),術(shù)中收集膽汁行細(xì)菌培養(yǎng)及藥物敏感測(cè)試,對(duì)膽汁培養(yǎng)陽性者行相關(guān)性分析。結(jié)果 共送檢93份膽汁,其中培養(yǎng)陽性60.2% (56/93),共檢出58株致病菌株,其中革蘭陽性菌占36.2% (21/58),革蘭陰性菌占63.8% (37/58),致病菌中以腸球菌、大腸埃希菌、肺炎克雷伯菌及葡萄球菌屬等多見。結(jié)論 膽道感染以腸道菌群為主,應(yīng)根據(jù)藥物敏感結(jié)果及時(shí)調(diào)整治療。相關(guān)性分析顯示低位梗阻及有腹部外傷史為膽系感染相關(guān)因素,梗阻時(shí)間及程度則與膽系感染無相關(guān)性。

細(xì)菌; 感染; 膽汁; 梗阻性黃疸; 經(jīng)皮肝穿膽汁引流術(shù)

惡性梗阻性黃疸(malignant obstructive jaundice,MOJ)是胰腺壺腹部腫瘤、膽管腫瘤及肝外膽管占位等疾病常見的臨床表現(xiàn)[1-4],患者由于腸道黏膜膽鹽缺乏、腸內(nèi)菌群失調(diào),易產(chǎn)生內(nèi)毒素及細(xì)菌移位,常繼發(fā)膽道感染甚至膿毒血癥,有較高的病死率。MOJ患者膽汁細(xì)菌培養(yǎng)及藥敏實(shí)驗(yàn)結(jié)果分析可為臨床抗菌藥物合理使用提供支持。

資 料 和 方 法

患者資料 選取2015年1月至2016年3月至復(fù)旦大學(xué)附屬腫瘤醫(yī)院行梗阻性黃疸診療的患者共93例,其中男性43例,女性50例,平均年齡(50.09±9.59)歲。納入標(biāo)準(zhǔn):(1)血清膽紅素大于50 μmol/L、直接膽紅素與總膽紅素比值大于70%;(2)尿膽紅素水平增高,尿膽原減少或消失;(3)丙氨酸轉(zhuǎn)氨酶(alanine aminotransferase,ALT)、天冬氨酸轉(zhuǎn)氨酶(aspertate aminotransferase,AST)正?；蛏?(4)堿性磷酸酶(alkaline phosphatase,ALP)和γ-谷氨酰轉(zhuǎn)移酶(gamma glutamyl transpeptidase,GGT)明顯升高;(5)影像學(xué)檢查(包括B超、CT、MRI以及MRCP等)顯示梗阻近端膽管及肝內(nèi)肝管擴(kuò)張。(6)病理學(xué)報(bào)告(細(xì)針穿刺、內(nèi)鏡活檢或手術(shù)標(biāo)本)見惡性腫瘤細(xì)胞證據(jù)。

膽汁采集 常規(guī)消毒鋪巾,根據(jù)肝內(nèi)膽管擴(kuò)張情況,優(yōu)勢(shì)膽管引流原則,選擇合適的經(jīng)皮穿刺點(diǎn),局部麻醉后,使用21G千葉針,在B超或數(shù)字剪影血管造影(digital subtraction angiography,DSA)導(dǎo)引下穿刺肝內(nèi)膽管成功后,抽取適量膽汁做細(xì)菌學(xué)檢測(cè),放置經(jīng)皮肝穿膽汁引流術(shù)(pertutaneous transhepatic biliary drainage,PTBD)外引流管。

菌株鑒定及藥敏測(cè)試 膽汁標(biāo)本細(xì)菌分離、純化參照國家衛(wèi)計(jì)委臨床檢驗(yàn)中心《檢驗(yàn)操作規(guī)程》進(jìn)行鑒定,采用法國生物梅里埃股份有限公司的VITEK2 Compact全自動(dòng)微生物鑒定/藥敏系統(tǒng)VITEK2 Compact AST-GP67及VITEK2 Compact AST-GN13藥敏卡進(jìn)行細(xì)菌鑒定和微生物敏感性試驗(yàn)。

統(tǒng)計(jì)學(xué)方法 應(yīng)用 SPSS 21.0 統(tǒng)計(jì)軟件進(jìn)行數(shù)據(jù)分析。分類資料比較采用χ2檢驗(yàn),危險(xiǎn)因素分析采用多因素Logistic回歸分析,P<0.05為差異有統(tǒng)計(jì)學(xué)意義。

結(jié) 果

患者基本情況 93例患者中,胰腺壺腹部腫瘤38例,肝外膽管癌19例,膽囊癌12例,原發(fā)性肝癌8例,胃腸道腫瘤肝門淋巴結(jié)轉(zhuǎn)移14例,其他2例;低位梗阻51例,高位梗阻42例;有腹部手術(shù)史25例,無腹部手術(shù)史68例;血清膽紅素水平輕度梗阻(50～171 μmol/L)27例,中度梗阻(172～342 μmol/L)42例,重度梗阻(>342 μmol/L) 24例。

膽汁細(xì)菌培養(yǎng)與藥敏 93例膽汁培養(yǎng)結(jié)果中,細(xì)菌培養(yǎng)陽性56例(60.2%),共培養(yǎng)出致病菌58株,其中革蘭陽性菌占36.2%(21/58),革蘭陰性菌占63.8% (37/58,圖1)。

引起膽道感染常見病原菌依次為:大腸埃希菌、腸球菌、肺炎克雷伯菌、葡萄球菌屬、鏈球菌屬等。藥敏試驗(yàn):革蘭陰性菌對(duì)亞胺培南/西司他丁敏感率最高(100%),其次為阿米卡星(86.5%)及第3、4代頭孢。革蘭陽性菌對(duì)萬古霉素(100%)、阿米卡星(90.5%)、左氧氟沙星(85.7%)均比較敏感(表1)。

膽管感染相關(guān)因素分析 低位梗阻患者中細(xì)菌培養(yǎng)陽性率為70.6% (36/51),高位梗阻者細(xì)菌培養(yǎng)陽性率為47.6% (20/42,χ2=5.072,P=0.024);輕度梗阻者膽汁培養(yǎng)陽性率為47.6% (17/27),中度梗阻者膽汁培養(yǎng)陽性率為54.8% (23/42),重度梗阻者膽汁培養(yǎng)陽性率為66.7% (16/24),3組差異無統(tǒng)計(jì)學(xué)意義(χ2=1.023,P=0.599)。有腹部手術(shù)史者膽汁細(xì)菌培養(yǎng)陽性率為80% (20/25),無腹部手術(shù)史者細(xì)菌培養(yǎng)陽性率為52.9% (36/68,χ2=5.587,P=0.018,表2)。

Logistic分析顯示低位梗阻與有腹腔手術(shù)史為膽管感染的相關(guān)性因素,而梗阻的程度及時(shí)間與膽管感染無顯著相關(guān)(表3)。

圖1 膽汁細(xì)菌培養(yǎng)陽性菌株分布情況

AntibioticsGram-negativebacteria(%)Total(n=37)E.coli(n=16)K.pneumoniae(n=9)Others(n=12)AntibioticsGram-positivebacteria(%)Total(n=21)E.faecalis(n=12)Others(n=9)Amikacin86.587.588.983.3Amikacin90.591.788.9Ampicillin16.212.522.216.7Tetracycline19.016.722.2Imipenem100100100100Ampicillin57.17533.3Co-trimoxazole16.212.511.125.0Moxifloxacin66.766.766.7Ciprofloxacin35.118.844.450.0Ciprofloxacin38.125.055.6Gentamicin32.425.033.341.7Erythromy-cin71.466.677.8Cefepime89.287.588.991.7Linezolid66.766.666.7Ceftriaxone81.175.088.983.3Gentamicin71.458.388.9Ceftazidime83.881.388.983.3Clindamycin61.97544.4Cefotetan67.656.377.875.0PenicillinG71.475.066.6Cefazolin48.637.544.466.7Vancomycin100100100Tobramycin51.443.855.658.3Levofloxacin85.783.388.9Levofloxacin54.150.055.658.3

E.coli:Escherichiacoli;K.pneumoniae:Klebsiellapneumoniae;E.faecalis:Enterococcusfaecalis.

表2 膽管感染相關(guān)因素的單因素分析

表3 多因素Logistic回歸分析

β:Coefficient of regression; SE:Standard error;OR:Odds ratio.

討 論

MOJ多由胰腺腫瘤、膽管壺腹癌及肝臟轉(zhuǎn)移瘤導(dǎo)致,患者常常伴發(fā)膽道感染,原因包括:(1)腸內(nèi)內(nèi)毒素和革蘭陰性菌群可能與膽汁感染或膿毒血癥有關(guān),腸內(nèi)黏膜膽汁缺乏會(huì)損害腸內(nèi)黏膜屏障功能進(jìn)而促進(jìn)細(xì)菌移位及腸內(nèi)毒素釋放入血;(2)同時(shí),腫瘤患者免疫力低下,體內(nèi)腫瘤壞死因子及IL-6水平升高,細(xì)胞免疫受抑,使巨噬細(xì)胞產(chǎn)生減少,清除細(xì)菌的能力下降[2,4-5]。

內(nèi)鏡逆行胰膽管造影(endoscopic retrograde cholangio pancreatography,ERCP)是常見的膽汁采集途徑[6-7],但由于樣品極易被腸道菌群污染而對(duì)培養(yǎng)結(jié)果產(chǎn)生影響,本中心采用PTBD采集膽汁。其具有創(chuàng)傷小、方便快捷、相對(duì)清潔、不受膽管狹窄部位限制的優(yōu)勢(shì),廣泛用于MOJ的診療,此外由于該方式膽汁采集途徑短、樣本極少受到腸道菌群污染,從而使培養(yǎng)結(jié)果更可信。

MOJ患者膽管感染相關(guān)因素分析結(jié)果顯示,低位梗阻患者更容易出現(xiàn)膽道感染并發(fā)癥,有腹腔手術(shù)史患者膽道感染發(fā)生率明顯高于無腹部手術(shù)史患者,提示兩者為膽道感染的易感因素。但本研究腹部手術(shù)史病例數(shù)相對(duì)較少,仍需要大樣本研究進(jìn)一步證實(shí);而MOJ程度及時(shí)間與膽道感染的關(guān)系,本研究結(jié)果并未提示有相關(guān)性。

膽汁培養(yǎng)結(jié)果顯示膽道感染致病菌以腸球菌、大腸埃希菌及肺炎克雷伯菌多見,其菌種常見于腸道細(xì)菌,提示病原菌來自腸道菌群。本研究未做厭氧菌培養(yǎng),膽系感染中常合并厭氧菌感染,且部分患者膽汁同時(shí)培養(yǎng)出2種致病菌,因此膽道系統(tǒng)感染除解除梗阻和通暢引流膽汁外,有效的抗感染治療依然要有細(xì)菌培養(yǎng)及藥物敏感檢測(cè)結(jié)果支持,而不是僅僅是根據(jù)臨床經(jīng)驗(yàn)用藥[8]。

MOJ患者膽道感染多來源于腸道菌群,以革蘭陰性菌為主,抗菌藥物應(yīng)根據(jù)膽汁培養(yǎng)及藥敏結(jié)果選擇,低位梗阻及有腹部手術(shù)史患者應(yīng)重視及預(yù)防膽管感染。

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Biliary tract infection and risk factors of patients with malignant obstructive jaundice

YANG Qing-hui, LI Wen-tao△

(DepartmentofInterventionalRadiology,ShanghaiCancerCenter-DepartmentofOncology,ShanghaiMedicalCollege,FudanUniversity,Shanghai200032,China)

Objective To investigate the information obtained by bile culture and susceptibility testing as while factors like styles of obstruction,abdominal surgical history,degree and time of jaundice related to bacterial infection of biliary tract for patients with malignant obstructive jaundice (MOJ). Methods A total of 93 patients with MOJ

percutaneous transhepatic biliary drainage (PTBD) during Jan.,2015 and Mar.,2016.Bile specimens were collected during the procedure for bacterial culture and susceptibility. Results A rate of 60.2% (56/93) patients had a positive bile culture and 58 strains were identified, in which gram-positive bacteria accounted for 36.2% (21/58) and gram-negative bacteria accounted for 63.8% (37/58).The most common bacteria wereEnterococcusFaecalis,EscherichiaColi,KlebsiellaPneumoniaandStaphylococcusEpidermidis.Conclusions The bile cultures indicated that a different antibacterial therapy should be managed in the patients of biliary infection complicated by malignant biliary jaundice.Low obstruction and abdominal surgery history are independent factors related to infection,while time and degree of jaundice shows no relationship to infection.

bacterial; infection; bile; malignant obstructive jaundice; pertutaneous transhepatic biliary drainage

R442.4

A

10.3969/j.issn.1672-8467.2017.04.016

2016-09-29;編輯:王蔚)

上海市科委科研計(jì)劃項(xiàng)目(16441900700)

△Corresponding author E-mail:liwentao89@126.com

*This work was supported by the Scientific Research Project of Science and Technology Commission of Shanghai Municipality (16441900700).