鄭晗晗，江學良

作者單位：250000山東省濟南市，濟南軍區(qū)總醫(yī)院消化科

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糞便菌群移植治療艱難梭菌感染有效性和安全性的Meta分析

鄭晗晗，江學良

作者單位：250000山東省濟南市，濟南軍區(qū)總醫(yī)院消化科

【摘要】目的探討糞便菌群移植(FMT)治療復(fù)發(fā)性、難治性、危重性艱難梭菌感染(CDI)的有效性和安全性。方法計算機檢索PubMed、EMBase、Cochrane Library、中國期刊全文數(shù)據(jù)庫，檢索時間從建庫至2015年5月。按照PICOS原則制定檢索策略,對檢索詞同時進行主題詞和自由詞檢索。提取文獻相關(guān)信息，包括樣本量、CDI類型、是否合并炎癥性腸病(IBD)、年齡、捐贈者、移植方式、糞便制劑、隨訪時間等。采用英國國立臨床優(yōu)化研究所(NICE)推薦的對病例系列的質(zhì)量評價清單評價納入文獻質(zhì)量。結(jié)果納入24篇文獻，共743例患者，663例獲得臨床緩解，臨床緩解率為89.2%，合并緩解率為87.6%〔95%CI(84.0%，90.4%)〕。亞組分析顯示，經(jīng)上消化道實施FMT的患者合并緩解率為81.5%〔95%CI(75.3%，86.5%)〕，低于經(jīng)下消化道實施FMT患者的合并緩解率89.7%〔95%CI(85.5%，92.7%)〕，差異有統(tǒng)計學意義(P<0.05)；采用冷凍制劑實施FMT的患者合并緩解率為85.5%〔95%CI(78.4%，90.6%)〕，與采用新鮮糞便制劑實施FMT患者的合并緩解率為88.3%〔95%CI(84.1%，91.5%)〕比較，差異無統(tǒng)計學意義(P>0.05)；合并IBD患者合并緩解率為72.7%〔95%CI(53.1%，86.3%)〕，與未合并IBD患者的合并緩解率87.8%〔95%CI(84.6%，90.4%)〕比較，差異無統(tǒng)計學意義(P>0.05)。11篇文獻發(fā)現(xiàn)了可能與FMT治療相關(guān)的不良反應(yīng)，如嘔吐、發(fā)熱、腹脹等，多為自限性,可在短時間內(nèi)緩解。接受FMT治療后死亡的患者中，死亡原因與患者本身其他疾病有關(guān)，沒有證據(jù)證明與FMT治療相關(guān)。結(jié)論FMT治療復(fù)發(fā)性、難治性、危重CDI安全有效，且經(jīng)下消化道實施FMT較上消化道有更高的臨床緩解率。 1.3資料提取文獻的審查和評價由2位作者獨立完成，通過閱讀文獻題目及，排除無關(guān)文獻，對其余文獻進一步閱讀和分析，決定最終是否能夠入選，最后將納入的文獻是否合格進行交叉核對，出現(xiàn)分歧時討論決定是否納入。文獻提取內(nèi)容包括：題目、第一作者、發(fā)表時間、樣本量、CDI類型、是否合并IBD、年齡、捐贈者、移植方式、糞便制劑、隨訪時間等。 2.1文獻檢索及質(zhì)量評價檢索出FMT治療CDI的相關(guān)文獻5 281篇，通過閱讀文獻題目及排除5 237篇，閱讀全文后，納入24篇[26-31,36-53]英文文獻，國內(nèi)尚無符合納入標準的文獻。文獻篩選流程圖見圖1。納入的24篇文獻中，3篇文獻[31,37,42]是多中心研究，4篇[27,28,36,51]沒有清楚明確地描述研究的假說或目的、目標，4篇[31,36,41,51]沒有清楚地報告納入和排除標準，5篇[29,44,47,50-51]沒有對測量的結(jié)局做出明確的定義，4篇[29,44-45,52]前瞻性地收集數(shù)據(jù)，9篇[26,28-29,38,41,44-45,47,52]準確地描述患者是連續(xù)招募的，只有1篇[36]文獻沒有清楚明確地描述研究的主要發(fā)現(xiàn)，沒有文獻對結(jié)局進行分層分析。多數(shù)文獻NICE評分≥4分，屬于高質(zhì)量文獻，5篇[27,36,39,50-51]在4分以下，屬于低質(zhì)量文獻。納入文獻的基本特征見表1。

全球范圍內(nèi)，復(fù)發(fā)性和難治性艱難梭菌感染(CDI)發(fā)病率、病死率不斷增加[1-4]。CDI初次發(fā)作后，30%的患者會復(fù)發(fā)，多次復(fù)發(fā)的患者，60%會再次復(fù)發(fā)[5-7]。危重CDI患者的病死率可高達58%[8-10]。而高毒菌株(NAP1/B1/027)的出現(xiàn)，使治療的失敗率繼續(xù)增加[11]。目前，傳統(tǒng)的治療方案效果并不理想，非達霉素雖能降低復(fù)發(fā)率，但其費用較高，且對多次復(fù)發(fā)患者的療效尚不明確[12-13]。

糞便菌群移植(FMT)能夠重塑腸道菌群的多樣性，使腸道功能得以恢復(fù)，從而抵御艱難梭菌及其產(chǎn)生的毒素[14- 15]。FMT可追溯至中國的東晉時期，距今約有1 700多年的歷史[16-17]，著名醫(yī)藥學家葛洪成功地用人糞清治療食物中毒、腹瀉、發(fā)熱并瀕臨死亡的患者[18]。受藥品安全及衛(wèi)生的相關(guān)管理規(guī)定，F(xiàn)MT并未得到廣泛應(yīng)用及發(fā)展。直到1958年Eiseman等[19]報道了FMT成功治療偽膜性腸炎患者，F(xiàn)MT的價值才逐漸得到認可。在隨后的50多年中，不斷有FMT成功治療CDI的報道[20-31]。

目前FMT治療CDI的相關(guān)研究有限，缺乏設(shè)計合理的大規(guī)模、多中心的隨機對照試驗，對FMT的長期有效性和安全性研究較少，對合適患者、糞便制劑與劑量、移植方式與次數(shù)的選擇等缺乏統(tǒng)一的標準。僅有的循證醫(yī)學證據(jù)[32]也存在主要結(jié)局指標定義不明確、樣本量較少等缺陷。因此，本研究增大樣本量，并對主要結(jié)局指標做出定義，進一步探討FMT治療CDI的有效性和安全性，并對不同移植方式、不同糞便制劑、是否合并炎癥性腸病(IBD)的患者療效進行亞組分析，為FMT的臨床應(yīng)用提供參考。

1資料與方法

1.1文獻納入與排除標準

1.1.1文獻納入標準(1)研究設(shè)計：接受FMT治療的復(fù)發(fā)性或難治性或危重CDI患者；未設(shè)有對照組；≥10例的病例系列；(2)研究對象：復(fù)發(fā)性或難治性或危重CDI患者；伴或不伴感染(如IBD)，有明確的患者臨床特征及結(jié)局；(3)干預(yù)措施：FMT治療，包括任何形式的FMT，如結(jié)腸鏡、鼻胃管、灌腸等，不限制FMT次數(shù)和糞便劑型；(4)結(jié)局指標：以腹瀉的臨床緩解作為主要結(jié)局指標[33]。

FMT治療后，患者的臨床癥狀一般在治療當時或48 h內(nèi)出現(xiàn)緩解，未緩解的患者在3～7 d再次給予FMT治療，因此，本研究綜合以上原因并結(jié)合臨床相關(guān)指南[33-34]，將腹瀉的臨床緩解定義為：FMT治療后大便次數(shù)減少或性狀改善，且在7 d內(nèi)不需其他干預(yù)治療。在FMT治療7 d后，緩解的患者出現(xiàn)癥狀復(fù)發(fā)或需要聯(lián)合其他藥物治療才能控制癥狀或使用其他抗生素后再次出現(xiàn)癥狀者，也認為已獲得了臨床緩解。

1.1.2文獻排除標準(1)使用非糞便來源的腸道細菌進行移植；(2)FMT治療CDI陰性的抗生素相關(guān)性腹瀉；(3)未報告FMT治療結(jié)果；(4)會議摘要、讀者來信、問卷調(diào)查；(5)聯(lián)合其他藥物治療CDI。

1.2文獻檢索策略計算機檢索PubMed、EMBase、Cochrane Library、中國期刊全文數(shù)據(jù)庫，檢索時間從建庫至2015年5月。按照PICOS(Patients，Intervention，Comparisons，Outcomes，Study)原則制定檢索策略,對檢索詞同時進行主題詞和自由詞檢索。英文檢索詞為“clostridium”“clostridium difficile”“fecal microbiota transplant”；中文檢索詞為“艱難梭菌感染”“糞便菌群移植”。語種限制為中、英文。

1.4文獻質(zhì)量評價采用英國國立臨床優(yōu)化研究所(NICE)推薦的對病例系列的質(zhì)量評價清單[32]評價納入文獻質(zhì)量，包括以下內(nèi)容：(1)為提高研究結(jié)果的代表性，病例系列中的病例最好來自不同級別的醫(yī)療機構(gòu)，開展多中心研究；(2)清楚明確地描述研究的假說或目的、目標；(3)清楚地報告納入和排除標準；(4)對測量的結(jié)局做出明確定義；(5)前瞻性收集數(shù)據(jù)；(6)準確地描述患者為連續(xù)招募；(7)清楚明確地描述研究的主要發(fā)現(xiàn)；(8)將結(jié)局進行分層分析及報告，如按照疾病分期、化驗結(jié)果異常、患者的特征等。每項1分，≥4分的文獻為高質(zhì)量文獻，否則為低質(zhì)量文獻。

1.5統(tǒng)計學方法采用MetaAnalyst Beta 3.13進行統(tǒng)計分析，采用I2和Q檢驗評價各文獻異質(zhì)性，當I2=0時，表明各文獻的變異僅由抽樣誤差引起；I2<25%表明各文獻存在輕度異質(zhì)性，25%～50%表明有中度異質(zhì)性，I2>50%或P<0.10時，認為各文獻有較大的異質(zhì)性。以腹瀉的臨床緩解作為主要的結(jié)局指標，采用隨機效應(yīng)模型[35]計算臨床緩解率、合并緩解率。以P<0.05為差異有統(tǒng)計學意義。

2結(jié)果

2.2Meta分析結(jié)果

2.2.1合并緩解率各文獻存在輕度異質(zhì)性(I2=23%，P=0.156)。納入文獻共743例患者，663例獲得臨床緩解，臨床緩解率為89.2%，合并緩解率為87.6%〔95%CI(84.0%，90.4%)，見圖2〕。

2.2.2不同移植方式的亞組分析9篇文獻[26-27,30,36,43,47,49,51-52]經(jīng)上消化道(胃鏡、鼻胃管、鼻十二指腸管、內(nèi)鏡引導下經(jīng)皮胃造瘺管、口服膠囊制劑)實施FMT,各文獻無異質(zhì)性(I2=0，P=0.933)。共192例患者，159例獲得臨床緩解，臨床緩解率為82.8%，合并緩解率為81.5%〔95%CI(75.3%，86.5%)，見圖3〕。19篇文獻[28-31,36-42,44-46,48-51,53]經(jīng)下消化道(腸鏡、灌腸)實施FMT，各文獻有輕度異質(zhì)性(I2=24%，P=0.170)。共551例患者，504例獲得臨床緩解，臨床緩解率為91.5%，合并緩解率為89.7%〔95%CI(85.5%，92.7%),見圖4〕。經(jīng)下消化道實施FMT的合并緩解率高于經(jīng)上消化道，合并緩解率之差為-8.2%〔95%CI(-14.2%，-2.2%)〕，差異有統(tǒng)計學意義(P<0.05)。

圖1　文獻篩選流程圖

第一作者發(fā)表時間樣本量(例)合并IBD(例)CDI類型平均年齡(歲)捐贈者移植方式糞便制劑隨訪時間NICE評分(分)Aas[26]2003180復(fù)發(fā)性73±9親屬、非親屬鼻胃管新鮮9年5Macconnachie[27]2009150復(fù)發(fā)性81.5非親屬鼻胃管新鮮平均16周2Yoon[38]2010120復(fù)發(fā)性、難治性66親屬結(jié)腸鏡新鮮3周～8年5Rohlke[37]2010190復(fù)發(fā)性49親屬、非親屬結(jié)腸鏡新鮮平均27.2個月5Garborg[36]2010402復(fù)發(fā)性75親屬胃鏡、結(jié)腸鏡新鮮80d1Mellow[28]2011130復(fù)發(fā)性、難治性63.5親屬結(jié)腸鏡新鮮平均5.3個月4Jorup-Ronstrom[39]2012321復(fù)發(fā)性75非親屬灌腸冷凍1～68個月3Kelly[41]2012260復(fù)發(fā)性59親屬結(jié)腸鏡新鮮平均10.7個月4Hamilton[29]20124314復(fù)發(fā)性NR非親屬結(jié)腸鏡冷凍、新鮮2個月5Kassam[40]2012270復(fù)發(fā)性、難治性69.4非親屬灌腸新鮮平均427d4Mattila[42]2012700復(fù)發(fā)性73親屬、非親屬結(jié)腸鏡新鮮12周～12個月5Rubin[43]2013750復(fù)發(fā)性63非親屬鼻胃管、胃鏡、PEG新鮮60d4Pathak[49]2014121復(fù)發(fā)性NR親屬、非親屬結(jié)腸鏡、NDT新鮮2～30個月4Russell[51]2014103復(fù)發(fā)性NR親屬鼻胃管、結(jié)腸鏡新鮮1個月～4年1Youngster[52]2014200復(fù)發(fā)性、難治性64.5非親屬口服膠囊制劑冷凍2～6個月6Zainah[30]2014140復(fù)發(fā)性、危重性73.4±11.9親屬、非親屬鼻胃管、結(jié)腸鏡新鮮7～100d4Ray[50]2014201復(fù)發(fā)性、難治性62親屬結(jié)腸鏡新鮮3.2個月3Kronman[47]2014103復(fù)發(fā)性5.4親屬、非親屬鼻胃管新鮮平均44d4Lee[48]2014940復(fù)發(fā)性、難治性71.8非親屬灌腸新鮮6～24個月4Dutta[45]2014270復(fù)發(fā)性64.5親屬、非親屬結(jié)腸鏡、小腸鏡新鮮9.7～34.0個月6Allegretti[44]2014229復(fù)發(fā)性、難治性NR親屬、非親屬結(jié)腸鏡新鮮平均3個月5Khan[46]2014200復(fù)發(fā)性、難治性NR親屬、非親屬結(jié)腸鏡新鮮3～6個月4Satokari[53]2015490復(fù)發(fā)性NR親屬、非親屬結(jié)腸鏡新鮮、冷凍12周～1年4Tvede[31]2015550復(fù)發(fā)性65.6非親屬灌腸冷凍30d4

注：CDI=艱難梭菌感染，IBD=炎癥性腸病，NR=沒有報道，PEG=內(nèi)鏡引導下經(jīng)皮胃造瘺管，NDT=鼻十二指腸管，NICE=英國國立臨床優(yōu)化研究所

Figure 2Forest plot for clinical remission rates of CDI patients treated by FMT

圖3　經(jīng)上消化道實施FMT治療CDI臨床緩解率的森林圖

Figure 3Forest plot of clinical remission rates of CDI patients treated by upper gastrointestinal FMT

圖4　經(jīng)下消化道實施FMT治療CDI臨床緩解率的森林圖

Figure 4Forest plot of clinical remission rates of CDI pateints treated by lower gastrointestinal FMT

2.2.3不同糞便制劑的亞組分析5篇文獻[29,31,39,52-53]采用冷凍制劑(冷凍的糞便混懸液、冷凍的膠囊制劑、冷凍培養(yǎng)的糞便菌株)實施FMT，各文獻無異質(zhì)性(I2=0，P=0.566)。共142例患者，123例獲得臨床緩解，臨床緩解率為86.6%，合并緩解率為85.5%〔95%CI(78.4%，90.6%),見圖5〕。21篇文獻[26-30,36-38,40-51,53]采用新鮮糞便制劑實施FMT，各文獻有中度異質(zhì)性(I2=26%，P=0.131)。共601例患者，540例獲得臨床緩解，合并緩解率為88.3%〔95%CI(84.1%，91.5%)，見圖6〕。采用冷凍制劑與新鮮制劑實施FMT的合并緩解率之差為-2.8%〔95%CI(-3.4%，9.0%)〕，差異無統(tǒng)計學意義(P>0.05)。

圖5　冷凍制劑治療CDI臨床緩解率的森林圖

Figure 5Forest plot of clinical remission rates of CDI pateints treated by frozen feces preparation

圖6　新鮮制劑治療CDI臨床緩解率的森林圖

Figure 6Forest plot of clinical remission rates of CDI patients treated by fresh feces preparation

2.2.4是否合并IBD的亞組分析8篇文獻[29,36,39,44,47,49-51]納入的部分患者合并IBD，各文獻有輕度異質(zhì)性(I2=2%，P=0.413)。共34例患者，27例患者獲得臨床緩解，臨床緩解率為79.4%，合并緩解率為72.7%〔95%CI(53.1%，86.3%)，見圖7〕。24篇文獻[26-31,36-53]納入的部分患者未合并IBD，各文獻有輕度異質(zhì)性(I2=11%，P=0.310)。共納入709例患者，636例獲得臨床緩解，臨床緩解率為89.7%，合并緩解率為87.8%〔95%CI(84.6%，90.4%)，見圖8〕。合并IBD與未合并IBD患者合并緩解率之差為-15.1%〔95%CI(-1.0%，30.3%)〕，差異無統(tǒng)計學意義(P>0.05)。

2.3不良反應(yīng)11篇文獻[26-27,29,31,44-45,47-48,50,52-53]發(fā)現(xiàn)了可能與FMT治療相關(guān)的不良反應(yīng)，如嘔吐、發(fā)熱、腹脹等，多為自限性,可在短時間內(nèi)緩解(見表2)。接受FMT治療后死亡的患者中，死亡原因與患者本身其他疾病有關(guān)，如惡性腫瘤、心血管疾病、器官功能衰竭等，沒有證據(jù)證明與FMT治療相關(guān)。在Aas等[26]研究中，1例患者經(jīng)FMT治療后，癥狀沒有改善，在FMT治療后的第3天發(fā)展為腹膜炎，并且很快死亡。該例患者在接受FMT時已患有嚴重的終末期腎病，需要腹膜透析治療，因此難以說明其死亡與FMT有關(guān)。

圖7　FMT治療CDI合并IBD的臨床緩解率的森林圖

Figure 7Forest plot of clinical remission rates of CDI patients combined with IBD treated by FMT

圖8　FMT治療CDI未合并IBD的臨床緩解率的森林圖

Figure 8Forest plot of clinical remission rates of CDI patients without IBD treated by FMT

表2　FMT治療CDI的不良反應(yīng)

注：NR=沒有報道

3討論

本研究采用NICE質(zhì)量評價工具對納入的病例系列進行質(zhì)量評價，雖然病例系列研究在治療療效評價中的證據(jù)級別低于隨機對照試驗、類試驗，但本研究納入的多數(shù)文獻質(zhì)量評分在4分及以上，為高質(zhì)量研究，僅5篇低于4分，文獻總體質(zhì)量較高。

FMT治療復(fù)發(fā)性、難治性或危重性CDI患者是有效的。本研究發(fā)現(xiàn)，F(xiàn)MT治療CDI的臨床緩解率為89.2%，合并緩解率為87.6%，與Kassam等[32]Meta分析結(jié)果(臨床緩解率為89.7%，合并緩解率為89.1%)相近，低于Sofi等[54]研究的合并緩解率91.2%，分析原因可能為本研究納入的樣本量大，部分患者合并其他胃腸道疾病等危險因素有關(guān)。

FMT治療復(fù)發(fā)性、難治性或危重CDI患者是安全的。FMT通過將健康者的糞便懸液或糞便菌群注入患者胃腸道，以達到修復(fù)患者受損的腸道菌群的目的，雖有一些輕度不良反應(yīng)的發(fā)生，如腹痛、發(fā)熱、惡心、嘔吐等，但均在短時間內(nèi)得到緩解，未發(fā)生與FMT治療相關(guān)的嚴重不良反應(yīng)?；颊邔MT的耐受性好，未見因FMT傳播疾病的報道。

本研究發(fā)現(xiàn)，經(jīng)下消化道實施FMT較上消化道有更高的臨床緩解率。分析可能的原因為：(1)若患者病情較重，通過結(jié)腸鏡實施FMT有誘發(fā)腸穿孔的風險，因此會選擇經(jīng)上消化道實施FMT[30]。故經(jīng)上消化道實施FMT治療的患者病情通常較經(jīng)下消化道實施患者嚴重；(2)經(jīng)上消化道注入的糞便制劑量較少；(3)經(jīng)下消化道實施FMT，可以使糞便菌群免受胃酸及胰酶的破壞，且直接作用于病變的腸道黏膜，使移植的糞便菌群最大限度發(fā)揮作用。近期一項研究發(fā)現(xiàn)，通過結(jié)腸鏡實施FMT治療CDI比萬古霉素或非達霉素更為經(jīng)濟有效[55]。

本研究未發(fā)現(xiàn)使用冷凍制劑與新鮮制劑的患者臨床緩解率存在差異，分析可能的原因為冷凍制劑和新鮮制劑有相同的有效菌株，雖然冷凍制劑經(jīng)過冷凍儲存，但其有效菌株并沒有被破壞。FMT治療CDI的有效菌株尚不明確，仍需進一步研究。

本研究同樣未發(fā)現(xiàn)CDI合并IBD與未合并IBD患者的臨床緩解率存在差異，分析可能的原因為CDI和IBD均涉及腸道菌群結(jié)構(gòu)的改變，F(xiàn)MT對CDI和IBD均發(fā)揮作用。最近發(fā)表的FMT治療活動性潰瘍性結(jié)腸炎的隨機對照試驗顯示，F(xiàn)MT治療組比安慰劑組有更高的臨床緩解率，并且差異有統(tǒng)計學意義，經(jīng)FMT治療后患者的腸道菌群多樣性較治療前增加[56]。

本研究局限性：(1)納入文獻均來自國外，研究對象以歐美人群居多，使研究結(jié)論在我國患者的推廣受到限制；(2)病例系列研究論證強度低于隨機對照試驗，在一定程度上增加了偏倚，可能會使緩解率增大。本研究納入文獻的患者均為10例及以上，減少個案報道和小病例系列的偏倚，且是目前樣本量最大的FMT治療CDI有效性的Meta分析，首次探討了不同制劑、是否合并IBD患者臨床緩解率的差異。在FMT廣泛應(yīng)用于治療CDI之前，期待設(shè)計合理的大樣本隨機對照試驗進行進一步研究。

作者貢獻:鄭晗晗進行課題設(shè)計、資料收集整理、數(shù)據(jù)分析、撰寫論文；江學良參與課題設(shè)計，進行質(zhì)量控制及審校。各作者均對文章負責。

本文無利益沖突。

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(本文編輯：吳立波)

·醫(yī)學循證·

【關(guān)鍵詞】難辨梭菌；糞便菌群移植；有效性研究；Meta分析

鄭晗晗，江學良.糞便菌群移植治療艱難梭菌感染有效性和安全性的Meta分析[J].中國全科醫(yī)學，2016，19(2)：199-205.[www.chinagp.net]

Zheng HH,Jiang XL.Fecal microbiota transplantation for clostridium difficile infection:a meta-analysis[J].Chinese General Practice，2016，19(2)：199-205.

Fecal Microbiota Transplantation for Clostridium Difficile Infection:A Meta-analysisZHENGHan-han,JIANGXue-liang.DepartmentofGastroenterology,theGeneralHospitalofJi′nanMilitaryCommand,Ji′nan250000,China

【Abstract】ObjectiveTo investigate the efficacy and safety of fecal microbiota transplantation(FMT) in recurrent,refractory and severe clostridium difficile infection(CDI).MethodsA computer-based research was conducted on PubMed,EMBase,Cochrane Library and CNKI,with the research time set from database establishment to May 2015.Searching strategy was made based on PICOS principle,and keywords were searched as both subject term and free term.Relevant information was extracted from literatures,including sample volume,CDI type,whether combined with IBD,age,donator,transplanting methods,feces preparation,follow-up period,etc.The quality evaluation inventory for cases recommended by National Institute for Health and Clinical Excellence (NICE) of Britain was employed in the literature quality evaluation.ResultsA total of 24 pieces of literature were included,and there were 743 patients concerned,of which 663 patients had clinical remission with a clinical remission rate of 89.2% and a merged remission rate of 87.6%〔95%CI(84.0%，90.4%)〕.The subgroup analysis showed that the merging remission rate of patients who received FMT through upper gastrointestinal tract was 81.5%〔95%CI(75.3%，86.5%)〕,lower (P<0.05) than that of patients who received FMT through lower gastrointestinal tract,which was 89.7%〔95%CI(85.5%，92.7%)〕;the merging remission rate of patients who underwent FMT using frozen feces preparation was 85.5%〔95%CI(78.4%，90.6%)〕,and the merging remission rate of patients who underwent FMT using fresh feces preparation was 88.3%〔95%CI(84.1%，91.5%)〕,without significant difference between them(P>0.05).The merging remission rate of patients combined with IBD was 72.7%〔95%CI(53.1%，86.3%)〕,and that of patients without IBD combined was 87.8%〔95%CI(84.6%，90.4%)〕,without significant differences between them (P>0.05).Adverse reactions that may be related with FMT treatment were found in 11 pieces of literatures,such as vomit,fever,abdominal distension,and most symptoms were self-confined and could remit soon.Among patients who died after FMT treatment,the cause of death was related with other diseases of these patients,and there were no evidences of the relation between FMT treatment and their death.ConclusionFMT is safe and effective for treating recurrent,refractory,and severe CDI.Lower gastrointestinal FMT delivery lead to higher clinical remission rate.

【Key words】Clostridium difficile；Fecal microbiota transplantation；Validation studies；Meta-analysis

收稿日期：(2015-06-23；修回日期：2015-11-25)

【中圖分類號】R 378.8

【文獻標識碼】A

doi：10.3969/j.issn.1007-9572.2016.02.016

通信作者：江學良，250000山東省濟南市，濟南軍區(qū)總醫(yī)院消化科；E-mail：jiangxueliang678@126.com