糞便療法：腸道感染病人的福音

糞便療法：腸道感染病人的福音

DENISE GRADY 報道 2013年01月18日

這種療法可能駭人聽聞，但是療效很好。
把健康人的糞便灌入病人的腸道，就可以迅速治癒一種嚴重的腸道感染。造成這種感染的病菌很危險，抗生素常常無法控制。

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Gretchen Ertl for The New York Times

梅利莎·卡布雷爾使用抗生素接受牙科診療後被感染。關於糞便療法，她說：「如果不是接受了這種療法，還不知道我現在會怎樣。」

這項新研究報告的高級作者約斯伯特·凱勒博士。

一項新研究發現，這種植入療法治癒了16名反覆感染艱難梭菌(Clostridium difficile)的患者中的15名。而在兩個各13人的對照組中，抗生素只治癒了一組患者中的3個人，及另一組患者中的4個人。這種療法之所以奏效， 似乎是因為恢復了腸道的正常菌群平衡，平衡的腸道菌群消滅了艱難梭菌。
這是植入療法與常規的抗生素療法之間的首次對照研究，研究是在荷蘭進行的。周三，《新英格蘭醫學雜誌》(New England Journal of Medicine)發表了這項研究的報告。
多年來，糞便灌注療法偶爾會被用作無計可施時最後的辦法，來治療這種令人虛弱的頑固感染。美國每年有1.4萬人死於這種感染。它通常是抗生素導致 的，抗生素會殺滅正常的腸道細菌，使人易於感染艱難梭菌。而艱難梭菌在許多醫院裡都很常見，病人接觸到艱難梭菌時，就會受到感染。
常規療法是使用更多抗生素，但約20%的病人會病情複發，而且他們中的許多人會反覆發病，出現嚴重腹瀉、嘔吐和高燒癥狀。
研究者稱，全球已有約500名感染此病的患者接受了糞便療法的治療。該療法使用鹽水等液體稀釋糞便，然後使用灌腸器、結腸鏡或從鼻腔插入通向胃部或小腸的軟管，將稀釋物注入腸道。
糞便會包含數百甚至數千種細菌，研究者還不知道哪些細菌具有療效。所以，目前糞便必須基本上完整施用。
多個醫學期刊曾報道過，這種療法的成功率很高，而且對那些患病數月的患者，產生了近乎神奇的療效。但是此前，還一直有懷疑的餘地，因為在此之前沒有開展過將這種怪誕療法與其他療法相對比的對照實驗。
這項新研究首次給出了懷疑者所要求的那種證據。該療法的支持者稱，他們希望這一結果能有助於讓糞便療法成為醫學界的主流療法，因為有些患者除此之外無法醫治。
羅德島普羅維登斯女子醫院(Women’s Medicine Collaborative)的腸胃病專家科琳·R·凱利博士(Dr. Colleen R. Kelly)說，“我們這些實施糞便療法的人知道它的療效多麼好。只是說服別人很困難。”凱利博士沒有參與上文所述的荷蘭研究。
她補充道，“這份論文很重要，希望它能鼓勵醫生們改變治療模式，多實施這種療法。”
艱難梭菌是個全球性問題。過去十年里，這種細菌出現了毒性越來越強的變種。在美國，每年有30萬住院的患者感染艱難梭菌。研究者們估計，醫院內外的病例總數可能有300萬例，治療花費每年逾10億美元。
糞便療法經常用於治療牛馬的腸道疾病。介紹中國傳統醫學的書籍中，也提到過四世紀時，讓患者口服糞便治療腹瀉的案例。一本書中將其稱為“黃龍湯”。
1958年，科羅拉多大學(University of Colorado)的本·艾斯曼博士(Dr. Ben Eiseman)發表了一篇報告，介紹了通過糞便灌腸為四名患者治療威脅生命的腸道感染的事例。
這項新研究報告的高級作者約斯伯特·凱勒博士(Dr. Josbert Keller)是荷蘭海牙哈加醫院(Hagaziekenhuis)的腸胃病專家。他說，在開展這項研究之前，他和他的同事已經對10個病例實施了糞便移植，而且幾乎全都產生了效果。
“在治療過頭四五名患者後，我們開始考慮，不能再繼續使用這種偏方一樣的療法而沒有證據了，”凱勒說，“大家都在笑話。”
研究人員對感染艱難梭菌數月之久，服用抗生素後至少複發一次的成年患者展開了研究。這些患者被隨機分配到三個小組裡，其中只有一個小組的16名患者 接受了糞便灌注。患者接受了四天萬古黴素(vancomycin)治療，清洗腸道，之後通過鼻管將糞便溶液灌注至小腸中。第二組13名患者清洗腸道並使用 了14天萬古黴素。第三組也有13名患者，僅使用萬古黴素治療。
糞便捐獻者接受了一系列疾病的檢查，從而確保不會讓患者感染。糞便被置於攪拌器內與鹽水混合，之後經過過濾。據凱勒博士描述，產生的溶液很像巧克力奶。
凱勒說，患者十分迫切地想要接受糞便療法，研究人員必須承諾，分配到只使用抗生素小組的患者，如果藥物無效，可以隨後接受糞便療法，患者才同意參加研究。
在接受糞便療法的16名患者中，有13名在接受第一次灌注後就痊癒了。另外三位患者又接受了來自不同捐獻者的灌注，其中兩人痊癒。而另外兩組沒有接受這種療法的患者，26人中只有7人痊癒。
最初未接受灌注而僅採用抗生素、之後又複發的患者中，有18人隨後又接受了灌注，其中有15人痊癒。
研究本來打算包括更多患者，但研究期限不得不縮短。原因是，由於抗生素組的患者與接受灌注的患者相比健康狀況極差，再繼續研究，難免違背道德。
對於那些已經嘗試過這種療法的醫生來說，實驗結果並不意外。明尼蘇達大學(University of Minnesota)腸胃病專家亞歷山大·霍魯茨博士(Dr. Alexander Khoruts)說，他已經對100多位感染艱難梭菌的患者進行了灌注療法。他說90%的情況下，首次灌注就能奏效，其餘的10%則在第二次接受治療後痊 癒。他說，這種療法可以利用冷凍再解凍後的大便溶液進行。

翻譯：梁英、王童鶴

Disgusting, Maybe, but Treatment Works, Study Finds

By DENISE GRADY January 18, 2013

The treatment may sound appalling, but it works.
Transplanting feces from a healthy person into the gut of one who is sick can quickly cure severe intestinal infections caused by a dangerous type of bacteria that antibiotics often cannot control.

A new study finds that such transplants cured 15 of 16 people who had recurring infections with Clostridium difficile bacteria, whereas antibiotics cured only 3 of 13 and 4 of 13 patients in two comparison groups. The treatment appears to work by restoring the gut’s normal balance of bacteria, which fight off C. difficile.
The study is the first to compare the transplants with standard antibiotic therapy. The research, conducted in the Netherlands, is being published Wednesday in The New England Journal of Medicine.
Fecal transplants have been used sporadically for years as a last resort to fight this stubborn and debilitating infection, which kills 14,000 people a year in the United States. The infection is usually caused by antibiotics, which can predispose people to C. difficile by killing normal gut bacteria. If patients are then exposed to C. difficile, which is common in many hospitals, it can take hold.
The usual treatment involves more antibiotics, but about 20 percent of patients relapse, and many of them suffer repeated attacks, with severe diarrhea, vomiting and fever.
Researchers say that worldwide, about 500 people with the infection have had fecal transplantation. It involves diluting stool with a liquid like salt water and then pumping it into the intestinal tract via an enema, a colonoscope or a tube run through the nose into the stomach or small intestine.
Stool can contain hundreds or even thousands of types of bacteria, and researchers do not yet know which ones have the curative powers. So for now, feces have to be used pretty much intact.
Medical journals have reported high success rates and seemingly miraculous cures in patients who had suffered for months. But until now there was room for doubt, because no controlled experiments had compared the outlandish-sounding remedy with other treatments.
The new research is the first to provide the type of evidence that skeptics have demanded, and proponents say they hope the results will help bring fecal transplants into the medical mainstream, because for some patients nothing else works.
“Those of us who do fecal transplant know how effective it is,” said Dr. Colleen R. Kelly, a gastroenterologist with the Women’s Medicine Collaborative in Providence, R.I., who was not part of the Dutch study. “The tricky part has been convincing everybody else.”
She added, “This is an important paper, and hopefully it will encourage people to change their practice patterns and offer this treatment more.”
C. difficile is a global problem. Increasingly toxic strains have emerged in the past decade. In the United States, more than 300,000 patients in hospitals contract C. difficile each year, and researchers estimate that the total number of cases, in and out of hospitals, may be three million. Treatment costs exceed $1 billion a year.
Fecal therapy has often been used to cure gut trouble in cows and horses. Books on traditional Chinese medicine mention giving it to people by mouth to cure diarrhea in the fourth century; one book called it yellow soup.
In 1958, Dr. Ben Eiseman, of the University of Colorado, published a report about using fecal enemas to cure four patients with life-threatening intestinal infections.
The senior author of the new study, Dr. Josbert Keller, a gastroenterologist at the Hagaziekenhuis hospital in The Hague, said that before conducting the research, he and his colleagues had performed the transplant in about 10 cases, and it almost always worked.
“After the first four or five patients, we started thinking, we can’t go on doing this kind of obscure treatment without evidence,” Dr. Keller said. “Everybody is laughing about it.”
The researchers studied adults who had been suffering from C. difficile for months and had had at least one relapse after antibiotics. They were picked at random to be in one of three groups. Only one group, 16 people, had the transplant: they took the antibiotic vancomycin for four days, had their intestines rinsed and then had the fecal solution pumped into their small intestines through a nose tube. A second group, 13 people, had the intestinal wash and 14 days of vancomycin, and a third, also 13, had only vancomycin.
The donors were tested for an array of diseases to make sure they did not infect the patients. Their specimens were mixed with saline in a blender and strained, to produce a solution that Dr. Keller said resembled chocolate milk.
Dr. Keller said patients were so eager to receive transplants that they would not join the study unless the researchers promised that those assigned to antibiotics alone would get transplants later if the drugs failed.
Among the 16 who received transplants, 13 were cured after the first infusion. The other three were given repeat infusions from different donors, and two were also cured. In the two groups of patients who did not receive transplants, only 7 of 26 were cured.
Of the patients who did not receive transplants at first and who relapsed after receiving antibiotics only, 18 were subsequently given transplants, and 15 were cured.
The study was originally meant to include more patients, but it had to be cut short because the antibiotic groups were faring so poorly compared with the transplant patients that it was considered unethical to continue.
The results come as no surprise to doctors who have tried the procedure. Dr. Alexander Khoruts, a gastroenterologist at the University of Minnesota, said he had performed the transplants in more than 100 patients with C. difficile. He said that it worked the first time in 90 percent, and that the other 10 percent were cured with a second treatment. The procedure can be done with a stool solution that has been frozen and thawed, he said.