Indian J Gastroenterol DOI 10.1007/s12664-014-0459-x
REVIEW ARTICLE
Fecal microbiota transplantation for management of Clostridium difficile infection Chetana Vaishnavi
Received: 24 August 2013 / Accepted: 30 March 2014 # Indian Society of Gastroenterology 2014
Abstract The widespread use of antibiotics has led Clostridium difficile infection (CDI) to become a common problem with pronounced medical and economic effects. The recurrence of CDI after treatment with standard antibiotics is becoming more common with the emergence of more resistant strains of C. difficile. As CDI is an antibiotic-associated disease, further treatment with antibiotic is best avoided. As the gut flora is severely disturbed in CDI, approaches that restore the gut microbiota may become good alternative modes of CDI therapies. Fecal microbiota transplantation (FMT) is the procedure of transplantation of fecal bacteria from a healthy donor individual into a patient for restoration of the normal colonic flora. Thus, FMT helps in the eradication of C. difficile and resolution of clinical symptoms such as diarrhea, cramping, and urgency. Though this approach to treatment is not new, presently, it has become an alternative and promising way of combating infections. The procedure is not in regular use because of the time required to identify a suitable donor, the risk of introducing opportunistic pathogens, and a general patient aversion to the transplant. However, FMT is gaining popularity because of its success rate as a panacea for recurrent attacks of CDI and is being increasingly used in clinical practice. This review describes the rationale, the indications, the results, the techniques, the potential donors, the benefits as well as the complications of fecal microbiota instillation to CDI patients in order to restore the normal gut flora.
Keywords Donors . Dysbiosis . Methods . Rationale
C. Vaishnavi (*) Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India e-mail: [email protected]
Introduction Clostridium difficile is a significant healthcare-associated enteric pathogen which is responsible for considerable morbidity and mortality. The normal intestinal flora which is an important part of the immune system gets disrupted by antibiotics leading to an overgrowth of drug-resistant C. difficile. The widespread use of antibiotics has led C. difficile infection (CDI) to become a common problem with pronounced medical and economic effects. The recurrence of CDI after treatment with standard antibiotics is becoming more common with the worldwide emergence of more resistant strains of C. difficile and unavailability of new antibacterial agents. Moreover, the use of antibacterial agents also disturbs normal human flora, which further inhibits defense against such pathogens. Recurrent CDI is also prevalent in India but is not widely recognized, and the extent of the disease is not known. Widespread unregulated and inappropriate prescribing of antibiotics in the country indicates that CDI could be prevalent even in areas where surveillance for the disease is absent. As CDI is an antibiotic-associated disease, further treatment with antibiotic is best avoided. Thus, the management of CDI has become a major challenge for the clinicians, and new methods of combating the disease are required. As the gut flora is severely disturbed in CDI, approaches that restore the gut microbiota may become good alternative modes of CDI therapies. Presently, infusion of donor fecal microbiota is becoming a promising alternative therapy for recurrent CDI in humans based on recently published studies [1–3]. This review describes the rationale, the indications, the results, the techniques, the potential donors, the benefits as well as the complications of fecal microbiota transplantation (FMT) to CDI patients in order to restore the normal gut flora.
Indian J Gastroenterol
Rationale for fecal microbiota transplantation FMT is the procedure of transplantation of fecal bacteria from a healthy donor individual into a patient for restoration of the normal colonic flora. The procedure is also known as stool transplant, fecal bacteriotherapy, fecal transfusion, fecal transplant, fecal enema, and human probiotic infusion. FMT is the method of employing harmless bacteria to displace pathogenic organisms. Though this approach to treatment is not new, presently, it has become an alternative and promising way of combating infections [4]. It is believed by clinicians that the addition of a normal microbial flora to a diseased colon may be quite useful in the treatment of colonic diseases. Theoretically, FMT may be regarded as replacing the gut microbiome which has been disrupted by various factors [5]. Bacterial interference is the method of using harmless commensal bacteria to displace pathogenic microorganisms such as C. difficile. Some decades ago, attempts to influence colonization of pathogenic bacteria with “harmless” bacteria were carried out in order to investigate bacterial interference. Colonization resistance gets reduced transiently after antibiotic treatment; during which period, the host becomes very susceptible to infection by pathogens such as C. difficile [6, 7]. At this time, the environmental C. difficile spores colonize [8, 9] or the intestinal C. difficile multiplies from a low-level carrier state [10]. FMT rebuilds colonization resistance and thereby suppresses the C. difficile in the gut milieu. Rohlke and Stollman [11] suggest the possibility that the transplantation of donated flora results in an immunological response that facilitates C. difficile eradication.
Indications for fecal microbiota transplantation Fecal transplantation is not new. Prescription of ingestion of donor feces as a therapeutic agent for a variety of conditions came from China as early as the fourth century [12]. Later on, Ralph Lewin reported that “consumption of fresh, warm camel feces has been recommended by Bedouins as a remedy for bacterial dysentery; its efficacy was confirmed by German soldiers in Africa during World War II” [12]. FMT has been used for indications like constipation, colitis, irritable bowel syndrome [13], ulcerative colitis [14], celiac disease [15], autoimmune disorders [16], neurological conditions [17], etc. FMT is now regarded as a promising alternative treatment for recurrent C. difficile disease and other forms of intestinal dysbiosis [18, 19]. The first known description of FMT in clinical medicine was published in 1958 outlining the successful treatment of four patients with pseudomembranous colitis much before C. difficile was the known cause [20]. The next report was by Bowden et al. [21]. Since that time, sporadic reports of FMT application using donor stool in the rectum or through colonoscopy or administered through
nasogastric tube followed [22–25]. Although the efficacy of this treatment method still remains undecided because no randomized trials have been performed, the yeast Saccharomyces boulardii was used for CDI with good result in a randomized trial [26]. In human health, bacteriotherapy was probably forgotten because of the continuous development of new, more potent antibacterial agents and because of fears about possible side effects. FMT is an alternative treatment given to a CDI patient who has recurrent or recalcitrant episodes of diarrhea despite antibiotic treatment for CDI. Bakken et al. [19] recommend that FMT be considered in patients with at least three episodes of mild to moderate recurrent CDI and failure with a tapered course of vancomycin or in those with at least two episodes of severe CDI requiring hospitalization. The authors also suggest that FMT should be considered if moderate CDI did not respond to vancomycin for at least 1 week. Severe CDI not responding to standard therapy after 2 days may also be considered for FMT earlier in the progression of CDI. Relapsing CDI in humans is linked to a pathological imbalance within the intestinal microbiota, termed as dysbiosis. Targeting a dysbiotic microbiota with a defined mixture of phylogenetically diverse bacteria can trigger major shifts in the microbial community structure that displaces C. difficile and, as a result, resolves disease and contagiousness. The mechanism of action may be the restoration of missing components of the flora including Bacteroidetes and Firmicutes in patients with recurrent CDI [27, 28]. The introduced fecal flora may also act similar to vancomycin, which originates from Bacillus thuringiensis, a soil bacterium producing bacteriocins against C. difficile. Thus, FMT helps in the eradication of C. difficile and resolution of clinical symptoms such as diarrhea, cramping, and urgency. Though FMT is not a formally approved modality, it is a viable option for patients who fail to eliminate the infection with conventional treatment. However, this kind of treatment is not yet widely used. As this does not represent research, research ethics approval is not required. However, institutional approval may be obtained, and informed consent taken from patients after informing them of the nature of treatment procedure, the available results in previously published reports as well as the possible risks of the procedures.
Results of C. difficile infection treatment with fecal microbiota transplantation During the last 10 years, with the emergence of hypervirulent C. difficile strains (ribotype 027 and 078) and consequent increased rate of severe CDI manifestations, nonantibiotic measures to combat CDI received a boost. The interest that has arisen in FMT is due to the increasing number of immunocompromised patients in hospitals, who are likely to acquire
Indian J Gastroenterol
CDI. You et al. [29] reported successful treatment of fulminant C. difficile infection with fecal bacteriotherapy. Yoon and Brandt [30] reported 12 cases from Bronz that were successfully treated with the administration of donor feces into the colon through colonoscopes. In another study from northern California and the University of Washington, 19 patients were successfully treated with fecal bacteriotherapy through colonoscope, and C. difficile was eradicated in a follow up of 6 months to 4 years [31]. In a recent study, the administration of Lactobacillus acidophilus reduced the severity of C. difficile infection in the experimental animals [32]. Borody et al. [33] treated six patients having inflammatory bowel disease (IBD) and CDI coinfection using FMT with improvement in colitis symptoms. Anderson et al. [34] identified eight case series/ reports with a total of 15 IBD patients with CDI coinfection in their review of other cases of successful treatment. They observed 100 % resolution of CDI with 86 % of the patients demonstrating improved response to IBD medications. Grehan et al. [5] used fecal bacteriotherapy in ten patients after classically cleansing the bowel with antibiotics and then infusing donor-processed fecal suspensions daily for 5–15 days. Initially, for the first infusion, they used a colonoscope, but subsequent ones were given over a 1-h period through nasojejunal tube or enemas or a combination of both. Gut flora was carefully analyzed at 4, 8, and 24 weeks following the infusions. The authors demonstrated that the donor flora was relatively stable in the microbiota of the feces of the recipient, suggesting that the manipulation of the colonic flora is effective and holds promise for new therapies in the treatment of CDI. Khoruts et al. [28] treated CDI by FMT and found that 14 days after the transplantation, the fecal bacterial flora was similar to that of their donor. Furthermore, C. difficile infection appeared to be cured. Thus, donor stool flora can survive for a significant period of time in the recipient and therefore may be helpful in the treatment of the disease. As Bacteroides does not survive for more than a few minutes outside the human gut, fresh material for bacteriotherapy is required. Low Bacteroides counts can be improved by attention to upper gut fermentation and consuming foods rich in fiber. Gough et al. [35] conducted a systematic literature review of FMT for recurrent CDI and pseudomembranous colitis. They reported that in 317 patients treated across 27 case series and reports, FMT was highly effective, showing disease resolution in 92 % of cases. Effectiveness varied by route of instillation, relationship to stool donor, volume of FMT given, and treatment before infusion. Death and adverse events were uncommon. These findings can guide physicians interested in implementing the procedure until better-designed studies are conducted to confirm best practices. In a small study, it was reported that a mixture of ten different facultative aerobic and anaerobic bacteria was able to resolve CDI [23], but sustained reproduction was not seen with the procedure. A success rate of 92 % has been achieved
with more than 2,500 CDI patients treated by fecal bacteriotherapy using donor samples. Randomized clinical trials to assess its efficacy and safety are underway. The procedure is not quite popular yet because of the time required to identify a suitable donor, the risk of introducing opportunistic pathogens, and a general patient aversion to the transplant [13]. There is hardly any literature on pediatric use of FMT. Russell et al. [36] reported successful FMT via nasogastric tube in a 2-year-old pediatric patient. Gough et al. [35], in their systematic FMT review, mentioned the patients’ age ranged from 2 to 95 years. In a randomized, controlled trial, fecal infusion from healthy donors was shown to be highly effective in treating recurrent C. difficile and was found to be more effective than vancomycin alone [37]. Now, it has become clear that fecal transplantation therapy is successful and is used by experts without any adverse effects.
Techniques for fecal microbiota transplantation The fecal transplant substance is prepared and administered in a clinical setting to make sure that necessary precautions are taken [13]. Briefly, the procedure of FMT involves single to multiple infusions of bacterial fecal flora taken from a healthy donor to the recipient. However, to initiate FMT, first and foremost, all antibiotics to the patients should be discontinued prior to the procedure. Bowel lavage, done by administration of polyethylene glycol electrolyte in the evening prior to FMT via colonoscopies or enemas, helps to flush out residual feces, antibiotics as well as C. difficile toxins and spores. However, these prerequisites are not required when FMT is administered via nasogastric tube. In a recent analysis by Gough et al. [35], it was observed that FMT had a relapse rate of 12 % when the patient received both bowel lavage and an antibiotic before FMT. Various routes can be employed to infuse the fecal microbiota. FMT may be administered to the proximal colon via colonoscope [24, 38, 39]; the distal lower gastrointestinal (GI) tract via enema [40–42] or rectal catheter [43, 44]; and the upper GI tract through a nasogastric tube [45–47], a nasoduodenal tube [48], or a gastroscope [38, 49]. The enema infusion is the simplest and the most acceptable procedure of FMT because of suitability and ease. However, colonoscopic FMT is more efficacious than enemas, as the latter may require multiple infusions and have their own inherent disadvantages. Upper GI tract FMT is not quite popular as the location of deposition of transplant is either in the stomach or duodenum, instead of the large intestine where it is actually required. Moreover, in patients with intestinal obstruction, colonoscopic infusions are helpful and suitable than the upper GI tract route. However, the upper GI route has been found to be useful for elderly population [36, 46], pediatric population
Indian J Gastroenterol
[36], and for those with comorbidities in the lower GI tract [47]. A stool volume of 5–300 g has been transplanted by different groups of workers via colonoscopy [11]. The infused volume ranged from 25 to 960 mL, the volume being lower when delivered through the upper GI tract and more via the colonoscopies to the lower GI tract [11]. Gustafsson et al. [50] used homogenized cow’s milk for preparing the fecal suspension but saline is the most frequently used fluid followed by water. Ideally, FMT of fresh donated sample is best done within 6 h [51] but not later than 24 h [19]. The volume of stool should be 50 g suspended in about 500 mL of fluid [35]. A heterogeneous mixture of the stool can be prepared preferably in normal saline or in water, using a simple blender, dedicated for FMT alone, or by vigorous manual shaking of the material in a tightly covered container. After filtering the suspension through sterile filters or strainers to ward off undigested food particles, the filtrate can be poured directly into a large syringe or into the colonoscope, endoscope, or nasogastric tube, etc. depending upon the intended mode of delivery (Table 1). An infectious diseases specialist at the University of Toronto reported FMT on seven cases in which do-it-yourselfers achieved 100 % clinical success [41]. They received stepby-step instructions about how to mix a small quantity of stool (1.7 oz) with slightly
REVIEW ARTICLE
Fecal microbiota transplantation for management of Clostridium difficile infection Chetana Vaishnavi
Received: 24 August 2013 / Accepted: 30 March 2014 # Indian Society of Gastroenterology 2014
Abstract The widespread use of antibiotics has led Clostridium difficile infection (CDI) to become a common problem with pronounced medical and economic effects. The recurrence of CDI after treatment with standard antibiotics is becoming more common with the emergence of more resistant strains of C. difficile. As CDI is an antibiotic-associated disease, further treatment with antibiotic is best avoided. As the gut flora is severely disturbed in CDI, approaches that restore the gut microbiota may become good alternative modes of CDI therapies. Fecal microbiota transplantation (FMT) is the procedure of transplantation of fecal bacteria from a healthy donor individual into a patient for restoration of the normal colonic flora. Thus, FMT helps in the eradication of C. difficile and resolution of clinical symptoms such as diarrhea, cramping, and urgency. Though this approach to treatment is not new, presently, it has become an alternative and promising way of combating infections. The procedure is not in regular use because of the time required to identify a suitable donor, the risk of introducing opportunistic pathogens, and a general patient aversion to the transplant. However, FMT is gaining popularity because of its success rate as a panacea for recurrent attacks of CDI and is being increasingly used in clinical practice. This review describes the rationale, the indications, the results, the techniques, the potential donors, the benefits as well as the complications of fecal microbiota instillation to CDI patients in order to restore the normal gut flora.
Keywords Donors . Dysbiosis . Methods . Rationale
C. Vaishnavi (*) Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India e-mail: [email protected]
Introduction Clostridium difficile is a significant healthcare-associated enteric pathogen which is responsible for considerable morbidity and mortality. The normal intestinal flora which is an important part of the immune system gets disrupted by antibiotics leading to an overgrowth of drug-resistant C. difficile. The widespread use of antibiotics has led C. difficile infection (CDI) to become a common problem with pronounced medical and economic effects. The recurrence of CDI after treatment with standard antibiotics is becoming more common with the worldwide emergence of more resistant strains of C. difficile and unavailability of new antibacterial agents. Moreover, the use of antibacterial agents also disturbs normal human flora, which further inhibits defense against such pathogens. Recurrent CDI is also prevalent in India but is not widely recognized, and the extent of the disease is not known. Widespread unregulated and inappropriate prescribing of antibiotics in the country indicates that CDI could be prevalent even in areas where surveillance for the disease is absent. As CDI is an antibiotic-associated disease, further treatment with antibiotic is best avoided. Thus, the management of CDI has become a major challenge for the clinicians, and new methods of combating the disease are required. As the gut flora is severely disturbed in CDI, approaches that restore the gut microbiota may become good alternative modes of CDI therapies. Presently, infusion of donor fecal microbiota is becoming a promising alternative therapy for recurrent CDI in humans based on recently published studies [1–3]. This review describes the rationale, the indications, the results, the techniques, the potential donors, the benefits as well as the complications of fecal microbiota transplantation (FMT) to CDI patients in order to restore the normal gut flora.
Indian J Gastroenterol
Rationale for fecal microbiota transplantation FMT is the procedure of transplantation of fecal bacteria from a healthy donor individual into a patient for restoration of the normal colonic flora. The procedure is also known as stool transplant, fecal bacteriotherapy, fecal transfusion, fecal transplant, fecal enema, and human probiotic infusion. FMT is the method of employing harmless bacteria to displace pathogenic organisms. Though this approach to treatment is not new, presently, it has become an alternative and promising way of combating infections [4]. It is believed by clinicians that the addition of a normal microbial flora to a diseased colon may be quite useful in the treatment of colonic diseases. Theoretically, FMT may be regarded as replacing the gut microbiome which has been disrupted by various factors [5]. Bacterial interference is the method of using harmless commensal bacteria to displace pathogenic microorganisms such as C. difficile. Some decades ago, attempts to influence colonization of pathogenic bacteria with “harmless” bacteria were carried out in order to investigate bacterial interference. Colonization resistance gets reduced transiently after antibiotic treatment; during which period, the host becomes very susceptible to infection by pathogens such as C. difficile [6, 7]. At this time, the environmental C. difficile spores colonize [8, 9] or the intestinal C. difficile multiplies from a low-level carrier state [10]. FMT rebuilds colonization resistance and thereby suppresses the C. difficile in the gut milieu. Rohlke and Stollman [11] suggest the possibility that the transplantation of donated flora results in an immunological response that facilitates C. difficile eradication.
Indications for fecal microbiota transplantation Fecal transplantation is not new. Prescription of ingestion of donor feces as a therapeutic agent for a variety of conditions came from China as early as the fourth century [12]. Later on, Ralph Lewin reported that “consumption of fresh, warm camel feces has been recommended by Bedouins as a remedy for bacterial dysentery; its efficacy was confirmed by German soldiers in Africa during World War II” [12]. FMT has been used for indications like constipation, colitis, irritable bowel syndrome [13], ulcerative colitis [14], celiac disease [15], autoimmune disorders [16], neurological conditions [17], etc. FMT is now regarded as a promising alternative treatment for recurrent C. difficile disease and other forms of intestinal dysbiosis [18, 19]. The first known description of FMT in clinical medicine was published in 1958 outlining the successful treatment of four patients with pseudomembranous colitis much before C. difficile was the known cause [20]. The next report was by Bowden et al. [21]. Since that time, sporadic reports of FMT application using donor stool in the rectum or through colonoscopy or administered through
nasogastric tube followed [22–25]. Although the efficacy of this treatment method still remains undecided because no randomized trials have been performed, the yeast Saccharomyces boulardii was used for CDI with good result in a randomized trial [26]. In human health, bacteriotherapy was probably forgotten because of the continuous development of new, more potent antibacterial agents and because of fears about possible side effects. FMT is an alternative treatment given to a CDI patient who has recurrent or recalcitrant episodes of diarrhea despite antibiotic treatment for CDI. Bakken et al. [19] recommend that FMT be considered in patients with at least three episodes of mild to moderate recurrent CDI and failure with a tapered course of vancomycin or in those with at least two episodes of severe CDI requiring hospitalization. The authors also suggest that FMT should be considered if moderate CDI did not respond to vancomycin for at least 1 week. Severe CDI not responding to standard therapy after 2 days may also be considered for FMT earlier in the progression of CDI. Relapsing CDI in humans is linked to a pathological imbalance within the intestinal microbiota, termed as dysbiosis. Targeting a dysbiotic microbiota with a defined mixture of phylogenetically diverse bacteria can trigger major shifts in the microbial community structure that displaces C. difficile and, as a result, resolves disease and contagiousness. The mechanism of action may be the restoration of missing components of the flora including Bacteroidetes and Firmicutes in patients with recurrent CDI [27, 28]. The introduced fecal flora may also act similar to vancomycin, which originates from Bacillus thuringiensis, a soil bacterium producing bacteriocins against C. difficile. Thus, FMT helps in the eradication of C. difficile and resolution of clinical symptoms such as diarrhea, cramping, and urgency. Though FMT is not a formally approved modality, it is a viable option for patients who fail to eliminate the infection with conventional treatment. However, this kind of treatment is not yet widely used. As this does not represent research, research ethics approval is not required. However, institutional approval may be obtained, and informed consent taken from patients after informing them of the nature of treatment procedure, the available results in previously published reports as well as the possible risks of the procedures.
Results of C. difficile infection treatment with fecal microbiota transplantation During the last 10 years, with the emergence of hypervirulent C. difficile strains (ribotype 027 and 078) and consequent increased rate of severe CDI manifestations, nonantibiotic measures to combat CDI received a boost. The interest that has arisen in FMT is due to the increasing number of immunocompromised patients in hospitals, who are likely to acquire
Indian J Gastroenterol
CDI. You et al. [29] reported successful treatment of fulminant C. difficile infection with fecal bacteriotherapy. Yoon and Brandt [30] reported 12 cases from Bronz that were successfully treated with the administration of donor feces into the colon through colonoscopes. In another study from northern California and the University of Washington, 19 patients were successfully treated with fecal bacteriotherapy through colonoscope, and C. difficile was eradicated in a follow up of 6 months to 4 years [31]. In a recent study, the administration of Lactobacillus acidophilus reduced the severity of C. difficile infection in the experimental animals [32]. Borody et al. [33] treated six patients having inflammatory bowel disease (IBD) and CDI coinfection using FMT with improvement in colitis symptoms. Anderson et al. [34] identified eight case series/ reports with a total of 15 IBD patients with CDI coinfection in their review of other cases of successful treatment. They observed 100 % resolution of CDI with 86 % of the patients demonstrating improved response to IBD medications. Grehan et al. [5] used fecal bacteriotherapy in ten patients after classically cleansing the bowel with antibiotics and then infusing donor-processed fecal suspensions daily for 5–15 days. Initially, for the first infusion, they used a colonoscope, but subsequent ones were given over a 1-h period through nasojejunal tube or enemas or a combination of both. Gut flora was carefully analyzed at 4, 8, and 24 weeks following the infusions. The authors demonstrated that the donor flora was relatively stable in the microbiota of the feces of the recipient, suggesting that the manipulation of the colonic flora is effective and holds promise for new therapies in the treatment of CDI. Khoruts et al. [28] treated CDI by FMT and found that 14 days after the transplantation, the fecal bacterial flora was similar to that of their donor. Furthermore, C. difficile infection appeared to be cured. Thus, donor stool flora can survive for a significant period of time in the recipient and therefore may be helpful in the treatment of the disease. As Bacteroides does not survive for more than a few minutes outside the human gut, fresh material for bacteriotherapy is required. Low Bacteroides counts can be improved by attention to upper gut fermentation and consuming foods rich in fiber. Gough et al. [35] conducted a systematic literature review of FMT for recurrent CDI and pseudomembranous colitis. They reported that in 317 patients treated across 27 case series and reports, FMT was highly effective, showing disease resolution in 92 % of cases. Effectiveness varied by route of instillation, relationship to stool donor, volume of FMT given, and treatment before infusion. Death and adverse events were uncommon. These findings can guide physicians interested in implementing the procedure until better-designed studies are conducted to confirm best practices. In a small study, it was reported that a mixture of ten different facultative aerobic and anaerobic bacteria was able to resolve CDI [23], but sustained reproduction was not seen with the procedure. A success rate of 92 % has been achieved
with more than 2,500 CDI patients treated by fecal bacteriotherapy using donor samples. Randomized clinical trials to assess its efficacy and safety are underway. The procedure is not quite popular yet because of the time required to identify a suitable donor, the risk of introducing opportunistic pathogens, and a general patient aversion to the transplant [13]. There is hardly any literature on pediatric use of FMT. Russell et al. [36] reported successful FMT via nasogastric tube in a 2-year-old pediatric patient. Gough et al. [35], in their systematic FMT review, mentioned the patients’ age ranged from 2 to 95 years. In a randomized, controlled trial, fecal infusion from healthy donors was shown to be highly effective in treating recurrent C. difficile and was found to be more effective than vancomycin alone [37]. Now, it has become clear that fecal transplantation therapy is successful and is used by experts without any adverse effects.
Techniques for fecal microbiota transplantation The fecal transplant substance is prepared and administered in a clinical setting to make sure that necessary precautions are taken [13]. Briefly, the procedure of FMT involves single to multiple infusions of bacterial fecal flora taken from a healthy donor to the recipient. However, to initiate FMT, first and foremost, all antibiotics to the patients should be discontinued prior to the procedure. Bowel lavage, done by administration of polyethylene glycol electrolyte in the evening prior to FMT via colonoscopies or enemas, helps to flush out residual feces, antibiotics as well as C. difficile toxins and spores. However, these prerequisites are not required when FMT is administered via nasogastric tube. In a recent analysis by Gough et al. [35], it was observed that FMT had a relapse rate of 12 % when the patient received both bowel lavage and an antibiotic before FMT. Various routes can be employed to infuse the fecal microbiota. FMT may be administered to the proximal colon via colonoscope [24, 38, 39]; the distal lower gastrointestinal (GI) tract via enema [40–42] or rectal catheter [43, 44]; and the upper GI tract through a nasogastric tube [45–47], a nasoduodenal tube [48], or a gastroscope [38, 49]. The enema infusion is the simplest and the most acceptable procedure of FMT because of suitability and ease. However, colonoscopic FMT is more efficacious than enemas, as the latter may require multiple infusions and have their own inherent disadvantages. Upper GI tract FMT is not quite popular as the location of deposition of transplant is either in the stomach or duodenum, instead of the large intestine where it is actually required. Moreover, in patients with intestinal obstruction, colonoscopic infusions are helpful and suitable than the upper GI tract route. However, the upper GI route has been found to be useful for elderly population [36, 46], pediatric population
Indian J Gastroenterol
[36], and for those with comorbidities in the lower GI tract [47]. A stool volume of 5–300 g has been transplanted by different groups of workers via colonoscopy [11]. The infused volume ranged from 25 to 960 mL, the volume being lower when delivered through the upper GI tract and more via the colonoscopies to the lower GI tract [11]. Gustafsson et al. [50] used homogenized cow’s milk for preparing the fecal suspension but saline is the most frequently used fluid followed by water. Ideally, FMT of fresh donated sample is best done within 6 h [51] but not later than 24 h [19]. The volume of stool should be 50 g suspended in about 500 mL of fluid [35]. A heterogeneous mixture of the stool can be prepared preferably in normal saline or in water, using a simple blender, dedicated for FMT alone, or by vigorous manual shaking of the material in a tightly covered container. After filtering the suspension through sterile filters or strainers to ward off undigested food particles, the filtrate can be poured directly into a large syringe or into the colonoscope, endoscope, or nasogastric tube, etc. depending upon the intended mode of delivery (Table 1). An infectious diseases specialist at the University of Toronto reported FMT on seven cases in which do-it-yourselfers achieved 100 % clinical success [41]. They received stepby-step instructions about how to mix a small quantity of stool (1.7 oz) with slightly
