Introduction
Gut microbiota is the name assigned to the complex community of microorganisms that occupy the human digestive tract. The accumulation of these microorganism species begins soon after birth, developing rapidly through early childhood. Various factors throughout life can affect the ecology and function of the microbiota, potentially resulting in dysbiosis, the alternation of microbiota such that an imbalance is created between beneficial and harmful bacteria throughout the gut9. Disruption of the gut microbiota is
associated with multiple diseases of the gastrointestinal tract (GIT), such as irritable bowel disease (IBD) and inflammatory bowel syndrome (IBS), as well as causation of Clostridium difficile infection. In order to combat this disruption, different bacteriotherapies exist. While probiotics, prebiotics, and symbiotics are more widely understood therapies, as are antibiotics, more novel approaches are emerging as well. One particularly interesting novel approach that is gaining acceptance and validity is fecal microbiota transplantation (FMT).
I. Gut Microbiota
Microbial communities colonize almost all surfaces of the human body, including the skin, nasal and oral cavity, urogenital tract, and GIT. In the gut, these communities are found in greater densities than elsewhere. The human GIT is colonized by thousands of species of microorganisms. At birth the GIT is essentially sterile, but microbial colonization begins shortly afterwards; the accumulation of intestinal microbiota continues rapidly until stabilization is achieved around two to four years of age9. Lactobacillus organisms are the
species become predominant throughout the distal ileum and colon; in the distal ileum Escherichia coli is most common, whereas in the colon species of the Bacteroides genus are more frequent10. Throughout the remainder of the life cycle, the gut microbiota remains
relatively stable. In general, a healthy microbiota is characterized by high diversity and ability to resist change under physiological stress. Unhealthy microbiota is the opposite, distinguished by lower species diversity, in addition to fewer beneficial microbes and the presence of pathobionts9.
Gut microbiota are crucial for many processes within the human body, including intestinal tract development, systemic immunity, colonic homeostasis, aiding in digestion, and the formation of certain nutrients9,10. Nutrients produced by microbial action in the
colon include vitamin K, vitamin B12, thiamin, and riboflavin. While these nutrients do not significantly contribute to the micronutrient needs of the host, they are used by intestinal mucosal cells10. In addition to nutrients, the gut microbiota also aid in the formation of
short chain fatty acids and certain gases. Butyrate, one of the short chain fatty acids produced, is of particular importance given that it is the primary energy source for colonocytes and inhibits intestinal cell proliferation. Intestinal cell proliferation can cause colitis symptoms; butyrate therefore aids in reducing such inflammation9.
have attracted the attention of drug developers. Some companies are in the early stages of developing pill versions of FMT, using the information available through the Human Microbiome Project. Aside from C. difficile, other potential targets for microbiome therapeutics include autoimmune diseases, inflammatory bowel diseases, asthma, diabetes, and even cancer.
II. Dysbiosis
Despite the stability of the gut microbiota throughout life, various factors can potentially play a role in disrupting the complex microorganism community established in the gut. Factors that may impact the gut microbiota include stress, alcohol, exercise, unnecessary use of antibiotics, excessive hygiene, and dietary choices4,9. Dietary antigens
interact with both the intestinal mucosa and directly with the microbiota as well. There is evidence that diet has profound effects on the composition of the gut microbiota4. For
instance, dietary patterns including regular red meat consumption tend to favor microorganisms of the Bacteroide genus, whereas vegetarian eating patterns favor Prevotella species9. The Western diet more generally, has been demonstrated to decrease
species diversity in the gut and therefore lead to a less healthy intestinal environment6. The
Western diet is unbalanced and relatively homogeneous in composition, therefore leading to less diversity among microorganisms colonizing the gut. Other causes of lower microbial diversity are Caesarean versus vaginal delivery, formula feeding versus breast milk, misuse of antibiotic treatments, and chlorinated versus non-chlorinated water6. Clearly, dietary
fiber diets stimulate microbial diversity, whereas lower fiber diets affect the gut microbiota makeup in such a way that can lead to decreased systemic immunity4,6. Originally only
polysaccharides were included as dietary fiber, but more recent definitions have expanded to include oligosaccharides as well, based on their physiological effects16. Dietary fibers are
defined as indigestible carbohydrates and lignin that are intrinsic and intact in plants16.
Oligosaccharides are the most well known prebiotics, and stimulate Bifidobacterium, a beneficial bacterial genus of the GIT. Other fiber sources have similar effects, including polydextrose, wheat dextrin, psyllium, banana, whole grain wheat, and whole grain corn. All prebiotics are fiber, but not all fiber are prebiotics16.
Microbial imbalance is associated with various human diseases of the GIT, namely IBD, both Crohn’s disease and ulcerative colitis (UC), and inflammatory bowel syndrome (IBS). Patients with IBD have overall reduced microbial biodiversity. More specifically, IBD patients have reduced anti-inflammatory associated Faecalibacterium prausnitzii, increased sulfide generating Desulfovibrio subspecies and Fusobacterium varium that can invade epithelium, reduced Bacteriodetes, and enriched Actinobacteria and Proteobacteria9. IBS patients have altered carbohydrate and protein energy metabolism in
the gut secondary to changes in the diversity of the gut microbiota. Poor absorption of dietary carbohydrate induces prolonged intestinal hydrogen production. Fecal samples from patients with diarrhea dominated IBS show increased Lactobacillus, Veillonella, Prevotella, and Parasporo, and decreased Bifidobacteria and Verrucomicrobium9.
to dysbiosis, the host becomes predisposed to certain infections including C. difficile. This infection was estimated to cause almost half a million infections in the United States in 2011, and 29,000 died within thirty days of the initial diagnosis12. Those most at risk
include people who have other illnesses requiring prolonged antibiotic use, as well as older adults12. The toxin expression of C. difficile causes gastrointestinal complications of ranging
severity11. Symptoms include watery diarrhea of at least three bowel movements a day for
two or more days, fever, loss of appetite, nausea, and abdominal pain and tenderness12.
Treatment for recurrent C. difficile is limited. Current protocol is to discontinue other antibiotics when possible and start another antibiotic such as metronidazole, vancomycin, or fidaxomicin by mouth for a minimum of 10 days. Return of infection occurs in about twenty percent of patients; the first return of C. difficile is generally treated using the same antibiotic used for the first occurrence, whereas it is recommended to manage all future infections with vancomycin or fidaxomicin12. Nationally, it is estimated that the average
cost of treatment per infection is about $4,000 with an average hospital stay of 3.6 days13.
III. Bacteriotherapies
and colon to produce short chain fatty acids, which serve as fuel for the surrounding cells lining the intestinal tract10. Probiotics are beneficial live microorganisms that suppress
potentially harmful microbes and as a result, contribute to a healthy GIT environment6,10.
Symbiotics are a combination of prebiotics and probiotics; they are prebiotic food ingredients that ferment to short chain fatty acids in the GIT10. Antibiotics have also been
studied extensively as the primary pharmacological approach to eradicating pathogens. While antibiotics are effective in doing so, they also nonspecifically reduce overall microbial diversity. This reduction of diversity enables opportunistic bacteria to colonize the gut lumen9. In fact twenty percent of patients who are treated pharmacologically for C.
difficile infection, have a recurrence of the infection within six months of completing their prescribed antibiotic course8.
IV. Fecal Microbiota Transplant (FMS)
The third category of bacteriotherapy is a more novel approach that has gained popularity more recently, secondary to its efficiency and safety especially as compared to antibiotics. This therapy is termed fecal microbiota transplantation (FMT), but is also commonly referred to as fecal transplant or stool transplant. Fecal transplants are used to restore biodiversity when the GIT has become severely dysbiosed, such is the case of recurrent C. difficile6. In short, this procedure is used to reestablish normal microbiota by
transplanting health donor stool into the symptomatic host9. The procedure itself involves
nasoduodenal tube, colonoscopy, oral fecal capsules, or self-administered enemas8. Each
route of administration has advantages and disadvantages, as with all other procedures. Use of a nasogastric tube for fecal transplant is the least effective method, with success rates ranging from seventy-three to eighty-three percent. However, it is easier to perform and poses lower risks to the patient than the other mentioned alternatives8. When given via
colonoscopy, the colonic muscosa may be examined directly and any abnormal findings documented, stool can be infused throughout the entire length of the colon, and patients tend to be sedated and tolerate the procedure well. Success rates when performed using this method range from eighty-six to as high as one hundred percent8. The risks associated
with colonoscopy administration are the same risks associated with any colonoscopy, such as perforation, infection, bleeding, and pain, but tend to be minimal1,8.
The most common indication for FMT is recurrent C. difficile infection, but due to the prominent success and efficiency, this procedure is being tested with other gastrointestinal diseases as well. As of 2012, there had been about 450 cases worldwide where FMT was reported as a treatment strategy used for the treatment of C. difficile1. FMT works by
with a current C. difficile infection may be a candidate for this procedure1. As for
contraindications, at present there currently are none1.
Efficiency of FMT is profound. As of 2012, there had been at least twenty seven published case series that address fecal transplants, including both small case series and individual case reports; on average, FMT cure rates were found to be ninety one to ninety three percent. One study by Kelly et al in 2012 reported the results of a retrospective, multicenter follow up study of patients with recurrent C. difficile who had received fecal transplants as treatment. The study found primary cure rates of ninety one percent and a secondary cure rate of ninety-eight percent8. In a more recent paper published in 2013, the
success rate for fecal transplants in treating recurrent C. difficile was reported to be nearly ninety percent3. An additional publication during 2013 reported similar results; this
publication evaluated data of two systematic reviews consisting of 317 patients across twenty-seven case series and 124 patients across seven case series, respectively. The first systematic review highlighted a disease improvement or resolution rate of ninety-two percent, while the second found eighty-three percent5. Based on these three publications,
the efficiency of FMT in treating C. difficile is greater than 80% in all studies.
Donor selection is another key component of FMT. Generally, after the patient is educated on the donor selection criteria, the patient them self finds a donor. The donor tends to be either someone the patient is intimate with or a first-degree relative, but can also be a complete stranger. It is preferred that the donor be someone that patient is intimate with, but other donors are suitable8. Criteria for donor selection is not extensive,
potential donors are excluded if they are known to have a current or past medical history that includes HIV or hepatitis B or C, or exposure to these infections within the past year1.
Additionally, if the potential donor has engaged in high-risk sexual behavior, illicit drug use, has been recently incarcerated, or had a tattoo or body piercing within the past six months they will be disqualified as a donor1. The potential donor must meet certain
gastrointestinal criteria as well; they will generally be excluded if they currently have or have a history of IBD, IBS, chronic constipation, or chronic diarrhea1. Other syndromes that
may disqualify an individual as a stool donor include metabolic syndrome, systemic autoimmunity, atopic disease, or chronic pain syndrome1. Lastly, they must not have
received antibiotics, or other major immunosuppressive medications, within the past three months for any reason. At this point donated human stool is being used for FMT procedures, hence the importance of donor selection. However, synthetic stool for use in fecal transplants is being studied given the increasing popularity of this procedure. University of Guelph researchers created synthetic feces, named RePOOPulate, after examination of the bacterial composition of stool from healthy volunteers. Two patients were treated with the created stool substitute; both showed marked improvement after three days and remained C. difficile-free months following the procedure14. While this was a
very small test, the results were promising and have opened the door for further testing in this area.
one of three therapies: a vancomycin regimen followed by bowel irrigation and infusion of donor feces via a nasogastric tube, a standard vancomycin regimen, or a standard vacomycin regimen followed by bowel irrigation. Bowel irrigation refers to the rapid administration of large volumes of osmotically balanced polyethylene glycol electrolyte solution to flush out the gastrointestinal tract in entirety. Participants included in this study were eighteen years or older, had a life expectancy of greater than 3 months, and had a history of C. difficile infection relapse after one or more completed courses of antibiotic therapy. Of the sixteen patients in the infusion group, eighty-one percent had complete resolution of C. difficile associated diarrhea after one infusion. The remaining three patients in the infusion group underwent a second infusion with feces from a different donor, and of the three, two showed resolution2. Four of the thirteen patients who received vancomycin
alone and three of the thirteen who received vancomycin followed by bowel irrigation, had resolution of C. difficile associated diarrhea; that is thirty-one and twenty-three percent, respectively. In conclusion it was determined that infusion of donor feces was significantly more effective for the treatment of C. difficile than use of a vancomycin course alone. While the overall findings of this study were conclusively positive, there were some side effects noted. A majority of the patients in the infusion group, ninety-four percent, had diarrhea, while thirty-one percent reported cramping, thirteen percent experienced belching, and three patients had constipation. However, all symptoms resolved within three hours following the procedure2. Interestingly and unique to this particular study, fecal microbiota
diversity had noticeably increased becoming indistinguishable from that of the donor2. This
study was successful in drawing many conclusions and studying this novel procedure, but they were left with several unknowns. The amount of feces required for optimal results and the importance of varying potential routes of infusion were not addressed in this study, and therefore remain inconclusive2.
Another study completed in 2012 by Jorup-Ronstrom et al discovered similar results regarding the effectiveness of FMT7. In this study, feces samples were donated from
Scandinavian middle-aged healthy donors and administered via enema to thirty-two patients. The donors were all healthy individuals, on an ordinary Western diet, absent of hepatitis A, B, and C, HIV, and C. difficile. Each patient on the other hand had at least three previous relapses of C difficile. Twenty-two patients were cured following the initial enema. Ten patients failed to respond fully; of these ten patients, three were cured following a second infusion given via enema and four after a second transplant given by colonoscopy7.
Description of the Case
Patient RS was a sixty-nine year old Caucasian male who lived at home with his spouse and previously ran a small business, but had since retired. The patient reported he was normally very active, cycled regularly, rarely used alcohol, and did not smoke. Medicare was his payer source. He was five foot eleven inches and weighed sixty-three kilograms at the time of admission. His body mass index, calculated using these measurements, was 19.4; this value is indicative of normal weight status. However, given that he was over the age of sixty-five, his ideal body mass index is between twenty three and twenty eight, and therefore he was underweight for age. Ideal body weight for his gender and height is seventy-nine kilograms, and based on his admission weight, he was eighty percent of his ideal weight. The weight used for dosing nutrition needs for patient RS was therefore his admission weight of sixty-three kilograms. Active hospital problems for the patient included chronic diarrhea, cardiac sarcoidosis, celiac disease, hypoatremia, hypocalcemia, and recurrent C. difficile. His past medical history additionally included ventricular tachycardia, placement of an implantable cardiac defibrillator, diverticulitis, and previous occurrences of C. difficile infection. Surgically, patient RS has undergone a cardiac ablasion.
I. Review of the course of patient RS
diagnosed with diverticulitis and started on Flagyl and Bactrim antibiotics. These medications were discontinued after three days secondary to side effects, and the patient then completed a ten-day Augmentin antibiotic course. Throughout this ten-day course the patient began to have blood in his stool and diarrhea continued, so he was checked for C. difficile and was found to be positive. At this point he was started on vancomycin for two weeks. Despite pharmacological interventions, his diarrhea worsened and the patient was having up to fifteen bowel movements per day. More recent to admission, he reported avoiding food and having seven to eight bloody bowel movements a day. Over the eight weeks leading up to admission, patient RS reported a twenty-one pound weight loss.
macronutrient needs were estimated to be 1890 to 2205 calories per day, or thirty to thirty five calories per kilogram per day, seventy six to 113 grams of protein per day, or 1.2 to 1.8 grams of protein per kilogram per day, and fluid needs of about one milliliter per calorie, or per medical team. The goals set for the patient included TPN to provide greater than eighty-five percent of goal macronutrients and transition to intake by mouth as soon as medically feasible. Only one recommendation was made at this time, which was to initiate TPN based on labs once the central line was placed and confirmed. Additionally, the nutrition diagnosis of patient RS was established as altered gastrointestinal function related to physiologic causes as evidenced by nothing by mouth (NPO) status and the need for TPN.
The following day, the medical team was working with the patient regarding line placement, overall plan, blood cultures pending, and fevers that developed overnight. Patient RS was therefore still waiting for placement of a power-line to start TPN. The team additionally noted at this time that the patient would likely require home TPN for several weeks, so a tunneled line was being pursued.
no additional questions at the time of the session; it was expected that the patient would be compliant with this diet throughout the remainder of his stay and after discharge.
On day five of his hospital stay, a dual lumen powerline was placed by vascular and interventional radiology (VIR) and the tip was confirmed by X-ray; the line was then used to start TPN that night at midnight. Also that morning, the patient underwent a stool transplant in gastrointestinal procedures in attempt to cure his recurrent C. difficile infection. His daughter served as the donor. Donor stool was prepared using saline and approximately 500 mililiters of the emulsified donor stool was instilled from the cecum to sigmoid colon using colonoscopy. The patient tolerated the procedure well and the C. difficile infection was alleviated. Despite alleviation of C difficile, the patient continued to have multiple gastrointestinal problems, namely diarrhea, secondary to severe UC. While the patient’s UC complicated his stay, he was cultured for C. difficile multiple times following the fecal transplant, all of which turned up negative. Thereby, the fecal transplant procedure was found to be successful in alleviating the patient of his recurrent C. difficile infection. There has been research studying stool transplants used for the treatment of UC, in addition to C. difficile. The results indicate that FMT may reduce UC related symptoms, but the results are not as conclusive in terms of achieving clinical remission.
1491, slightly less than had been estimated. It was decided to feed at 120 percent of the REE, 1560 calories, via TPN, as the patient was eating by mouth as well. However, after two days and further discussion amongst the nutrition support team, it was decided that given the patient’s continued diarrhea and likely minimal absorption, in addition to his malnourished state, that goal calories should be advanced further. At that time and continued throughout the remainder of the patient’ stay, calorie goals were set at 1800 despite additional intake by mouth(see Appendix A).
While continuing on TPN, the patient began to work on increasing intake by mouth, following a gluten free diet. For the first few days, the patient showed signs of tolerance, with no reported nausea, vomiting, or abdominal pain. Patient RS additionally reported decreased frequency of bowel movements, although all stools remained loose. However, within the next week, the patient suffered multiple episodes of loose blood loss via rectum. A flex sigmoidoscopy completed after these episodes showed worsening colitis and correlated worsening clinical presentation. The medical team had previously mentioned a possible surgery consult regarding continued bowel concerns and unresponsiveness to steroids, but the patient preferred to avoid surgery if at all possible. Given the severity of his symptoms however, patient RS underwent an urgent colectomy with ostomy placement and tolerated the procedure well. Following the procedure, the patient remained on TPN in addition to oral intake.
Discussion
Patient RS was a complicated case. He initially presented with chronic diarrhea, which was attributed primarily to a C. difficile infection upon his admission to UNC Hospitals. This infection was likely caused by antibiotic use months previously, started by his primary care provider to treat his recently diagnosed diverticulitis. The broad-spectrum antibiotic course prescribed to patient RS is typical treatment for diverticulitis and acts to control the inflammation in the colon. Antibiotics accomplish this by reducing intestinal bacteria and suppressing the intestine’s immune system. In most patients this is effective treatment for acute diverticulitis; however, there are side effects to such an antibiotic course. One such side effect is the development of C. difficile infection. As discussed previously, C. difficile is found in the human gut, but is suppressed by various other microorganisms that cohabitate the intestinal tract. When the diversity of these microorganisms is reduced by broad-spectrum antibiotic use, the risk of developing C. difficile infection is significantly increased due to the lack of suppressive microorganisms. Therefore, this was likely the primary cause of his presenting infection.
The patient’s case was further complicated by his underlying chronic UC. Chronic diarrhea is a side effect of this condition as well. The congealed effects of the patient’s chronic UC, acute diverticulitis followed by treatment with an antibiotic course, and subsequent development of C. difficile, caused severe diarrheal effects that lasted for months. Secondary to the severity of the patient’s diarrhea, he also experienced significant associated weight loss and a resultant malnourished state.
order to treat his recurrent C. difficile infection. Despite other complicating factors to the patient’s course of stay, this procedure was successful in eliminating his infection without further use of antibiotics. His case serves to strengthen the research conducted, evidence collected, and conclusions made regarding the efficiency of fecal transplants in treating recurrent C. difficile. FMT is a beneficial alternative to more typical bacteriotherapes for this condition.
While FMT was successful in eliminating the patient’s C. difficile infection, it was not as efficient in treating his UC, which ultimately lengthened the patient’s hospital stay. There has been research regarding FMT and treatment of UC as well, but the data is not as conclusive as that for the treatment of C. difficile. Some data indicates that multiple FMT procedures may need to be completed in order to see improvement of symptoms or clinical remission, but overall there are few reports available.
Since the patient’s underlying UC was not successfully treated by FMT, the patient’s diarrheal symptoms continued. It was at this point of the patient’s stay that the medical team began discussing the potential need for surgery. The patient resisted the idea of surgery, preferring to try steroidal routes of treatment instead. When this failed to alleviate symptoms and the patient’s course of stay showed little improvement, it was then that surgery was deemed necessary and an urgent colectomy was preformed. After surgery, the patient’s status improved tremendously; he was able to tolerate sufficient intake by mouth to meet his nutritional needs without TPN and his ostomy output decreased to an adequate daily amount. Therefore, not long after his surgery he was discharged to home.
course, that ultimately lead to a C. difficile infection, was done prior to admission. One option would have been pursuing surgery earlier on in the course of stay to treat his underlying UC. However, it is understandable to pursue other treatment options before electing to perform surgery, especially for a condition that typically can be managed by other means. While this case did highlight the efficiency of FMT for the treatment of recurrent C. difficile, it is unfortunate that patient RS continued to have complicating factors that ultimately lead to necessary surgery. It may seem as if FMT was a meaningless undertaking given the ultimate outcome, but at the time that procedure was performed it was not thought that the patient would require surgery.
Conclusion
In conclusion, FMT is an effective therapy in the treatment of C. difficile infection, despite the novelty of the procedure. There are minimal adverse effects associated with the procedure and no current contraindications. Additionally, donor selection is a relatively simple and speedy process, and the results of the procedure are promising.
Patient RS served as an example to further enhance these conclusions. His course was complicated by a variety of other factors, including UC and a recent diagnosis of celiac disease, but FMT was successful in eliminating his C. difficile infection.
References
1. Brandt LJ. Fecal transplantation for the treatment of Clostridium difficile infection. Gastroenterology & Hepatology. 2012; 8(3): 191-194.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365524/pdf/GH-08-191.pdf 2. Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent
Clostridium difficile. The New England Journal of Medicine. 2013; 368(5): 407-415. DOI: 10.1056/NEJMoa1205037.
3. Kunde S, Pham A, Bonczyk S, et al. Safety, tolerability, and clinical response after fecal transplantation in children and young adults with ulcerative colitis. JPGN. 2013; 56(6): 597-601. DOI: 10.1097/MPG.0b013e318292fa0d.
4. Maslowski KM, Mackay CR. Diet, gut microbiota and immune responses. Nature
America, Inc. 2011; 12(1): 5-9. http://dx.doi.org.libproxy.lib.unc.edu/10.1038/ni0111-5 5. Angelberger S, Reinisch W, Makristathis A, et al. Temporal bacterial community
dynamics vary among ulcerative colitis patients after fecal microbiota transplantation. Am J Gastroenterol. 2013; 108: 1620-1630. doi:10.1038/ajg.2013.257.
6. Abbeele P, Verstraete W, Aidy S, et al. Prebiotics, faecal transplants and microbial network units to stimulate biodiversity of the human gut microbiome. Microbial Biotechnology. 2013; 6(4): 335-40. doi: 10.1111/1751-7915.12049.
7. Jorup-Ronstrom C, Hakanson A, Sandell S, et al. Fecal transplant against relapsing Clostridium difficile-associated diarrhea in 32 patients. Scandinavian Journal of Gastroenterology. 2012; 47(5), 548-552. DOI: 10.3109/00365521.2012.672587. 8. Boyle M, Ruth-Sahd L, Zhou Z. Fecal microbiota transplant to treat recurrent
Clostridium difficile infections. Critical Care Nurse. 2015; 35(2), 51-64. http://dx.doi.org.libproxy.lib.unc.edu/10.4037/ccn2015356.
9. Chan YK, Estaki M, Gibson DL. Clinical consequences of diet-induced dysbiosis. Annals of Nutrition & Metabolism. 2013; 63(suppl 2): 28–40.
http://dx.doi.org.libproxy.lib.unc.edu/10.1159/000354902.
10.Mahan L. Krause’s food & the nutrition care process (13th ed.). St. Louis, MO:
Elsevier/Saunders; 2012.
11.Bien J, Palagani V, Bozko P. The intestinal microbiota dysbiosis and Clostridium difficile infection: is there a relationship with inflammatory bowel disease? Therap Adv
Gastroenterol. 2013; 6(1), 53-68. doi: 10.1177/1756283X12454590.
12.Healthcare-associated infections (HAIs). Centers for Disease Control and Prevention Web Site. http://www.cdc.gov/HAI/organisms/cdiff/Cdiff_infect.html. Updated February 25, 2015. Accessed October 18, 2015.
13.Hedge DD, Strain JD, Heins JR, Farver DK. New advances in the treatment of Clostridium difficile infection (CDI). Ther Clin Risk Manag. 2008;4(5), 949-964.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2621401/pdf/tcrm-4-949.pdf 14.Petrof EO, Gloor GB, Vanner SJ, et al. Stool substitute transplant therapy for the
eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut, Microbiome. 2013;1(3): 1-12. DOI: 10.1186/2049-2618-1-3.
15.Rupnik M, Wilcox MH, Gerding DN. Clostridium difficile infection: New developments in epidemiology and pathogenesis. Nat Rev Microbiol. 2009; 7(7): 526-36.
APPENDIX
A. Patient RS—Nutrition Therapy Throughout Stay, with Labs 8/26
— 8/30
8/31 9/1 9/2 9/3 9/4 9/ 5
9/6 9/7 9/8 9/9 9/1 0 9/1 1 9/12 — 9/14
9/15 9/1 6
9/1 7
9/1 8
9/19 9/20 9/21 9/22 9/23 9/2 4— 9/2 5 LABS
Na 128 135 141 140 139 133 133 133 138 136 136 130 130 127 138 136 137 136 134 134 K 3.9 3.6 3.8 4.0 4.6 4.4 3.8 4.1 3.7 4.0 4.7 3.8 4.3 3.6 3.7 3.4 3.6 3.4 4.2 4.2 Cl 97 99 104 106 106 100 101 105 107 108 102 104 103 99 106 105 106 103 102 105 CO2 24 30 30 27 27 29 26 22 27 24 36 23 21 21 26 30 28 31 29 26
BUN 3 10 12 14 15 15 15 17 20 17 16 12 8 10 14 19 17 15 16 13
SCr 0.65 0.54 0.59 0.5 7
0.55 0.5 7 0.5 7 0.5 3 0.5 8 0.5 4 0.6 8
0.56 0.6 1
0.4 5
0.6 0
0.56 0.51 0.60 0.51 0.58
Glucose 102 205 149 141 134 143 128 101 127 143 114 69 406 98 143 120 135 88 92 127 Ca 7.4 7.2 7.5 7.5 7.5 7.1 7.1 7.1 6.7 6.8 6.9 6.5 6.0 6.8 6.8 6.6 6.6 6.5 6.9 6.7 Mg 1.7 2.1 2.1 1.8 1.7 1.6 1.9 2.0 2.0 2.1 1.8 1.9 1.6 1.6 1.8 1.6 2.0 1.6 1.8 1.8 Phos 2.3 3.2 1.8 3.1 3.2 2.8 3.4 3.3 2.6 4.3 1.8 4.5 2.1 3.2 2.6 2.3 3.5 3.2 3.2 TG 72
N O L A B S TPN
Volume 144
0 144 0 144 0 144 0 14 40 144 0 144 0 144 0 144 0 144 0 144 0 144 0 144 0 144 0 144 0 144 0 144 0 144 0 144 0
Rate 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60 60
Total
Kcals 1640 1560 1560 1800 1800 1800 1800 1800 1800 1800 1800 1800 1800 1800 1800 1800 1800 1800 1800 Amino
Acids
90 95 95 100 10 0
100 100 100 100 100 100 100 100 100 100 100 100 100 100
Dextrose 200 200 200 250 25
0 250 250 250 250 250 250 250 250 250 250 250 250 250 250
Lipds 60 50 50 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55 55
Na
Acetate 75 75 75 75 85 85 100 100 100 85 85 85 85 85
Na Cl 110 185 175 100 10
0 100 170 170 85 85 60 60 60 85 85 85 85 170 85 Phos as
Na 15 9 9 15 15 30 30 30 30 39 30 30 33 33 33 33 33 33
Acetate Phos as K
15 15 30 30 15 15 15 15 15 15 15 21 21 15 15 15 15 15 15
K Cl 40 40 40 20 60 60
Famotidi ne/ Thiamin/ Octreotid e - / 200 / - - / 200 / - - / 200 / - - / 200 / - - / 20 0 / - - / 200 / - - / 200 / - - / 200 / - - / 200 / - - / 200 / - - / 200 / - - / 200 / - - / 200 / - - / 200 / - - / 200 / - - / 200 / - - / 200 / - - / 200 / - - / 200 / - MVI/Trac
e 10 / 1 10 / 1 10 / 1 10 / - 10 / - 10 / - 10 / - 10 / 1 10 / 1 10 / 1 10 / - 10 / 1 10 / 1 10 / - 10 / - 10 / - 10 / - 10 / 1 10 / 1
Zn/Se 2.5 /
60 2. 5 / 60 2.5 / 60 2.5 / 60 2.5 / 60 2.5 / 60 2.5 / 60 2.5 / 60 2.5 / 60 DIET* CL/ NPO /GF
GF GF GF GF GF G
B. Sample of Registered Dietitian Notes for Patient RS.
08/25/15: Parenteral Nutrition Consult
Reason for Consult:
Assess and assist with TPN management
Physical Examination:
Height: 180.3 cm (5' 11") BMI: 19.4 Admit Weight: 63.1 kg Ideal Body Weight 78.74 kg Current Weight: 63.05 kg (139 lb) Percentage Ideal
Body Weight
80%
Dosing Weight: 63 kg Adjusted Body Weight
N/A
Weight history:
Wt Readings from Last 3 Encounters: 08/26/15 63.05 kg (139 lb)
08/25/15 63.2 kg (139 lb 5.3 oz)
Labs:
BMP - Results in Past 2 Days
Result Component Current Result
BUN/FP 5 (L) (8/26/2015)
Chloride 99 (8/26/2015)
CO2 23 (8/26/2015)
Creatinine Whole Blood, POC
0.92 (8/26/2015)
EST.GFR (MDRD) Not in Time Range
Glucose 68 (8/26/2015)
Potassium/FP 4.4 (8/26/2015) Sodium Serum 134 (L)
(8/26/2015)
ASPEN Guidelines for Start of TPN:
Evidence of protein-calorie malnutrition upon admission Anticipated duration of PN of at least 5-7 days
Documented inability to utilize the GI tract
Parenteral Access:
Placement Date: Placed by:
PICC ordered, not yet placed
69 yo male with persistent diarrhea x 8 weeks following multiple antibiotic courses and treatment for cdiff now with bloody stools, poor PO and continued diarrhea x 5/day or more within 30 min of eating food. S/p UGI and Colonoscopy today with inflammation diverticulitis IBD vs cdiff being worked up as well as Bx from samples taken during procedures today.
Current nutrition therapy order:
Nutrition Orders
Nutrition Therapy Clear Liquid starting at 08/26 1520
Nutrition Assessment:
Pt currently unable to meet needs via clear liquids and has not met nutritional needs for months. Has lost weight over the past few months from ~75kg to 63.1 kg which is 15% of his total body weight, which is significant.
ASPEN/Malnutrition Screening:
Pt meets criteria for moderate malnutrition d/t weight loss and poor po intake for over a week.
Estimated Macro-Nutrient Needs: (dosing weight = 63) Estimated Energy Needs:
1890-2205 kcals/dau (30-35/kg) Estimated Protein Needs:
76-113g protein/day (1.2-1.8g/kg) Estimated Fluid Needs:
Per team, ~1mL/kcal Nutrition Goals:
Provide > 85% of goal macronutrients via TPN Transition to po as soon as medically feasible
Action/Recommendations:
Will initiate TPN based on labs once line is placed and confirmed.
Recommended TPN Formula:
Recent TPN Orders (Show up to 1 orders ; newest on the right.) None
Nutrition Diagnosis:
Altered GI function as related to physiologic causes-being worked up as evidenced by NPO status and need for TPN.
Risk Protocols:
Nutrition Support/Adult TPN Service Protocol
8/31/15: Parenteral Nutrition Follow-Up
Labs:
BMP -
Results in Past 2 Days
Result Component Current Result BUN/FP 3 (L) (8/31/2015) Chloride 97 (L) (8/31/2015)
CO2 24 (8/31/2015)
Creatinine Whole Blood, POC
0.65 (L) (8/31/2015) EST.GFR (MDRD) Not in Time
Range
Glucose 102 (8/31/2015)
Potassium/FP 3.9 (8/31/2015) Sodium Serum 128 (L)
(8/31/2015)
Lab Results
Component Value Date
CALCIUM 7.4* 08/31/2015
PHOS 2.3* 08/31/2015
Recent Labs
Lab Units 08/31/15 0354 MAGNESIUM mg/dL 1.7
Nutrition Progress:
8/31: Dual lumen powerline placed this AM via VIR; TPN to start at midnight. No IVF currently running; current order for IVF has expired. Pt now s/p stool transplant in GI procedures this morning.
8/27: Pt has not yet started on TPN. Consulted again, d/w team this morning regarding line, plan, blood cultures pending, and fevers over night. Awaiting placement of powerline for TPN initiation. Team feels pt may need home TPN for several weeks, thus a tunneled line is being pursued.
Nutrition History:
69 yo male with persistent diarrhea x 8 weeks following multiple antibiotic courses and treatment for cdiff now with bloody stools, poor PO and continued diarrhea x 5/day or more within 30 min of eating food. S/p UGI and Colonoscopy today with inflammation diverticulitis IBD vs cdiff being worked up as well as Bx from samples taken during procedures today.
Current nutrition therapy order: Nutrition Orders
Adult 3-in-1 TPN at 60 mL/hr starting at 09/01 0000
Nutrition Goals:
Provide > 85% of goal macronutrients via TPN Transition to po as soon as medically feasible
Action/Recommendations: Initiate TPN
Monitor for refeeding syndrome-replete electrolytes as indicated Will order MET cart
Recommended TPN Formula:
Recent TPN Orders (Show up to 1 orders ; newest on the right.)
Start date and time 09/01/2015 0000
Adult 3-in-1 TPN
[1185365696]
Order Status Active
Macro Ingredients
amino acid (CLINISOL) 15% 90 g
dextrose 200 g
Electrolytes
sodium acetate 75 mEq
sodium chloride 110 mEq
sodium phosphate 15 mmol
potassium phosphate 15 mmol
Additives
mvi, adult no.4 with vit K 3,300 unit- 150 mcg/10 mL
10 mL
trace elements-5 (CONCENTRATED) Cr-Cu-Mn-Se-Zn
1 mL
Medications
thiamine 200 mg
QS Base
sterile water 166.29 mL
Lipids
fat emulsion 20 % 60 g
Calorie Contribution
Proteins 360 kcal
Dextrose 680 kcal
Lipids 600 kcal
Total 1,640 kcal
Electrolyte Ion Calculated Amount
Sodium 205 mEq
Magnesium --
Aluminum --
Phosphate 30 mmol
Chloride 110 mEq
Acetate 75 mEq
Other
Total Protein 90 g
Total Protein/kg 1.47 g/kg
Glucose Infusion Rate 2.27 mg/kg/min
Osmolarity 1,662.64
Volume 1,440 mL
Rate 60 mL/hr
Dosing Weight 61.2 kg
Infusion Site Central
Admin Instructions
--
Nutrition Diagnosis:
Altered GI function as related to physciologic causes as evidenced by NPO status and need for TPN.
Risk Protocols:
Nutrition Support/Adult TPN Service Protocol
9/11/15: Parenteral Nutrition Follow Up—Sign Off
Reason for Follow-Up: Sign off from Adult TPN Service
Nutrition Progress:
Patient on TPN from 9/1 to 9/10.
9/11/15: Pt transferred to MICU this AM secondary to bright red blood stool, lightheadedness, and hypotension. Per MD, will continue as planned with gluten free diet and d/c of TPN; pt did receive TPN until midnight last night and has been NPO today for scheduled sigmoidoscopy.
Current nutrition therapy order: NPO currently for procedure; plan to resume pt on gluten free PO diet s/p procedure.
Current Diet order: Nutrition Orders
NPO Sips with meds; Procedure/Test starting at 09/11 0001
time.
Dietitian Action/Recommendations:
Recommend continue current nutrition therapy
Recommend provide nutritional supplements per pt preference, when diet advanced from NPO Sign off to service RD to monitor at high nutrition risk
Risk Protocols:
Acute High Risk / Level III
9/15/15: Parenteral Nutrition Consult
Reason for Consult:
Assess and assist with TPN management
Physical Examination:
Height: 180.3 cm (5' 11") BMI: 19.5 Admit Weight: 63.1 kg Ideal Body Weight 78.74 kg Current Weight: 63.504 kg (140 lb) Percentage Ideal
Body Weight
80%
Dosing Weight: 63 kg Adjusted Body Weight
n/a
Weight history:
Wt Readings from Last 3 Encounters: 09/14/15 63.504 kg (140 lb)
08/25/15 63.2 kg (139 lb 5.3 oz)
Labs: BMP -
Results in Past 2 Days
Result Component Current Result
BUN/FP 12 (9/15/2015)
Chloride 104 (9/15/2015)
CO2 23 (9/15/2015)
Creatinine Whole Blood, POC
0.56 (L) (9/15/2015) EST.GFR (MDRD) Not in Time
Range
Glucose 69 (9/15/2015)
Potassium/FP 3.8 (9/15/2015) Sodium Serum 130 (L)
(9/15/2015)
Lab Results
Component Value Date
CALCIUM 6.5* 09/15/2015
Recent Labs
Lab Units 09/15/15 1137 MAGNESIUM mg/dL 1.9
ASPEN Guidelines for Start of TPN:
Evidence of protein-calorie malnutrition upon admission Anticipated duration of PN of at least 5-7 days
Documented inability to utilize the GI tract
Parenteral Access: Replacement Date: 9/15 Placed by: VIR
Internal Jugular Powerline Tunneled Double lumen
Tip located in the proximal Right atrium
Nutrition Assessment:
9/15/15: Pt transferred from MICU to MDU service overnight; upon visit pt having rapid response and returning to MICU. Per MD note, sigmoidoscopy findings from procedure 9/11 indicate worsening of his colitis with severe edema and friability; GI recommend colectomy over remicade given severity of colitis and anticipated poor response to medication. Pt currently seeking second opinions from GI contacts at Brigham and Women's. Pt associates severe malnutrition to poor eating opportunities with procedures and had been declining replacement of power line for TPN yesterday. However, Op note this AM indicate pt is undergoing tunneled central venous dual lumen powerline exchange to restart TPN.
9/11/15: Pt transferred to MICU this AM secondary to bright red blood stool, lightheadedness, and hypotension. Per MD, will continue as planned with gluten free diet and d/c of TPN; pt did receive TPN until midnight last night and has been NPO today for scheduled sigmoidoscopy.
Pt on TPN 9/1 to 9/10; discontinued secondary to adequate gluten free PO intake.
Nutrition History:
69 yo male with persistent diarrhea x 8 weeks following multiple antibiotic courses and treatment for cdiff now with bloody stools, poor PO and continued diarrhea x 5/day or more within 30 min of eating food. S/p UGI and Colonoscopy today with inflammation diverticulitis IBD vs cdiff being worked up as well as Bx from samples taken during procedures today.
Current nutrition therapy order: Nutrition Orders
Adult 3-in-1 TPN at 60 mL/hr starting at 09/16 0000
Estimated Macro-Nutrient Needs: (dosing weight = 63 kg) Estimated Energy Needs: 1890 - 2205 kcal (25-30 kcal/kg) Estimated Protein Needs: 76 - 113 gm (1.2-1.8 gm/kg) Estimated Fluid Needs: per MD
MET cart completed 9/1: RQ 0.79, MEE 1491 x 120% = 1789 kcal
Nutrition Goals:
Provide > 85% of goal macronutrients via TPN Transition to po as soon as medically feasible
Action/Recommendations: Replete potassium
Replete phosphorus
Recommended TPN Formula:
Recent TPN Orders (Show up to 1 orders ; newest on the right.)
Start date and time 09/16/2015 0000
Adult 3-in-1 TPN
[1187687415]
Order Status Active
Macro Ingredients
amino acid (CLINISOL) 15% 100 g
dextrose 250 g
Electrolytes
sodium acetate 100 mEq
sodium chloride 60 mEq
sodium phosphate 30 mmol
potassium phosphate 21 mmol
Additives
mvi, adult no.4 with vit K 3,300 unit- 150 mcg/10 mL
10 mL
trace elements-5 (CONCENTRATED) Cr-Cu-Mn-Se-Zn
1 mL
Medications
thiamine 200 mg
QS Base
sterile water 46.19 mL
Lipids
fat emulsion 20 % 55 g
Calorie Contribution
Proteins 400 kcal
Total 1,800 kcal
Electrolyte Ion Calculated Amount
Sodium 200 mEq
Potassium 30.8 mEq
Calcium --
Magnesium --
Aluminum --
Phosphate 51 mmol
Chloride 60 mEq
Acetate 100 mEq
Other
Total Protein 100 g
Total Protein/kg 1.57 g/kg
Glucose Infusion Rate 2.73 mg/kg/min
Osmolarity 1,908.65
Volume 1,440 mL
Rate 60 mL/hr
Dosing Weight 63.5 kg
Infusion Site Central
Admin Instructions
--
Nutrition Diagnosis:
Altered GI function as related to physciological causes as evidenced by NPO status and need for TPN.
Risk Protocols:
Nutrition Support/Adult TPN Service Protocol
9/23/15: Parenteral Nutrition Follow-Up—Sign Off
Reason for Follow-Up: Sign off from Adult TPN Service
Nutrition Progress:
Patient on TPN from 9/16 to 9/23.
9/23: Per MD progress note, 2/2 increasing leukocytosis, d/c central line and therefore TPN to r/o infection. Pt eating well per pt and RN; calorie count not indicative of meeting estimated needs, but PO intake is improving. Ostomy output 500 mL yesterday and 100 mL today.
Current nutrition therapy order: Regular diet.
Nutrition Therapy General (Regular) starting at 09/18 1327
Assessment:
Current Medical Nutrition Therapy is appropriate although not meeting nutrient needs at this time. PO intake is improving; likely not meeting needs at this time.
Dietitian Action/Recommendations:
Recommend continue current nutrition therapy
Recommend nutritional supplements per pt preference. Sign off to service RD to monitor at high nutrition risk
Risk Protocols:
C. Weight Trend Throughout Stay
61 62 63 64 65 66 67
21-Aug 26-Aug 31-Aug 5-Sep 10-Sep 15-Sep 20-Sep 25-Sep
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