1. Clostridium difficile Prevention and Treatment Katrina Beining & Christina Gardner Introduction Clostridium difficile (C. diff) is a gram-positive, spore-forming bacteria that causes infectious diarrhea due to the use of antibiotics. This intake of antibiotics causes a dysbiosis in the gut microbiota 1. Diarrhea occurs as a result and is known as Clostridium difficile- Associated Diarrhea (CDAD). The incidence of this disease can result in increased mortality, prolonged hospital stays, and increased health care costs 1. Symptoms include watery diarrhea (10-12 times/day), abdominal pain, loss of appetite, fever, blood in stool, and weight loss. This is contracted mostly in hospitals and long-term care facilities. About 10-15% of hospitalized patients on antibiotics contract this disease, targeting more of the elderly population 1. It’s estimated 80% of deaths from this bacteria occur in hospitals 1. C. diff is contagious and can be prevented with correct hand washing techniques. C. diff research has supported taking probiotics during and after antibiotic treatments and undergoing fecal transplants to prevent and treat. Lactobacillus sp. Probiotic Research Lactobacillus GG – survives digestive environment of gastrointestinal tract 2 o Works well when combined with other probiotics o Most safe probiotic to consume for human GI tract 2 o In four children, 100% were cured within 5-7 days of treatment 2 Lactobacillus acidophilus and casei – combined in all studies for significant effect o L. acidophilus and casei occur naturally in GI tract of humans o 2013 study showed 3.2% recurrence rate with L. casei vs. 20% in non-probiotic group 3 o 2007 study showed with 44 patients with probiotic, only 2.3% positive for C. diff with dose of 5.0x10 9 4 colony forming units vs. 45 in placebo at 15.9% positive o 2010 – Duration of diarrhea was 32% shorter in group with higher dosage of probiotics(100 billion c.f.u.) 5 o Consumption of 100g drink with Lactobacillus casei, Lactobacillus bulgaricus, and Streptococcus thermophilus for a week after antibiotic consumption decreased risk by 22% 6 Fecal Transplant Research Imbalance of microbes in gut causes disease and inflammation 8 Fecal transplantation might be a way to artificially create a gut microbiome that is more favorable Stool from a healthy donor is screened for pathogens before transplantation Transplant usually done via colonoscopy, enema, or enteral tube Fecal Transplantation for the treatment of C. diff: - 90.7% of C. diff patients cured with fecal transplant in 2014 Meta-analysis: 1 control trial in meta-analysis, but successful with 43 patients 9 - 2012 study found 92% effective in fecal transplant in C. diff patients after one treatment 10 - 89% cure rate of C. diff in 2014 study on immuno- compromised population 11 -2013 study shows that fecal microbiota continued to change for >16 weeks after fecal transplantation 12 Also shows promise in patients with Inflammatory Bowel Disease, including Ulcerative Colitis 12 In May of 2012, FDA announced that human feces is a drug requiring physicians to fill out IND forms 13 - Many people believed this delayed treatment for those who needed it, so the FDA retracted the law 13 Currently, no laws or restrictions for human feces but increasing need demands a decision to be made 13 Summary Human intestine is most important part of immune system Imbalance of GI bacteria causes disease and inflammation 8 Hand washing as a preventative measure is most important when dealing with C. diff Lactobacillus sp. and Saccharomyces boulardii most effective probiotics to keep from formation of C. diff associated diarrhea 2,3,4,5,6,7 Combination of different probiotic species may increase efficacy and reduce reoccurrence of bacteria Fecal transplants shown to be effective in most cases of C. diff 9,10,11,12 Research also suggests fecal transplantation for IBD 13 Lack of control studies and studies with children in fecal transplant research 9 Practical Applications Education on preventing spread of C. diff to health care employees and public Dietitians order probiotics in diet when patients taking antibiotics in hospitals. Have probiotics on hand in hospital kitchen Call for more research involving control studies, children, and long-term effects of fecal transplantation Human stool banks possibly in the near future 13 New regulations on fecal transplants o No rules in place thus far 13 Saccharomyces boulardii Research Resistant to low pH of stomach Data show production of proteases that inhibits effects of C. diff toxins A and B -Double blind study: placebo had 9.0% of patients develop diarrhea and 1.4% with probiotic group 7 Authors, Year Study Type # of cases S. boulardii duration therapy S. boulardii Placebop Adam et al. 1977 DBPC3887 days4.5%17.5%<0.001 Surawichz et al. 1989 DBPC18028 days9.5%22.0%<0.05 McFarland et al. 1995 DBPC19328 days7.2%14.6%<0.05 DBPC – double-blind placebo-controlled Table 4. Studies of effectiveness of S. boulardii in the prevention of AAD 7