Running head: PROBIOTIC THERAPY TO PREVENT C. DIFF 1[Type text][Type text][Type text]

PROBIOTIC THERAPY TO PREVENT C. DIFF 2

Probiotic Therapy to Reduce the Occurrence of C. diff Associated DiarrheaPICO Paper AssignmentShannon M. MurphyNURS 612 Medical Surgical NursingUniversity of New Hampshire

AbstractClostridium difficile associated diarrhea is an all too common complication of antibiotic therapy that can cause prolonged hospitalization, life-threatening symptoms, and if untreated or serious enough it can lead to death. It is thought that if patients who are receiving antibiotics prophylactically use probiotics such as Lactobacillus will be at a decreased risk of developing a C. difficile infection. In this paper I will explore three studies that examine the use of prophylactic Lactobacillus probiotic therapy with adults patients receiving antibiotics.Keywords: Clostridium difficile, C. diff, probiotic, Lactobacillus, antibiotic

In adult patients being treated with antibiotics, how does the prophylactic use of Lactobacillus probiotic therapy compare to the lack of probiotic therapy in preventing the development of Clostridium difficile associated diarrhea.

Every day patients are prescribed antibiotics to treat various infections and unfortunately diarrhea is a common side effect of the treatment. In most cases, the diarrhea is self-limiting but in others a more serious infection might be to blame. When a patient receives an antibiotic the goal is to kill a certain bacteria that is present in the body, however occasionally the antibiotic can eradicate more than the culprit bacteria that it was intended for such as those in the human intestines. When the normal and healthy bacteria in the intestines are killed, more room is made for dangerous bacteria to multiply. Naturally found in soil, Clostridium difficile is a spore forming bacteria that is sometimes found in the intestines of a healthy person who has come into contact with it. The bacteria commonly referred to as C. diff is generally transmitted through a fecal oral route, however because it is spore forming the bacteria can live on objects for months and it can lay dormant in the intestines of a person for a lifetime. In instances where a patient takes an antibiotic that wipes out all the healthy bacteria, or normal flora, then the C. diff will begin to multiply and take over the intestine. As it begins to take over, the bacteria release toxins that cause irritation to the intestines that can cause diarrhea and in extreme cases, a perforated bowel (Walters & Zuckerbraun, 2014). In a recent study, Walters and Zuckerbraun (2014) estimate that C. diff infections occur in 500,000 patients treated with antibiotics annually with a 9% mortality rate among the cases. At this point in time, the patients are treated with a new antibiotic, generally Flagyl or Vancomycin and although the efforts are usually successful, C. diff infections are notoriously resistant and often require long hospital stays and costly interventions. In an effort to prevent the development of a C. diff infection from taking place, prophylaxis probiotic therapy has been incorporated into to treatment for many patients who are set to begin treatment with antibiotics. Probiotics are living microscopic organisms such as bacteria and yeast that are either the same as or very similar to the normal flora found in the intestines. Probiotic treatment can be administered in the form of pills or a drink and generally contains actual or replicated Lactobacillus, a bacteria that is populated in the human intestine through the breakdown of dairy products. Although its actually benefits on the digestive system are not known, it is thought to aid in food digestion and prevent other bacteria such as C. diff from becoming over populated. Probiotic therapy is generally started when the patient begins antibiotic therapy and is continued past the stop date of the antibiotic regime in an effort to replace any of the normal flora that the antibiotics might inadvertently kill through the treatment thus preventing space for C. diff to take over (Probiotics, 2008). With this new prophylactic intervention being used, one must then question its effectiveness. Through a review of the literature published I will evaluate whether or not the use of prophylactic lactobacillus based probiotics lessen the occurrence of Clostridium difficile associated diarrhea in adult patients being treated with antibiotics compared to those who are not receiving probiotics. In order to obtain the articles that I referenced in this paper, I utilized EBSCOhosts advanced search feature. This tool allowed me to search through many databases provided by the library at the University of New Hampshire including CINHAL, MEDLINE, PubMed, and the Cochrane Database of Systematic Reviews. In order to generate my search I used keywords Clostridium difficile, C. diff, C. difficile, probiotics, Lactobacillus, and treatment. Originally my search yielded 182 articles so in an effort to find more specific sources I limited my search to only include articles published between 2005 and 2015, those that were written in English, as well as only ones that included a full text or included a link to one. With the new limitations set only 37 articles remained. At this point I further limited the sources by excluding those that concentrated on pediatric patients, cancer patients or neonates and those that studied probiotics that did not contain Lactobacillus. At the end of my search I was left with three articles that met the qualifications for inclusion. In the first article, researchers Ziakas and Mylonaks (2014) performed a randomized, double blind, placebo controlled trial study using 2,981 patients in five different UK hospitals. Their study included only patients who were over 65 and received antibiotics in the last 7 days or were about to start treatment. Patients who had experienced diarrhea in the past 24 hours, had been treated for a C. diff infection in the past 3 months, were immunocompromised, or had previous adverse reactions to probiotics were excluded from the study. Participating patients were randomly divided into two groups and given either one probiotic capsule containing Lactobacilus acidophilus or a placebo pill once a day for 21 days. The patients were all followed for 12 weeks after their completion of the probiotic therapy. At the conclusion of the study the results stated that the in the group receiving the probiotic 0.8% of the patients developed a C. diff infection compared to 1.2% of the patients in the placebo group. The results conclude that the probiotics did not produce a significant decrease in the occurrence of C. difficile associated diarrhea. Although this study did contain a relatively large sample size, there are many issues to consider when evaluating its execution. Because this study includes patients who have started antibiotic therapy within the past seven days, there is the possibility for a large gap between the start of antibiotic therapy and the probiotic therapy. It could be argued that the development of C. diff in the patients receiving the probiotics could be a result of therapy being initiated too late. Another consideration is the fact that the study took place in five different hospitals. This could potentially lead to discrepancies in the way that the administration of the probiotic is carried out and the risks that the patients may have been at. It is hard to say whether or not one hospital had more exposure to the C. difficile bacteria and a difference in exposure between hospitals could alter the results. Another factor to consider with this study is the rigid length of time that the probiotic is given for. All the patients receive the probiotic for 21 days regardless of how long they are on antibiotic therapy. This can present as both good and bad. In some ways, the regimented time frame allows for a greater sense of unison between the patient treatments. On the other hand, it can also present as a problem because if a patient receives antibiotics for a longer period of time such as 14 days, they will receive less probiotic treatment after the antibiotic therapy is over than the patient who only receives seven days of antibiotics. In a second study performed by Gao, Mubasher, Fang, Reifer, and Miller (2010) the effects of a Lactobacillus probiotic is again examined with respect to the development of a C. diff infection. A randomized double blind placebo controlled trial was used and 255 patients in one hospital were involved. In order to be included in the study the patients must have started antibiotic therapy within the last 36 hours and had to have been free of diarrhea for the past 48 hours. Patients with a history of a C. diff infection were excluded as well as those who were immunocompromised, had a disease that affected the bowel, or those who were NPO. This study also compared the doses of probiotics so therefore the participants were broken up into three groups. The first group received two probiotic pills, the second received one probiotic pill and one placebo pill, and the third received two placebo pills. The pills were continued 5 days after therapy ended and the patients were followed for 21 days after completion. The results of the study reported that the patients who received two probiotic pills had a 1.2% occurrence of C. diff associated diarrhea, the group that received one pill had a 9.4% occurrence, and the group that received two placebo pills had a 23.8% occurrence. As a result, the study supports that the probiotic pills, regardless of the dosing, did cause a decreased incidence of C. diff associated diarrhea.In this particular study, the experiment was performed all within one hospital. This allowed for a more controlled environment of all the participants because they were all exposed to the same factors in the same facility. In contrast to the previous study, the probiotic treatment was initiated within 36 hours of the antibiotic treatment thus narrowing the gap between the two and lessening the risk of developing the infection before the probiotic therapy is initiated. The placebo pills were also continued for five days after the end of the antibiotic therapy regardless of the length of time that the antibiotics were administered for unlike the Ziakas and Mylonaks (2014) study. Again, this can present itself as a good or a bad aspect. Positively, all the patients receive the same amount of probiotic therapy after the conclusion of their antibiotic therapy, however if one patient receives 14 days of antibiotics he or she will receive more probiotic therapy overall than a patient that receives seven days of antibiotics. In a final study performed by Hickson et al. (2007) a randomized, double blind, placebo controlled trial was carried out. The study involved 135 patients in three London hospitals who were all over the age of 50 and started receiving antibiotics within the past 48 hours. Patients who were immunocompromised, had recently undergone bowel surgery, had artificial heart valves, had a history of rheumatic heart disease or infective endocarditis, had used probiotics prior to admission, had received two or more antibiotics in the past four weeks, were NPO, had any sign of diarrhea on admission, had a history of of reoccurring diarrhea, had a bowel pathology, or were sensitive to lactose or dairy were excluded from the study. The participating patients were randomly divided into two groups and given either 100g of a Lactobacillus probiotic drink or a sterile milkshake containing no probiotics twice a day 30 minutes before meals or 1-2 hours after meals. The drinks were all discontinued one week after completion. At the end of the study the results reported that 0% of the patients who received the probiotic drink developed C. diff associated diarrhea compared to 12% of those who received the placebo sterile milkshake thus producing significant results. In this study, the sample size was slightly smaller than the others, however it the exclusion factors included were very thorough and eliminated any patients that could have presented with outlying results. Similar to the Ziakas and Mylonaks (2014) study, the trials performed by Hickson et al. (2007) also took place in three different hospitals, which could cause discrepancies in the delivery of the drinks as well as presented the participants with different environmental risks. This study also continued the probiotic a set number of days after completion of the antibiotic therapy as opposed to a set number of days overall which might have created varying treatment times but it also allowed for a consistent treatment time after discontinuation of antibiotics between patients. A window of 48 hours after antibiotic therapy initiation for the start of the probiotics reduces the chance of development of a C. diff infection before the probiotics have been started just like in the Gao, Mubasher, Fang, Reifer, and Miller (2010) study, which reflects positively on the results, presented. After evaluating the three studies presented in this paper, I can conclude that probiotics do seem to be linked to a decreased occurrence of C. difficile associated diarrhea in adult patients being treated with antibiotics. Although the Ziakas and Mylonaks (2014) states that their results showed insignificant results, I would argue that this study is somewhat questionable because of the large window of time they allowed to occur between the start of the antibiotic therapy and the probiotic therapy. Walters and Zuckerbraun (2014) declare that the majority of C. difficile infections occur within the first week of antibiotic treatment, and therefore starting prophylactic treatment up to seven days after the antibiotics are started puts the patient at risk for developing the infection before the probiotics can be started. I feel that the statistically significant results obtained from the Hickson et al. (2007) and the Gao, Mubasher, Fang, Reifer, and Miller (2010) studies are more relevant because the start of probiotic therapy was more consistent and within a closer proximity to the start of antibiotic therapy thus creating more reliable results. With the results of the two more reliable study supporting the use of Lactobacillus probiotic therapy to decrease the occurrence of C. difficile associated diarrhea in adults receiving antibiotic therapy I would suggest that probiotics be initiated into the care plan of all patients receiving antibiotic therapy. McGlone et al. (2014) estimate that treating one patient with C. diff associated diarrhea costs the hospital around $9,179-$11,456 adding up to an annual cost of over $496 million. This cost is monumental and when compared to the cost of treating patients prophylactically with Lactobacillus antibiotics is obscene. Hickson et al. (2007) claim that prophylactic treatment with a probiotic drink costs about $120. The comparison between $120 and $11,456 creates an obvious need for change and a movement towards proactive treatment strategies. That being said, with Walters and Zuckerbraun (2014) claiming that on average C. diff causes 45,000 deaths a year it is obvious that changes need to be made in order to battle this notoriously difficult bacteria. Moving forward, I feel that there is a need for more studies that examine possible negative effects of probiotic therapy in patients receiving antibiotics. I feel that if negative effects can be ruled out, probiotic therapy should be seriously considered for high-risk patients regardless of whether or not all studies display significant results supporting the use. I also think that more studies that examine the doses and therapeutic range of probiotics as well as the best probiotics to use would be beneficial. References CitedGao, X. W., Mubasher, M., Fang, C. Y., Reifer, C., & Miller, L. E. (2010). Dose response efficacy of a proprietary probiotic Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic associated diarrhea and clostridium difficile-associated diarrhea prophylaxis in adult patients. American Journal of Gastroenterology, 105(7). doi:10.1038/adg.2010.11Hickson, M., DSouza, A. L., Muthu, N., Rogers, T. R., Want, S., Rajkumar, C., & Bulpitt, C. (2007). Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: Randomised double blind placebo controlled trial. BBJ, 335(80).McGlone, S. M., Bailey, R. R., Zimmer, S. M., Popovich, M. J., Tian, Y., Ufberg, P., Muder, R. R., & Lee, B. Y. (2012). The economic burden of clostridium difficile. Clinical Microbiology and Infection, 18(3), 282-289.Probiotics: What they are and what they can do for you. (2008). American Gastroenterological Association. Retrieved from: www.gastro.org/patient-center/diet-medications/probioticsWalters, P. R., & Zuckerbraun, B. S. (2014). Clostridium difficile infection: Clinical challenges and management strategies. Critical Care Nursing, 34(4), 24-35. Ziakas, P. D., & Mylonakis, E. (2014). Probiotics did not prevent antibiotic associated or C. difficile diarrhea in hospitalized older patients. Annals of International Medicine, 160(12).