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C. Difficile & Probiotics, May 2010 Formatted & Edited


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Probiotics for the Control of Clostridium difficile

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C. Difficile & Probiotics, May 2010 Formatted & Edited

  1. 1. Advancing Your Products with Proven Science NMR News: Volume 3, Issue 5, May 2010 Probiotics for the Control of Clostridium difficile By: Charles Spielholz, Ph.D. Abstract: Clostridium difficile is a bacterium that can cause serious infections of the human intestine. Resistant to many commonly used antibiotics, C. difficile is transferred from patient- to-patient by an oral-fecal route. Infection of susceptible people by C. difficile is on the rise in hospitals, nursing homes, and long-term care facilities. C. difficile gains a foothold in the intestine while patients are treated with antibiotics that kill both pathogenic bacteria and the natural population of harmless bacteria residing in the intestines. Preliminary clinical trials indicate probiotics may help prevent C. difficile infections in hospitals and similar settings. However, additional clinical trials are required in order to establish treatment protocols. Clostridium difficile is a gram positive, difficile infection can also cause a more serious spore forming anaerobic bacillus that causes condition, pseudomembranous colitis, a life intestinal disease in humans. The bacteria attain threatening inflammation of the colon (large a foothold in the human intestinal tract when intestine). C. difficile is responsible for populations of bacteria that are part of the approximately 25% of the AAD cases in the normal flora and fauna of the digestive tract are United States. It is also responsible for at least compromised by factors such as antibiotic use. half of all the cases of antibiotic-associated C. difficile infection is a significant cause of colitis and probably all of the cases of antibiotic-associated diarrhea (AAD). C. pseudomembranous colitis (1, 2). The incidence 1
  2. 2. Advancing Your Products with Proven Science NMR News: Volume 3, Issue 5, May 2010 of C. difficile infections has been increasing vancomycin). Such an approach greatly dramatically over the past decade (2, 3). Up to attenuates the population of C. difficile and stops 20% of individuals with C. difficile infections the infection. However this approach does not die because of the infection (4). The bacteria are replace the natural population of microbiota that generally transferred by an oral-fecal route. populated the digestive tract before antibiotic treatment. Lack of natural populations of native In addition to antibiotic use, risk factors microbiota appears to play a role in making an for intestinal infections by C. difficile include individual susceptible to recurrence of C. aging, hospitalizations, surgery, and stays in difficile infections (5). Therefore, proposals to long-term care facilities. Diabetics and those add microbiota back to the digestive tract have taking medications to suppress the immune been put forward and have been tested in system are also at increased risk for C. difficile preliminary clinical trials. In addition, there are infections. Elderly people, who are at increased reports of C. difficile resistance to metronidazole risk for surgery, diabetes, injury, infections and and vancomycin. Such reports strongly indicate a who are more likely to receive antibiotic need to develop additional approaches to treating treatment and to live in long-term care facilities, this infection. are particularly prone to C. difficile infection, AAD and pseudomembranous colitis. One approach to adding microbiota back to the digestive tract is to simply ingest Standard treatment of C. difficile probiotics. Probiotics are live microorganisms generally involves replacement of the antibiotics that, when fed to a host organism, confer a health in use with antibiotics that have activity against benefit. Probiotics generally consist of yeast C. difficile (the antibiotics in most common use and/or bacteria and can be administered through for this purpose are metronidzole and a functional food. Probiotics can also be 2
  3. 3. Advancing Your Products with Proven Science NMR News: Volume 3, Issue 5, May 2010 administered in the form of supplements or tested for their potential in the prevention and suppositories. Foods like yogurt are well known treatment of C. difficile infections (6, 7). For sources of probiotics. It is always critical that probiotics composed of bacterial species, a small the specific species and strain of probiotic be number of reports indicate that probiotics are matched to the desired effect or condition. The potentially useful in decreasing the potential for best species and strains of probiotics for specific acquiring a C. difficile infection while confined conditions can only be determined through well in a hospital or similar institution. Patients designed clinical trials. admitted to a hospital free of C. difficile infection and receiving combinations of bacterial The literature contains a variety of probiotics (Lactobacillus and Bifidobacterium) reports regarding treatment of C. difficile in a double-blind, placebo-controlled clinical infections with probiotics. Generally, the reports trial were less likely to test positive for C. show that treatment of C. difficile infections with difficile toxins then control patients receiving probiotics can be useful. However, a clear, well placebo (8). This observation indicated that defined protocol for using probiotics to treat C. administration of bacterial based probiotics could difficile has not yet been established. A brief be useful in preventing patients from developing review of some of the reports in the medical C. difficile infections in settings like hospitals or literature will provide a basic understanding of long-term care facilities. Unfortunately, the the current status of use of probiotics for C. results of this study were compromised by the difficile infection. low number of patients enrolled. An Bacterial strains from the genus observational pilot study produced data that Lactobacillus and Bifidobacterium and a yeast supported this conclusion (9); however that study strain from the genus Saccharomyces have been was of limited value for generating strong 3
  4. 4. Advancing Your Products with Proven Science NMR News: Volume 3, Issue 5, May 2010 conclusions because it did not include a placebo Use of Saccharomyces species and control group. Another double-blind, placebo- strains as a probiotic for the prevention of C. controlled clinical trial using an additional difficile infection has also been explored. In a bacterial strain from the genus Steptococcus randomized clinical trial, patients with an active showed that patients receiving the probiotic C. difficile infection who were treated with combination were less likely to develop diarrhea Saccharomyces were less likely to experience a in a hospital setting and were less likely to recurrence of the infection by nearly half relative express C. difficile toxins (10). This study to placebo (13). Further examination of the data provided further support for the idea that the showed that this difference was especially administration of bacterial probiotics could play significant for those patients who had at least one a role in the prevention of C. difficile infections prior C. difficile infection. In a separate double- in hospitals or, by extension, long term care blind, placebo-controlled study, Saccharomyces facilities. However, not all clinical trials using was shown to prevent recurrence of C. difficile bacterial based probiotics have been unequivocal infections in patients on low dose antibiotic (7, 11). Discrepancies in reports are probably treatment, but not patients on high does due to the fact that different studies are antibiotic treatment (14). The medical literature performed under different conditions with does not appear to contain any controlled clinical different patient populations, different probiotics, trials using Saccharomyces for primary and different end points (12). The results of prevention of C. difficile infections. these clinical trials should allow for the planning These results are very promising. and development of well defined studies that Providing functional foods to patients in either a could lead to well defined treatment protocols. hospital or long term care facility may be a very easy and inexpensive method of preventing C. 4
  5. 5. Advancing Your Products with Proven Science NMR News: Volume 3, Issue 5, May 2010 difficile infections. Treatment with probiotics with less dependence on antibiotics and may also help to slow the rate of appearance of decreased risk of causing the evolution of C. difficile strains that are resistant to antibiotics. additional antibiotic resistant forms of this Additional clinical trials are needed to precisely pathogen. define the type of patient that would most likely References benefit from the use of probiotics. Well 1) Aslam S, Hamill RJ, Musher DM. 2005. Treatment of designed clinical trials will also allow Clostridium difficile-associated disease: old therapies and determination of the best species and strains of new strategies. Lancet Infect Dis. 5:549-557. probiotics to use along with the best dose regime 2) Owens RC. 2007 Clostridium difficile-associated disease: changing epidemiology and implications for and will also identify any side effects or adverse management. Drugs.67:487-502 reactions (6, 11, 15, 16). 3) Surowiec D, Kuyumjian AG, Wynd MA, Cicogna CE. 2006. Past, present, and future therapies for Clostridium Probiotics may offer a way to prevent difficile-associated disease. Ann Pharmacother. 40:2155- infections by C. difficile in hospitals, nursing 2163. homes, or long-term care facilities. The working 4) Pepin J, Saheb N, Coulombe MA, Alary ME, Corriveau MP, Authier S, Leblanc M, Rivard G, Bettez M, Primeau hypothesis used to explain this benefit of V, Nguyen M, Jacob CE, Lanthier L. 2005. Emergence of probiotics is based on the idea that microbes fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study comprising the probiotic preparation are able to during an epidemic in Quebec. Clin Infect Dis. 41:1254- repopulate the lost flora and fauna of the 1260. digestive tract and prevent opportunistic species 5) Pepin J, Alary ME, Valiquette L, Raiche E, Ruel J, Fulop K, Godin D, Bourassa C. 2005. Increasing risk of like C. difficile from establishing a colony. If relapse after treatment of Clostridium difficile colitis in future clinical trials show that the promise of Quebec, Canada. Clin Infect Dis. 40:1591-1597 preliminary studies is real, then probiotics could 6) Boyle RJ, Robins-Browne RM, Tang ML. 2006. Probiotic use in clinical practice: what are the risks? Am J provide a method to control C. difficile infection Clin Nutr. 83:1256-1264. 5
  6. 6. Advancing Your Products with Proven Science NMR News: Volume 3, Issue 5, May 2010 7) Katz JA. 2006. Probiotics for the prevention of 14) Surawicz CM, McFarland LV, Greenberg RN, Rubin antibiotic-associated diarrhea and Clostridium difficile M, Fekety R, Mulligan ME, Garcia RJ, Brandmarker S, diarrhea. J Clin Gastroenterol. 40:249-255. Bowen K, Borjal D, Elmer GW. 2000. The search for a better treatment for recurrent Clostridium difficile disease: 8) Plummer S, Weaver MA, Harris JC, Dee P, Hunter J. use of high-dose vancomycin combined with 2004. Clostridium difficile pilot study: effects of probiotic Saccharomyces boulardii. Clin Infect Dis. 31:1012-1017. supplementation on the incidence of C. difficile diarrhoea. Int Microbiol. 7:59-62. 15) Borriello SP, Hammes WP, Holzapfel W, Marteau P, Schrezenmeir J, Vaara M, Valtonen V. 2003. Safety of 9) Graul T, Cain AM, Karpa KD. 2009. Lactobacillus and probiotics that contain lactobacilli or bifidobacteria. Clin bifidobacteria combinations: a strategy to reduce hospital- Infect Dis. 36:775-780. acquired Clostridium difficile diarrhea incidence and mortality. Med Hypotheses. 73:194-198. 16) Munoz P, Bouza E, Cuenca-Estrella M, Eiros JM, Perez MJ, Sanchez-Somolinos M, Rincon C, Hortal J, 10) Hickson M, D'Souza AL, Muthu N, Rogers TR, Want Pelaez T. 2005. Saccharomyces cerevisiae fungemia: an S, Rajkumar C, Bulpitt CJ. 2007. Use of probiotic emerging infectious disease. Clin Infect Dis. 40:1625- Lactobacillus preparation to prevent diarrhoea associated 1634. with antibiotics: randomised double blind placebo controlled trial. BMJ. 335:80-85. 11) Segarra-Newnham M. 2007. Probiotics for Clostridium difficile-associated diarrhea: focus on Lactobacillus rhamnosus GG and Saccharomyces boulardii. Ann Pharmacother. 41:1212-1221. 12) Lawrence SJ, Korzenik JR, Mundy LM. 2005. Probiotics for recurrent Clostridium difficile disease. J Med Microbiol. 54:905-906. 13) McFarland LV, Surawicz CM, Greenberg RN, Fekety R, Elmer GW, Moyer KA, Melcher SA, Bowen KE, Cox JL, Noorani Z, Harrington G, Rubin M, Greenwald D. 1994. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA. 271:1913-1918. 6