Archive for category Clostridium Difficile
Nutr Clin Prac ’09: Reviewing probiotics for use as preventive therapies in C-difficile associated diseases
Imhoff A, et al. Is there a future for probiotics in preventing Clostridium difficile-associated disease and treatment of recurrent episodes? Nutr Clin Prac 2009 24(1):15-32.
Due to morbidity, mortality, and high costs associated with eradicating Clostridium difficile once this organism causes colitis, this bacterium has been termed one of the most ecologically relevant microorganisms of the present day. Symptoms associated with C. difficile diarrhea often first present during or shortly after a course of antibiotic therapy.
During the past 5 years, the virulence of this organism has increased. C. difficile–associated disease (CDAD) has reached epidemic proportions in some hospital settings, prompting Medicare to propose adding CDAD to the list of hospital-acquired conditions for which reimbursements may be cut. Thus, it is imperative that effective preventive strategies be implemented in hospitals to decrease CDAD infections.
It is plausible that probiotic supplements may offer a safe and effective means of preventing both initial CDAD episodes as well as CDAD recurrences. This review critically examines the current literature in which probiotic supplements have been studied for efficacy in CDAD prevention.
This analysis will guide practitioners in applying available probiotic data to CDAD clinical scenarios and will assist researchers in the appropriate design of future studies as examination continues into the role that probiotics may have in CDAD prevention.
Bartlett JG. Narrative review: The new epidemic of Clostridium difficile-associated enteric disease. Ann Intern Med. 2006 Nov 21;145(10):758-764. Review.
Antibiotic-associated diarrhea and colitis were well established soon after antibiotics became available. Early work implicated Staphylococcus aureus, but in 1978 Clostridium difficile became the established pathogen in the vast majority of cases.
In the first 5 years (1978 through 1983), the most common cause was clindamycin, the standard diagnostic test was the cytotoxin assay, and standard management was to withdraw the implicated antibiotic and treat with oral vancomycin. Most patients responded well, but 25% relapsed when vancomycin was withdrawn.
During the next 20 years (1983 through 2003), the most commonly implicated antibiotics were the cephalosporins, which reflected the rates of use; the enzyme immunoassay replaced the cytotoxin assay because of speed of results and technical ease of performance; and metronidazole replaced vancomycin as standard treatment, and principles of containment hospitals became infection control and antibiotic control.
During the recent past (2003 to 2006), C. difficile has been more frequent, more severe, more refractory to standard therapy, and more likely to relapse. This pattern is widly distributed in the United States, Canada, and Europe and is now attributed to a new strain of C. difficile designated BI, NAP1, or ribotype 027 (which are synonymous terms). This strain appears more virulent, possibly because of production of large amounts of toxins, and fluoroquinolones are now major inducing agents along with cephalosporins, which presumably reflects newly acquired in vitro resistance and escalating rates of use.
The recent experience does not change principles of management of the individual patient, but it does serve to emphasize the need for better diagnostics, early recognition, improved methods to manage severe disease and relapsing disease, and greater attention to infection control and antibiotic restraint.
Cremonini F, et al. Probiotics in antibiotic-associated diarrhea. Dig Liver Dis 2002;34 Suppl 2:S78-80.
Antibiotic-associated diarrhoea is a common event. In some cases, it could represent a life-threatening event. Clostridium difficile colitis is a further distinct complication of antibiotic administration. Treatment options for antibiotic-associated diarrhoea and Clostridium difficile colitis include supplementation with several types of probiotics, as overviewed in this paper.
Three randomised, double-blind, controlled clinical trials show a therapeutic effect of Saccharomyces boulardii in antibiotic-associated diarrhoea. The efficacy of Lactobacillus acidophilus and bulgaricus has also been ascertained in two double-blind controlled studies. Other studies focusing on Lactobacillus as a new preventive agent for antibiotic-associated diarrhoea are not double-blind.
Among these, a positive effect of Lactobacillus rhamnosus GG, Bifidobacterium longum and Enterococcus faecium SF68 has been reported.
Effectiveness of probiotics in antibiotic-associated diarrhoea has, therefore, a consistent scientific rationale, however few studies have performed an assessment of bacterial recovery in stools, and this approach may be helpful in deciding a more rigorous dose standardisation.
BMJ ’07: Probiotic blend shown to reduce diarrhea associated with antibiotics and C difficile in seniors
Hickson M et al. Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: Randomised double blind placebo controlled trial. BMJ 2007;14;335 (7610) :80.
To determine the efficacy of a probiotic drink containing Lactobacillus for the prevention of any diarrhoea associated with antibiotic use and that caused by Clostridium difficile.
Randomised double blind placebo controlled study.
135 hospital patients (mean age 74) taking antibiotics. Exclusions included diarrhoea on admission, bowel pathology that could result in diarrhoea, antibiotic use in the previous four weeks, severe illness, immunosuppression, bowel surgery, artificial heart valves, and history of rheumatic heart disease or infective endocarditis.
Consumption of a 100 g (97 ml) drink containing Lactobacillus casei, L bulgaricus, and Streptococcus thermophilus twice a day during a course of antibiotics and for one week after the course finished. The placebo group received a longlife sterile milkshake.
MAIN OUTCOME MEASURES:
Primary outcome: occurrence of antibiotic associated diarrhoea. Secondary outcome: presence of C difficile toxin and diarrhoea.
7/57 (12%) of the probiotic group developed diarrhoea associated with antibiotic use compared with 19/56 (34%) in the placebo group (P=0.007). Logistic regression to control for other factors gave an odds ratio 0.25 (95% confidence interval 0.07 to 0.85) for use of the probiotic, with low albumin and sodium also increasing the risk of diarrhoea. The absolute risk reduction was 21.6% (6.6% to 36.6%), and the number needed to treat was 5 (3 to 15). No one in the probiotic group and 9/53 (17%) in the placebo group had diarrhoea caused by C difficile (P=0.001). The absolute risk reduction was 17% (7% to 27%), and the number needed to treat was 6 (4 to 14).
Consumption of a probiotic drink containing L casei, L bulgaricus, and S thermophilus can reduce the incidence of antibiotic associated diarrhoea and C difficile associated diarrhoea. This has the potential to decrease morbidity, healthcare costs, and mortality if used routinely in patients aged over 50.
Am J Gastro ’06: Meta-analysis reports effectiveness of 3 probiotics for AAD and S. boulardii for C-diff
McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol 2006; 101:812-822.
Antibiotic-associated diarrhea (AAD) is a common complication of most antibiotics and Clostridium difficile disease (CDD), which also is incited by antibiotics, is a leading cause of nosocomial outbreaks of diarrhea and colitis. The use of probiotics for these two related diseases remains controversial.
To compare the efficacy of probiotics for the prevention of AAD and the treatment of CDD based on the published randomized, controlled clinical trials.
PubMed, Medline, Google Scholar, NIH registry of clinical trials, metaRegister, and Cochrane Central Register of Controlled Trials were searched from 1977 to 2005, unrestricted by language. Secondary searches of reference lists, authors, reviews, commentaries, associated diseases, books, and meeting abstracts.
Trials were included in which specific probiotics given to either prevent or treat the diseases of interest. Trials were required to be randomized, controlled, blinded efficacy trials in humans published in peer-reviewed journals. Trials that were excluded were pre-clinical, safety, Phase 1 studies in volunteers, reviews, duplicate reports, trials of unspecified probiotics, trials of prebiotics, not the disease being studied, or inconsistent outcome measures. Thirty-one of 180 screened studies (totally 3,164 subjects) met the inclusion and exclusion criteria.
One reviewer identified studies and abstracted data on sample size, population characteristics, treatments, and outcomes.
From 25 randomized controlled trials (RCTs), probiotics significantly reduced the relative risk of AAD (RR = 0.43, 95% CI 0.31, 0.58, p < 0.001). From six randomized trials, probiotics had significant efficacy for CDD (RR = 0.59, 95% CI 0.41, 0.85, p = 0.005).
A variety of different types of probiotics show promise as effective therapies for these two diseases. Using meta-analyses, three types of probiotics (Saccharomyces boulardii, Lactobacillus rhamnosus GG, and probiotic mixtures) significantly reduced the development of antibiotic-associated diarrhea. Only S. boulardii was effective for CDD.
Am J Gastro ’10: Significant benefits with higher dose probiotics measured in patients at risk for C-diff and antibiotic-associated diarrhea
Gao XW, Mubasher M, et al. Dose–Response Efficacy of a Proprietary Probiotic Formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for Antibiotic-Associated Diarrhea and Clostridium difficile-Associated Diarrhea Prophylaxis in Adult Patients. Am J Gastroenterology, 2010; 105:1636-1641.
OBJECTIVES: Standard therapies for antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) have limited efficacy. Probiotic prophylaxis is a promising alternative for reduction of AAD and CDAD incidence.
METHODS: In this single-center, randomized, double-blind, placebo-controlled dose-ranging study, we randomized 255 adult inpatients to one of three groups: two probiotic capsules per day (Pro-2, n=86), one probiotic capsule and one placebo capsule per day (Pro-1, n=85), or two placebo capsules per day (n=84). Each probiotic capsule contained 50 billion c.f.u. of live organisms (Lactobacillus acidophilus CL1285® +Lactobacillus casei LBC80R® Bio-K+CL1285). Probiotic prophylaxis began within 36 h of initial antibiotic administration, continued for 5 days after the last antibiotic dose, and patients were followed for an additional 21 days.
RESULTS: Pro-2 (15.5%) had a lower AAD incidence vs. Pro-1 (28.2%). Each probiotic group had a lower AAD incidence vs. placebo (44.1%). In patients who acquired AAD, Pro-2 (2.8 days) and Pro-1 (4.1 days) had shorter symptom duration vs. placebo (6.4 days). Similarly, Pro-2 (1.2%) had a lower CDAD incidence vs. Pro-1 (9.4%). Each treatment group had a lower CDAD incidence vs. placebo (23.8%). Gastrointestinal symptoms were less common in the treatment groups vs. placebo and in Pro-2 vs. Pro-1.
CONCLUSIONS: The proprietary probiotic blend used in this study was well tolerated and effective for reducing risk of AAD and, in particular, CDAD in hospitalized patients on antibiotics. A dose-ranging effect was shown with 100 billion c.f.u., yielding superior outcomes and fewer gastrointestinal events compared to 50 billion c.f.u.
Clin Infect Dis ’00: Patients using S. boulardii with antibiotics had significantly greater reduction in recurrence of C-diff
Surawicz CM, McFarland LV, Greenberg RN, et al. The search for better treatment for recurrent Clostridium difficile disease: Use of high-dose vancomycin combined with Saccharomyces boulardii. Clin Infect Dis 2000;31:1012-1017.
Recurrent Clostridium difficile disease (CDD) is a difficult clinical problem because antibiotic therapy often does not prevent further recurrences. In a previous study, the biotherapeutic agent Saccharomyces boulardii was used in combination with standard antibiotics and was found to be effective in reducing subsequent recurrences of CDD.
In an effort to further refine a standard regimen, we tested patients receiving a regimen of a standard antibiotic for 10 days and then added either S. boulardii (1 g/day for 28 days) or placebo. A significant decrease in recurrences was observed only in patients treated with high-dose vancomycin (2 g/day) and S. boulardii (16.7%), compared with those who received high-dose vancomycin and placebo (50%; P=.05). No serious adverse reactions were observed in these patients.
Comparison of data from this trial with data from previous studies indicates that recurrent CDD may respond to a short course of high-dose vancomycin or to longer courses of low-dose vancomycin when either is combined with S. boulardii.
Marteau, PR. Probiotics in clinical conditions. Clin Rev Allergy Immunol 2002;22:255-273.
Probiotics are nonpathogenic microorganisms which, when ingested, exert a positive influence on the health or physiology of the host. Their mechanisms of action and effects are now studied using the same pharmacological approach as for drugs.
This article summarizes and comments on evidence for the positive effects of probiotics in various clinical situations. Substantial evidence can be achieved when randomized controlled trials or meta-analyses show positive results.
The clinical situations studied include prevention or treatment of antibiotic-associated disorders, gastroenteritis, and diarrhea, lactose intolerance, intestinal infections and colonization by pathogenic bacteria (including Helicobacter pylori and Clostridium difficile), traveler’s diarrhea, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), colonic cancer, urogenital infections and tumors, allergy (especially atopic eczema), vaccination, and cholesterol lowering.
Current probiotics have an excellent safety record–another topic discussed in this article.
Nutr Clin Prac ’09: Probiotics can reduce diarrhea; may also reduce rate and recurrence of C-diff (Clostridium difficile)
Rohde CL, Bartolini V, Jones N. The Use of Probiotics in the Prevention and Treatment of Antibiotic-Associated Diarrhea With Special Interest in Clostridium difficile–Associated Diarrhea. Nutr Clin Practice, 2009;24(1):33-40.
Antimicrobials are effective agents used to combat virulent bacterial, yeast, and fungal infections that may otherwise cause rampant disease leading to skyrocketing social/economic costs and possible epidemic morbidity and mortality rates.
Antibiotics are designed to attack specific bacterial pathogens but, in the process, indiscreetly reduce the number of beneficial human microbiota that is part of the gut-associated lymphatic tissue. Broad-spectrum antibiotics can upset this uniquely balanced gut ratio, allowing pathogens to propagate in a largely unrestrained environment, which may result in antibiotic-induced diarrhea.
Critical illness, age, immunosuppression, exposure to nosocomial microorganisms and the length of hospitalization are additional factors that contribute to the overgrowth of opportunistic pathogens. In mild to moderate cases of diarrhea, absorptive impairment may occur, thereby reducing micro/macronutrient assimilation, resulting in malnutrition and growth issues in children. In severe cases, infectious diarrhea can have devastating complications.
Of particular interest is the bacterium Clostridium difficile, which has the potential to cause a host of symptoms ranging from mild diarrhea to severe life-threatening conditions. C. difficile infection can increase mortality rates by 10%–30%.
Probiotic supplementation may prevent and treat antibiotic-associated diarrhea. Specific probiotics may modulate the intestinal mucosa by antagonizing pathogens through the production of antimicrobial compounds and chemicals, thereby reducing the rate of nosocomial infection and recurrence of C. difficile.
Marteau PR, de Vrese M, et al. Protection from gastrointestinal diseases with the use of probiotics. Am J Clin Nutrition, 2001;73(2):430S-436S
Probiotics are nonpathogenic microorganisms that, when ingested, exert a positive influence on the health or physiology of the host. They can influence intestinal physiology either directly or indirectly through modulation of the endogenous ecosystem or immune system.
The results that have been shown with a sufficient level of proof to enable probiotics to be used as treatments for gastrointestinal disturbances are
1) the good tolerance of yogurt compared with milk in subjects with primary or secondary lactose maldigestion,
2) the use of Saccharomyces boulardii and Enterococcus faecium SF 68 to prevent or shorten the duration of antibiotic-associated diarrhea,
3) the use of S. boulardii to prevent further recurrence of Clostridium difficile–associated diarrhea, and
4) the use of fermented milks containing Lactobacillus rhamnosus GG to shorten the duration of diarrhea in infants with rotavirus enteritis (and probably also in gastroenteritis of other causes).
Effects that are otherwise suggested for diverse probiotics include alleviation of diarrhea of miscellaneous causes; prophylaxis of gastrointestinal infections, which includes traveler’s diarrhea; and immunomodulation. Trials of gastrointestinal diseases that involve the ecosystem are currently being performed, eg, Helicobacter pylori infections, inflammatory bowel disease, and colon cancer.