Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children.
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ABSTRACT:
SUBMITTER: Goldenberg JZ
PROVIDER: S-EPMC6486212 | biostudies-literature | 2017 Dec
REPOSITORIES: biostudies-literature
Publications
Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children.
Goldenberg Joshua Z JZ Yap Christina C Lytvyn Lyubov L Lo Calvin Ka-Fung CK Beardsley Jennifer J Mertz Dominik D Johnston Bradley C BC
The Cochrane database of systematic reviews 20171219
<h4>Background</h4>Antibiotics can disturb gastrointestinal microbiota which may lead to reduced resistance to pathogens such as Clostridium difficile (C. difficile). Probiotics are live microbial preparations that, when administered in adequate amounts, may confer a health benefit to the host, and are a potential C. difficile prevention strategy. Recent clinical practice guidelines do not recommend probiotic prophylaxis, even though probiotics have the highest quality evidence among cited proph ...[more]
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Project description:PURPOSE OF REVIEW:Probiotics may prevent Clostridium difficile infection (CDI), a leading healthcare-associated infection in the United States. However, prior studies were limited by heterogeneity in products and patient populations. Recent clinical evidence and new approaches to probiotic development are reviewed. RECENT FINDINGS:Probiotic use may reduce incident CDI in high-risk populations by as much as 50%, though prior clinical trials have yielded conflicting results. Combining probiotics with prebiotics improves growth and engraftment in the host. Bacillus clausii and Lactobacillus reuteri secrete compounds that directly inhibit C. difficile. Organisms that produce secondary bile acids, such as Clostridium scindens, enhance C. difficile colonization resistance. Nontoxigenic C. difficile, which provides nutritional niche competition, may prevent CDI. Refinements to fecal microbiota transplantation (FMT) blur the line between probiotics and FMT. These include a quality-controlled stool product (RBX2660), purified Firmicutes spores (SER-109) and sterile fecal filtrate. Bacteriophages may treat CDI but have unknown safety and efficacy in humans. SUMMARY:There have been a number of advances in probiotics and our understanding of their role in prevention of CDI, but a number of important safety and efficacy questions remain. An improved understanding of the native microbiota structure and function will allow for continued development of rationally designed probiotic therapy to provide enhanced protection against CDI.
| S-EPMC6335148 | biostudies-other
Project description:BackgroundRecent meta-analyses of the efficacy of probiotics for preventing diarrhea associated with Clostridium difficile have concluded there is a large effect favouring probiotics. We reexamined this evidence, which contradicts the results of a more recent large randomized controlled trial that found no benefit of Lactobacillus probiotics for preventing C. difficile-associated diarrhea.MethodsWe performed a systematic review of the efficacy of treatment with Lactobacillus probiotics for preventing nosocomial C. difficile-associated diarrhea in adults and carried out a meta-analysis using a Bayesian hierarchical model. We used credibility analysis and meta-regression to characterize the heterogeneity between studies.ResultsTen studies met our inclusion criteria. The pooled risk ratio was highly statistically significant, at 0.25 (95% credible interval 0.08-0.47). However, the 95% prediction interval for the risk ratio in a future study, 0.02-1.34, was wider than the credible interval, owing to heterogeneity between studies. Furthermore, a credibility analysis showed that the strength of the evidence was weaker than the observed number of cases of C. difficile-associated diarrhea across studies would suggest. Meta-regression suggested that the beneficial effect of probiotics was more likely to be reported in studies with an increased risk of C. difficile-associated diarrhea in the control group, although this association was not statistically significant.InterpretationAccounting for between-study heterogeneity showed that there is considerable uncertainty regarding the apparently large efficacy estimate associated with Lactobacillus probiotic treatment in preventing C. difficile-associated diarrhea. Most studies to date have been carried out in populations with a low risk of C. difficile-associated diarrhea, such that the evidence is inconclusive and inadequate to support a policy concerning routine use of probiotics in to prevent this condition.
| S-EPMC5173486 | biostudies-literature
Project description:For many years, it has been known that Clostridium difficile (CD) is the primary cause of health-care-associated infectious diarrhea, afflicting approximately 1% of hospitalized patients. CD may be simply carried or lead to a mild disease, but in a relevant number of patients, it can cause a very severe, potentially fatal, disease. In this narrative review, the present possibilities of CD infection (CDI) prevention will be discussed. Interventions usually recommended for infection control and prevention can be effective in reducing CDI incidence. However, in order to overcome limitations of these measures and reduce the risk of new CDI episodes, novel strategies have been developed. As most of the cases of CDI follow antibiotic use, attempts to rationalize antibiotic prescriptions have been implemented. Moreover, to reconstitute normal gut microbiota composition and suppress CD colonization in patients given antimicrobial drugs, administration of probiotics has been suggested. Finally, active and passive immunization has been studied. Vaccines containing inactivated CD toxins or components of CD spores have been studied. Passive immunization with monoclonal antibodies against CD toxins or the administration of hyperimmune whey derived from colostrum or breast milk from immunized cows has been tried. However, most advanced methods have significant limitations as they cannot prevent colonization and development of primary CDI. Only the availability of vaccines able to face these problems can allow a resolutive approach to the total burden due to this pathogen.
| S-EPMC7690700 | biostudies-literature
Project description:BackgroundThe recent increase in the number and severity of cases of nosocomial Clostridium difficile-associated diarrhea (CDAD) has prompted interest in the use of probiotics for the prevention and treatment of this disease. We performed a systematic review of randomized controlled trials to assess the effectiveness of probiotic therapy.MethodsWe searched the PubMed, EMBASE, INAHTA, HEN and Cochrane Collaboration databases to identify trials in which the prevention or treatment of CDAD with probiotic therapy was the primary or secondary outcome. We extracted data on the number of patients randomly assigned to receive probiotic or placebo, the number of patients with CDAD, the type of probiotic, criteria for diagnosing CDAD, persistence of infection after treatment, compliance and adverse effects.ResultsWe identified 4 eligible studies in which prevention (n = 1) or treatment (n = 3) of CDAD was the primary outcome. The benefit of probiotic therapy seen in 2 of the studies was restricted to subgroups characterized by severe CDAD and increased use of vancomycin. The remaining 2 studies were too methodologically flawed for us to draw meaningful conclusions. We also identified 4 trials in which prevention of antibiotic-associated diarrhea with probiotics was the primary outcome and prevention of CDAD a secondary outcome. These studies were limited primarily by too few CDAD cases and provided no evidence of effective prophylaxis. Overall, heterogeneity in choice and dose of probiotic and in criteria for diagnosing CDAD makes it difficult to synthesize information from the 8 studies.InterpretationStudies conducted to date provide insufficient evidence for the routine clinical use of probiotics to prevent or treat CDAD. Better designed and larger studies are needed.
| S-EPMC1174857 | biostudies-literature
Project description: Not available
| S-EPMC6490796 | biostudies-literature
Project description:BackgroundUp to 60% of foals develop diarrhea within 6 months after birth. Preventive measures are limited but potentially probiotics could be used.ObjectiveTo evaluate the effect of a newly designed probiotic on the incidence of foal diarrhea in a randomized field trial.AnimalsSeventy-two healthy neonatal foals.MethodsRandomized, placebo-controlled field trial. Foals were administered a placebo or probiotic for 3 weeks and monitored for an additional week. A total of 3 fecal samples were taken from each foal at biweekly intervals. Statistical modeling was applied for comparison of incidence and duration of diarrhea and fecal shedding of Clostridium perfringens and Clostridium difficile between treatment and age groups.ResultsThe overall incidence of diarrhea was 41 of 72 (59%) and did not differ (P = 0.37) between treatment groups. Foals treated with probiotics were more likely to develop diarrhea requiring veterinary intervention (P = 0.007). Age had a significant effect on incidence of diarrhea (P < 0.001); foals 8-15 days old having the highest probability of developing diarrhea. Duration of diarrhea and soft feces were not significantly different between groups. The prevalence of C. perfringens shedding was 55% with no difference between treatment groups (P = 0.23). The prevalence of C. difficile shedding was 11%.Conclusion and clinical importanceThere was no benefit of administering a 3-week course of probiotics, but potential adverse effects were noted. Whether the probiotics lacked a clinical effect, or the choice of strains or dose was inadequate, is unknown. Clostridial shedding was not influenced by probiotics despite in vitro activity of probiotics.
| S-EPMC4895414 | biostudies-literature
Project description:BackgroundClostridium difficile is the most common cause of hospital-acquired infections, responsible for >450000 infections annually in the USA. Probiotics provide a promising, well-tolerated adjunct therapy to standard C. difficile infection (CDI) treatment regimens, but there is a paucity of data regarding their effectiveness for the treatment of an initial CDI.ObjectivesWe conducted a pilot randomized controlled trial of 33 participants from February 2013 to February 2015 to determine the feasibility and health outcomes of adjunct probiotic use in patients with an initial mild to moderate CDI.MethodsThe intervention was a 28 day, once-daily course of a four-strain oral probiotic capsule containing Lactobacillus acidophilus NCFM, Lactobacillus paracasei Lpc-37, Bifidobacterium lactis Bi-07 and B. lactis Bl-04. The control placebo was identical in taste and appearance. Registered at clinicaltrials.gov: trial registration number = NCT01680874.ResultsProbiotic adjunct therapy was associated with a significant improvement in diarrhoea outcomes. The primary duration of diarrhoea outcome (0.0 versus 1.0 days; P = 0.039) and two exploratory outcomes, total diarrhoea days (3.5 versus 12.0 days; P = 0.005) and rate of diarrhoea (0.1 versus 0.3 days of diarrhoea/stool diary days submitted; P = 0.009), all decreased in participants with probiotic use compared with placebo. There was no significant difference in the rate of CDI recurrence or functional improvement over time between treatment groups.ConclusionsProbiotics are a promising adjunct therapy for treatment of an initial CDI and should be further explored in a larger randomized controlled trial.
| S-EPMC5890711 | biostudies-literature
Project description:Antibiotic usage is the most commonly cited risk factor for hospital-acquired Clostridium difficile infections (CDI). The increased risk is due to disruption of the indigenous microbiome and a subsequent decrease in colonization resistance by the perturbed bacterial community; however, the specific changes in the microbiome that lead to increased risk are poorly understood. We developed statistical models that incorporated microbiome data with clinical and demographic data to better understand why individuals develop CDI. The 16S rRNA genes were sequenced from the feces of 338 individuals, including cases, diarrheal controls, and nondiarrheal controls. We modeled CDI and diarrheal status using multiple clinical variables, including age, antibiotic use, antacid use, and other known risk factors using logit regression. This base model was compared to models that incorporated microbiome data, using diversity metrics, community types, or specific bacterial populations, to identify characteristics of the microbiome associated with CDI susceptibility or resistance. The addition of microbiome data significantly improved our ability to distinguish CDI status when comparing cases or diarrheal controls to nondiarrheal controls. However, only when we assigned samples to community types was it possible to differentiate cases from diarrheal controls. Several bacterial species within the Ruminococcaceae, Lachnospiraceae, Bacteroides, and Porphyromonadaceae were largely absent in cases and highly associated with nondiarrheal controls. The improved discriminatory ability of our microbiome-based models confirms the theory that factors affecting the microbiome influence CDI. IMPORTANCE The gut microbiome, composed of the trillions of bacteria residing in the gastrointestinal tract, is responsible for a number of critical functions within the host. These include digestion, immune system stimulation, and colonization resistance. The microbiome's role in colonization resistance, which is the ability to prevent and limit pathogen colonization and growth, is key for protection against Clostridium difficile infections. However, the bacteria that are important for colonization resistance have not yet been elucidated. Using statistical modeling techniques and different representations of the microbiome, we demonstrated that several community types and the loss of several bacterial populations, including Bacteroides, Lachnospiraceae, and Ruminococcaceae, are associated with CDI. Our results emphasize the importance of considering the microbiome in mediating colonization resistance and may also direct the design of future multispecies probiotic therapies.
| S-EPMC4010826 | biostudies-other
Project description:IntroductionThe prevalence of Clostridium difficile infection is rapidly increasing worldwide, but prevalence is difficult to estimate in developing countries where awareness, diagnostic resources, and surveillance protocols are limited. As diarrhea is the hallmark symptom, we conducted a systematic review and meta-analysis to determine the prevalence and incidence of C. difficile infection in patients in these regions who presented with diarrhea.MethodsWe conducted a systematic literature search of MEDLINE/PubMed, Scopus, and Latin-American and Caribbean Health Sciences Literature databases to identify and analyze data from recent studies providing prevalence or incidence rates of C. difficile-associated diarrhea in developing countries within four regions: Africa-Middle East, developing Asia, Latin America, and China. Our objectives were to determine the current prevalence and incidence density rates of first episodes of C. difficile-associated diarrhea in developing countries.ResultsWithin the regions included in our analysis, prevalence of C. difficile infection in patients with diarrhea was 15% (95% CI 13-17%) (including community and hospitalized patients), with no significant difference across regions. The incidence of C. difficile infection in 17 studies including this information was 8.5 per 10,000 patient-days (95% CI 5.83-12.46). Prevalence was significantly higher in hospitalized patients versus community patients (p = 0.0227).ConclusionOur prevalence estimate of 15% is concerning; however, low awareness and inconsistent diagnostic and surveillance protocols suggest this is markedly underestimated. Enhanced awareness and management of C. difficile infection in patients with diarrhea, along with improvements in infection control and surveillance practices, should be implemented to reduce prevalence of C. difficile-associated diarrhea in developing countries.FundingPfizer Inc.
| S-EPMC6374231 | biostudies-literature
Project description: Not available
| S-EPMC6464548 | biostudies-literature