|
1
|
Yang H, Kuang Y, Wang L, Ma X, Gálvez JAV, Lu J, Dai Y, Liu S, Yao J, Chen X, Cao Y. Pterostilbene attenuates intestinal barrier damage and secondary liver oxidative stress in a murine model of Clostridium difficile infection by regulating the gut microbiota. Food Funct 2025; 16:3325-3343. [PMID: 40190207 DOI: 10.1039/d4fo06413e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/07/2025]
Abstract
Clostridium difficile infection (CDI) is a significant infectious disease with limited treatment options. Pterostilbene, an active compound found in blueberries, is known for its antioxidant and anti-inflammatory properties. This study investigated the effects of pterostilbene on intestinal barrier damage and secondary liver oxidative stress induced by CDI in mice. Pathological changes in the colon and liver, the levels of anti-inflammatory cytokines and antioxidants, and the expression of related genes were evaluated. Additionally, 16S rRNA sequencing and targeted metabolomics analyses of the gut microbiota and bile acids were conducted. Pterostilbene reduced the abundance of harmful bacteria such as Enterococcus, while increasing beneficial bacteria like Lactobacillus, thereby reshaping the gut microbiota and bile acid profile and reducing the accumulation of T-βMCA. This process activated intestinal FXR signaling, which alleviated colonic inflammation and reduced intestinal permeability. The reduction in intestinal permeability prevented the translocation of bacteria and bacterial toxins into the liver via the portal vein, thereby reducing liver inflammation and oxidative stress. Pterostilbene presented a promising strategy for maintaining intestinal health through the regulation of dysbiosis and bile acid disturbances caused by CDI. When integrated into the food system, pterostilbene has the potential to improve intestinal health, mitigate the risk of CDI associated with contaminated agricultural products, and enhance public health and food safety. Additionally, we identified that regulating the intestinal bile acid profile and the FXR receptor could serve as potential therapeutic targets for CDI, thereby facilitating the development of novel treatment options and dietary strategies.
Collapse
Affiliation(s)
- Hao Yang
- College of Animal Science and Technology, Northwest A&F University, No. 3 Taicheng Road, Yangling, Shaanxi, 712100, China.
| | - Yanling Kuang
- College of Animal Science and Technology, Northwest A&F University, No. 3 Taicheng Road, Yangling, Shaanxi, 712100, China.
| | - Lamei Wang
- College of Animal Science and Technology, Northwest A&F University, No. 3 Taicheng Road, Yangling, Shaanxi, 712100, China.
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.
| | - Xinru Ma
- College of Animal Science and Technology, Northwest A&F University, No. 3 Taicheng Road, Yangling, Shaanxi, 712100, China.
| | - Javier A Villafuerte Gálvez
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.
| | - Jing Lu
- College of Animal Science and Technology, Northwest A&F University, No. 3 Taicheng Road, Yangling, Shaanxi, 712100, China.
| | - Yanfei Dai
- College of Animal Science and Technology, Northwest A&F University, No. 3 Taicheng Road, Yangling, Shaanxi, 712100, China.
| | - Shimin Liu
- Institute of Agriculture, The University of Western Australia, Perth, Australia
| | - Junhu Yao
- College of Animal Science and Technology, Northwest A&F University, No. 3 Taicheng Road, Yangling, Shaanxi, 712100, China.
| | - Xinhua Chen
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.
| | - Yangchun Cao
- College of Animal Science and Technology, Northwest A&F University, No. 3 Taicheng Road, Yangling, Shaanxi, 712100, China.
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.
| |
Collapse
|
|
2
|
Bacteraemia Caused by Probiotic Strains of Lacticaseibacillus rhamnosus—Case Studies Highlighting the Need for Careful Thought before Using Microbes for Health Benefits. Pathogens 2022; 11:pathogens11090977. [PMID: 36145409 PMCID: PMC9504050 DOI: 10.3390/pathogens11090977] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 08/16/2022] [Accepted: 08/24/2022] [Indexed: 11/16/2022] Open
Abstract
Lactic acid bacteria belonging to Lactobacillus spp. and Lacticaseibacillus spp. are a natural part of fermented milk and other food products, probiotic supplements and human microbiota. They mainly belong to mucosal microflora, especially oral, vaginal and intestinal. Lacticaseibacillus spp. strains included in probiotics are generally characterised as safe microorganisms, and the species are concerned bacteria with very low pathogenic potential. However, infections caused by Lactobacillus spp. and Lacticaseibacillus spp., including bacteraemia and endocarditis, occur occasionally. The aim of the study was to present two cases of bacteraemia due to Lacticaseibacillus rhamnosus associated with the use of a probiotic product. It afflicted patients in intensive care units. The investigation was preliminarily based on clinical and microbiological recognition of the cases. The initial observation was laboratory confirmed with the application of pulsed-field gel electrophoresis (PFGE) results. Identical PFGE patterns were obtained for the evaluated strains and the strains derived from a commercially available probiotic that was administered to those patients. The increasing number of studies describing opportunistic infections due to probiotic strains of Lacticaseibacillus spp. should result in verifying the safety of probiotic formulations used in immunocompromised patients and forming detailed guidelines for the use of probiotics among patients from several risk groups.
Collapse
|
|
3
|
Bai Y, Ma K, Li J, Ren Z, Zhang J, Shan A. Lactobacillus rhamnosus GG ameliorates DON-induced intestinal damage depending on the enrichment of beneficial bacteria in weaned piglets. J Anim Sci Biotechnol 2022; 13:90. [PMID: 35962456 PMCID: PMC9375241 DOI: 10.1186/s40104-022-00737-9] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 06/01/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Deoxynivalenol (DON) is one of the most common environmental pollutants that induces intestinal inflammation and microbiota dysbiosis. Lactobacillus rhamnosus GG (LGG) is a probiotic that not only has anti-inflammatory effects, but also shows protective effect on the intestinal barrier. However, it is still unknown whether LGG exerts beneficial effects against DON-induced intestinal damage in piglets. In this work, a total of 36 weaned piglets were randomized to one of four treatment groups for 21 d. The treatment groups were CON (basal diet); LGG (basal diet supplemented with 1.77 × 1011 CFU/kg LGG); DON (DON-contaminated diet) and LGG + DON (DON-contaminated diet supplemented with 1.77 × 1011 CFU/kg LGG). RESULT Supplementation of LGG can enhance growth performance of piglets exposed to DON by improving intestinal barrier function. LGG has a mitigating effect on intestinal inflammation induced by DON exposure, largely through repression of the TLR4/NF-κB signaling pathway. Furthermore, supplementation of LGG increased the relative abundances of beneficial bacteria (e.g., Collinsella, Lactobacillus, Ruminococcus_torques_group and Anaerofustis), and decreased the relative abundances of harmful bacteria (e.g., Parabacteroides and Ruminiclostridium_6), and also promoted the production of SCFAs. CONCLUSIONS LGG ameliorates DON-induced intestinal damage, which may provide theoretical support for the application of LGG to alleviate the adverse effects induced by DON exposure.
Collapse
Affiliation(s)
- Yongsong Bai
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, P. R. China
| | - Kaidi Ma
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, P. R. China
| | - Jibo Li
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, P. R. China
| | - Zhongshuai Ren
- College of Animal Sciences, Jilin University, Key Laboratory of Zoonosis Research, Ministry of Education, Changchun, 130062, P. R. China
| | - Jing Zhang
- College of Animal Sciences, Jilin University, Key Laboratory of Zoonosis Research, Ministry of Education, Changchun, 130062, P. R. China.
| | - Anshan Shan
- Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, P. R. China.
| |
Collapse
|
|
4
|
Sasi M, Kumar S, Hasan M, S R A, Garcia-Gutierrez E, Kumari S, Prakash O, Nain L, Sachdev A, Dahuja A. Current trends in the development of soy-based foods containing probiotics and paving the path for soy-synbiotics. Crit Rev Food Sci Nutr 2022; 63:9995-10013. [PMID: 35611888 DOI: 10.1080/10408398.2022.2078272] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
In the world of highly processed foods, special attention is drawn to the nutrient composition and safety of consumed food products. Foods fortified with probiotic bacteria confer beneficial effects on human health and are categorized as functional foods. The salubrious activities of probiotics include the synthesis of vital bioactives, prevention of inflammatory diseases, anticancerous, hypocholesterolemic, and antidiarrheal effects. Soy foods are exemplary delivery vehicles for probiotics and prebiotics and there are diverse strategies to enhance their functionality like employing mixed culture fermentation, engineering probiotics, and incorporating prebiotics in fermented soy foods. High potential is ascribed to the concurrent use of probiotics and prebiotics in one product, termed as "synbiotics," which implicates synergy, in which a prebiotic ingredient particularly favors the growth and activity of a probiotic micro-organism. The insights on emended bioactive profile, metabolic role, and potential health benefits of advanced soy-based probiotic and synbiotic hold a promise which can be profitably implemented to meet consumer needs. This article reviews the available knowledge about strategies to enhance the nutraceutical potential, mechanisms, and health-promoting effects of advanced soy-based probiotics. Traditional fermentation merged with diverse strategies to improve the efficiency and health benefits of probiotics considered vital, are also discussed.
Collapse
Affiliation(s)
- Minnu Sasi
- Division of Biochemistry, ICAR-Indian Agricultural Research Institute, New Delhi, India
| | - Sandeep Kumar
- Division of Biochemistry, ICAR-Indian Agricultural Research Institute, New Delhi, India
- Quality and Productivity Improvement Division, ICAR-Indian Institute of Natural Resins and Gums, Ranchi, India
| | - Muzaffar Hasan
- Division of Biochemistry, ICAR-Indian Agricultural Research Institute, New Delhi, India
- Agro Produce Processing Division, ICAR-Central Institute of Agricultural Engineering, Bhopal, India
| | - Arpitha S R
- Division of Biochemistry, ICAR-Indian Agricultural Research Institute, New Delhi, India
| | | | - Sweta Kumari
- Division of Biochemistry, ICAR-Indian Agricultural Research Institute, New Delhi, India
| | - Om Prakash
- National Centre for Microbial Resource (NCMR), National Centre for Cell Science, Pune, India
| | - Lata Nain
- Division of Microbiology, ICAR-Indian Agricultural Research Institute, New Delhi, India
| | - Archana Sachdev
- Division of Biochemistry, ICAR-Indian Agricultural Research Institute, New Delhi, India
| | - Anil Dahuja
- Division of Biochemistry, ICAR-Indian Agricultural Research Institute, New Delhi, India
| |
Collapse
|
|
5
|
Keikha M, Kamali H. The impact of Saccharomyces boulardii adjuvant supplementation on alternation of gut microbiota after H. pylori eradication; a metagenomics analysis. GENE REPORTS 2022; 26:101499. [DOI: 10.1016/j.genrep.2022.101499] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
|
|
6
|
In vitro and in vivo anti-clostridial activity of newly isolated Pediococcus acidilactici SPM138 against Clostridium difficile. Anaerobe 2019; 61:102146. [PMID: 31887433 DOI: 10.1016/j.anaerobe.2019.102146] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Revised: 12/03/2019] [Accepted: 12/23/2019] [Indexed: 11/23/2022]
Abstract
Clostridium difficile infection (CDI) has become a growing health concern, as evident from the increase in the mortality rate among elderly or hospitalized patients. Treatment of CDI is usually based on antibiotics (metronidazole and vancomycin), but it has some limitations, including cost and antibiotic resistance. Probiotics could offer an effective remedy to prevent CDI and could be an auxiliary agent in treatment CDI. Here, the anti-clostridial activity of a newly isolated probiotic strain, Pediococcus acidilactici SPM138 (SPM138) was evaluated. The cultivation of C. difficile (CD) with SPM138, inhibited the growth of CD and significantly reduced CD toxins level. The result of MTT assay showed that, incubation with 25% CD culture supernatant decreased the survival rate of HT-29 cells to less than 20%. However, the survival rate of these cells increased to 98% in the presence of the 25% CD + SPM138 supernatant. The mRNA expression of IL-6, IL-8 and PTGS2 in HT-29 cells decreased by more than 60% upon incubation with CD + SPM138 co-cultures as compared to the levels observed after treatment with CD supernatant only. The concentration of IL-8 also decreased by more than 60% upon treatment with CD + SPM138 co-culture supernatant. In a C. difficile PCR ribotype 027-infected mouse model, the concentration of CD toxin in stool samples of SPM138-fed mice was only 37% of that reported in C. difficile 027-infected group. These findings show that P. acidilactici SPM138 may be a promising probiotic in CDI.
Collapse
|
|
7
|
Zoumpopoulou G, Tsakalidou E, Thomas L. An Overview of Probiotic Research. PROBIOTIC DAIRY PRODUCTS 2017:293-357. [DOI: 10.1002/9781119214137.ch8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
8
|
Aroutcheva A, Auclair J, Frappier M, Millette M, Lolans K, de Montigny D, Carrière S, Sokalski S, Trick WE, Weinstein RA. Importance of Molecular Methods to Determine Whether a Probiotic is the Source of Lactobacillus Bacteremia. Probiotics Antimicrob Proteins 2016; 8:31-40. [PMID: 26915093 DOI: 10.1007/s12602-016-9209-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
There has been an increasing interest in the use of probiotic products for the prevention of Clostridium difficile infection (CDI). Bio-K+(®) is a commercial probiotic product comprising three strains of lactobacilli--Lactobacillus acidophilus CL1285(®), Lact. casei LBC80R(®) and Lact. rhamnosus CLR2(®)--that have been applied to prevent CDI. Generally considered as safe, lactobacilli have potential to cause bacteremia, endocarditis and other infections. The source of Lactobacillus bacteremia can be normal human flora or lactobacilli-containing probiotic. The aim of this study was to assess whether probiotic lactobacilli caused bacteremia and to show the value of molecular identification and typing techniques to determine probiotic and patient strain relatedness. We report an episode of Lactobacillus bacteremia in a 69-year-old man admitted to a hospital with severe congestive heart failure. During his hospitalization, he required long-term antibiotic therapy. Additionally, the patient received Bio-K+(®) probiotic as part of a quality improvement project to prevent CDI. Subsequently, Lactobacillus bacteremia occurred. Two independent blinded laboratory evaluations, using pulse field gel electrophoresis, 16S rRNA gene sequencing and DNA fingerprint analysis (rep-PCR), were performed to determine whether the recovered Lact. acidophilus originated from the probiotic product. Ultimately, the patient strain was identified as Lact. casei and both laboratories found no genetic relation between the patient's strain and any of the probiotic lactobacilli. This clinical case of lactobacillus bacteremia in the setting of probiotic exposure demonstrates the value of using discriminatory molecular methods to clearly determine whether there were a link between the patient's isolate and the probiotic strains.
Collapse
Affiliation(s)
- Alla Aroutcheva
- Division of Infectious Diseases, John H. Stroger Hospital of Cook County, 1901 W. Harrison St, Chicago, IL, 60612, USA.
| | - Julie Auclair
- Bio-K+ Pharma, 495 Armand-Frappier Boulevard, Laval, QC, H7V 4B3, Canada
| | - Martin Frappier
- Bio-K+ Pharma, 495 Armand-Frappier Boulevard, Laval, QC, H7V 4B3, Canada
| | - Mathieu Millette
- Bio-K+ Pharma, 495 Armand-Frappier Boulevard, Laval, QC, H7V 4B3, Canada
| | - Karen Lolans
- Rush University Medical Center, 600 S Paulina St, Chicago, IL, 60612, USA
| | | | - Serge Carrière
- Bio-K+ Pharma, 495 Armand-Frappier Boulevard, Laval, QC, H7V 4B3, Canada
| | - Stephen Sokalski
- Advocate Christ Medical Center, 4440 W 95th St, Oak Lawn, IL, 60453, USA
| | - William E Trick
- Division of Infectious Diseases, John H. Stroger Hospital of Cook County, 1901 W. Harrison St, Chicago, IL, 60612, USA
- Rush University Medical Center, 600 S Paulina St, Chicago, IL, 60612, USA
| | - Robert A Weinstein
- Division of Infectious Diseases, John H. Stroger Hospital of Cook County, 1901 W. Harrison St, Chicago, IL, 60612, USA
- Rush University Medical Center, 600 S Paulina St, Chicago, IL, 60612, USA
| |
Collapse
|
|
9
|
Karpa KD. Probiotics for Clostridium difficile Diarrhea: Putting It into Perspective. Ann Pharmacother 2016; 41:1284-7. [PMID: 17595302 DOI: 10.1345/aph.1k228] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Clostridium difficile diarrhea is an expensive, life-threatening infection associated with serious morbidity and mortality, even among previously healthy individuals. Relapses from the infection are common following standard antibiotic treatments, with 3–5% of patients who contract C. difficile diarrhea unable to discontinue vancomycin due to continual relapses. Such patients may have a focal immunodeficiency in which they tail to mount an immune response against C. difficile. For these individuals, antimicrobial therapies are unable to eradicate the microorganism because no antibiotics are capable of killing C. difficile spores. Although they are considered alternative medicine, probiotics have provided a safe and effective means of restoring gastrointestinal flora and alleviating diarrhea, particularly for individuals experiencing multiple relapses.
Collapse
|
|
10
|
Epidemiology, Diagnosis, and Management of Clostridium difficile Infection in Patients with Inflammatory Bowel Disease. Inflamm Bowel Dis 2016; 22:1744-54. [PMID: 27120571 PMCID: PMC4911291 DOI: 10.1097/mib.0000000000000793] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Clostridium difficile infection (CDI) is a major source of morbidity and mortality for the U.S. health care system and frequently complicates the course of inflammatory bowel disease (IBD). Patients with IBD are more likely to be colonized with C. difficile and develop active infection than the general population. They are also more likely to have severe CDI and develop subsequent complications such as IBD flare, colectomy, or death. Even after successful initial treatment and recovery, recurrent CDI is common. Management of CDI in IBD is fraught with diagnostic and therapeutic challenges because the clinical presentations of CDI and IBD flare have considerable overlap. Fecal microbiota transplantation can be successful in curing recurrent CDI when other treatments have failed, but may also trigger IBD flare and this warrants caution. New experimental treatments including vaccines, monoclonal antibodies, and nontoxigenic strains of C. difficile offer promise but are not yet available for clinicians. A better understanding of the complex relationship between the gut microbiota, CDI, and IBD is needed.
Collapse
|
|
11
|
Lactobacillus rhamnosus GG Intake Modifies Preschool Children's Intestinal Microbiota, Alleviates Penicillin-Associated Changes, and Reduces Antibiotic Use. PLoS One 2016; 11:e0154012. [PMID: 27111772 PMCID: PMC4844131 DOI: 10.1371/journal.pone.0154012] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Accepted: 04/07/2016] [Indexed: 01/12/2023] Open
Abstract
Antibiotic use is considered among the most severe causes of disturbance to children’s developing intestinal microbiota, and frequently causes adverse gastrointestinal effects ranging from mild and transient diarrhoea to life-threatening infections. Probiotics are commonly advocated to help in preventing antibiotic-associated gastrointestinal symptoms. However, it is currently unknown whether probiotics alleviate the antibiotic-associated changes in children’s microbiota. Furthermore, it is not known how long-term probiotic consumption influences the developing microbiota of children. We analysed the influence of long-term Lactobacillus rhamnosus GG intake on preschool children’s antibiotic use, and antibiotic-associated gastrointestinal complaints in a double blind, randomized placebo-controlled trial with 231 children aged 2–7. In addition, we analysed the effect of L. rhanmosus GG on the intestinal microbiota in a subset of 88 children. The results show that long-term L. rhamnosus GG supplementation has an influence on the composition of the intestinal microbiota in children, causing an increase in the abundance of Prevotella, Lactococcus, and Ruminococcus, and a decrease in Escherichia. The treatment appeared to prevent some of the changes in the microbiota associated with penicillin use, but not those associated with macrolide use. The treatment, however, did reduce the frequency of gastrointestinal complaints after a macrolide course. Finally, the treatment appeared to prevent certain bacterial infections for up to 3 years after the trial, as indicated by reduced antibiotic use. Trial Registration: ClinicalTrials.gov NCT01014676
Collapse
|
|
12
|
Abstract
IMPORTANCE Since 2000, the incidence and severity of Clostridium difficile infection (CDI) have increased. OBJECTIVE To review current evidence regarding best practices for the diagnosis and treatment of CDI in adults (age ≥ 18 years). EVIDENCE REVIEW Ovid MEDLINE and Cochrane databases were searched using keywords relevant to the diagnosis and treatment of CDI in adults. Articles published between January 1978 and October 31, 2014, were selected for inclusion based on targeted keyword searches, manual review of bibliographies, and whether the article was a guideline, systematic review, or meta-analysis published within the past 10 years. Of 4682 articles initially identified, 196 were selected for full review. Of these, the most pertinent 116 articles were included. Clinical trials, large observational studies, and more recently published articles were prioritized in the selection process. FINDINGS Laboratory testing cannot distinguish between asymptomatic colonization and symptomatic infection with C difficile. Diagnostic approaches are complex due to the availability of multiple testing strategies. Multistep algorithms using polymerase chain reaction (PCR) for the toxin gene(s) or single-step PCR on liquid stool samples have the best test performance characteristics (for multistep: sensitivity was 0.68-1.00 and specificity was 0.92-1.00; and for single step: sensitivity was 0.86-0.92 and specificity was 0.94-0.97). Vancomycin and metronidazole are first-line therapies for most patients, although treatment failures have been associated with metronidazole in severe or complicated cases of CDI. Recent data demonstrate clinical success rates of 66.3% for metronidazole vs 78.5% for vancomycin for severe CDI. Newer therapies show promising results, including fidaxomicin (similar clinical cure rates to vancomycin, with lower recurrence rates for fidaxomicin, 15.4% vs vancomycin, 25.3%; P = .005) and fecal microbiota transplantation (response rates of 83%-94% for recurrent CDI). CONCLUSIONS AND RELEVANCE Diagnostic testing for CDI should be performed only in symptomatic patients. Treatment strategies should be based on disease severity, history of prior CDI, and the individual patient's risk of recurrence. Vancomycin is the treatment of choice for severe or complicated CDI, with or without adjunctive therapies. Metronidazole is appropriate for mild disease. Fidaxomicin is a therapeutic option for patients with recurrent CDI or a high risk of recurrence. Fecal microbiota transplantation is associated with symptom resolution of recurrent CDI but its role in primary and severe CDI is not established.
Collapse
Affiliation(s)
- Natasha Bagdasarian
- Division of Infectious Disease and Department of Infection Control, St John Hospital and Medical Center, Detroit, Michigan
- Wayne State University, Department of Internal Medicine, Detroit, Michigan
| | - Krishna Rao
- University of Michigan Medical School, Department of Internal Medicine, Division of Infectious Diseases, University of Michigan Health System, Ann Arbor, Michigan
- Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan
| | - Preeti N. Malani
- University of Michigan Medical School, Department of Internal Medicine, Division of Infectious Diseases, University of Michigan Health System, Ann Arbor, Michigan
- Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan
| |
Collapse
|
|
13
|
IV ECO, III ECO, Johnson DA. Clinical update for the diagnosis and treatment of Clostridium difficile infection. World J Gastrointest Pharmacol Ther 2014; 5:1-26. [PMID: 24729930 PMCID: PMC3951810 DOI: 10.4292/wjgpt.v5.i1.1] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2013] [Revised: 10/06/2013] [Accepted: 12/09/2013] [Indexed: 02/06/2023] Open
Abstract
Clostridium difficile infection (CDI) presents a rapidly evolving challenge in the battle against hospital-acquired infections. Recent advances in CDI diagnosis and management include rapid changes in diagnostic approach with the introduction of newer tests, such as detection of glutamate dehydrogenase in stool and polymerase chain reaction to detect the gene for toxin production, which will soon revolutionize the diagnostic approach to CDI. New medications and multiple medical society guidelines have introduced changing concepts in the definitions of severity of CDI and the choice of therapeutic agents, while rapid expansion of data on the efficacy of fecal microbiota transplantation heralds a revolutionary change in the management of patients suffering multiple relapses of CDI. Through a comprehensive review of current medical literature, this article aims to offer an intensive review of the current state of CDI diagnosis, discuss the strengths and limitations of available laboratory tests, compare both current and future treatments options and offer recommendations for best practice strategies.
Collapse
|
|
14
|
Urben LM, Wiedmar J, Boettcher E, Cavallazzi R, Martindale RG, McClave SA. Bugs or drugs: are probiotics safe for use in the critically ill? Curr Gastroenterol Rep 2014; 16:388. [PMID: 24986534 DOI: 10.1007/s11894-014-0388-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
Probiotics are living microorganisms which have demonstrated many benefits in prevention, mitigation, and treatment of various disease states in critically ill populations. These diseases include antibiotic-associated diarrhea, Clostridium difficile diarrhea, ventilator-associated pneumonia, clearance of vancomycin-resistant enterococci from the GI tract, pancreatitis, liver transplant, major abdominal surgery, and trauma. However, their use has been severely limited due to a variety of factors including a general naïveté within the physician community, lack of regulation, and safety concerns. This article focuses on uses for probiotics in prevention and treatment, addresses current concerns regarding their use as well as proposing a protocol for safe use of probiotics in the critically ill patient.
Collapse
Affiliation(s)
- Lindsay M Urben
- Department of Pharmacy, University of Louisville Hospital, Louisville, KY, USA
| | | | | | | | | | | |
Collapse
|
|
15
|
Vieira AT, Teixeira MM, Martins FS. The role of probiotics and prebiotics in inducing gut immunity. Front Immunol 2013; 4:445. [PMID: 24376446 PMCID: PMC3859913 DOI: 10.3389/fimmu.2013.00445] [Citation(s) in RCA: 163] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2013] [Accepted: 11/26/2013] [Indexed: 12/13/2022] Open
Abstract
The gut immune system is influenced by many factors, including dietary components and commensal bacteria. Nutrients that affect gut immunity and strategies that restore a healthy gut microbial community by affecting the microbial composition are being developed as new therapeutic approaches to treat several inflammatory diseases. Although probiotics (live microorganisms) and prebiotics (food components) have shown promise as treatments for several diseases in both clinical and animal studies, an understanding of the molecular mechanisms behind the direct and indirect effects on the gut immune response will facilitate better and possibly more efficient therapy for diseases. In this review, we will first describe the concept of prebiotics, probiotics, and symbiotics and cover the most recently well-established scientific findings regarding the direct and indirect mechanisms by which these dietary approaches can influence gut immunity. Emphasis will be placed on the relationship of diet, the microbiota, and the gut immune system. Second, we will highlight recent results from our group, which suggest a new dietary manipulation that includes the use of nutrient products (organic selenium and Lithothamnium muelleri) and probiotics (Saccharomyces boulardii UFMG 905 and Bifidobacterium sp.) that can stimulate and manipulate the gut immune response, inducing intestinal homeostasis. Furthermore, the purpose of this review is to discuss and translate all of this knowledge into therapeutic strategies and into treatment for extra-intestinal compartment pathologies. We will conclude by discussing perspectives and molecular advances regarding the use of prebiotics or probiotics as new therapeutic strategies that manipulate the microbial composition and the gut immune responses of the host.
Collapse
Affiliation(s)
- Angélica T Vieira
- Immunopharmacology Group, Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais , Belo Horizonte , Brazil
| | - Mauro M Teixeira
- Immunopharmacology Group, Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais , Belo Horizonte , Brazil
| | - Flaviano S Martins
- Immunopharmacology Group, Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais , Belo Horizonte , Brazil ; Department of Microbiology, Institute of Biological Sciences, Federal University of Minas Gerais , Belo Horizonte , Brazil
| |
Collapse
|
|
16
|
Avery L, Hasan M. Fecal Bacteriotherapy for Clostridium difficile Infections — Its Time Has Come. ACTA ACUST UNITED AC 2013. [DOI: 10.1016/j.clinmicnews.2013.07.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
|
|
17
|
Pant C, Deshpande A, Altaf MA, Minocha A, Sferra TJ. Clostridium difficile infection in children: a comprehensive review. Curr Med Res Opin 2013; 29:967-84. [PMID: 23659563 DOI: 10.1185/03007995.2013.803058] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
OBJECTIVE To provide a comprehensive review of the literature relating to Clostridium difficile (C. difficile) infection (CDI) in the pediatric population. METHODS Two investigators conducted independent searches of PubMed, Web of Science, and Scopus until March 31st, 2013. All databases were searched using the terms 'Clostridium difficile infection', 'Clostridium difficile associated diarrhea' 'antibiotic associated diarrhea', 'C. difficile', in combination with 'pediatric' and 'paediatric'. Articles which discussed pediatric CDI were reviewed and relevant cross references also read and evaluated for inclusion. Selection bias could be a possible limitation of this approach. FINDINGS There is strong evidence for an increased incidence of pediatric CDI. Increasingly, the infection is being acquired from the community, often without a preceding history of antibiotic use. The severity of the disease has remained unchanged. Several medical conditions may be associated with the development of pediatric CDI. Infection prevention and control with antimicrobial stewardship are of paramount importance. It is important to consider the age of the child while testing for CDI. Traditional therapy with metronidazole or vancomycin remains the mainstay of treatment. Newer antibiotics such as fidaxomicin appear promising especially for the treatment of recurrent infection. Conservative surgical options may be a life-saving measure in severe or fulminant cases. CONCLUSIONS Pediatric providers should be cognizant of the increased incidence of CDI in children. Early and judicious testing coupled with the timely institution of therapy will help to secure better outcomes for this disease.
Collapse
Affiliation(s)
- Chaitanya Pant
- Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | | | | | | | | |
Collapse
|
|
18
|
Shah SA, Tsapepas DS, Kubin CJ, Martin ST, Mohan S, Ratner LE, Pereira M, Kapur S, Dadhania D, Walker-McDermott JK. Risk factors associated with Clostridium difficile infection after kidney and pancreas transplantation. Transpl Infect Dis 2013; 15:502-9. [PMID: 23890202 DOI: 10.1111/tid.12113] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2012] [Revised: 01/07/2013] [Accepted: 01/29/2013] [Indexed: 01/21/2023]
Abstract
BACKGROUND Clostridium difficile infection (CDI) is a common cause of nosocomial antibiotic-associated diarrhea with an increased incidence reported in solid organ transplant recipients. We sought to determine if kidney and/or pancreas transplant recipients possess unique risk factors for CDI. METHODS Between January 2009 and February 2011, 942 kidney and 56 pancreas transplants were performed at the 2 centers. Of these, 28 recipients (kidney, n = 24; pancreas, n = 4) developed CDI. Cases were matched to controls (n = 56) in a 1:2 ratio. RESULTS Those with CDI were mostly male patients (82% vs. 48%, P = 0.003), deceased-donor organ recipients (86% vs. 64%, P = 0.045), more likely to have leukopenia (18% vs. 4%, P = 0.038), and had undergone a gastrointestinal procedure within 3 months preceding CDI diagnosis (18% vs. 4%, P = 0.038). Cases had higher cumulative and restricted antimicrobial exposure in days (37 ± 79 vs. 8 ± 12, P = 0.009 and 27 ± 69 vs. 7 ± 10, P = 0.032). Cephalosporin use was more common among cases (43% vs. 16%, P = 0.008). CONCLUSION Careful antimicrobial selection and assurance of optimal treatment duration in the kidney and pancreas transplant population is prudent. Clinicians should have a heightened awareness of CDI risk particularly during periods of leukopenia and in the setting of gastrointestinal procedures.
Collapse
Affiliation(s)
- S A Shah
- Department of Pharmacy, NewYork-Presbyterian Hospital, New York, New York, USA
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
19
|
Protective effect of bifidobacteria in an experimental model ofClostridium difficileassociated colitis. J DAIRY RES 2013; 80:263-9. [DOI: 10.1017/s0022029913000216] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
The aim of this study was to evaluate the ability ofBifidobacteriumstrains to prevent the effects associated withClostridium difficileinfection in a hamster model of enterocolitis. After clindamycin treatment (30 mg/kg), animals were infected intragastrically withC. difficile(5×108CFU per animal). Seven days prior to antibiotic administration, probiotic treatment was started by administering bacterial suspensions of bifidobacteria in drinking water. Strains CIDCA 531, CIDCA 5310, CIDCA 5316, CIDCA 5320, CIDCA 5323 and CIDCA 5325 were used. Treatment was continued during all the experimental period. Development of diarrhoea, enterocolitis and mortality were evaluated. All the infected animals belonging to the placebo group developed enterocolitis (5/5) and only two dead (2/5) whereas in the group administered withBifidobacterium bifidumstrain CIDCA 5310 the ratio of animals with enterocolitis or dead decreased significantly (1/5 and 0/5 respectively). Biological activity of caecum contents was evaluated in vitro on Vero cells. Animals treated with strain CIDCA 5310 presented lower biological activity than those belonging to the placebo group. The present study shows the potential of selected strains of bifidobacteria to antagonise, in vivo, the virulence ofC. difficile.
Collapse
|
|
20
|
Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, McFarland LV, Mellow M, Zuckerbraun BS. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol 2013; 108:478-98; quiz 499. [PMID: 23439232 DOI: 10.1038/ajg.2013.4] [Citation(s) in RCA: 1184] [Impact Index Per Article: 98.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Clostridium difficile infection (CDI) is a leading cause of hospital-associated gastrointestinal illness and places a high burden on our health-care system. Patients with CDI typically have extended lengths-of-stay in hospitals, and CDI is a frequent cause of large hospital outbreaks of disease. This guideline provides recommendations for the diagnosis and management of patients with CDI as well as for the prevention and control of outbreaks while supplementing previously published guidelines. New molecular diagnostic stool tests will likely replace current enzyme immunoassay tests. We suggest treatment of patients be stratified depending on whether they have mild-to-moderate, severe, or complicated disease. Therapy with metronidazole remains the choice for mild-to-moderate disease but may not be adequate for patients with severe or complicated disease. We propose a classification of disease severity to guide therapy that is useful for clinicians. We review current treatment options for patients with recurrent CDI and recommendations for the control and prevention of outbreaks of CDI.
Collapse
Affiliation(s)
- Christina M Surawicz
- Division of Gastroenterology, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98104, USA.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
21
|
The role of acute care surgery in the treatment of severe, complicated Clostridium difficile-associated disease. J Trauma Acute Care Surg 2012; 73:789-800. [PMID: 23026914 DOI: 10.1097/ta.0b013e318265d19f] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Clostridium difficile associated disease (CDAD) is the result of colonic bacterial overgrowth with this gram positive anaerobic organism and the production of toxins that typically induce diarrhea. Most patients with CDAD respond to treatment with oral metronidazole or vancomycin, but a subset of patients will develop a severe systemic illness, multiple organ failure, and death. There are no reliable combinations of clinical or laboratory findings that will distinguish patients who will respond to medical therapy and those who will progress to a more complicated state. Early surgical consultation should be considered in patients with ileus, severe abdominal pain, significant tenderness, immunosuppression, advanced age, high white blood cell or band counts, acute renal failure, mental status changes, or cardiopulmonary compromise. The standard operation for fulminant colitis is subtotal colectomy but the high mortality of the operation, and the long-term morbidity even in survivors combine to act as deterrents to early surgical consultation and operation. Novel operative approaches that preserve the colon and minimize operative morbidity may prove to remove the barriers to earlier surgical treatment for fulminant CDAD and improve outcomes.
Collapse
|
|
22
|
Tsai YT, Cheng PC, Pan TM. The immunomodulatory effects of lactic acid bacteria for improving immune functions and benefits. Appl Microbiol Biotechnol 2012; 96:853-62. [DOI: 10.1007/s00253-012-4407-3] [Citation(s) in RCA: 178] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2012] [Revised: 08/30/2012] [Accepted: 09/04/2012] [Indexed: 12/12/2022]
|
|
23
|
Butler MM, Shinabarger DL, Citron DM, Kelly CP, Dvoskin S, Wright GE, Feng H, Tzipori S, Bowlin TL. MBX-500, a hybrid antibiotic with in vitro and in vivo efficacy against toxigenic Clostridium difficile. Antimicrob Agents Chemother 2012; 56:4786-92. [PMID: 22733075 PMCID: PMC3421853 DOI: 10.1128/aac.00508-12] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2012] [Accepted: 06/19/2012] [Indexed: 12/18/2022] Open
Abstract
Clostridium difficile infection (CDI) causes moderate to severe disease, resulting in diarrhea and pseudomembranous colitis. CDI is difficult to treat due to production of inflammation-inducing toxins, resistance development, and high probability of recurrence. Only two antibiotics are approved for the treatment of CDI, and the pipeline for therapeutic agents contains few new drugs. MBX-500 is a hybrid antibacterial, composed of an anilinouracil DNA polymerase inhibitor linked to a fluoroquinolone DNA gyrase/topoisomerase inhibitor, with potential as a new therapeutic for CDI treatment. Since MBX-500 inhibits three bacterial targets, it has been previously shown to be minimally susceptible to resistance development. In the present study, the in vitro and in vivo efficacies of MBX-500 were explored against the Gram-positive anaerobe, C. difficile. MBX-500 displayed potency across nearly 50 isolates, including those of the fluoroquinolone-resistant, toxin-overproducing NAP1/027 ribotype, performing as well as comparator antibiotics vancomycin and metronidazole. Furthermore, MBX-500 was a narrow-spectrum agent, displaying poor activity against many other gut anaerobes. MBX-500 was active in acute and recurrent infections in a toxigenic hamster model of CDI, exhibiting full protection against acute infections and prevention of recurrence in 70% of the animals. Hamsters treated with MBX-500 displayed significantly greater weight gain than did those treated with vancomycin. Finally, MBX-500 was efficacious in a murine model of CDI, again demonstrating a fully protective effect and permitting near-normal weight gain in the treated animals. These selective anti-CDI features support the further development of MBX 500 for the treatment of CDI.
Collapse
|
|
24
|
Fouhy F, Ross RP, Fitzgerald GF, Stanton C, Cotter PD. Composition of the early intestinal microbiota: knowledge, knowledge gaps and the use of high-throughput sequencing to address these gaps. Gut Microbes 2012; 3:203-20. [PMID: 22572829 PMCID: PMC3427213 DOI: 10.4161/gmic.20169] [Citation(s) in RCA: 165] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The colonization, development and maturation of the newborn gastrointestinal tract that begins immediately at birth and continues for two years, is modulated by numerous factors including mode of delivery, feeding regime, maternal diet/weight, probiotic and prebiotic use and antibiotic exposure pre-, peri- and post-natally. While in the past, culture-based approaches were used to assess the impact of these factors on the gut microbiota, these have now largely been replaced by culture-independent DNA-based approaches and most recently, high-throughput sequencing-based forms thereof. The aim of this review is to summarize recent research into the modulatory factors that impact on the acquisition and development of the infant gut microbiota, to outline the knowledge recently gained through the use of culture-independent techniques and, in particular, highlight advances in high-throughput sequencing and how these technologies have, and will continue to, fill gaps in our knowledge with respect to the human intestinal microbiota.
Collapse
Affiliation(s)
- Fiona Fouhy
- Teagasc Food Research Centre; Moorepark; Fermoy, Cork Ireland,Microbiology Department; University College Cork; Cork, Ireland
| | - R. Paul Ross
- Teagasc Food Research Centre; Moorepark; Fermoy, Cork Ireland,Alimentary Pharmabiotic Centre; Cork, Ireland
| | - Gerald F. Fitzgerald
- Microbiology Department; University College Cork; Cork, Ireland,Alimentary Pharmabiotic Centre; Cork, Ireland
| | - Catherine Stanton
- Teagasc Food Research Centre; Moorepark; Fermoy, Cork Ireland,Alimentary Pharmabiotic Centre; Cork, Ireland,Correspondence to: Catherine Stanton, and Paul D. Cotter,
| | - Paul D. Cotter
- Teagasc Food Research Centre; Moorepark; Fermoy, Cork Ireland,Alimentary Pharmabiotic Centre; Cork, Ireland,Correspondence to: Catherine Stanton, and Paul D. Cotter,
| |
Collapse
|
|
25
|
Clostridium difficile Infection and Proton Pump Inhibitor Use in Hospitalized Pediatric Cystic Fibrosis Patients. Gastroenterol Res Pract 2011; 2011:345012. [PMID: 22144994 PMCID: PMC3226314 DOI: 10.1155/2011/345012] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2011] [Revised: 09/19/2011] [Accepted: 09/20/2011] [Indexed: 01/03/2023] Open
Abstract
Children with cystic fibrosis (CF) often take proton pump inhibitors (PPIs), which helps improve efficacy of fat absorption with pancreatic enzyme replacement therapy. However, PPI use is known to be associated with Clostridium difficile-(C. diff-) associated diarrhea (CDAD). We retrospectively evaluated the incidence of C. diff infection from all pediatric hospital admissions over a 5-year period at a single tertiary children's hospital. We found significantly more C. diff-positive stool tests in hospitalized patients with CF compared to patients with no diagnosis of CF. However, use of a PPI was not associated with an increased risk of CDAD in hospitalized CF patients. In summary, C. diff infection is more common in hospitalized pediatric CF patients although PPI use may not be a risk factor for CDAD development in this patient population.
Collapse
|
|
26
|
Abstract
Clostridium difficile infection (CDI) is one of the most prevalent nosocomial infections. A dramatic increase in the incidence and severity of CDI has been noted in the past decade. Current recommendations suggest metronidazole as first-line therapy in mild to moderately severe CDI and oral vancomycin in individuals with severe CDI, or when metronidazole fails or is contradicted. Alterations of the colonic microbiota, usually caused by antimicrobial therapy, seem to play a critical role in CDI pathogenesis. Probiotics are live microorganisms that confer a health benefit to the host, and have been used in CDI. Although a wide variety of probiotics have been studied, the exact role of probiotics in preventing and treating CDI is not clear. In this study, we reviewed the current literature and recommendations on the most commonly studied protiotic agents (Saccharomyces boulardii, Lactobacillus species, and probiotic mixtures) used to prevent or treat CDI. Lactobacillus-containing probiotic mixtures and S. boulardii may be effective in the prevention of CDI in high-risk antibiotic recipients but this finding is based on small, individual studies, and further, larger, well-controlled studies are needed to confirm preliminary positive findings and to better delineate the efficacy of probiotics in CDI prevention or treatment.
Collapse
|
|
27
|
Hautmann MG, Hipp M, Kölbl O. Clostridium difficile-associated diarrhea in radiooncology: an underestimated problem for the feasibility of the radiooncological treatment? Radiat Oncol 2011; 6:89. [PMID: 21806799 PMCID: PMC3160362 DOI: 10.1186/1748-717x-6-89] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2011] [Accepted: 08/01/2011] [Indexed: 01/01/2023] Open
|
|
28
|
Hedge DD, Strain JD, Heins JR, Farver DK. New advances in the treatment of Clostridium difficile infection (CDI). Ther Clin Risk Manag 2011; 4:949-64. [PMID: 19209277 PMCID: PMC2621401 DOI: 10.2147/tcrm.s3145] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Clostridium difficile infections (CDI) have increased in frequency throughout the world. In addition to an increase in frequency, recent CDI epidemics have been linked to a hypervirulent C. difficile strain resulting in greater severity of disease. Although most mild to moderate cases of CDI continue to respond to metronidazole or vancomycin, refractory and recurrent cases of CDI may require alternative therapies. This review provides a brief overview of CDI and summarizes studies involving alternative antibiotics, toxin binders, probiotics, and immunological therapies that can be considered for treatment of acute and recurrent CDI in severe and refractory situations.
Collapse
Affiliation(s)
- Dennis D Hedge
- South Dakota State University College of Pharmacy, Brookings, SD 57007, USA
| | | | | | | |
Collapse
|
|
29
|
Woo TDH, Oka K, Takahashi M, Hojo F, Osaki T, Hanawa T, Kurata S, Yonezawa H, Kamiya S. Inhibition of the cytotoxic effect of Clostridium difficile in vitro by Clostridium butyricum MIYAIRI 588 strain. J Med Microbiol 2011; 60:1617-1625. [PMID: 21700738 DOI: 10.1099/jmm.0.033423-0] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
In contrast to most modern pharmaceuticals, probiotics are used in many parts of the world with little or no research data on the complex system of interactions that each strain may elicit in the human body. Research on probiotics has recently become more significant, as probiotics have begun to be prescribed by clinicians as an alternative for some gut infections, especially when antibiotics are contraindicated. This study attempted to elucidate the inhibitory interaction between the Japanese probiotic strain Clostridium butyricum MIYAIRI 588 (CBM588) and the hospital pathogen Clostridium difficile, which is responsible for a large proportion of antibiotic-associated diarrhoea and colitis. CBM588 has previously shown effectiveness against C. difficile in vivo, and here it was found that the toxicity of C. difficile in in vitro co-culture with CBM588 was greatly decreased or absent. This was dependent on the inoculation ratio and was not accounted for by the small degree of growth and mRNA inhibition observed. CBM588 and its cell-free supernatant also had no effect on toxin already secreted into the culture medium, and culture of the two strains separated by a semi-permeable membrane resulted in loss of the inhibition. Therefore, it was concluded that the detoxification probably occurred by the inhibition of toxin protein production and that this required close proximity or contact between the two species. The low-pH conditions caused by organic acid secretion were also observed to have inhibitory effects on C. difficile growth, metabolism and toxicity.
Collapse
Affiliation(s)
- Timothy D H Woo
- Department of Infectious Diseases, Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka, Tokyo 181-8611, Japan
| | - Kentaro Oka
- Miyarisan Pharmaceuticals, Hanishina-gun, Sakaki-machi 102-15, Nagano 389-0682, Japan
| | - Motomichi Takahashi
- Miyarisan Pharmaceuticals, Hanishina-gun, Sakaki-machi 102-15, Nagano 389-0682, Japan
| | - Fuhito Hojo
- Department of Infectious Diseases, Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka, Tokyo 181-8611, Japan
| | - Takako Osaki
- Department of Infectious Diseases, Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka, Tokyo 181-8611, Japan
| | - Tomoko Hanawa
- Department of Infectious Diseases, Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka, Tokyo 181-8611, Japan
| | - Satoshi Kurata
- Department of Infectious Diseases, Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka, Tokyo 181-8611, Japan
| | - Hideo Yonezawa
- Department of Infectious Diseases, Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka, Tokyo 181-8611, Japan
| | - Shigeru Kamiya
- Department of Infectious Diseases, Kyorin University School of Medicine, Shinkawa 6-20-2, Mitaka, Tokyo 181-8611, Japan
| |
Collapse
|
|
30
|
Abstract
The intestinal microbiota plays a key role in maintaining the normal function of the human gastrointestinal tract. Many probiotics are derived from human gut flora, and have been confirmed to be valuable in the management of gastrointestinal diseases. Probiotic effects are strain-specific, they do not act through the same mechanisms, and nor are all probiotics good for health. Nevertheless, they do have several common characters in that they exert anti-inflammatory effects, they employ different strategies to antagonize competing microorganisms, and they induce cytoprotective changes in the host either through enhancement of barrier function, or through up-regulation of the expression of cytoprotective host proteins. In this review we focus on several probiotics: a Gram-negative probiotic (Escherichia coli Nissle1917), a Gram-positive probiotic bacterium (Lactobacillus Rhamnosus GG, LGG), a bacterial mixture (VSL#3), and a yeast probiotic (Saccharomyces boulardii).
Collapse
|
|
31
|
Lesperance K, Causey MW, Spencer M, Steele SR. The morbidity of Clostridium difficile infection after elective colonic resection-results from a national population database. Am J Surg 2011; 201:141-8. [PMID: 21266214 DOI: 10.1016/j.amjsurg.2010.09.017] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2009] [Revised: 09/07/2010] [Accepted: 09/07/2010] [Indexed: 11/29/2022]
Abstract
BACKGROUND Clostridium difficile (CD), a gram-positive rod bacterium, resides normally within the human colon. Antibiotic treatment alters normal colonic flora, potentiating abnormal overgrowth of CD. METHODS This study examined the 2004 to 2006 Nationwide Inpatient Sample to determine outcomes of CD colitis after 695,010 elective colonic resections. RESULTS CD infection, occurring in 1.4% of patients, was associated with higher pulmonary (12.1% vs 6.4%) and gastrointestinal (12.8% vs 10.5%) complications as well as an increased length of stay (22.6 vs 10.9 days) and mortality (16.2% vs 4.9%; all P < .001). CD colitis patients more frequently held Medicare insurance (68% vs 51%) and underwent small segmental colonic resection as opposed to a defined anatomic resection (20.0% vs 9.9%; P < .001). An underlying diagnosis of colon cancer was associated with a lower incidence of CD colitis (odds ratio, .71; 95% confidence interval, .59-.84; P < .001). CONCLUSIONS CD colitis is associated with worse outcomes after elective colonic resection.
Collapse
Affiliation(s)
- Kelly Lesperance
- Department of Surgery, Madigan Army Medical Center, Tacoma, WA 98433, USA
| | | | | | | |
Collapse
|
|
32
|
Abdeen SJ, Swett RJ, Feig AL. Peptide inhibitors targeting Clostridium difficile toxins A and B. ACS Chem Biol 2010; 5:1097-103. [PMID: 20863124 DOI: 10.1021/cb100209b] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Clostridium difficile causes severe hospital-acquired antibiotic-associated diarrhea due to the activity of two large protein toxins. Current treatments suffer from a high relapse rate and are generating resistant strains; thus new methods of dealing with these infections that target the virulence factors directly are of interest. Phage display was used to identify peptides that bind to the catalytic domain of C. difficile Toxin A. Library screening and subsequent quantitative binding and inhibition studies showed that several of these peptides are potent inhibitors. Fragment-based computational docking of these peptides elucidated the binding modes within the active site. These antitoxin peptides may serve as potential lead compounds to further engineer peptidomimetic inhibitors of the clostridial toxins.
Collapse
Affiliation(s)
- Sanofar J. Abdeen
- Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, Michigan 48202, United States
| | - Rebecca J. Swett
- Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, Michigan 48202, United States
| | - Andrew L. Feig
- Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, Michigan 48202, United States
| |
Collapse
|
|
33
|
Tsai YT, Cheng PC, Pan TM. Immunomodulating activity of Lactobacillus paracasei subsp. paracasei NTU 101 in enterohemorrhagic Escherichia coli O157H7-infected mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2010; 58:11265-72. [PMID: 20942489 DOI: 10.1021/jf103011z] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/22/2023]
Abstract
The present study investigated the immunomodulating activity of Lactobacillus paracasei subsp. paracasei NTU 101 in enterohemorrhagic Escherichia coli O157:H7-infected BALB/c mice. Mice were given L. paracasei subsp. paracasei NTU 101 (10(8) colony-forming units) for 7 days, before and after the challenge with E. coli O157:H7. Feeding Lactobacillus for 7 days resulted in an increased postchallenge weight gain and lower cumulative morbidity rates. We observed the upregulation of dendritic cells, helper T cell activation, and antibody production in post- and pretreated mice, compared with untreated mice in the E. coli O157:H7 infection group. Moreover, Lactobacillus can down-regulate the expression of toll-like receptors (TLRs) on macrophages and proinflammatory cytokines, and chemokines in the post- or prefeeding mice induce by E. coli O157:H7 infection. These results demonstrated the inhibition of inflammation among the mice in the pretreated group than in the post-treated group by modulating their immune response. These findings suggest that L. paracasei subsp. paracasei NTU 101 may be an effective candidate for use as a probiotic in the prevention of infection caused by E. coli O157:H7 in humans.
Collapse
Affiliation(s)
- Yueh-Ting Tsai
- Department of Biochemical Science & Technology, College of Life Science, National Taiwan University, Taipei 10617, Taiwan
| | | | | |
Collapse
|
|
34
|
Abstract
Depending on intended use of a probiotic (drug vs. dietary supplement), regulatory requirements differ greatly. For dietary supplements, premarketing demonstration of safety and efficacy and approval by the Food and Drug Administration are not required; only premarket notification is required. Saccharomyces boulardii is a probiotic regulated as a dietary supplement intended for use by the general healthy population, not as a drug to prevent, treat, or mitigate disease. However, since recent increases in incidence and severity of Clostridium difficile infection, probiotics have been used to treat recurrent and/or refractory disease in hospitalized patients. Saccharomyces fungemia secondary to use of the probiotic has been described for patients who are critically ill, are receiving nutrition enterally, or have a central venous catheter. Before use of a probiotic is considered for hospitalized patients, careful assessment of risk versus benefit must be made. To ensure patient safety, probiotics should be properly handled during administration.
Collapse
Affiliation(s)
- Veena Venugopalan
- University of Southern California, Los Angeles, California 90033, USA
| | | | | |
Collapse
|
|
35
|
LEWIS JONATHANDN, THOMAS LINDAV, WEIR WILLIAM. The potential of probiotic fermented milk products in reducing risk of antibiotic-associated diarrhoea andClostridium difficiledisease. INT J DAIRY TECHNOL 2009. [DOI: 10.1111/j.1471-0307.2009.00518.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
|
|
36
|
Dugoua JJ, Machado M, Zhu X, Chen X, Koren G, Einarson TR. Probiotic safety in pregnancy: a systematic review and meta-analysis of randomized controlled trials of Lactobacillus, Bifidobacterium, and Saccharomyces spp. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2009; 31:542-552. [PMID: 19646321 DOI: 10.1016/s1701-2163(16)34218-9] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Our objective in this study was to review systematically the evidence for safety of Lactobacillus, Bifidobacterium and Saccharomyces spp. during pregnancy and to conduct a meta-analysis of randomized controlled trials (RCTs). Eleven databases were searched from inception to September 2007 for RCTs of probiotic use during pregnancy. Two independent reviewers searched databases. Random-effects models combined data. Eleven studies on Lactobacillus and/or Bifidobacterium examined 1505 patients for four outcomes with no data heterogeneity; no miscarriage data were reported. Five studies reported Caesarean section outcomes (OR 0.88; 95% CI 0.65 to 1.19). Six studies reported birth weight (weighted difference 45 g; 95% CI -181 to 271). Three studies reported gestational age (weighted difference 0.4 weeks; 95%CI -0.4 to 1.2). No malformations were reported in the probiotic group. No RCTs were available for Saccharomyces during pregnancy. Lactobacillus and Bifidobacterium had no effect on the incidence of Caesarean section, birth weight, or gestational age. The safety of Saccharomyces during pregnancy is unknown.
Collapse
Affiliation(s)
- Jean-Jacques Dugoua
- Graduate Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto ON; Motherisk Program, Hospital for Sick Children, Toronto ON
| | - Marcio Machado
- Toronto Health Economics and Technology Assessment Collaborative (THETA), University of Toronto, Toronto ON
| | - Xu Zhu
- Graduate Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto ON
| | - Xin Chen
- Graduate Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto ON
| | - Gideon Koren
- Graduate Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto ON; Motherisk Program, Hospital for Sick Children, Toronto ON; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto ON
| | - Thomas R Einarson
- Graduate Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto ON; Motherisk Program, Hospital for Sick Children, Toronto ON; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto ON
| |
Collapse
|
|
37
|
Leffler DA, Lamont JT. Treatment of Clostridium difficile-associated disease. Gastroenterology 2009; 136:1899-912. [PMID: 19457418 DOI: 10.1053/j.gastro.2008.12.070] [Citation(s) in RCA: 91] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2008] [Revised: 12/12/2008] [Accepted: 12/22/2008] [Indexed: 02/07/2023]
Abstract
Clostridium difficile infection is an increasing burden to the health care system, totaling more than $1 billion/year in the United States. Treatment of patients with C difficile infection with metronidazole or vancomycin reduces morbidity and mortality, although the number of patients that do not respond to metronidazole is increasing. Despite initial response rates of greater than 90%, 15%-30% of patients have a relapse in symptoms after successful initial therapy, usually in the first few weeks after treatment is discontinued. Failure to develop specific antibody response has recently been identified as a critical factor in recurrence. The review discusses the different management strategies for initial and recurrent symptomatic C difficile infections.
Collapse
Affiliation(s)
- Daniel A Leffler
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
| | | |
Collapse
|
|
38
|
Preidis GA, Versalovic J. Targeting the human microbiome with antibiotics, probiotics, and prebiotics: gastroenterology enters the metagenomics era. Gastroenterology 2009; 136:2015-31. [PMID: 19462507 PMCID: PMC4108289 DOI: 10.1053/j.gastro.2009.01.072] [Citation(s) in RCA: 326] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Studies of metagenomics and the human microbiome will tremendously expand our knowledge of the composition of microbial communities in the human body. As our understanding of microbial variation and corresponding genetic parameters is refined, this information can be applied to rational remodeling or "tailoring" of human-associated microbial communities and their associated functions. Physiologic features such as the development of innate and adaptive immunity, relative susceptibilities to infections, immune tolerance, bioavailability of nutrients, and intestinal barrier function may be modified by changing the composition and functions of the microbial communities. The specialty of gastroenterology will be affected profoundly by the ability to modify the gastrointestinal microbiota through the rational deployment of antibiotics, probiotics, and prebiotics. Antibiotics might be used to remove or suppress undesirable components of the human microbiome. Probiotics can introduce missing microbial components with known beneficial functions for the human host. Prebiotics can enhance the proliferation of beneficial microbes or probiotics, to maximize sustainable changes in the human microbiome. Combinations of these approaches might provide synergistic and effective therapies for specific disorders. The human microbiome could be manipulated by such "smart" strategies to prevent and treat acute gastroenteritis, antibiotic-associated diarrhea and colitis, inflammatory bowel disease, irritable bowel syndrome, necrotizing enterocolitis, and a variety of other disorders.
Collapse
Affiliation(s)
- Geoffrey A. Preidis
- Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas
- Departments of Pathology, Texas Children’s Hospital and Baylor College of Medicine, Houston, Texas
| | - James Versalovic
- Departments of Pathology, Texas Children’s Hospital and Baylor College of Medicine, Houston, Texas
| |
Collapse
|
|
39
|
Abstract
A new, hypervirulent strain of Clostridium difficile, called NAP1/BI/027, has been implicated in C. difficile outbreaks associated with increased morbidity and mortality since the early 2000s. The epidemic strain is resistant to fluoroquinolones in vitro, which was infrequent prior to 2001. The name of this strain reflects its characteristics, demonstrated by different typing methods: pulsed-field gel electrophoresis (NAP1), restriction endonuclease analysis (BI) and polymerase chain reaction (027). In 2004 and 2005, the US Centers for Disease Control and Prevention (CDC) emphasized that the risk of C. difficile-associated diarrhea (CDAD) is increased, not only by the usual factors, including antibiotic exposure, but also gastrointestinal surgery/manipulation, prolonged length of stay in a healthcare setting, serious underlying illness, immune-compromising conditions, and aging. Patients on proton pump inhibitors (PPIs) have an elevated risk, as do peripartum women and heart transplant recipients. Before 2002, toxic megacolon in C. difficile-associated colitis (CDAC), was rare, but its incidence has increased dramatically. Up to two-thirds of hospitalized patients may be infected with C. difficile. Asymptomatic carriers admitted to healthcare facilities can transmit the organism to other susceptible patients, thereby becoming vectors. Fulminant colitis is reported more frequently during outbreaks of C. difficile infection in patients with inflammatory bowel disease (IBD). C. difficile infection with IBD carries a higher mortality than without underlying IBD. This article reviews the latest information on C. difficile infection, including presentation, vulnerable hosts and choice of antibiotics, alternative therapies, and probiotics and immunotherapy. We review contact precautions for patients with known or suspected C. difficile-associated disease. Healthcare institutions require accurate and rapid diagnosis for early detection of possible outbreaks, to initiate specific therapy and implement effective control measures. A comprehensive C. difficile infection control management rapid response team (RRT) is recommended for each health care facility. A communication network between RRTs is recommended, in coordination with each country’s department of health. Our aim is to convey a comprehensive source of information and to guide healthcare professionals in the difficult decisions that they face when caring for these oftentimes very ill patients.
Collapse
|
|
40
|
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 Pract 2009; 24:33-40. [PMID: 19244146 DOI: 10.1177/0884533608329297] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
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.
Collapse
Affiliation(s)
- Cynthia L Rohde
- RML Specialty Hospital, Food and Nutrition Services, 5601 South County Line Rd, Hinsdale, IL 60321, USA.
| | | | | |
Collapse
|
|
41
|
Abstract
PURPOSE OF REVIEW To provide a general understanding of Clostridium difficile infection with a focus on recent publications that evaluate the disease in solid organ transplant recipients. RECENT FINDINGS The incidence of C. difficile infection is increasing worldwide. Epidemics due to a hypervirulent C. difficile strain are associated with an escalating severity of disease. New evidence further supports basing initial treatment choice on disease severity. SUMMARY C. difficile is a significant pathogen in solid organ transplant recipients. Multiple risk factors are found in this population that may result in more severe disease. A high index of suspicion is necessary for the early diagnosis and treatment of C. difficile infection in transplant recipients. Metronidazole and vancomycin show equivalent efficacy in the treatment for mild-to-moderate disease, but vancomycin has demonstrated superiority in the treatment of severe disease. Surgical intervention is also an important consideration in the treatment of solid organ transplant recipients with severe colitis. Rigorous infection control practices are essential for preventing the spread of C. difficile within the hospital environment.
Collapse
|
|
42
|
Bartlett JG. New antimicrobial agents for patients with Clostridium difficile infections. Curr Infect Dis Rep 2009; 11:21-8. [PMID: 19094821 DOI: 10.1007/s11908-009-0004-8] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Current drug treatment of Clostridium difficile infection (CDI) focuses on metronidazole and vancomycin. Early studies showed equivalence, but more recent reports indicate that oral vancomycin is preferred for serious CDI. Recent work has demonstrated a need for new drugs due to challenges with the NAP-1 strain, which appears to cause more refractory disease that is more likely to relapse. These two distinctive facets of treatment are the most challenging. This review discusses new agents in development: antibiotics, probiotics, immune response products, and agents to bind C. difficile toxins. None are likely to be more effective than oral vancomycin for acute infection. However, several may be as effective, without causing relapse or promoting unnecessary antibiotic use for multiple conditions. The greatest promise is with agents used to interrupt relapses. In this category the leading new agents appear to be antibiotics (rifaximin, nitazoxanide, difimicin, ramoplanin), toxin-binding agents (tolevamer), probiotics (Saccharomyces -boulardii and Lactobacillus ramosus), and immune agents (toxoid vaccine and hyperimmune globulin). The drugs that appear most promising based on recent trials are rifaximin, tolevamer, and difimicin, which appear promising for reducing relapses.
Collapse
Affiliation(s)
- John G Bartlett
- Johns Hopkins University School of Medicine, 1830 East Monument Street, Room 447, Baltimore, MD 21205, USA.
| |
Collapse
|
|
43
|
Park HS, Han DS. Management of Antibiotics-Associated Diarrhea. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2009; 54:5-12. [DOI: 10.4166/kjg.2009.54.1.5] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Affiliation(s)
- Hye Sun Park
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Dong Soo Han
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| |
Collapse
|
|
44
|
Affiliation(s)
- Ciarán P Kelly
- Gastroenterology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
| | | |
Collapse
|
|
45
|
Pham M, Lemberg DA, Day AS. Probiotics: sorting the evidence from the myths. Med J Aust 2008; 188:304-308. [PMID: 18312197 DOI: 10.5694/j.1326-5377.2008.tb01627.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2007] [Accepted: 09/24/2007] [Indexed: 10/10/2023]
Abstract
Probiotics consist of yeast or bacteria, especially lactic acid bacteria. They are available as capsules, powder, fermented milks or yoghurts. Probiotics exhibit strain-specific differences in their resistance to acid and bile, ability to colonise the gastrointestinal tract, clinical efficacy, and benefits to the health of the host. There is level I evidence for the use of probiotics in treating acute infectious diarrhoea and preventing antibiotic-associated diarrhoea, with Lactobacillus rhamnosus GG and Saccharomyces boulardii having the most evidence to support their use for these conditions. There is level II evidence that S. boulardii combined with high-dose vancomycin is more effective than the antibiotic alone in preventing recurrent Clostridium difficile diarrhoea. There is level I evidence that probiotics prevent traveller's diarrhoea. There is level I evidence for use of the high-potency probiotic VSL#3 in preventing pouchitis, and level II evidence for this agent in preventing relapse in patients with ulcerative colitis. Probiotics are generally regarded as safe and well tolerated. Some probiotics may be contraindicated in patients who are immunocompromised or have severe underlying illness, as they have been reported to cause fungaemia and bacteraemia.
Collapse
Affiliation(s)
- Mimi Pham
- Department of Gastroenterology, Sydney Children's Hospital, and School of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia
| | | | | |
Collapse
|
|
46
|
Reid G, Anukam K, Koyama T. Probiotic products in Canada with clinical evidence: what can gastroenterologists recommend? CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2008; 22:169-75. [PMID: 18299736 PMCID: PMC2659138 DOI: 10.1155/2008/843892] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/08/2007] [Accepted: 08/22/2007] [Indexed: 02/07/2023]
Abstract
Probiotics, defined as 'live microorganisms, which when administered in adequate amounts, confer a health benefit on the host', are finally becoming an option for gastroenterologists in Canada, after being available for many years in Japan, Europe and the United States of America. Unfortunately, Health Canada and the US Food and Drug Administration have not controlled the use of the term 'probiotic' or put into place United Nations and World Health Organization guidelines. The net result is that a host of products called 'probiotics' are available but are not truly probiotic. The aim of the present review was to discuss the rationale for probiotics in gastroenterology, and specifically examine which products are options for physicians in Canada, and which ones patients might be using. It is hoped that by clarifying what probiotics are, and the strengths and limitations of their use, specialists will be better placed to make recommendations on the role of these products in patient care. In due course, more clinically documented probiotics will emerge, some with therapeutic effects based on a better understanding of disease processes.
Collapse
Affiliation(s)
- G Reid
- Department of Microbiology, University of Western Ontario, London, Canada.
| | | | | |
Collapse
|
|
47
|
Vanderhoof J, Young R. Probiotics in the United States. Clin Infect Dis 2008; 46 Suppl 2:S67-72; discussion S144-51. [DOI: 10.1086/523339] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
|