Saccharomyces boulardii prophylaxis for targeted antibiotics and infectious indications to reduce healthcare facility-onset Clostridioides difficile infection

BackgroundProbiotic prophylaxis for Clostridioides difficile infection (CDI) is controversial stemming from deficits in strain and disease specificity considerations and concern for adverse effects. Here risk for healthcare facility-onset CDI (HO-CDI) dependent on concomitant antibiotic and infectious indication is assessed to identify opportunities for targeted prophylaxis.MethodsRetrospective matched-cohort study from January 2016 through March 2019. Patient-admissions administered high risk antibiotics were categorized by Saccharomyces boulardii administration and matched 1:1 to non-recipients. Unadjusted and adjusted HO-CDI risk estimated using Cox proportional hazards regression.ResultsS. boulardii administration was associated with 48% risk reduction for HO-CDI compared to non-recipients (aHR 0.52, 95% CI: 0.31–0.87). Patient-admissions administered antibiotics and S. boulardii for a pneumonia indication exhibited a 57% reduction in risk for HO-CDI (aHR 0.43, 95% CI: 0.19–0.95). Administration of S. boulardii with ceftriaxone was associated with a 76% reduced risk of HO-CDI (aHR 0.24, 95% CI: 0.11–0.53) compared to ceftriaxone without S. boulardii, number needed to treat of 100.ConclusionsS. boulardii administration is associated with a significant HO-CDI risk reduction for inpatients receiving antibiotics associated with CDI. Institutions interested in targeted use of S. boulardii to limit potential adverse effects may consider prophylaxis for inpatients with pneumonia or receiving ceftriaxone.     

Functional Heterologous Protein Expression by Genetically Engineered Probiotic Yeast Saccharomyces boulardii

Recent studies have suggested the potential of probiotic organisms to be adapted for the synthesis and delivery of oral therapeutics. The probiotic yeast Saccharomyces boulardii would be especially well suited for this purpose due to its ability, in contrast to probiotic prokaryotes, to perform eukaryotic post translational modifications. This probiotic yeast thus has the potential to express a broad array of therapeutic proteins. Currently, however, use of wild type (WT) S. boulardii relies on antibiotic resistance for the selection of transformed yeast. Here we report the creation of auxotrophic mutant strains of S. boulardii that can be selected without antibiotics and demonstrate that these yeast can express functional recombinant protein even when recovered from gastrointestinal immune tissues in mice. A UV mutagenesis approach was employed to generate three uracil auxotrophic S. boulardii mutants that show a low rate of reversion to wild type growth. These mutants can express recombinant protein and are resistant in vitro to low pH, bile acid salts, and anaerobic conditions. Critically, oral gavage experiments using C57BL/6 mice demonstrate that mutant S. boulardii survive and are taken up into gastrointestinal immune tissues on a similar level as WT S. boulardii. Mutant yeast recovered from gastrointestinal immune tissues furthermore retain expression of functional recombinant protein. These data show that auxotrophic mutant S. boulardii can safely express recombinant protein without antibiotic selection and can deliver recombinant protein to gastrointestinal immune tissues. These auxotrophic mutants of S. boulardii pave the way for future experiments to test the ability of S. boulardii to deliver therapeutics and mediate protection against gastrointestinal disorders.     

Quality control of fifteen probiotic products containing Saccharomyces boulardii

Aims: The yeast Saccharomyces boulardii is used as a probiotic for the prevention and treatment of diarrhoea. In this study, the quality of 15 probiotic products containing S. boulardii was verified. Methods and Results: Using microsatellite typing, the identity of all Saccharomyces strains in the products was confirmed as S. boulardii. Additionally, solid‐phase cytometry (SPC) and a plate method were used to enumerate S. boulardii cells. SPC was not only able to produce results more rapidly than plating (4 h compared to 48 h) but the cell counts obtained with SPC were significantly higher than the plate counts. Finally, we found that <1% of the S. boulardii cells survived 120 min in gastric conditions and storage for 3 months at 40°C with 75% relative humidity. Conclusions: We developed a SPC method for the quantification of viable S. boulardii cells in probiotics. Additionally, we demonstrated that gastric conditions and storage have a marked effect on the viability of the yeast cells. Significance and Impact of the Study: To our knowledge, this is the first time SPC is used for the quality control of probiotics with S. boulardii. Additionally, we demonstrated the need for gastric protection and accurate storage.     

Synthesis and characterization of N-(4-azidophenylthio)phthalimide: A cleavable, photoactivable crosslinking reagent that reacts with sulfhydryl groups

The cleavable, photoaffinity label precursor, N-(4-azidophenylthio)phthalimide has been synthesized and purified. The recrystallized product was identified by infrared spectroscopy and nuclear magnetic resonance spectroscopy. The compound modifies free thiol groups to yield the corresponding S-4-azidophenylthio derivatives. In order to examine the biological applications of this compound, yeast iso-1-cytochrome c, containing a single free cysteine residue, was modified and characterized. The 102-S-(4-azidophenylthio)-iso-1-cytochrome c was found to contain 1 mol of label/mol of cytochrome c. The photoaffinity labeling of purified, detergent-solubilized yeast cytochrome c oxidase was examined. Photolysis products of crosslinking could be analyzed on sodium dodecyl sulfate-polyacrylamide gels in the absence of reducing agents. The crosslinked products were readily cleaved by dithiothreitol. The use of this compound as a sulfhydryl-specific photolabile, bifunctional crosslinking reagent is discussed.     

Anti-salmonella properties of kefir yeast isolates: An in vitro screening for potential infection control

The rise of antibiotic resistance has increased the need for alternative ways of preventing and treating enteropathogenic bacterial infection. Various probiotic bacteria have been used in animal and human. However, Saccharomyces boulardii is the only yeast currently used in humans as probiotic. There is scarce research conducted on yeast species commonly found in kefir despite its claimed potential preventative and curative effects. This work focused on adhesion properties, and antibacterial metabolites produced by Kluyveromyces lactis and Saccharomyces unisporus isolated from traditional kefir grains compared to Saccharomyces boulardii strains. Adhesion and sedimentation assay, slide agglutination, microscopy and turbidimetry assay were used to analyze adhesion of Salmonella Arizonae and Salmonella Typhimurium onto yeast cells. Salmonella growth inhibition due to the antimicrobial metabolites produced by yeasts in killer toxin medium was analyzed by slab on the lawn, turbidimetry, tube dilution and solid agar plating assays. Alcohol and antimicrobial proteins production by yeasts in killer toxin medium were analyzed using gas chromatography and shotgun proteomics, respectively. Salmonella adhered onto viable and non-viable yeast isolates cell wall. Adhesion was visualized using scanning electron microscope. Yeasts-fermented killer toxin medium showed Salmonella growth inhibition. The highest alcohol concentration detected was 1.55%, and proteins with known antimicrobial properties including cathelicidin, xanthine dehydrogenase, mucin-1, lactadherin, lactoperoxidase, serum amyloid A protein and lactotransferrin were detected in yeasts fermented killer medium. These proteins are suggested to be responsible for the observed growth inhibition effect of yeasts-fermented killer toxin medium. Kluyveromyces lactis and Saccharomyces unisporus have anti-salmonella effect comparable to Saccharomyces boulardii strains, and therefore have potential to control Salmonella infection.     

C. difficile infection (CDI) in a long-term acute care facility (LTAC)

BackgroundC. difficile infection (CDI) is a common nosocomial infection in hospitals and impacts increased hospital cost and length of stay. Since scant information is available about the incidence and prevalence of CDI in Long-term acute care hospitals (LTACs), we therefore studied this at one local facility.MethodsDemographic and other data, and a fresh stool sample were obtained from all new LTAC admissions not carrying a prior diagnosis of CDI during the study period (July 23 to August 22, 2007). A GDH test for C. difficile antigen was performed. All initially positive stools were tested for toxins A and B and a sample was frozen for culture and typing. All antigen-negative patients were monitored for the development of diarrhea during the course of their LTAC hospitalization and, if clinically indicated, a sample was sent for toxins A and B testing and if positive, a stool sample was frozen and stored for culture and typing. Therapy of CDI was noted.Results36 patients were admitted during the study period. 4 of 31 (12.9%) of patients tested were antigen (+) on admission of which 2 (6.5%) were asymptomatic carriers and 2 (6.5%) had unsuspected active disease, including one with the BI epidemic strain. In follow-up, 20/36 (55.5%) developed diarrhea of which an additional 5 (13.8%) patients had developed CDI (average, hospital day 38) in the hospital. Therapy was instituted with vancomycin in 5/7 patients and metronidazole in 2/7 patients. During that quarter, the rate of nosocomial acquired CDI was 3.12 per 1000 patient days.ConclusionsC. difficile carriage and unsuspected clinical CDI occurs, including with the BI epidemic strain disease, in an important minority of patients, which may act as a reservoir for spread. New strategies for detection and prevention of CDI are needed.     

Interaction of Saccharomyces boulardii with Salmonella enterica Serovar Typhimurium Protects Mice and Modifies T84 Cell Response to the Infection

Background

Salmonella pathogenesis engages host cells in two-way biochemical interactions: phagocytosis of bacteria by recruitment of cellular small GTP-binding proteins induced by the bacteria, and by triggering a pro-inflammatory response through activation of MAPKs and nuclear translocation of NF-κB. Worldwide interest in the use of functional foods containing probiotic bacteria for health promotion and disease prevention has increased significantly. Saccharomyces boulardii is a non-pathogenic yeast used as a probiotic in infectious diarrhea.

Methodology/Principal Findings

In this study, we reported that S. boulardii (Sb) protected mice from Salmonella enterica serovar Typhimurium (ST)-induced death and prevented bacterial translocation to the liver. At a molecular level, using T84 human colorectal cancer cells, we demonstrate that incubation with Sb before infection totally abolished Salmonella invasion. This correlates with a decrease of activation of Rac1. Sb preserved T84 barrier function and decreased ST-induced IL-8 synthesis. This anti-inflammatory effect was correlated with an inhibitory effect of Sb on ST-induced activation of the MAPKs ERK1/2, p38 and JNK as well as on activation of NF-κB. Electron and confocal microscopy experiments showed an adhesion of bacteria to yeast cells, which could represent one of the mechanisms by which Sb exerts its protective effects.

Conclusions

Sb shows modulating effects on permeability, inflammation, and signal transduction pathway in T84 cells infected by ST and an in vivo protective effect against ST infection. The present results also demonstrate that Sb modifies invasive properties of Salmonella.     

Capric Acid Secreted by S. boulardii Inhibits C. albicans Filamentous Growth,Adhesion and Biofilm Formation

Candidiasis are life-threatening systemic fungal diseases, especially of gastro intestinal track, skin and mucous membranes lining various body cavities like the nostrils, the mouth, the lips, the eyelids, the ears or the genital area. Due to increasing resistance of candidiasis to existing drugs, it is very important to look for new strategies helping the treatment of such fungal diseases. One promising strategy is the use of the probiotic microorganisms, which when administered in adequate amounts confer a health benefit. Such a probiotic microorganism is yeast Saccharomyces boulardii, a close relative of baker yeast. Saccharomyces boulardii cells and their extract affect the virulence factors of the important human fungal pathogen C. albicans, its hyphae formation, adhesion and biofilm development. Extract prepared from S. boulardii culture filtrate was fractionated and GC-MS analysis showed that the active fraction contained, apart from 2-phenylethanol, caproic, caprylic and capric acid whose presence was confirmed by ESI-MS analysis. Biological activity was tested on C. albicans using extract and pure identified compounds. Our study demonstrated that this probiotic yeast secretes into the medium active compounds reducing candidal virulence factors. The chief compound inhibiting filamentous C. albicans growth comparably to S. boulardii extract was capric acid, which is thus responsible for inhibition of hyphae formation. It also reduced candidal adhesion and biofilm formation, though three times less than the extract, which thus contains other factors suppressing C. albicans adherence. The expression profile of selected genes associated with C. albicans virulence by real-time PCR showed a reduced expression of HWP1, INO1 and CSH1 genes in C. albicans cells treated with capric acid and S. boulardii extract. Hence capric acid secreted by S. boulardii is responsible for inhibition of C. albicans filamentation and partially also adhesion and biofilm formation.     

Estudios de la viabilidad y la vitalidad frente al congelado de la levadura probiótica Saccharomyces boulardii: efecto del preacondicionamiento fisiológico

The aim of this study was to evaluate the vitality and viability of the probiotic yeast Saccharomyces boulardii after freezing/thawing and the physiological preconditioning effect on these properties. The results indicate that the specific growth rate (0.3/h^?1) and biomass (2-3 × 10⁸ cells/ml) of S. boulardii obtained in flasks shaken at 28 °C and at 37 °C were similar. Batch cultures of the yeast in bioreactors using glucose or sugar-cane molasses as carbon sources, reached yields of 0.28 g biomass/g sugar consumed, after 10 h incubation at 28 °C; the same results were obtained in fed batch fermentations. On the other hand, in batch cultures, the vitality of cells recovered during the exponential growth phase was greater than the vitality of cells from the stationary phase of growth. Vitality of cells from fed-batch fermentations was similar to that of stationary growing cells from batch fermentations. Survival to freezing at –20 °C and subsequent thawing of cells from batch cultures was 0.31% for cells in exponential phase of growth and 11.5% for cells in stationary phase. Pre-treatment of this yeast in media with water activity (a_w) 0.98 increased the survival to freezing of S. boulardii cells stored at –20 °C for 2 months by 10 fold. Exposure of the yeast to media of reduced a_w and/or freezing/thawing process negatively affected cell vitality. It was concluded that stress conditions studied herein decrease vitality of S. boulardii. Besides, the yeast strain studied presented good tolerance to bile salts even at low pH values.     

Yeast Modulation of Human Dendritic Cell Cytokine Secretion: An In Vitro Study

Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. The concept of individual microorganisms influencing the makeup of T cell subsets via interactions with intestinal dendritic cells (DCs) appears to constitute the foundation for immunoregulatory effects of probiotics, and several studies have reported probiotic strains resulting in reduction of intestinal inflammation through modulation of DC function. Consequent to a focus on Saccharomyces boulardii as the fundamental probiotic yeast, very little is known about hundreds of non-Saccharomyces yeasts in terms of their interaction with the human gastrointestinal immune system. The aim of the present study was to evaluate 170 yeast strains representing 75 diverse species for modulation of inflammatory cytokine secretion by human DCs in vitro, as compared to cytokine responses induced by a S. boulardii reference strain with probiotic properties documented in clinical trials. Furthermore, we investigated whether cytokine inducing interactions between yeasts and human DCs are dependent upon yeast viability or rather a product of membrane interactions regardless of yeast metabolic function. We demonstrate high diversity in yeast induced cytokine profiles and employ multivariate data analysis to reveal distinct clustering of yeasts inducing similar cytokine profiles in DCs, highlighting clear species distinction within specific yeast genera. The observed differences in induced DC cytokine profiles add to the currently very limited knowledge of the cross-talk between yeasts and human immune cells and provide a foundation for selecting yeast strains for further characterization and development toward potentially novel yeast probiotics. Additionally, we present data to support a hypothesis that the interaction between yeasts and human DCs does not solely depend on yeast viability, a concept which may suggest a need for further classifications beyond the current definition of a probiotic.     

In vitro investigation of <Emphasis Type="Italic">Debaryomyces hansenii</Emphasis> strains for potential probiotic properties

In this study, 23 Debaryomyces hansenii strains, isolated from cheese and fish gut, were investigated in vitro for potential probiotic properties i.e. (1) survival under in vitro GI (gastrointestinal) conditions with different oxygen levels, (2) adhesion to Caco-2 intestinal epithelial cells and mucin, and (3) modulation of pro- and anti-inflammatory cytokine secretion by human monocyte-derived dendritic cells. As references two commercially available probiotic Saccharomyces cerevisiae var. boulardii (S. boulardii) strains were included in the study. Our results demonstrate that the different D. hansenii yeast strains had very diverse properties which could potentially lead to different probiotic effects. One strain of D. hansenii (DI 09) was capable of surviving GI stress conditions, although not to the same degree as the S. boulardii strains. This DI 09 strain, however, adhered more strongly to Caco-2 cells and mucin than the S. boulardii strains. Additionally, two D. hansenii strains (DI 10 and DI 15) elicited a higher IL-10/IL-12 ratio than the S. boulardii strains, indicating a higher anti-inflammatory effects on human dendritic cells. Finally, one strain of D. hansenii (DI 02) was evaluated as the best probiotic candidate because of its outstanding ability to survive the GI stresses, to adhere to Caco-2 cells and mucin and to induce a high IL-10/IL-12 ratio. In conclusion, this study shows that strains of D. hansenii may offer promising probiotic traits relevant for further study.     

Comparative study of Bifidobacteriumanimalis, Escherichiacoli, Lactobacilluscasei and Saccharomycesboulardii probiotic properties

The present work investigates some probiotic properties of four different microorganisms (Bifidobacterium animalis var. lactis BB-12, Escherichia coli EMO, Lactobacillus casei and Saccharomyces boulardii). In vitro and in vivo tests were carried out to compare cell wall hydrophobicity, production of antagonistic substances, survival capacity in the gastrointestinal tract of germ-free mice without pathological consequence, and immune modulation by stimulation of Küpffer cells, intestinal sIgA and IL-10 levels. In vitro antagonism against pathogenic bacteria and yeast was only observed for the probiotic bacteria B. animalis and L. casei. The hydrophobic property of the cell wall was higher for B. animalis and E. coli EMO, and this property could be responsible for a better ability to colonize the gastrointestinal tract of germ-free mice. Higher levels of sIgA were observed mainly for S. boulardii, followed by E. coli EMO and B. animalis, and only S. boulardii induced a significant higher level of IL-10. In conclusion, for a probiotic use, S. boulardii presented better characteristics in terms of immunomodulation, and B. animalis and L. casei for antagonistic substance production. The knowledge of the different probiotic properties could be used to choice the better microorganism depending on the therapeutic or prophylactic application.     

Asymptomatic Carriers of Toxigenic C. difficile in Long-Term Care Facilities: A Meta-Analysis of Prevalence and Risk Factors

BackgroundThe impact of Clostridium difficile colonization in C. difficile infection (CDI) is inadequately explored. As a result, asymptomatic carriage is not considered in the development of infection control policies and the burden of carrier state in long-term care facilities (LTCFs) is unknown.PurposeTo explore the epidemiology of C. difficile colonization in LTCFs, identify predisposing factors and describe its impact on healthcare management.ResultsBased on data from 9 eligible studies that met the specified criteria and included 1,371 subjects, we found that 14.8% (95%CI 7.6%-24.0%) of LTCF residents are asymptomatic carriers of toxigenic C. difficile. Colonization estimates were significantly higher in facilities with prior CDI outbreak (30.1% vs. 6.5%, p = 0.01). Patient history of CDI (OR 6.07; 95% CI 2.06–17.88; effect derived from 3 studies), prior hospitalization (OR 2.11; 95% CI 1.08–4.13; derived from 3 studies) and antimicrobial use within previous 3 months (OR 3.68; 95% CI 2.04–6.62; derived from 4 studies) were associated with colonization. The predicted colonization rate at admission was 8.9%.ConclusionAsymptomatic carriage of toxigenic C. difficile represents a significant burden in LTCFs and is associated with prior CDI outbreaks in the facility, a history of CDI, prior hospitalization and antimicrobial use. These findings can impact infection control measures at LTCFs.     

In vitro and in vivo antiparasitic activity of Physalis angulata L. concentrated ethanolic extract against Trypanosoma cruzi

BackgroundThe current treatment of Chagas disease, endemic in Latin America and emerging in several countries, is limited by the frequent side effects and variable efficacy of benznidazole. Natural products are an important source for the search for new drugs.Aim/hypothesisConsidering the great potential of natural products as antiparasitic agents, we investigated the anti-Trypanosoma cruzi activity of a concentrated ethanolic extract of Physalis angulata (EEPA).MethodsCytotoxicity to mammalian cells was determined using mouse peritoneal macrophages. The antiparasitic activity was evaluated against axenic epimastigote and bloodstream trypomastigote forms of T. cruzi, and against amastigote forms using T. cruzi-infected macrophages. Cell death mechanism was determined in trypomastigotes by flow cytometry analysis after annexin V and propidium iodide staining. The efficacy of EEPA was examined in vivo in an acute model of infection by monitoring blood parasitaemia and survival rate 30 days after treatment. The effect against trypomastigotes of EEPA and benznidazole acting in combination was evaluated.ResultsEEPA effectively inhibits the epimastigote growth (IC₅₀ 2.9 ± 0.1 µM) and reduces bloodstream trypomastigote viability (EC₅₀ 1.7 ± 0.5 µM). It causes parasite cell death by necrosis. EEPA impairs parasite infectivity as well as amastigote development in concentrations noncytotoxic to mammalian cells. In mice acutely-infected with T. cruzi, EEPA reduced the blood parasitaemia in 72.7%. When combined with benznidazole, EEPA showed a synergistic anti-T. cruzi activity, displaying CI values of 0.8 ± 0.07 at EC₅₀ and 0.83 ± 0.1 at EC₉₀.ConclusionEEPA has antiparasitic activity against T. cruzi, causing cell death by necrosis and showing synergistic activity with benznidazole. These findings were reinforced by the observed efficacy of EEPA in reducing parasite load in T. cruzi-mice. Therefore, this represents an important source of antiparasitic natural products.     

儿童重症监护病房医院感染暴发白色念珠菌血流感染4例分析

摘要 目的：探讨儿童重症监护病房白色念珠菌血流感染暴发的临床表现、危险因素、控制措施等,为预防和控制院内白色念珠菌血流感染暴发提供科学依据。方法：以2018年7月我院儿童重症监护病房发生的4例白色念珠菌血流感染暴发患儿为研究对象,分析患儿临床情况、临床特征、危险因素、暴发原因以及采取的预防控制措施。结果：4例医院感染暴发白色念珠菌血流感染患儿均存在基础疾病、有机械通气史、存在中心静脉或动脉置管、静脉或动脉置管前后均使用碘伏消毒、曾使用广谱抗生素、输血制品,白色念珠菌血流感染后最突出的临床表现均是发热。药敏方面,医院感染暴发的4例白色念珠菌感染患儿对唑类及5-氟胞嘧啶均耐药,但对两性霉素B均敏感。经拔除血管置管、减少或者避免广谱抗菌药的应用,根据药敏使用卡泊芬净及两性霉素B抗真菌等积极治疗,1例患儿放弃治疗后死亡,3例患儿顺利出院。通过Fisher确切概率法分析可知,留置中心静脉或动脉置管是儿童重症监护病房发生医院感染暴发白色念珠菌血流感染的危险因素（P<0.05）。结论：留置中心静脉或动脉置管是儿童重症监护病房发生医院感染暴发白色念珠菌血流感染的危险因素,医院感染暴发白色念珠菌血流感染患儿最突出的临床表现是发热,唑类及5-氟胞嘧啶耐药的患儿使用卡泊芬净及两性霉素B可能获得较好的治疗效果。     

Application of Saccharomyces cerevisiae var. boulardii in food processing: a review

Probiotics are increasingly being added to food in order to develop products with health‐promoting properties. Particularly, Saccharomyces cereviceae var. boulardii yeast is recently being investigated like a starting‐culture for development of functional and probiotic foods. Although the literature is abundant on the beneficial effects of S. boulardii on health, slight information is available on the effects of supplementing this probiotic to food systems. The aim of this paper is to examine the applications of S. boulardii to different food matrices and its implication in food processing (stability, sensorial properties and other technological implications) and the concomitant effects on nutrition and health.     

Kind Discrimination and Competitive Exclusion Mediated by Contact-Dependent Growth Inhibition Systems Shape Biofilm Community Structure

Contact-Dependent Growth Inhibition (CDI) is a phenomenon in which bacteria use the toxic C-terminus of a large exoprotein (called BcpA in Burkholderia species) to inhibit the growth of neighboring bacteria upon cell-cell contact. CDI systems are present in a wide range of Gram-negative proteobacteria and a hallmark feature is polymorphism amongst the exoprotein C-termini (BcpA-CT in Burkholderia) and amongst the small immunity proteins (BcpI) that protect against CDI in an allele-specific manner. In addition to CDI, the BcpAIOB proteins of Burkholderia thailandensis mediate biofilm formation, and they do so independent of BcpA-mediated interbacterial competition, suggesting a cooperative role for CDI system proteins in this process. CDI has previously only been demonstrated between CDI⁺ and CDI⁻ bacteria, leaving the roles of CDI system-mediated interbacterial competition and of CDI system diversity in nature unknown. We constructed B. thailandensis strains that differed only in the BcpA-CT and BcpI proteins they produced. When co-cultured on agar, these strains each participated in CDI and the outcome of the competition depended on both CDI system efficiency and relative bacterial numbers initially. Strains also participated in CDI during biofilm development, resulting in pillar structures that were composed of only a single BcpA-CT/BcpI type. Moreover, a strain producing BcpA-CT/BcpI proteins of one type was prevented from joining a pre-established biofilm community composed of bacteria producing BcpA-CT/BcpI proteins of a different type, unless it also produced the BcpI protein of the established strain. Bacteria can therefore use CDI systems for kind recognition and competitive exclusion of ‘non-self’ bacteria from a pre-established biofilm. Our data indicate that CDI systems function in both cooperative and competitive behaviors to build microbial communities that are composed of only bacteria that are related via their CDI system alleles.     

Invasive infections caused by Saprochaete capitata in patients with haematological malignancies: Report of five cases and review of the antifungal therapy

BackgroundSaprochaete capitata (formerly known as Geotrichum capitatum and Blastoschizomyces capitatus) is a ubiquitous fungus found in soil, water, air, plants and dairy products. It colonizes the skin, and bronchial and intestinal tract of healthy people producing serious opportunistic infections in patients with haematological malignancies, especially in those with acute leukaemia. Since 1960s its presence is being increasingly recognized in this group of patients. The clinical spectrum of S. capitata disseminated infections is very similar to that produced by Candida, being easily misinterpreted. The associated high mortality and low susceptibility to fluconazole and echinocandins of S. capitata require the acknowledgement of this emergent infection so that it can be properly treated.Case reportWe report 5 new cases of S. capitata disseminated infection in patients with advanced haematological malignancies observed in the haematology unit between the years 2004 and 2010, and review the state-of-the-art for diagnosis and treatment of this infection.ConclusionsBased on our experience, the prophylactic use of or the empirical antifungal treatment with fluconazole and/or echinocandins would not be adequate for oncohaematological patients in those hospitals where S. capitata infection may be highly prevalent.     

Evidence-based review of probiotics for antibiotic-associated diarrhea and Clostridium difficile infections

Probiotics are living microbes taken to confer a health benefit on the host. Although probiotics have a long history of use in Europe and Asia and have been on the U.S. market for over 14 years, there is still confusion about how to effectively use them. The use of probiotics for the prevention of antibiotic-associated diarrhea (AAD) and the treatment of Clostridium difficile infections (CDI) has been tested in randomized controlled clinical trials.This paper will review the evidence supporting probiotic therapy for these two diseases and also review the advantages and disadvantages of probiotics. The advantages of probiotic therapy include multiple mechanisms of action against pathogens, the ability to interact with the host's natural defense systems, survival to the target organ and a good risk to benefit ratio. Disadvantages of probiotics include lack of standardization for clinical trial designs, variations in regulatory standards, poor quality control for some products and infrequent serious adverse reactions. Overall, probiotics offer a promising strategy for the prevention and treatment for AAD and CDI