Search

Clostridium difficile is a gram-positive intestine bacterium that causes a severe diarrhea and could eventually be lethal. The main virulence factor is related to the release of two major exotoxins, toxin A (TcdA) and toxin B (TcdB). Recent C. difficile-associated disease (CDAD) outbreaks have been caused by hypervirulent strains which secrete an additional binary toxin (CDTa/CDTb). Vaccination against these toxins is considered the best way to combat the CDAD. Recently, a novel tetravalent C. difficile vaccine candidate containing all four toxins produced from a baculovirus expression system has been developed. A dose assay to release this tetravalent C. difficile vaccine was developed using tandem ion-exchange HPLC chromatography. A sequential weak cation exchange (carboxyl group) and weak anion exchange (tertiary amine group) columns were employed. The four C. difficile vaccine antigen pIs range from 4.4 to 8.6. The final optimized separation employs salt gradient elution at two different pHs. The standard analytical parameters such as LOD, LOQ, linearity, accuracy, precision and repeatability were evaluated for this method and it was deemed acceptable as a quantitative assay for vaccine release. Furthermore, the developed method was utilized for monitoring the stability of the tetravalent C. difficile vaccine in final container., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Clinicians have traditionally dichotomized bacteria as friendly commensals or harmful pathogens. However, the line separating the two has become blurred with the recognition that the intestinal microbiome is a complex entity in which species can shift sides-from friend to foe and back again-based on crucial factors in their local environment. Significant disruptions in the homeostasis of the microbiome, a phenomenon called dysbiosis, is increasingly associated with a host of untoward effects. Patients in the ICU are at high risk for dysbiosis given the high rate of antibiotic use, acute changes in diet, and the stress of critical illness. Probiotics are living microbes of human origin that when ingested in sufficient quantities, can colonize sites such as the oropharynx and GI tract and provide benefits to the host. In recent years, we have increasingly explored the utility of using probiotics to reverse the intestinal dysbiosis associated with critical illness, thereby reducing select ICU complications associated with increased morbidity and mortality. Although these preliminary efforts have demonstrated varying degrees of success, our present studies suffer from a host of limitations that hinder the strength of their conclusions and the generalizability of their results. Probiotic investigations have been further hobbled by current regulatory requirements, which were designed to serve as the framework for pharmaceutical research. Although such measures are intended to ensure patient safety, they inadvertently impose barriers that stifle innovation regarding nutraceuticals. This review strives to summarize the current evidence regarding the efficacy and safety of probiotics in the ICU as well as to provide an overview of the obstacles probiotic researchers face going forward., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Clostridium difficile is an anaerobic, gram positive, sporulating, toxin-producing bacillus which causes a spectrum of clinical disease ranging from an asymptomatic carrier state to toxic megacolon and fulminant disease. Infection with C. difficile is an expensive and pervasive health care burden. The current theory regarding the development of C. difficile infection (CDI) suggests that disruption of the structure and/or function of an individual's normal intestinal microbiota enables colonization by C. difficile, and in the absence of an effective immune response, the bacteria causes illness. In this article we discuss the role of the colonic microbiota in the development of CDI and the potential role of probiotics in preventing and treating CDI. We review the evidence from in vitro laboratory and pre-clinical studies, as well as evidence from clinical studies and discuss the current recommendations for the use of probiotics for CDI in clinical practice., (Copyright © 2016. Published by Elsevier Ltd.)

A combination of infection control interventions, consisting of education, isolation, hand hygiene, contact precautions, and environmental disinfection, was implemented in the medical intensive care unit (MICU). The strict restriction of the use of antimicrobial agents was not included in this study. Following the interventions, the incidence of Clostridium difficile infection (CDI) in the MICU decreased significantly, by 67%, from 4.70 to 1.53 cases/1000 patient days (p = 0.012), while the hospital-wide incidence of CDI increased significantly from 0.93 to 1.17 cases/1000 patient-days (p = 0.021). A multifaceted approach to minimize C. difficile exposure can be effective in reducing the incidence of hospital-acquired CDI under conditions that do not allow for a restriction in the use of antimicrobial agents., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Antibiotic-associated diarrhoea (AAD) occurs most frequently in older (≥65 years) inpatients exposed to broad-spectrum antibiotics. When caused by Clostridium difficile, AAD can result in life-threatening illness. Although underlying disease mechanisms are not well understood, microbial preparations have been assessed in the prevention of AAD. However, studies have been mostly small single-centre trials with varying quality, providing insufficient data to reliably assess effectiveness. We aimed to do a pragmatic efficacy trial in older inpatients who would be representative of those admitted to National Health Service (NHS) and similar secondary care institutions and to recruit a sufficient number of patients to generate a definitive result., Methods: We did a multicentre, randomised, double-blind, placebo-controlled, pragmatic, efficacy trial of inpatients aged 65 years and older and exposed to one or more oral or parenteral antibiotics. A computer-generated randomisation scheme was used to allocate participants (in a 1:1 ratio) to receive either a multistrain preparation of lactobacilli and bifidobacteria, with a total of 6 × 10(10) organisms, one per day for 21 days, or an identical placebo. Patients, study staff, and specimen and data analysts were masked to assignment. The primary outcomes were occurrence of AAD within 8 weeks and C difficile diarrhoea (CDD) within 12 weeks of recruitment. Analysis was by modified intention-to-treat. This trial is registered, number ISRCTN70017204., Findings: Of 17,420 patients screened, 1493 were randomly assigned to the microbial preparation group and 1488 to the placebo group. 1470 and 1471, respectively, were included in the analyses of the primary endpoints. AAD (including CDD) occurred in 159 (10·8%) participants in the microbial preparation group and 153 (10·4%) participants in the placebo group (relative risk [RR] 1·04; 95% CI 0·84-1·28; p=0·71). CDD was an uncommon cause of AAD and occurred in 12 (0·8%) participants in the microbial preparation group and 17 (1·2%) participants in the placebo group (RR 0·71; 95% CI 0·34-1·47; p=0·35). 578 (19·7%) participants had one or more serious adverse event; the frequency of serious adverse events was much the same in the two study groups and none was attributed to participation in the trial., Interpretation: We identified no evidence that a multistrain preparation of lactobacilli and bifidobacteria was effective in prevention of AAD or CDD. An improved understanding of the pathophysiology of AAD is needed to guide future studies., Funding: Health Technology Assessment programme; National Institute for Health Research, UK., (Copyright © 2013 Allen et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.)

Background: Clostridium difficile-associated diarrhea (CDAD) has shown increasing incidence, morbidity, and mortality in recent years. We assessed the number of CDAD tests requested, CDAD positivity rates, the use of alcohol-based hand rubs, and antimicrobial utilization., Methods: We collected information on every adult patient (>18 years) who developed diarrhea and had a positive stool test for C. difficile toxin from June 2005 to December 2009 at a tertiary care hospital. A time-series analysis was performed using monthly data on the incidence of C. difficile infection (CDI) (i.e., cases of infection per 1000 patient-days), as well as the consumption of alcohol-based hand rubs (in liters/1000-patient days) and antibiotics (in defined daily doses per 1000 patient-days)., Results: The mean number of annual requests for C. difficile tests was 1031, and the rates per 1000 patient-days for each year from 2005 to 2009 were 0.30, 0.46, 0.39, 0.31, and 0.40 overall in the hospital, and 0.18, 0.10, 0.53, 0.38, and 0.37 in the intensive care unit (ICU). The use of alcohol-based hand rubs per 1000 patient-days increased from 37.4 to 73.0, and from 41.5 to 129.4 in the hospital and in the ICU, respectively., Conclusions: The incidence of CDI in the hospital and ICU remained low, despite the increased use of alcohol-based hand rubs and antimicrobials., (Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

First defined in the mid-1990s, prebiotics, which alter the composition and activity of gastrointestinal (GI) microbiota to improve health and well-being, have generated scientific and consumer interest and regulatory debate. The Life Sciences Research Organization, Inc. (LSRO) held a workshop, Prebiotics and the Health Benefits of Fiber: Future Research and Goals, in February 2011 to assess the current state of the science and the international regulatory environment for prebiotics, identify research gaps, and create a strategy for future research. A developing body of evidence supports a role for prebiotics in reducing the risk and severity of GI infection and inflammation, including diarrhea, inflammatory bowel disease, and ulcerative colitis as well as bowel function disorders, including irritable bowel syndrome. Prebiotics also increase the bioavailability and uptake of minerals and data suggest that they reduce the risk of obesity by promoting satiety and weight loss. Additional research is needed to define the relationship between the consumption of different prebiotics and improvement of human health. New information derived from the characterization of the composition and function of different prebiotics as well as the interactions among and between gut microbiota and the human host would improve our understanding of the effects of prebiotics on health and disease and could assist in surmounting regulatory issues related to prebiotic use.

Clostridium difficile infection (CDI) management has become more daunting over the past decade because of alarming increases in CDI incidence and severity both in the hospital and in the community. This increase has concomitantly caused significant escalation of the health-care economic burden caused by CDI, and it will likely be translated to increased ICU admission and attributable mortality. Some possible causes for difficulty in management of CDI are as follows: (1) inability to predict and prevent development of severe/complicated or relapsing CDI in patients who initially present with mild symptoms; (2) lack of a method to determine who would have benefited a priori from initiating vancomycin treatment first instead of treatment with metronidazole; (3) lack of sensitive and specific CDI diagnostics; (4) changing epidemiology of CDI, including the emergence of a hypervirulent, epidemic C difficile strain associated with increased morbidity and mortality; (5) association of certain high-usage nonantimicrobial medications with CDI; and (6) lack of treatment regimens that leave the normal intestinal flora undisturbed while treating the primary infection. The objective of this article is to present current management and prevention guidelines for CDI based on recommendations by the Society for Healthcare Epidemiology of America and Infectious Diseases Society of America and potential new clinical management strategies on the horizon.

Infection with Clostridium difficile is currently the leading cause of infectious diarrhea in hospitalized patients, and recent surveillance data indicate that C. difficile has surpassed methicillin-resistant Staphylococcus aureus as the number one cause of hospital-acquired infections in some areas of the USA. In addition, concern over C. difficile has increased over the past decade due to the appearance of new hypervirulent strains. Metronidazole and vancomycin have remained the treatments of choice for initial therapy of primary infection with C. difficile for the past 25 years, but the persistence of spores leads to a recurrence of infection in an estimated 20-25% of patients. Patients who have one recurrent episode have up to a 65% chance of having additional recurrence. While the judicious use of antimicrobials in accordance with antibiotic stewardship guidelines remains the most effective method for the control of C. difficile, the high recurrence rate, increasing incidence, and changing epidemiology of C. difficile has led to an increased interest in the study of alternative strategies for the prevention and treatment of C. difficile disease. These alternative strategies attempt to eliminate C. difficile spores, replenish the normal gut flora, reduce the C. difficile toxin load in the bowel, or bolster the patient's own immune response to the C. difficile toxins. To evaluate the available evidence on these alternative strategies, we conducted a literature search of MEDLINE (1966-March 2011) and International Pharmaceutical Abstracts (1970-March 2011). Available citations from these articles were also utilized. The aim of this review is to summarize the available evidence for alternative treatment strategies for C. difficile disease and to make recommendations for their place in therapy., (Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: A series of infection control measures were introduced at the University Hospitals of Leicester NHS Trust in 2006-2007 to reduce the incidence of Clostridium difficile infection., Aim: The aim of this study was to assess the impact of these measures on the incidence of C. difficile and to record the associated mortality in hip fracture patients., Patients and Methods: A case matched comparison of mortality was conducted between C. difficile positive patients and C. difficile negative patients admitted with a hip fracture between 1st January 2003 and 30th September 2007. An interrupted time series analysis was performed to assess the effect of various infection control policies on the incidence of C. difficile infection., Results: The interrupted time series analysis showed that the only effective measure was changing antimicrobial prophylaxis to Co-amoxiclav in May 2007. This reduced the incidence of C. difficile from 7.1 to 1.5% (p<0.001). Six-month mortality in C. difficile positive patients was 71% 1 year before introduction of a diarrhoea treatment policy and 65% 1 year after (p=0.5) indicating treatment was ineffective. A matched cohort comparison over a 57-month period from January 2003 to September 2007 showed that the 6-month mortality was 67% in 170 C. difficile positive patients, 27% in 3247 C. difficile negative patients and 29% in the 170 C. difficile negative matched patients., Conclusion: This 38% excess mortality indicated that C. difficile increased mortality and did not simply colonise the sickest patients. Changing prophylaxis to Co-amoxiclav was the most effective measure. This reduced the incidence of C. difficile by 80% and thus reduced mortality by prevention rather than cure.

Clostridium difficile-associated diarrhoea (CDAD) presents mainly as a nosocomial infection, usually after antimicrobial therapy. Many outbreaks have been attributed to C. difficile, some due to a new hyper-virulent strain that may cause more severe disease and a worse patient outcome. As a result of CDAD, large numbers of C. difficile spores may be excreted by affected patients. Spores then survive for months in the environment; they cannot be destroyed by standard alcohol-based hand disinfection, and persist despite usual environmental cleaning agents. All these factors increase the risk of C. difficile transmission. Once CDAD is diagnosed in a patient, immediate implementation of appropriate infection control measures is mandatory in order to prevent further spread within the hospital. The quality and quantity of antibiotic prescribing should be reviewed to minimise the selective pressure for CDAD. This article provides a review of the literature that can be used for evidence-based guidelines to limit the spread of C. difficile. These include early diagnosis of CDAD, surveillance of CDAD cases, education of staff, appropriate use of isolation precautions, hand hygiene, protective clothing, environmental cleaning and cleaning of medical equipment, good antibiotic stewardship, and specific measures during outbreaks. Existing local protocols and practices for the control of C. difficile should be carefully reviewed and modified if necessary.

Background: Clostridium difficile-associated diarrhea (CDAD) is a potentially preventable and often troublesome gastrointestinal complication after cardiac surgery., Methods: A retrospective study was performed of 8,405 cardiac surgery patients at two institutions between January 1997 and August 2004. Preoperative cardiac risk factors, perioperative factors including blood product transfusion, antibiotic utilization, and postoperative morbidity and mortality were recorded. Univariate and multivariate analyses were performed comparing C. difficile patients with a control group matched by date of surgery and institution., Results: Sixty-six of the 8,405 patients identified with toxin-positive CDAD produced an overall incidence of 0.79% (0.70% at institution A and 1.09% at institution B), with a peak overall incidence of 5.45% in June 2003. Independent prognostic factors for CDAD by multivariate analysis included advancing age (odds ratio [OR] 1.028, 95% confidence interval [CI]: 1.001 to 1.056; p = 0.034), female sex (OR 2.026, 95% CI: 1.102 to 3.722; p = 0.022), blood product transfusion (OR 3.277, 95% CI: 1.292 to 8.311; p = 0.006), and increasing cumulative days of antibiotic administration (OR 1.046, 95% CI: 1.014 to 1.080; p = 0.004). There were no differences in the proportion of fluoroquinolones, cephalosporins, or penicillin derivatives administered between groups. The diagnosis of CDAD was associated with a greater median length of mechanical ventilation (25 hours versus 12 hours, p < 0.001), longer intensive care unit stay (5 days versus 2 days, p < 0.001), and extended hospital stay (21 days versus 7 days, p < 0.001), with no difference in 30-day mortality (7.6% versus 9.5%, p = 0.80)., Conclusions: Although the overall incidence of CDAD was low, alteration in transfusion practices and antibiotic utilization may impact the development of CDAD among cardiac surgical patients.

Clostridium difficile should be suspected in patients who present with nosocomial diarrhoea. It is more common in the elderly or in patients with a debilitating underlying condition who have received antimicrobial agents, and up to 20-25% of patients may experience a relapse. The reference method for diagnosis is the cell culture cytotoxin test which detects the presence of toxin B in a cellular culture of human fibroblasts, but recovering C. difficile in culture allows the performance of a ''second-look" cell culture assay that enhances the potential for diagnosis. Oral metronidazole (500 mg tid or 250 mg every 6 hrs) and oral vancomycin (125 mg every 6 hrs) administered for 1014 days have similar therapeutic efficacy, with response rates near 90-97%. C. difficile strains resistant to metronidazole and with intermediate resistance to vancomycin have been described. The administration of probiotics such as Saccharomyces boulardii, Lactobacillus sp. or brewer's yeast for prophylaxis of CDAD remains controversial.

Saccharomyces boulardii is a selected strain of yeast that may have applications in the prevention and treatment of intestinal infections. The animal models and in vitro studies developed to elucidate the mechanisms of this protection are reviewed and discussed.

Clostridium difficile is responsible for 10-25% of cases of antibiotic-associated diarrhea (AAD) and for virtually all cases of antibiotic-associated pseudo-membranous colitis (PMC). This anaerobic spore-forming bacterium has been identified as the leading cause of nosocomial infectious diarrhea in adults. Pathogenesis relies on a disruption of the normal bacterial flora of the colon, a colonization by C. difficile and the release of toxins A and B that cause mucosal damage and inflammation. Incidence of C. difficile intestinal disorders usually varies from one to 40 per thousand patient admissions. Risk factors for C. difficile-associated diarrhea include antimicrobial therapy, older age (> 65 years), antineoplastic chemotherapy, and length of hospital stay. Nosocomial transmission of C. difficile via oro-fecal route occurs in 3-30% of total patient admissions but it remains asymptomatic in more than 66% of cases. Persistent environmental contamination and carrying of the organism on the hands of hospital staff are common. Measures that are effective in reducing cross-infection consist of an accurate and rapid diagnosis, an appropriate treatment, an implementation of enteric precautions for symptomatic patients, a reinforcement of hand-washing and a daily environmental disinfection. C. difficile is a common cause of infectious diarrhea and should be therefore systematically investigated in patients with nosocomial diarrhea.

Clostridium difficile-associated disease (CDAD), a gastrointestinal infection with a wide range of manifestations whose primary symptom is diarrhea, occurs when antibiotic medications, or rarely other drugs or conditions, disrupt the normal colonic microflora, making it susceptible to the growth of toxigenic C difficile. It is a significant nosocomial infection and an increased incidence has been noted in recent years. Although infrequently seen in midwifery practices, it does occur and may increase with the growing usage of intrapartal antibiotics. Midwives may evaluate and treat a client with an initial episode of mild to moderate CDAD; they also may manage collaboratively or refer for medical management those clients with recurrent or severe disease. This article reviews the epidemiology, pathogenesis, clinical presentation, prevention, and midwifery management of initial and recurrent CDAD. The limitation in the use of oral vancomycin due to the emergence of vancomycin-resistant enterococcus, resulting in metronidazole becoming the primary agent for treatment of CDAD, and the implications of this in the treatment of CDAD during pregnancy and lactation are addressed.

Feeding of breast milk in the first weeks of life appears to have a strong protective effect against necrotising enterocolitis. Nevertheless breast milk also seems to be positively linked to the development of jaundice and to late haemorrhagic disease in infants who have not received vitamin K supplements. There is no consistent evidence that other childhood conditions such as insulin dependent diabetes or cancer are less prevalent among children who have been breast fed. Among adult conditions suggested to be less prevalent in the breast fed, only single reports of significant findings for multiple sclerosis and breast cancer exist and convincing corroboration is not available. There are a number of studies that indicate a relationship between breast feeding and later cholesterol levels--and one that has considered the mortality of ischaemic heart disease among adult males. There is some suggestion that breast feeding (during the first year of life) is the optimal protection against future raised lipid levels and mortality from coronary heart disease, but the evidence is far from conclusive. The major health advantage of breast feeding that has been clearly demonstrated remains in the protection of the infant from certain infections in early life. If there are other long-term health advantages they have yet to be fully elucidated and confirmed.

Clostridium difficile diarrhoea represents a significant health-service burden. We recently experienced an outbreak of C difficile diarrhoea associated with increased use of cefotaxime. The question we pose in this paper is how did the introduction and withdrawal of a single antibiotic so greatly affect rates of C difficile diarrhoea? Other antibiotics had nearly as high a risk of causing diarrhoea as cefotaxime, and the majority of patients never received cefotaxime. We believe that such outbreaks of C difficile diarrhoea are best understood in terms of a population model, and that taking antibiotics like cefotaxime should be thought of as a population rather than an individual risk factor. We postulate a herd-immunity model of C difficile diarrhoea, and examine the implications of this hypothesis.

The importance of breast milk in protecting the newborn from infection is recognized worldwide. Infant morbidity and mortality have been directly affected by a decline in breastfeeding. Health care providers are working toward meeting the national goal of increased initiation and duration of breastfeeding. This article focuses on the protective factors transferred to the infant through breast milk. A discussion of maximizing the immunologic benefits of breast milk for the high-risk infant is presented.

The aim of this study was to evaluate the influence of an hyperosmolar solution of theophylline and of blood transfusion in the occurrence of necrotizing enterocolitis (NEC). By the end of 1982, theophylline previously given in alcoholic solution (osmolality greater than 4000 mosm/kg) was given in a preparation of sodium benzoate isoosmotic to the plasma; in addition, blood was irradiated for 20 minutes by X-Rays (5000 rads) before every transfusion. In the same unit of premature infants, the incidence of NEC was 6.7% in 1981-82; it decreased to 2.7% in 1983-84 (p less than 0.02). In the same periods of time, the incidence of NEC in very low birth weight infants (less than 1500 g) decreased from 18% to 4.7% (p less than 0.001) while the number of these very low birth weight infants had increased significantly. The incidence of blood transfusion prior to NEC was found in 67% of the patients. These data suggest a beneficial role of reducing the osmolality of theophylline and of X-Rays irradiation of blood before transfusion as a prophylaxis of NEC in premature infants.