Clostridium difficile: A common inhabitant of the colon flora in human infants and sometimes in adults. It produces a toxin that causes pseudomembranous enterocolitis (ENTEROCOLITIS, PSEUDOMEMBRANOUS) in patients receiving antibiotic therapy.Clostridium Infections: Infections with bacteria of the genus CLOSTRIDIUM.Clostridium: A genus of motile or nonmotile gram-positive bacteria of the family Clostridiaceae. Many species have been identified with some being pathogenic. They occur in water, soil, and in the intestinal tract of humans and lower animals.Enterocolitis, Pseudomembranous: An acute inflammation of the INTESTINAL MUCOSA that is characterized by the presence of pseudomembranes or plaques in the SMALL INTESTINE (pseudomembranous enteritis) and the LARGE INTESTINE (pseudomembranous colitis). It is commonly associated with antibiotic therapy and CLOSTRIDIUM DIFFICILE colonization.Bacterial Toxins: Toxic substances formed in or elaborated by bacteria; they are usually proteins with high molecular weight and antigenicity; some are used as antibiotics and some to skin test for the presence of or susceptibility to certain diseases.Ribotyping: RESTRICTION FRAGMENT LENGTH POLYMORPHISM analysis of rRNA genes that is used for differentiating between species or strains.Enterotoxins: Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc.; most common enterotoxins are produced by bacteria.Feces: Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.Clostridium botulinum: A species of anaerobic, gram-positive, rod-shaped bacteria in the family Clostridiaceae that produces proteins with characteristic neurotoxicity. It is the etiologic agent of BOTULISM in humans, wild fowl, HORSES; and CATTLE. Seven subtypes (sometimes called antigenic types, or strains) exist, each producing a different botulinum toxin (BOTULINUM TOXINS). The organism and its spores are widely distributed in nature.Diarrhea: An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight.Cytotoxins: Substances that are toxic to cells; they may be involved in immunity or may be contained in venoms. These are distinguished from CYTOSTATIC AGENTS in degree of effect. Some of them are used as CYTOTOXIC ANTIBIOTICS. The mechanism of action of many of these are as ALKYLATING AGENTS or MITOSIS MODULATORS.Bacterial Proteins: Proteins found in any species of bacterium.Metronidazole: A nitroimidazole used to treat AMEBIASIS; VAGINITIS; TRICHOMONAS INFECTIONS; GIARDIASIS; ANAEROBIC BACTERIA; and TREPONEMAL INFECTIONS. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed).Cross Infection: Any infection which a patient contracts in a health-care institution.Anti-Bacterial Agents: Substances that reduce the growth or reproduction of BACTERIA.Spores, Bacterial: Heat and stain resistant, metabolically inactive bodies formed within the vegetative cells of bacteria of the genera Bacillus and Clostridium.Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to RISTOCETIN that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear.Clostridium sordellii: A species of gram-positive bacteria in the family Clostridiaceae, found in INTESTINES and SOIL.Clostridium acetobutylicum: A species of gram-positive bacteria in the family Clostridiaceae, used for the industrial production of SOLVENTS.Antitoxins: Antisera from immunized animals that is purified and used as a passive immunizing agent against specific BACTERIAL TOXINS.Clostridium tetani: The cause of TETANUS in humans and domestic animals. It is a common inhabitant of human and horse intestines as well as soil. Two components make up its potent exotoxin activity, a neurotoxin and a hemolytic toxin.Clindamycin: An antibacterial agent that is a semisynthetic analog of LINCOMYCIN.Clostridium thermocellum: A species of gram-positive, thermophilic, cellulolytic bacteria in the family Clostridaceae. It degrades and ferments CELLOBIOSE and CELLULOSE to ETHANOL in the CELLULOSOME.Botulinum Toxins: Toxic proteins produced from the species CLOSTRIDIUM BOTULINUM. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon ENDOCYTOSIS into PRESYNAPTIC NERVE ENDINGS. Once inside the cell the botulinum toxin light chain cleaves specific SNARE proteins which are essential for secretion of ACETYLCHOLINE by SYNAPTIC VESICLES. This inhibition of acetylcholine release results in muscular PARALYSIS.Cecum: The blind sac or outpouching area of the LARGE INTESTINE that is below the entrance of the SMALL INTESTINE. It has a worm-like extension, the vermiform APPENDIX.Bacteriological Techniques: Techniques used in studying bacteria.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.ADP Ribose Transferases: Enzymes that transfer the ADP-RIBOSE group of NAD or NADP to proteins or other small molecules. Transfer of ADP-ribose to water (i.e., hydrolysis) is catalyzed by the NADASES. The mono(ADP-ribose)transferases transfer a single ADP-ribose. POLY(ADP-RIBOSE) POLYMERASES transfer multiple units of ADP-ribose to protein targets, building POLY ADENOSINE DIPHOSPHATE RIBOSE in linear or branched chains.DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.Bacterial Typing Techniques: Procedures for identifying types and strains of bacteria. The most frequently employed typing systems are BACTERIOPHAGE TYPING and SEROTYPING as well as bacteriocin typing and biotyping.Cecal Diseases: Pathological developments in the CECUM.Enteritis: Inflammation of any segment of the SMALL INTESTINE.Bacteria, AnaerobicClostridium butyricum: Type species of the genus CLOSTRIDIUM, a gram-positive bacteria in the family Clostridiaceae. It is used as a source of PROBIOTICS.Mesocricetus: A genus of the family Muridae having three species. The present domesticated strains were developed from individuals brought from Syria. They are widely used in biomedical research.Microbial Sensitivity Tests: Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN.Caproates: Derivatives of caproic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain a carboxy terminated six carbon aliphatic structure.Toxoids: Preparations of pathogenic organisms or their derivatives made nontoxic and intended for active immunologic prophylaxis. They include deactivated toxins. Anatoxin toxoids are distinct from anatoxins that are TROPANES found in CYANOBACTERIA.Germ-Free Life: Animals not contaminated by or associated with any foreign organisms.Drug Resistance, Bacterial: The ability of bacteria to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Hospitals, AnimalAza CompoundsMolecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Clostridium septicum: A species of gram-positive bacteria in the family Clostridiaceae. Infections have a strong association with malignancies and also with GAS GANGRENE.Aminoglycosides: Glycosylated compounds in which there is an amino substituent on the glycoside. Some of them are clinically important ANTIBIOTICS.Disease Outbreaks: Sudden increase in the incidence of a disease. The concept includes EPIDEMICS and PANDEMICS.Intestines: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.Enterocolitis: Inflammation of the MUCOSA of both the SMALL INTESTINE and the LARGE INTESTINE. Etiology includes ISCHEMIA, infections, allergic, and immune responses.Glutamate Dehydrogenase: An enzyme that catalyzes the conversion of L-glutamate and water to 2-oxoglutarate and NH3 in the presence of NAD+. (From Enzyme Nomenclature, 1992) EC 1.4.1.2.Gastrointestinal Tract: Generally refers to the digestive structures stretching from the MOUTH to ANUS, but does not include the accessory glandular organs (LIVER; BILIARY TRACT; PANCREAS).Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.CresolsClostridium beijerinckii: A species of gram-positive bacteria in the family Clostridiaceae, capable of solventogenesis, and isolated from SOIL, infected WOUNDS, fermenting OLIVES, and spoiled CANDY.Rifamycins: A group of ANTI-BACTERIAL AGENTS characterized by a chromophoric naphthohydroquinone group spanned by an aliphatic bridge not previously found in other known ANTI-BACTERIAL AGENTS. They have been isolated from fermentation broths of Streptomyces mediterranei.Sensitivity and Specificity: Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)Clostridium perfringens: The most common etiologic agent of GAS GANGRENE. It is differentiable into several distinct types based on the distribution of twelve different toxins.Botulism: A disease caused by potent protein NEUROTOXINS produced by CLOSTRIDIUM BOTULINUM which interfere with the presynaptic release of ACETYLCHOLINE at the NEUROMUSCULAR JUNCTION. Clinical features include abdominal pain, vomiting, acute PARALYSIS (including respiratory paralysis), blurred vision, and DIPLOPIA. Botulism may be classified into several subtypes (e.g., food-borne, infant, wound, and others). (From Adams et al., Principles of Neurology, 6th ed, p1208)rho GTP-Binding Proteins: A large family of MONOMERIC GTP-BINDING PROTEINS that are involved in regulation of actin organization, gene expression and cell cycle progression. This enzyme was formerly listed as EC 3.6.1.47.Probiotics: Live microbial DIETARY SUPPLEMENTS which beneficially affect the host animal by improving its intestinal microbial balance. Antibiotics and other related compounds are not included in this definition. In humans, lactobacilli are commonly used as probiotics, either as single species or in mixed culture with other bacteria. Other genera that have been used are bifidobacteria and streptococci. (J. Nutr. 1995;125:1401-12)Hospitals: Institutions with an organized medical staff which provide medical care to patients.Enterococcus: A genus of gram-positive, coccoid bacteria consisting of organisms causing variable hemolysis that are normal flora of the intestinal tract. Previously thought to be a member of the genus STREPTOCOCCUS, it is now recognized as a separate genus.Environmental Microbiology: The study of microorganisms living in a variety of environments (air, soil, water, etc.) and their pathogenic relationship to other organisms including man.Colony Count, Microbial: Enumeration by direct count of viable, isolated bacterial, archaeal, or fungal CELLS or SPORES capable of growth on solid CULTURE MEDIA. The method is used routinely by environmental microbiologists for quantifying organisms in AIR; FOOD; and WATER; by clinicians for measuring patients' microbial load; and in antimicrobial drug testing.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Tenuazonic Acid: 3-Acetyl-5-sec-butyl-4-hydroxy-3-pyrrolin-2-one. A metabolite found in a strain of the fungus Alternaria tenuis Auct. which functions as an antibiotic with antiviral and antineoplastic properties, and may also act as a mycotoxin.Latex Fixation Tests: Passive agglutination tests in which antigen is adsorbed onto latex particles which then clump in the presence of antibody specific for the adsorbed antigen. (From Stedman, 26th ed)Gene Expression Regulation, Bacterial: Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.Streptogramin B: A specific streptogramin group B antibiotic produced by Streptomyces graminofaciens and other bacteria.Genes, Bacterial: The functional hereditary units of BACTERIA.Molecular Epidemiology: The application of molecular biology to the answering of epidemiological questions. The examination of patterns of changes in DNA to implicate particular carcinogens and the use of molecular markers to predict which individuals are at highest risk for a disease are common examples.Molecular Diagnostic Techniques: MOLECULAR BIOLOGY techniques used in the diagnosis of disease.Clostridium botulinum type A: Subtype of CLOSTRIDIUM BOTULINUM that produces BOTULINUM TOXINS, TYPE A which is neurotoxic to humans and animals.Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection.Bacterial Load: Measurable quantity of bacteria in an object, organism, or organism compartment.Infection Control: Programs of disease surveillance, generally within health care facilities, designed to investigate, prevent, and control the spread of infections and their causative microorganisms.Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its VIRULENCE FACTORS.Bacterial Shedding: The expelling of bacteria from the body. Important routes include the respiratory tract, genital tract, and intestinal tract.Ileitis: Inflammation of any segment of the ILEUM and the ILEOCECAL VALVE.Ileum: The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.Clostridium cellulolyticum: A species of gram-positive bacteria in the family Clostridiaceae. It is a cellulolytic, mesophilic species isolated from decayed GRASS.Carrier State: The condition of harboring an infective organism without manifesting symptoms of infection. The organism must be readily transmissible to another susceptible host.Prophages: Genomes of temperate BACTERIOPHAGES integrated into the DNA of their bacterial host cell. The prophages can be duplicated for many cell generations until some stimulus induces its activation and virulence.Recurrence: The return of a sign, symptom, or disease after a remission.Vero Cells: A CELL LINE derived from the kidney of the African green (vervet) monkey, (CERCOPITHECUS AETHIOPS) used primarily in virus replication studies and plaque assays.Intestinal Mucosa: Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.Colon: The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON.Clostridium cellulovorans: A species of gram-positive, cellulolytic bacteria in the family Clostridiaceae. It produces CELLULOSOMES which are involved in plant CELL WALL degradation.Clostridium chauvoei: A species of gram-positive bacteria in the family Clostridiaceae isolated from infected CATTLE; SHEEP; and other animals. It causes blackleg in cattle and sheep and is transmitted through soil-borne spores.Caco-2 Cells: Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells, such as ENTEROCYTES. These cells are valuable in vitro tools for studies related to intestinal cell function and differentiation.QuinolinesColitis: Inflammation of the COLON section of the large intestine (INTESTINE, LARGE), usually with symptoms such as DIARRHEA (often with blood and mucus), ABDOMINAL PAIN, and FEVER.Fluoroquinolones: A group of QUINOLONES with at least one fluorine atom and a piperazinyl group.

Antimicrobial activities of synthetic bismuth compounds against Clostridium difficile. (1/1505)

Clostridium difficile is a major nosocomial pathogen responsible for pseudomembranous colitis and many cases of antibiotic-associated diarrhea. Because of potential relapse of disease with current antimicrobial therapy protocols, there is a need for additional and/or alternative antimicrobial agents for the treatment of disease caused by C. difficile. We have synthesized a systematic series of 14 structurally simple bismuth compounds and assessed their biological activities against C. difficile and four other gastrointestinal species, including Helicobacter pylori. Here, we report on the activities of six compounds that exhibit antibacterial activities against C. difficile, and some of the compounds have MICs of less than 1 microgram/ml. Also tested, for comparison, were the activities of bismuth subcitrate and ranitidine bismuth citrate obtained from commercial sources. C. difficile and H. pylori were more sensitive both to the synthetic bismuth compounds and to the commercial products than were Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis, and the last three species were markedly resistant to the commercial bismuth salts. Testing with human foreskin fibroblast cells revealed that some of the synthetic compounds were more cytotoxic than others. Killing curves for C. difficile treated with the more active compounds revealed rapid death, and electron microscopy showed that the bismuth of these compounds was rapidly incorporated by C. difficile. Energy dispersive spectroscopy X-ray microanalysis of C. difficile cells containing electron-dense material confirmed the presence of internalized bismuth. Internalized bismuth was not observed in C. difficile treated with synthetic bismuth compounds that lacked antimicrobial activity, which suggests that the uptake of the metal is required for killing activity. The nature of the carrier would seem to determine whether bismuth is transported into susceptible bacteria like C. difficile.  (+info)

How intestinal bacteria cause disease. (2/1505)

An improved understanding of how intestinal bacteria cause disease has become increasingly important because of the emergence of new enteric pathogens, increasing threats of drug resistance, and a growing awareness of their importance in malnutrition and diarrhea. Reviewed here are the varied ways that intestinal bacteria cause disease, which provide fundamental lessons about microbial pathogenesis as well as cell signaling. Following colonization, enteric pathogens may adhere to or invade the epithelium or may produce secretory exotoxins or cytotoxins. In addition, by direct or indirect effects, they may trigger secondary mediator release of cytokines that attract inflammatory cells, which release further products, such as prostaglandins or platelet-activating factor, which can also trigger secretion. An improved understanding of pathogenesis not only opens new approaches to treatment and control but may also suggest improved simple means of diagnosis and even vaccine development.  (+info)

A novel cytotoxin from Clostridium difficile serogroup F is a functional hybrid between two other large clostridial cytotoxins. (3/1505)

The large clostridial cytotoxins (LCTs) constitute a group of high molecular weight clostridial cytotoxins that inactivate cellular small GTP-binding proteins. We demonstrate that a novel LCT (TcdB-1470) from Clostridium difficile strain 1470 is a functional hybrid between "reference" TcdB-10463 and Clostridium sordellii TcsL-1522. It bound to the same specific receptor as TcdB-10463 but glucosylated the same GTP-binding proteins as TcsL-1522. All three toxins had equal enzymatic potencies but were equally cytotoxic only when microinjected. When applied extracellularly TcdB-1470 and TcdB-10463 were considerably more potent cytotoxins than TcsL-1522. The small GTP-binding protein R-Ras was identified as a target for TcdB-1470 and also for TcsL-1522 but not for TcdB-10463. R-Ras is known to control integrin-extracellular matrix interactions from inside the cell. Its glucosylation may be a major determinant for the cell rounding and detachment induced by the two R-Ras-attacking toxins. In contrast, fibroblasts treated with TcdB-10463 were arborized and remained attached, with phosphotyrosine containing structures located at the cell-to-cell contacts and beta3-integrin remaining at the tips of cellular protrusions. These components were absent from cells treated with the R-Ras-inactivating toxins. The novel hybrid toxin will broaden the utility of the LCTs for clarifying the functions of several small GTPases, now including also R-Ras.  (+info)

Immunogenicity of a Salmonella typhimurium aroA aroD vaccine expressing a nontoxic domain of Clostridium difficile toxin A. (4/1505)

The C-terminal repeat domain of Clostridium difficile toxin A harbors toxin-neutralizing epitopes and is considered to be a candidate component of a vaccine against C. difficile-associated disease (CDAD). Fourteen of the 38 C-terminal toxin A repeats (14CDTA) were cloned into pTECH-1 in frame with the immunogenic fragment C of tetanus toxin (TETC) to generate plasmid p56TETC. Expression of the TETC-14CDTA fusion protein was driven from the anaerobically inducible nirB promoter within attenuated Salmonella typhimurium BRD509 (aroA aroD). The TETC-14CDTA fusion protein was purified and shown to bind to known toxin A receptors found on the surface of rabbit erythrocytes. Intranasal (i.n.) and intragastric (i.g.) immunization with 10(7) and 10(10) CFU, respectively, of BRD509(p56TETC) generated significant (P < 0.05) anti-toxin A serum responses after a single dose. Antibody titers were elevated following a boosting dose with either live vaccine or a subcutaneous injection of 0.5 microgram of purified 14CDTA protein. Importantly, serum from mice immunized with BRD509(p56TETC) neutralized toxin A cytotoxicity. Both i.n. and i.g. immunizations also generated toxin A-specific immunoglobulin A on the pulmonary and intestinal mucosa, respectively. Intranasal vaccination induced consistently higher serum and mucosal anti-toxin A antibody responses. Significant anti-tetanus toxoid serum and mucosal antibodies were also generated by both immunization routes. The availability of live attenuated Salmonella typhi for human use may allow the development of a multivalent mucosal vaccine against CDAD, tetanus, and typhoid.  (+info)

Factors associated with prolonged symptoms and severe disease due to Clostridium difficile. (5/1505)

OBJECTIVE: toxigenic Clostridium difficile is responsible for a spectrum of disease severity ranging from mild diarrhoea to fulminant colitis. This study attempts to determine the proportion of patients in each category of severity and evaluate the risk factors for a more prolonged and complicated course. DESIGN: prospective cohort study. SETTING: university teaching hospital. SUBJECTS: all patients with symptomatic C. difficile infection during 4 months of an outbreak (January-April 1995); n=73; median age 74 years (range 17-91). MEASUREMENTS: incidence of C. difficile-associated disease (CDAD); severity of disease; percentage of patients in each category of severity; risk factors for severe disease/prolonged symptoms (univariate and multivariable analyses). RESULTS: the incidence of CDAD was 0.93%. Of the cases identified, 18 (24.7%) had mild, self-limiting disease; 26 (35.6%) had moderately severe disease; 23 (31.5%) had prolonged symptoms and six (8.2%) had a complicated course. Although CDAD was more common in older patients (P < 0.001), increasing age was not a risk factor for severity. Significant risk factors for severe CDAD included low Barthel and abbreviated mental test scores (P < 0.01, P < 0.001 respectively) and recent endoscopy (P=0.03). Logistic regression analysis revealed the following independent predictors of severe CDAD: endoscopy [odds ratios (OR) 4.0, P=0.03] and cognitive impairment (OR 11.0, P < 0.01). A trend towards significance was noted for nasogastric tube insertion (OR 3.1, P=0.08). Complications of infection included dehydration, malnutrition and faecal incontinence (which was statistically significantly associated with more severe disease; P < 0.01). CONCLUSION: risk factors for severity of CDAD include functional disability, cognitive impairment, and recent endoscopy. Anticipation of severe CDAD may limit morbidity and mortality.  (+info)

Incidence and outcome of Clostridium difficile infection following autologous peripheral blood stem cell transplantation. (6/1505)

A retrospective evaluation of 200 consecutive recipients of autologous peripheral blood stem cell transplantation (PBSCT) was conducted to ascertain the incidence and outcome of infection with Clostridium difficile. The diagnosis was confirmed in 14 patients with diarrhea (15 episodes) at a median of 33 days after stem cell infusion. Five patients were neutropenic at the time of diagnosis. Every individual had adverse known risk factors such as recent or current use of antibiotic, corticosteroid and antiviral therapy, recent administration of myeloablative chemotherapy and numerous, prolonged periods of hospitalization. Diarrhea, frequently hemorrhagic, was the most common presenting feature along with fever, abdominal cramps and abdominal distention. Diagnosis was established by the stool-cytotoxin test. Response to standard treatment with oral vancomycin or metronidazole was prompt despite the presence of several adverse prognostic features in these patients. There was only one instance of relapse which was also treated successfully. Several transplant-related variables such as age, sex, underlying malignancy, myelo-ablative regimen, duration of neutropenia, and prophylactic use of oral ampicillin underwent statistical analysis but failed to be predictive of C. difficile infection in such a setting. Finally, C. difficile is not uncommon after autologous PBSCT and must be included in the differential diagnosis in any such patient with diarrhea.  (+info)

Suppression of toxin production in Clostridium difficile VPI 10463 by amino acids. (7/1505)

The impact of various growth conditions on the expression of toxins and other proteins by Clostridium difficile VPI 10463 was studied. During non-starved conditions, the rate of toxin synthesis paralleled that of total protein during both exponential growth and stationary phase, and in both defined and complex media. Biotin limitation reduced growth rate and bulk protein synthesis, whereas toxin expression continued, leading to a 50- to 200-fold increase in intracellular toxin levels. Concomitantly, several 22 kDa proteins were up-regulated as revealed by two-dimensional PAGE analysis. The toxin yield was 30-fold higher in peptone yeast extract (PY) than in PY containing glucose (PYG). By contrast, glucose limitation reduced toxin yields by 20- to 100-fold in defined media. By elevating the buffering capacity and bicarbonate concentration, toxin yields were increased by 10-fold in PY and PYG. The high toxin production by C. difficile during growth in PY was lowered 100-fold by adding a blend of nine amino acids and several 60-100 kDa proteins were concomitantly down-regulated. It was concluded that toxin expression in C. difficile VPI 10463 was not affected by growth rate, growth phase, catabolite repression or the stringent response. Instead the co-expression of toxins and a few specific additional proteins appeared to be influenced by metabolic pathways involving CO2 assimilation, carboxylation reactions and metabolism of certain amino acids.  (+info)

Evaluation of two rapid assays for detection of Clostridium difficile toxin A in stool specimens. (8/1505)

Rapid laboratory diagnosis of Clostridium difficile-associated diarrhea (CDAD) is highly desirable in the setting of hospital cost containment. We tested 654 stool specimens to compare the performance of two assays for rapid detection of toxin A, the Immunocard Toxin A test (Meridian Diagnostics, Inc.) and the Culturette Brand Toxin CD enzyme immunoassay (EIA) (Becton Dickinson Microbiology Systems), with a cytotoxin assay (Cytotoxi Test; Advanced Clinical Diagnostics) and culture on cycloserine-cefoxitin-fructose agar followed by determination of the production of toxins A and B. A chart review was performed for patients whose stool specimens provided positive results on one to three of the assays. With the "gold standard" of all four assays positive or chart review evidence of CDAD, 97 (14.8%) stool specimens were positive by one or more assays and 557 (85.2%) were negative by all methods. Total agreement for all assays was 90.5% (592 of 654). The sensitivity, specificity, positive predictive value, and negative predictive value for toxigenic culture were 94.7, 98.6, 87.1, and 99.5%, respectively, for toxigenic culture; 87.7, 98.6, 86.2, and 98.8%, respectively, for the cytotoxin assay; 71.9, 99.3, 91.1, and 97.3%, respectively, for the Immunocard; and 68.4, 99.1, 88.6, and 96.9%, respectively, for the Culturette EIA. While easy to perform and highly specific, these rapid assays do not appear to be sufficient for accurate diagnosis of CDAD.  (+info)

  • Univariate and multivariate analysis of risk factors for severe clostridium difficile -associated diarrhoea: Importance of co-morbidity and serum C-reactive protein. (eurekalert.org)
  • Clostridium difficile, the most common cause of hospital-associated diarrhoea in developed countries, presents major public health challenges. (edu.au)
  • The emergence of a new and highly toxic strain of C. difficile that is resistant to fluoroquinolone antibiotics such as ciprofloxacin and levofloxacin, said to be causing geographically dispersed outbreaks in North America, was reported in 2005. (wikipedia.org)
  • The antibiotics destroy the good bacteria that usually protect patients, leaving C. difficile bacteria to take over. (opb.org)
  • From a single clinician prescribing unnecessary antibiotics, to a nurse or a doctor who doesn't recognized C. difficile symptoms and doesn't order a test. (opb.org)
  • The incidence and severity of CDI has increased significantly over the last decade, and the book explains why C. difficile , recently reclassified as Clostridioides difficile , remains a significant challenge, also from economic perspective, to health care systems all over the world. (springer.com)
  • The book closes with a summary of the history and the achievements of the European Society of Clinical Microbiology and Infectious Diseases Study Group for Clostridium difficile (ESGCD) written by the current and past presidents of the Society. (springer.com)
  • Centers for Disease Control and Prevention (CDC), Severe Clostridium difficile -associated disease in populations previously at low risk-four states, 2005. (jamanetwork.com)
  • Choudhry MNSoran HZiglam HM Overuse and inappropriate prescribing of proton pump inhibitors in patients with Clostridium difficile -associated disease. (jamanetwork.com)
  • Lowe DOMamdani MMKopp ALow DEJuurlink DN Proton pump inhibitors and hospitalization for Clostridium difficile -associated disease: a population-based study. (jamanetwork.com)
  • Glutamate dehydrogenase (GDH), an enzyme present in high copy numbers in many organisms, has proved to be a sensitive screening marker for Clostridium difficile. (r-biopharm.com)
  • Aseeri MSchroeder TKramer JZackula R Gastric acid suppression by proton pump inhibitors as a risk factor for Clostridium difficile -associated diarrhea in hospitalized patients. (jamanetwork.com)
  • Dial SAlrasadi KManoukian CHuang AMenzies D Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case-control studies. (jamanetwork.com)
  • 2017. Microencapsulation of Clostridium difficile specific bacteriophages using microfluidic glass capillary devices for colon delivery using pH triggered release. (lboro.ac.uk)
  • We assessed strains of C. difficile in a sample of patients with recurrent CDI in Western Australia from October 2011 to July 2017. (edu.au)
  • Clostridium difficile , a major nosocomial pathogen shown to be a primary cause of antibiotic-associated disease, has emerged as a highly transmissible and frequently antibiotic-resistant organism, causing a considerable burden on health care systems worldwide. (springer.com)
  • C. difficile may flourish after antibiotic use because that balance is upset. (apic.org)
  • Clostridium difficile has rapidly emerged as the leading cause of antibiotic-associated diarrheal disease, with the transcontinental spread of various PCR ribotypes, including 001, 017, 027 and 078. (pnas.org)
  • Normal bacterial flora that are susceptible to the antibiotic are eliminated from the digestive tract, while C. difficile that are resistant to the antibiotic remain and begin to overgrow, or new types (strains) of C. difficile are acquired. (labcorp.com)
  • Treatment typically involves discontinuing use of the original antibiotic and administering specific oral antibiotic therapy targeting C. difficile . (labcorp.com)
  • However, it has been reported that preexposure to antibiotics is not a requirement for C. difficile spore germination but that germination and outgrowth in mouse ileal contents can be enhanced with antibiotic treatment ( 8 - 10 ). (asm.org)
  • Because Clostridium difficile disease primarily occurs after antibiotic use, it is important to restrict the use of antibiotics to the treatment of diseases in which they are essential. (verywellhealth.com)
  • C. difficile most commonly affects older adults in hospitals or in long-term care facilities and typically occurs after use of antibiotic medications. (virginiamason.org)
  • Program surveillance coordinators received laboratory reports of positive stool C. difficile tests from residents of catchment areas. (cdc.gov)
  • Stool enzyme immunoassay (EIA) for C difficile was positive. (medscape.com)
  • Testing of stool for the presence of C. difficile toxin confirms the diagnosis of CDI. (nih.gov)
  • However, performance of an enzyme immunoassay is the usual method by which CDI is confirmed, but this test appears to be relatively insensitive, compared with the cell cytotoxicity assay and stool culture for toxigenic C. difficile on selective medium. (nih.gov)
  • Data from an active population- and laboratory-based CDI surveillance in 10 US geographic areas during 2010-2011 were used to identify cases (ie, residents with C difficile- positive stool without a positive test in the previous 8 weeks). (aappublications.org)
  • This comparative study will be carried out in the hospital microbiology laboratory of a tertiary academic health center, St. Joseph's Healthcare (SJH) affiliated with McMaster University, Hamilton, ON on 500 individual stool samples from patients greater than 12 months of age to determine an efficacy of distinction between current gold standard and other methods of testing for Clostridium difficile. (bioportfolio.com)
  • Clostridium difficile has been recently reclassified and renamed as Clostridioides difficile, but since many people still use the former name, it will be used for the purposes of this article. (labcorp.com)
  • Nosocomial Clostridium difficile colonisation and disease. (nih.gov)
  • Clostridium difficile es el principal agente etiológico de la diarrea nosocomial de origen infeccioso. (proz.com)
  • Although the incubation period for Clostridium difficile is not precisely known, researchers suggest that the incubation period is about seven days if the conditions are favorable for bacterial proliferation. (medicinenet.com)
  • After donor-feces infusion, patients showed increased fecal bacterial diversity, similar to that in healthy donors, with an increase in Bacteroidetes species and clostridium clusters IV and XIVa and a decrease in Proteobacteria species. (nih.gov)
  • REP3123 is a new narrow spectrum antibacterial agent that in vitro prevents the growth of C. difficile by in hibiting an essential enzyme inthe bacterial cell called methionyl tRNA synthetase, which blocks the organism from synthesizing proteins. (emaxhealth.com)
  • The purpose of this study is to determine the safety and tolerability of a modified C. difficile vaccine at 3 dose levels compared with a placebo control administered via intramuscular inj. (bioportfolio.com)
  • Records that included an International Classification of Diseases (ICD) code-9 for CDI and a corresponding Current Procedural Terminology code for C. difficile assay were used to identify patients with CDI. (hindawi.com)
  • The latter included an Xpert C. difficile /Epi Assay or an Xpert C. difficile Assay. (hindawi.com)
  • METHODS: Laboratory records at a university-affiliated pediatric hospital were reviewed for all C difficile toxin-positive stools (cell culture cytotoxin assay) between 2000 and 2003. (hindawi.com)
  • Recently, a novel ultrasensitive immunocytotoxicity (ICT) assay capable of detecting TcdA at concentrations as low as 0.1-1 pg/ml was developed by our lab [ 19 ], and toxemia was identified in animals infected with C . difficile [ 20 , 21 ]. (plos.org)
  • The resulting ecological changes in the gut reduce a person's intrinsic ability to resist the colonization of several pathogens, including C. difficile ( 3 - 7 ). (asm.org)
  • Emergent hypervirulent variants of C. difficile are associated with increased transmission, morbidity and mortality and have caused epidemics in North America and Europe. (nps.org.au)
  • The National Prevalence Study of Clostridium difficile in U.S. Healthcare Facilities" indicates that 13 out of every 1,000 hospitalized patients were either infected or colonized with C. difficile . (apic.org)
  • 60 (21%) of 282 patients were culture-positive for C difficile during their hospital stay, of whom 51 were symptom-free faecal excretors. (nih.gov)
  • Tallene fra den skærpede overvågning opdateres retrospektivt og er baseret på prøvedato (ny episode registreres, hvis der er over 6 måneder mellem en patients positive fund). (ssi.dk)
  • In the other 10 episodes (nine patients), there was a severe unusual illness which was associated with detection of C difficile. (biomedsearch.com)
  • Bacteraemia was often a presenting feature in neutropenic patients subsequently shown to have C difficile. (biomedsearch.com)
  • We analyzed the potential for C . difficile toxemia in patients, determined its characteristics, and assessed challenges. (plos.org)
  • If bezlotoxumab - a selective, fully-human, monoclonal antibody designed to neutralise C. difficile toxin - gains approval, it will give patients access to a treatment to prevent the superbug from recurring for the first time. (pharmatimes.com)
  • Approximately 30% of patients admitted to hospitals in the United States are asymptomatic carriers of C difficile , with prevalence increasing to 50% in patients with a history of long-term hospitalization. (uspharmacist.com)
  • At Virginia Mason, physicians specializing in infectious diseases and gastroenterology work closely to develop individualized care plans to effectively diagnose and treat C. difficile. (virginiamason.org)