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PubMed1989

Evolution of the caecal epithelial barrier during Clostridium difficile infection in the mouse.

The most striking effect of Clostridium difficile infection is its degrading of the intestinal barrier. The aim of this study is to establish whether the cellular or paracellular constituent of the barrier is the initial target of the toxins produced by C difficile. Accordingly, the caecal epithelium of C3H/He mice was challenged under three experimental conditions with the C difficile strain VPI 10463: (1) by in vivo inoculation of axenic mice, (2) by adding the toxins to ligated caeca in vivo, and (3) by adding them to the mucosal side of isolated caeca in Ussing chambers. Under all three conditions, the epithelial barrier was tested in caeca mounted in these chambers. The transepithelial potential difference (PD), electrical conductance (G), and intact and degraded Horseradish peroxidase (HRP) fluxes were used as indexes of permeability. Results were as follows: (1) In axenic mice, C difficile caused severe infection, produced toxins A and B, reduced PD, and enhanced G and intact HRP fluxes without changing degraded HRP fluxes, (2) four hours after the toxins were added to ligated caeca in vivo, PD was relatively unaltered, but G, and intact and degraded HRP fluxes increased, and (3) when toxins were added to caeca during two hours in the Ussing chambers, the only modification observed was an increase in degraded-HRP fluxes. These results indicate that the C difficile toxins gradually cause intestinal lesions. After an apparent resistance, they stimulate the endocytotic process and then increase paracellular permeability and finally cause loss of cell viability.

Animals↗
PubMed1998

Enterocolitis associated with Clostridium perfringens infection in neonatal foals: 54 cases (1988-1997).

OBJECTIVE: To identify clinical signs, physical examination findings, results of diagnostic tests, treatments administered, and clinical outcome of neonatal foals with enterocolitis associated with Clostridium perfringens infection. DESIGN: Retrospective study. ANIMALS: 54 neonatal foals. RESULTS: Most foals had acute onset of obtunded mentation, colic, or diarrhea and developed leukopenia, neutropenia, an abnormally high number of band neutrophils, toxic WBC, and hypoproteinemia within 24 hours after admission, despite high serum IgG concentrations (> 800 mg/dl). Abdominocentesis and abdominal radiography of some foals revealed exudative peritonitis and gaseous distention of the small and large intestine, respectively. Cytologic examination of feces revealed spores or gram-positive rods in 8 of 10 foals. The most common genotypes of C perfringens isolates were type A and C, alone or in combination. Treatment did not alter mortality rate for most foals that had a positive culture for C perfringens type C. Of 54 foals, 29 (54%) that had C perfringens-associated enterocolitis died. Foals that had a culture that yielded C perfringens had higher sepsis scores, IgG concentrations, and mortality rates, compared with the overall hospital population of neonatal foals. CLINICAL IMPLICATIONS: Foals less than 7 days old that have enterocolitis associated with C perfringens infections, especially type C, have a guarded prognosis. Cytologic examination of feces to determine spore counts and detect rods may be a means for early identification of C perfringens infections. Polymerase chain reaction assays to determine genotype are important for designing preventive treatment regimens.

Animals↗
PubMed1977

Clostridium septicum infection in childhood leukemia: report of a case and review of the literature.

Overwhelming Clostridium septicum infection is a rare occurrence in children. It is seen almost exclusively as a complication of acute leukemia. A high index of suspicion in the leukemic child with an acute abdomen is the key to early diagnosis and improved survival. A case in a 13-year-old girl with acute myelogenous leukemia is reported and six pediatric cases in the literature were reviewed.

Adolescent↗
PubMed1998

Antibodies to recombinant Clostridium difficile toxins A and B are an effective treatment and prevent relapse of C. difficile-associated disease in a hamster model of infection.

Clostridium difficile causes antibiotic-associated diarrhea and colitis in humans through the actions of toxin A and toxin B on the colonic mucosa. At present, broad-spectrum antibiotic drugs are used to treat this disease, and patients suffer from high relapse rates after termination of treatment. This study examined the role of both toxins in pathogenesis and the ability of orally administered avian antibodies against recombinant epitopes of toxin A and toxin B to treat C. difficile-associated disease (CDAD). DNA fragments representing the entire gene of each toxin were cloned, expressed, and affinity purified. Hens were immunized with these purified recombinant-protein fragments of toxin A and toxin B. Toxin-neutralizing antibodies fractionated from egg yolks were evaluated by a toxin neutralization assay in Syrian hamsters. The carboxy-terminal region of each toxin was most effective in generating toxin-neutralizing antibodies. With a hamster infection model, antibodies to both toxins A and B (CDAD antitoxin) were required to prevent morbidity and mortality from infection. In contrast to vancomycin, CDAD antitoxin prevented relapse and subsequent C. difficile reinfection in the hamsters. These results indicate that CDAD antitoxin may be effective in the treatment and management of CDAD in humans.

Animals↗
PubMed2000

Clostridium difficile infections in HIV-positive patients.

The prevalence of Clostridium difficile infections in HIV-positive patients with regard to the presence of its enterotoxin was investigated. Enzyme immunoassay (EIA, Meridian Diagnostic Inc) was used for the detection of C. difficile enterotoxin in stool specimens collected from 201 HIV-positive and 271 HIV-negative diarrheal patients. Culture was performed on cycloserine cefoxitin fructose agar. Chromosomal DNA types of C. difficile isolates were determined by pulsed-field gel electrophoresis (PFGE). In the HIV-positive group, C. difficile enterotoxin was found in 58.8% and 12.6% of diarrheal and non-diarrheal patients, repectively, whereas this toxin was found in 36.5% of HIV-negative-diarrheal patients. However, 13.6% of stool samples were negative by toxin assay, but were positive for C. difficile by culture and latex agglutination test. Among 11 isolates from both HIV-positive and HIV-negative patients, 6 patterns of PFGE type were observed: A, B, C, D, E and F.

AIDS-Related Opportunistic Infections↗
PubMed1993

Clostridium perfringens infection of an anterior iliac crest bone graft donor site. A case report.

Postoperative infection of elective surgical wounds with Clostridium species has been linked to gastrointestinal tract lesions. A 55-year-old man with a history of peptic ulcer disease was treated by open reduction and internal fixation with autogeneic cancellous bone grafting from an anterior iliac crest donor site for nonunion of the clavicle. A mild serosanguinous drainage from the Penrose drain site at the iliac crest had ceased on postoperative Day 11; the patient complained of pain and a brownish drainage on postoperative Day 15. The infection was documented with cultures positive for Clostridium perfringens. Aggressive emergent surgical and antibiotic therapy resulted in complete clinical recovery. The wound infection did not advance to severe tissue damage and myonecrosis. This case represents the first reported infection of an iliac crest bone graft site with C. perfringens.

Bone Transplantation↗
PubMed1988

Clostridium perfringens infection in a total knee arthroplasty. A case report.

A 66-year-old woman with a painful total knee arthroplasty and turbid fluid aspirates had her prosthesis removed for a presumed diagnosis of infection. The intraoperative cultures were positive for Clostridium perfringens, and the patient did well after a course of intravenous antibiotics prior to reimplantation. Clostridium perfringens is a rare cause of pyarthrosis in both nonoperative and prosthetic joints. This report details the first case of clostridial infection involving a patient with a total knee arthroplasty.

Aged↗
PubMed1991

Clostridium septicum infection. Beware of associated cancer.

For reasons that are not fully understood, there is an association between Clostridium septicum infection and carcinoma. In this article, Dr Kirchner describes the examination and treatment of a patient with C septicum infection in whom metastatic cancer was found on laparotomy.

Adenocarcinoma↗
PubMed2006

Clostridium perfringens infection of pancreatic necrosis: absolute indication for early surgical intervention.

It is generally accepted that the surgical treatment of pancreatic necrosis should be delayed as long as possible and after there is laboratory confirmation of infection, determined by image guided fine-needle aspiration. Two cases of severe necrotizing pancreatitis are presented where gas developed in the pancreatic bed, detected by CT scanning, within 2--4 days of the onset of symptoms. Bacteriology studies showed clostridium perfringens and other gram negative flora. The presence of retroperitoneal gas in this context is an absolute indication for early surgical intervention.

Aged↗
PubMedDate not supplied

Postpartum uterine infection with Clostridium perfringens.

Clostridium perfringens is commonly present in the female genital tract. Uterine infection with this organism is a potentially fatal disease infrequently seen in obstetric practice. The manifestations of C. perfringens uterine infection are variable, ranging from endometritis to gas gangrene with fulminant septicemia. The usual precipitating event has been septic abortion, but such infections can also occur spontaneously in uterine tumors and after complicated deliveries requiring mechanical intervention. Diagnosis may be aided by radiologic techniques, and treatment involves high-dose penicillin and possibly surgery. We report two cases and review the clinical presentation and the diagnostic and therapeutic aspects of this disease.

Adult↗
PubMed1999

Enterocolitis associated with dual infection by Clostridium piliforme and feline panleukopenia virus in three kittens.

Dual infection by Clostridium piliforme and feline panleukopenia virus (FPLV) was found in three kittens. In all cases, we found focal necrosis and desquamation of epithelial cells with occasional neutrophil infiltration in the large intestine. Large filamentous bacilli and spores were observed in the epithelium by using the Warthin-Starry method. Electron microscopy revealed the vegetative forms with characteristic peritrichous flagella and spore forms. Immunohistochemically, these bacilli showed a positive reaction with mouse antisera against the RT and MSK C. piliforme strains. Polymerase chain reaction (PCR) using cecum specimens demonstrated the 196-bp band specific to C. piliforme 16S rRNA. All three kittens were also diagnosed as FPLV-infected on the basis of the characteristic mucosal lesions, including intranuclear inclusions and PCR study for the FPLV genomic DNA. The PCR techniques are useful for confirming the C. piliforme and FPLV infection in spontaneous cases.

Animals↗
PubMed2004

Treatment of Clostridium difficile Infection.

With the introduction of broad-spectrum antibiotics into clinical practice, Clostridium difficile infection has become the most common cause of infectious diarrhea in hospitalized patients. Although mild cases may resolve by discontinuing antibiotics, thus allowing re-establishment of colonic microflora, oral metronidazole or vancomycin is indicated if the process is more severe. Metronidazole may be given intravenously, with intracolonic therapeutic levels achieved by excretion of drug into bile and exudation across inflamed tissue. Vancomycin is preferred treatment of severe cases. Bacitracin given orally is a therapeutic alternative and cholestyramine is a useful adjunct. Most patients with diarrhea or colitis caused by C. difficile respond to initial therapy; however, up to 20% experience relapse when treatment is discontinued. Repeating initial therapy for 10 to 14 days is indicated for first relapse. Multiple relapses require prolonged treatment with vancomycin, which may be supplemented with cholestyramine. Saccharomyces boulardii alone or in combination with vancomycin has been reported to be an effective therapeutic alternative for recurrent infection. Intravenous immunoglobulin can be effective in patients with severe recurrent Clostridium difficile colitis and immune deficiency or low pretreatment levels of serum antitoxin. Surgery is indicated only if recurrent infections are severe and associated with serious complications.

Journal Article↗
PubMed2003

Necrotic hepatitis due to Clostridium perfringens infection in newly hatched broiler chicks.

Multiple necrotic hepatitis lesions of 5 newly hatched broiler chicks in three flocks derived from two hatcheries were examined pathologically. The livers were brittle, and multiple yellowish or green foci were scattered on the surface and cut surface. The main histological finding was well demarcated multi-focal necrosis in the liver. Many Gram-positive large bacilli that reacted positively with polyclonal anti-Clostridium perfringens serum were observed in necrotic areas.

Animals↗
PubMed1998

Bacterial translocation, intestinal microflora and morphological changes of intestinal mucosa in experimental models of Clostridium difficile infection.

Bacteraemia and subsequent sepsis is one possible complication of Clostridium difficile infection. The aim of this study was to examine a correlation between bacterial translocation with morphological changes of intestinal mucosa and shifts of intestinal microflora in experimental models of C. difficile infection. A mouse model was used to study post-antibiotic shifts and mild C. difficile infection, and hamsters were used to study fatal enterocolitis. The influence of pro- and pre-biotics (lactobacilli and xylitol) were also studied in the hamster model. The quantitative composition of luminal and mucosal microflora was evaluated in different intestinal loci, inflammatory changes of mucosa were estimated in histological sections and bacterial translocation was detected in samples from blood, liver, spleen and mesenteric lymph nodes. In cases of mild C. difficile infection, the extent of disturbance of intestinal microflora appeared to be a more important promoting factor in translocation than inflammatory activity in the mucosa. Translocation was frequent in fatal enterocolitis, with facultative species predominating in the intestinal mucosa and also C. difficile in some cases. The combination of lactobacilli and xylitol had some protective effect against C. difficile infection in these models.

Ampicillin↗