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PubMed1997

A prospective study of Clostridium difficile infection and colonization in pediatric oncology patients.

BACKGROUND: Patients with cancer often receive broad spectrum antibiotics in addition to antineoplastic chemotherapy. Both treatments predispose adult oncology patients to infection and colonization with Clostridium difficile, but the role of this pathogen in pediatric oncology patients is poorly defined. METHODS: A prospective study of 149 fecal samples from symptomatic pediatric oncology patients and 58 samples from asymptomatic patients was performed. Each sample was analyzed for the presence of C. difficile and its toxins A and B. RESULTS: In 8.7% of the symptomatic samples and 19% of the asymptomatic samples toxigenic C. difficile was found. No association was found between either the use of antibiotics and/or the administration of chemotherapy and the presence of toxigenic C. difficile. Younger children were more likely to be infected or colonized with C. difficile, and there was no evidence of nosocomial transmission of C. difficile within the study population. CONCLUSIONS: As toxigenic C. difficile may form part of the normal flora in young children, this study indicates that in the absence of a defined outbreak, C. difficile does not appear to be an important pathogen in pediatric oncology patients.

Adolescent↗
PubMed1996

Immune response to Clostridium difficile infection.

Clostridium difficile produces two toxins (A and B) which cause antibiotic-associated diarrhoea and pseudomembranous colitis. One of the most puzzling aspects of C. difficile infection is the wide spectrum of clinical presentation which ranges from asymptomatic carriage to fulminant, life-threatening colitis. This review examines the hypothesis that immune responses to C. difficile underlie these dramatic variations in disease presentation and course. Animals can be protected from C. difficile colitis by passive or active immunization against toxins A and B. Human antibody responses to these toxins are evident in approximately 60% of the general population. A number of clinical studies indicate that antitoxin responses in both serum and intestinal secretions may be protective whereas an inadequate immune response predisposes to severe or recurrent C. difficile diarrhoea. Thus there is now considerable interest in developing methods for passive and active immunization to combat this prevalent nosocomial intestinal pathogen.

Animals↗
PubMed2006

Continuation of antibiotics is associated with failure of metronidazole for Clostridium difficile-associated diarrhea.

BACKGROUND: Metronidazole is first-line therapy for C. difficile-associated diarrhea primarily because of its low cost relative to vancomycin. Currently, it is unknown which patients will fail metronidazole therapy. Our goal was to prospectively evaluate risk factors for metronidazole failure. STUDY: Included patients had symptomatic C. difficile-associated diarrhea, either mild or severe. Once enrolled, detailed baseline data were gathered. All interviews were performed daily while the patient was in the hospital for up to 14 days. If discharged prior to 14 days, the patient received a follow-up phone call on day 5 and day 14. Enrolled patients were given a daily stool survey to complete. RESULTS: We enrolled 27 patients with C. difficile-associated diarrhea. All patients (10 of 10) who had their offending antibiotic(s) discontinued had symptomatic resolution of diarrhea by day 14 of metronidazole treatment. Conversely, 59% (10 of 17) of patients who remained on antibiotics during treatment had symptomatic resolution by day 14 (P=0.02). The risk ratio for treatment failure was 2.0 (95% confidence interval, 1.29-3.10) in patients who remained on antibiotics. In our treatment group, there would be one additional metronidazole treatment success for every 2.4 patients who discontinued antibiotics. CONCLUSION: Patients who remain on antibiotics while undergoing treatment of C. difficile-associated diarrhea have a high likelihood of treatment failure with metronidazole.

Aged↗
PubMed2004

Leukemoid reaction due to Clostridium dificile infection in acquired immunodeficiency syndrome: two case reports and a review of the literature.

The clinical presentation of colitis associated with Clostridium difficile infection in immunosuppressed patients with acquired immunodeficiency syndrome (AIDS) has not been completely characterized. Previous reports suggest that these patients present with low blood leukocyte counts, consistent with the impaired myelopoiesis that can occur with human immunodeficiency virus (HIV) infection. In contrast, we describe the cases of two patients with colitis associated with C difficile infection who developed intense leukemoid reactions despite being in advanced stages of AIDS. To the best of our knowledge, these are the first described cases of leukemoid reaction associated with C difficile or other bacterial infection in AIDS patients. We review the literature on C difficile colitis in patients infected with HIV and suggest that severe C difficile infection should be considered in such patients presenting with leukemoid reaction and diarrhea.

AIDS-Related Opportunistic Infections↗
PubMed2005

PCR ribotyping of Clostridium difficile isolates originating from human and animal sources.

Molecular typing of Clostridium difficile isolates from animals and humans may be useful for evaluation of the possibility for interspecies transmission. The objective of this study was to evaluate C. difficile isolates from domestic animals and humans using PCR ribotyping. Isolates were also tested using PCR for the presence of genes encoding toxins A and B. One hundred and thirty-three isolates of C. difficile from dogs (n = 92), horses (n = 21) and humans (n = 20), plus one each from a cat and a calf, were evaluated. Overall, 23 ribotypes were identified. Of these, nine were identified from dogs, 12 from horses, seven from humans and one each from the cat and calf. In dogs, humans and horses, one or two different ribotypes predominated. Overall, 25 % of isolates from humans were indistinguishable from isolates from one or more animal species. Genes encoding C. difficile toxins A and B were detected in all human, equine and bovine isolates, and in 69 % of canine isolates. While different ribotypes appear to predominate in different mammalian species, several indistinguishable strains may be found in multiple species. This suggests that there is a potential for interspecies transmission of C. difficile and epidemiological studies are warranted.

Animals↗
PubMed1994

Toxins A and B of Clostridium difficile.

The toxins produced by Clostridium difficile share several functional properties with other bacterial toxins, like the heat-labile enterotoxin of Escherichia coli and cholera toxin. However, functional and structural differences also exist. Like cholera toxin, their main target is the disruption of the microfilaments in the cell. However, since these effects are not reversible, as found with cholera toxin, additional mechanisms add to the cytotoxic potential of these toxins. Unlike most bacterial toxins, which are built from two structurally and functionally different small polypeptide chains, the functional and binding properties of the toxins of C. difficile are confined within one large polypeptide chain, making them the largest bacterial toxins known so far.

Bacterial Proteins↗
PubMed2006

In vitro killing of nosocomial pathogens by acid and acidified nitrite.

Exposure to pH 1 or 2 buffers or acidic gastric contents resulted in the killing of vancomycin-resistant Enterococcus sp., Klebsiella pneumoniae, Staphylococcus aureus, and Candida glabrata but not Clostridium difficile spores. Nitrite enhanced killing under acidic conditions, but significant killing of C. difficile spores required nitrite concentrations above usual physiological levels.

Acids↗
PubMed2001

Safety and immunogenicity of increasing doses of a Clostridium difficile toxoid vaccine administered to healthy adults.

Clostridium difficile is a major cause of nosocomial diarrhea in industrialized countries. Although most illnesses respond to available therapy, infection can increase morbidity, prolong hospitalization, and produce life-threatening colitis. Vaccines are being explored as an alternative means for protecting high-risk individuals. We assessed the safety, immunogenicity, and dose response of a parenteral vaccine containing C. difficile toxoids A and B. Thirty healthy adults were assigned to receive four spaced inoculations on days 1, 8, 30, and 60 with one of three doses of vaccine (6.25, 25, or 100 microg). At each dose level, subjects were randomized, in a double-blind fashion, to receive either the soluble toxoids (n = 5) or toxoids adsorbed to alum (n = 5). Subjects were monitored for clinical and immunologic responses to vaccination. Vaccination was generally well tolerated, with occasional, usually mild, systemic reactions (abdominal pain, arthralgia, and diarrhea). The most common local reaction, mild arm pain, was reported by all recipients of the toxoid-alum formulation. Nearly all subjects (> or = 90%) developed vigorous serum antibody responses to both toxins, as measured by immunoglobulin G (IgG) enzyme-linked immunosorbent assay and neutralization of cytotoxicity, whereas fecal IgA increases occurred in approximately 50%. Statistically significant effects of dose and formulation on immunogenicity were not seen, although antibody levels tended to be higher with the alum-adjuvanted formulations and with increasing doses of soluble toxoid. Serum antibody responses among the toxoid-alum group appeared to plateau at 25 microg. We concluded that the C. difficile toxoid vaccine is safe and immunogenic in healthy volunteers. Further development as a prophylactic vaccine or for producing C. difficile hyperimmune globulin is justified.

Adolescent↗
PubMed1995

Clostridium difficile infection in hamsters fed an atherogenic diet.

Diarrhea and unexpected death were encountered in a group of young Syrian hamsters (Mesocricetus auratus) used for hyperlipoproteinemia and atherosclerosis research. The animals were fed an atherogenic diet containing 18% saturated fat and 0.366% cholesterol. Mortality began 45 days after hamsters were placed on this atherogenic diet. The atherogenic studies were aborted at 74 days because of high mortality. Toxigenic Clostridium difficile was isolated from animals found dead or euthanatized because of illness. Signs observed were unexpected death and acute liquid diarrhea. Characteristic pathologic changes were necrosis and hemorrhage of the intestinal mucosa with acute inflammation. Hepatic lipidosis was a consistent finding presumed to be associated with the consumption of the atherogenic diet. The study was repeated by placing 23 hamsters on the atherogenic diet and 10 hamsters on the control diet. In animals fed the atherogenic diet, the average time to mortality differed between studies, but clinical signs, gross and histologic lesions, culture findings, and toxin results in both atherogenic diet groups were similar. C. difficile was not isolated from the feeds. No antibiotics were found in the atherogenic diet. The results from these studies suggest that hamsters fed an atherogenic diet have increased susceptibility to disease caused by C. difficile as compared with hamsters fed a normal fat and cholesterol diet.

Animals↗
PubMedDate not supplied

[Six years evaluation of Clostridium difficile associated diarrhea].

This study was aimed to detect the presence of Clostridium difficile toxin in the stool samples of patients with antibiotic-associated diarrhea or pseudomembranous colitis, and to relate its presence with the clinical findings of the patients. Between January 1997-April 2003, a total of 726 stool samples were investigated for C. difficile toxin A and/or B by enzyme immunoassay. Of them, 68 (9.4%) were found positive for C. difficile toxin (62 were toxin A, 6 were toxin B). C. difficile associated diarrhea were found to be related mostly with the use of beta-lactam/beta-lactamase inhibitor combinations (32/68), followed by aminoglycosides (12/68), and cephalosporins (8/68). The ages of the patients were between 1-86 years old (mean: 43.3 years), and 36 (52.9%) of them had an underlying conditions. Chronic obstructive pulmonary disease and chronic renal failure were the underlying disease in 18, malignancy in 11, and others (diabetes, hepatitis, transplantation, multiple sclerosis) in 7 of the patients. In conclusion, toxin detection and knowledge of the risk factors are the beneficial guidelines for the diagnosis of C. difficile associated diarrhea in the routine setting.

Adolescent↗
PubMed2005

[Profile of toxigenicity of Clostridium difficile strains isolated from paediatric patients with clinical diagnosis of antibiotic associated diarrhea (AAD)].

This study was performed to determine profile of toxigenicity of 18 Clostridium difficile strains isolated from paeditric patients suffering from antibiotic associated diarrhea (AAD). Toxigenicity of C. difficile strains was tested for detection toxin A and toxin B by phenotypic methods and for detection of the tcdA and tcdB genes using of PCR. Changes in the repeating regions of the tcdA genes were detected with the NK9/NKV011 primer pairs. For detection of binary toxin (CDT) cdtA and cdtB genes, cdtApos/cdtArev i cdtBpos/cdtBrev two pair primers in PCR was used. Among C. difficile strains was detected three profiles of toxigenicity: C. difficile strains possesing of tcdA and tcdB genes but not possesing cdtA and cdtB genes of binary toxin (A+B+CDT-), strains possesing tcdA and tcdB and cdtA and cdtB genes (A+B+CDT+), strains with deletion of toxin A gene (A-B+CDT-). This is the first report on the occurence of binary positive C. difficile strains isolated from paediatric patients.

ADP Ribose Transferases↗
PubMed1991

Clinical manifestation of Clostridium difficile enteritis in Calcutta.

233 cases with acute diarrhoea investigated, Clostridium difficile was isolated as a sole pathogen from 17 (7.3%) cases. The Major clinical features of these cases were watery diarrhoea (82.4%), bloody stool (17.6%), vomiting (64.8%), fever (17.6%) and abdominal pain (2.5%). Fourteen (82.4%) of 17 C difficile isolates were found to produce cytotoxin as detected by Verocell assay.

Child↗
PubMed1990

Clostridium difficile associated disease in Thailand.

Over a twenty-six month period 383 fecal specimens from 269 diarrheal patients and 114 control patients were examined for Clostridium difficile and its cytotoxin. C. difficile was isolated from 13 (4.8%) of overall age group of diarrheal patients and from 3 (2.6%) of controls. Fecal cytotoxin was detected in 106 (52.5%) of 203 diarrheal patients and in 17 (22.4%) of 76 controls. Sixty-one percent of antibiotic-associated diarrheal patients (less than 3 years) and 51% of non-antibiotic associated diarrhea patients had fecal cytotoxin. Enteric pathogens other than C. difficile were detected in 0.7-7.4% of the patients studied. These data suggest that C. difficile associated disease may be frequently encountered in such a developing region studied. Routine diagnosis for C. difficile in diarrheal patients appears to be warranted.

Adolescent↗
PubMedDate not supplied

Low levels of coagulation inhibitors in patients with Clostridium difficile infection.

To investigate levels of coagulation inhibitors in sera from patients with Clostridium difficile-associated diarrhoea and colitis, commercially available antigen assays were used for immunochemical determination of antithrombin III, protein C and free protein S. Sera from patients with Clostridium difficile-associated diarrhoea and colitis showed significantly lowered levels of all measured inhibitors as compared to controls (Student's t test). Protein C (mean +/- SD): 0.70 +/- 0.30 vs. 1.28 +/- 0.23, t = 6.61, p less than 0.001; antithrombin: 0.70 +/- 0.21 vs. 0.90 +/- 0.17, t = 3.12, p less than 0.01; free protein S: 0.27 +/- 0.06 vs. 0.37 +/- 0.08, t = 3.7, p less than 0.001. Infection with C. difficile may lead to loss of coagulation inhibitors and constitutes a risk for thromboembolic complications.

Aged↗
PubMed2006

"Diversion" colitis caused by Clostridium difficile infection: report of a case.

Recurrent ulcerative colitis and/or diversion colitis occur commonly in the rectal remnant after colectomy for ulcerative colitis. We report a case in which such a patient's symptoms of rectal discharge were initially thought to be the result of one or both of these diagnoses, on both clinical and histologic grounds. However, examination of the discharge revealed Clostridium difficile infection. Treatment with metronidazole suppositories improved his symptoms and avoided further inappropriate intervention.

Administration, Rectal↗