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PubMed2005

Passive immunisation of hamsters against Clostridium difficile infection using antibodies to surface layer proteins.

Clostridium difficile is a major cause of antibiotic-associated diarrhoea and the primary cause of pseudomembraneous colitis in hospitalised patients. We assessed the protective effect of anti-surface layer protein (SLP) antibodies on C. difficile infection in a lethal hamster challenge model. Post-challenge survival was significantly prolonged in the anti-SLP treated group compared with control groups (P=0.0281 and P=0.0283). The potential mechanism of action of the antiserum was shown to be through enhancement of C. difficile phagocytosis. This report indicates that anti-SLP antibodies can modulate the course of C. difficile infection and may therefore merit closer investigation for use as constituents of multi-component vaccines against C. difficile associated diarrhoea.

Animals↗
PubMed2000

Leukocytosis as a harbinger and surrogate marker of Clostridium difficile infection in hospitalized patients with diarrhea.

OBJECTIVES: Clostridium difficile is the etiological agent of antibiotic-associated diarrhea and pseudomembranous colitis and is a leading cause of nosocomial diarrhea. The objective of the study was to examine if leukocytosis could be a harbinger and surrogate marker of C. difficile infection in hospitalized patients. METHODS: We retrospectively examined the medical records of 70 hospitalized patients who presented with diarrhea of variable severity and who underwent stool examination for enteric pathogens, including C. difficile. We specifically recorded the white blood cell count and the pattern and severity of leukocytosis in two groups of patients--those who were C. difficile-positive and those who were negative. RESULTS: Leukocytosis was common in C. difficile-positive patients, compared to in C. difficile-negative patients (mean 15,800/mm3 vs 7700/mm3, p < 0.01). Review of the 35 C. difficile-positive patients revealed three patterns: Pattern A) sudden WBC increase coinciding with the onset of symptoms suggestive of C. difficile; Pattern B) unexplained leukocytosis preceding the appearance of C. difficile-related diarrhea and serving as a harbinger of the infection; and Pattern C) worsening of pre-existing leukocytosis as a surrogate marker of C. difficile infection. Treatment with metronidazole led to amelioration of symptoms and normalization of the leukocyte count in all cases. CONCLUSIONS: Infection with C. difficile should be considered in the differential diagnosis of sudden onset of leukocytosis in hospitalized patients previously or concurrently treated with antibiotics. Doing so may obviate the need for expensive and time-consuming tests for other etiologies.

Clostridioides difficile↗
PubMed1997

Isolated meningeal vasculopathy associated with Clostridium septicum infection.

A 28-year-old patient with acute lymphoblastic leukemia and neutropenia developed necrotizing enterocolitis and Clostridium septicum bacteremia, followed by rhabdomyolysis, skin rash, and acute neurologic changes. Numerous cortical leptomeningeal enhancements were present on head MRI. Meningeal and brain biopsy showed segmental, full-thickness lysis of smooth muscle cells of medium-sized meningeal vessels with overall preservation of the structure of the vessel wall.

Adult↗
PubMed1993

Diagnosis and monitoring of Clostridium difficile infections with the polymerase chain reaction.

Toxigenic Clostridium difficile is the etiologic agent of pseudomembranous colitis. We have developed an assay system for the rapid direct detection of toxigenic C. difficile in human stool samples. After DNA extraction, polymerase chain reaction (PCR) amplification is undertaken with primers targeting specific sequences in the C. difficile 16S rRNA gene. Next, toxigenic strains of C. difficile are distinguished from nontoxigenic strains by PCR amplification of toxin A and/or B gene sequences. This study included 12 patients with C. difficile colitis, seven of whom had clinical relapses after discontinuation of vancomycin therapy. We detected toxigenic C. difficile in stools from four (57%) of these seven patients before relapse--at a time when no toxin B was detectable in stools and results of anaerobic culture were negative. The PCR assay is 100-fold more sensitive than anaerobic culture methods. The course of the infection in one patient (both during and after therapy) was monitored by the PCR technique. The multigene analysis approach permitted the detection of colonization with a nontoxigenic strain when this patient's relapses had cleared. This clinically applicable assay allows earlier detection of infection with toxigenic C. difficile. The result is more timely therapeutic intervention.

Aged↗
PubMed2000

[The risk factors for Clostridium difficile infection in elderly patients. A case-control study].

BACKGROUND: To study the main risk factors associated with Clostridium difficile infection in a geriatric unit. PATIENTS AND METHOD: Retrospective case-control study. RESULTS: In a multivariate analysis, tube feeding (OR = 6.73; IC 95%, 1.01-45.35) and length of antibiotic therapy (OR = 1.15; IC, 95% 1.01-1.28) were independent variables which associated with C. difficile infection. CONCLUSIONS: Antibiotic treatment, tube feeding and fragility are associated with C. difficile infection.

Aged↗
PubMed2000

Clostridium difficile infection: risk factors, medical and surgical management.

BACKGROUND: Clostridium difficile has become recognized as a cause of nosocomial infection which may progress to a fulminant disease. METHODS: Literature review using electronic literature research back to 1966 utilizing Medline and Current Contents. All publications on antibiotic-associated diarrhea, antibiotic-associated colitis, and pseudomembranous colitis as well as C. difficile infection were included. We addressed established and potential risk factors for C. difficile disease such as an impaired immune system and cost benefits of different diagnostic tests. An algorithm is outlined for diagnosis and both medical and surgical management of mild, moderate and severe C. difficile disease. RESULTS: Diagnosis of C. difficile infection should be suspected in patients with diarrhea, who have received antibiotics within 2 months or whose symptoms started after hospitalization. A stool specimen should be tested for the presence of leukocytes and C. difficile toxins. If this is negative and symptoms persist, stool should be tested with 'rapid' enzyme immunoabsorbent and stool cytotoxin assays, which are the most cost-effective tests. Endoscopy and other imaging studies are reserved for severe and rapidly progressive courses. Oral metronidazole or vancomycin are the antibiotics of choice. Surgery is rarely required for selected patients refractory to medical treatment. The threshold for surgery in severe cases with risk factors including an impaired immune system should be low. CONCLUSION: C. difficile infection has been recognized with increased frequency as a nosocomial infection. Early diagnosis with immunoassays of the stool and prompt medical therapy have a high cure rate. Metronidazole has supplanted oral vancomycin as the drug of first choice for treating C. difficile infections.

Bacterial Toxins↗
PubMed1998

Incidence and impact of Clostridium difficile infection in the UK, 1993-1996.

Questionnaires were sent to 360 UK medical microbiologists to determine the incidence of Clostridium difficile infection in the UK between 1993-1996, and to establish the current laboratory testing protocols. Replies were received from 104 laboratories (29% response rate), 86, 7, 4 and 3% of which are in England, Scotland, Wales and Northern Ireland, respectively. The laboratories serve a total of approximately 90,000 hospital beds (median 750). C. difficile testing was performed by 83% of the laboratories, and 52, 45 and 31% used toxin A +/- B kits, cell cytotoxicity, and culture +/- isolate toxigenicity testing methods, respectively. Forty-seven percent of laboratories only performed testing when specifically requested, 19% if antibiotic use was stated, 15% tested all diarrhoeal specimens, and 14% examined all specimens except those from infants and community patients. The annual totals of positive C. difficile reports and cases increased from 3132 to 12,775, and from 1576 to 8211, respectively, between 1993-1996. In 1993 C. difficile infection caused ward closures in 5% of hospitals but 16% in 1996. Antibiotic policy changes, due to C. difficile infection, occurred in 21% of hospitals in 1996 compared with only 4% in 1993. C. difficile infection appears to be increasing markedly in the UK with major implications on hospital inpatient activity. Wide variations in laboratory selection and testing methods are likely to be masking the true epidemiology of C. difficile infection, and consensus is required on optimal protocols.

Aged↗
PubMed1998

Reduction in vancomycin-resistant Enterococcus and Clostridium difficile infections following change to tympanic thermometers.

OBJECTIVE: To contain a nosocomial outbreak of vancomycin-resistant Enterococcus (VRE). DESIGN: Intervention study, with comparison of incidence rates before and after intervention to assess whether changes in incidence followed the intervention and were greater than expected based on trends observed before the intervention. SETTING: A 343-bed acute-care hospital serving a predominantly elderly population referred from nursing homes, as well as patients admitted from the community. METHODS: Interventions strategies were tested on three high-risk nursing stations. These included enhanced environmental sanitation; intensive staff retraining in Universal Precautions, body substance isolation, and proper use of gloves; and the use of tympanic thermometers to avoid possible rectal or oral VRE transmission during temperature taking. RESULTS: Nosocomial VRE infections were reduced by 48% 9 months after switching to tympanic thermometers; incidence of Clostridium difficile infections also was reduced. As a result, tympanic thermometers were introduced facilitywide; additional observation for 20 months showed a risk reduction of 60% for VRE and 40% for C difficile. CONCLUSION: Cross-transmission of VRE and C difficile during temperature taking may result in bowel colonization, placing the patient at increased risk for infection. This risk may be reduced by the use of tympanic thermometers.

Anti-Bacterial Agents↗
PubMed1988

Hemorrhagic necrotizing enterocolitis associated with Clostridium difficile infection in four foals.

Severe hemorrhagic necrotizing enterocolitis was determined to be the cause of death for 4 foals. Toxigenic Clostridium difficile was isolated form the intestine of each foal, and large, gram-positive, rod-shaped bacteria lined the surface of necrotic villi. This finding of toxigenic C difficile associated with enteritis in foals adds another possible cause to the list of infectious agents that should be considered when evaluating foals with enteritis. Definitive diagnosis requires a thorough diagnostic evaluation, including procedures that will identify the organism and demonstrate its toxigenicity.

Animals↗
PubMed1982

Possible foodborne transmission in a case of pseudomembranous colitis due to Clostridium difficile: influence of gastrointestinal secretions on Clostridium difficile infection.

A 78-yr-old woman with a history of hypochlorhydria was found to have pseudomembranous colitis due to Clostridium difficile. She had not received previous antimicrobial therapy. Her onset of disease followed ingestion of possibly contaminated canned salmon, suggesting possible oral transmission of disease. We assessed the possibility of ingested Clostridium difficile organisms or cytotoxin surviving passage through the upper gastrointestinal tract. Normal gastric juice, hypochlorhydric gastric juice, and duodenal secretions were obtained from volunteers and tested for their ability to kill Clostridium difficile organisms or inactivate toxin. These in vitro studies indicated that the primary upper gastrointestinal barriers for ingested Clostridium difficile and cytotoxin were pH-dependent. We suggest that oral transmission of disease due to Clostridium difficile may occur in hypochlorhydric patients.

Aged↗
PubMed1976

Clostridium perfringens infection complicating chemotherapy for choriocarcinoma.

A case of Clostridium perfringens sepsis and gas gangrene complicating chemotherapy for gestational choriocarcinoma is reported. The infection was eradicated using antibiotics, surgery, and hyperbaric oxygen therapy. The pathophysiology, diagnosis, and treatment of this unusual but often lethal complication are reviewed.

Anti-Bacterial Agents↗
PubMed1983

Household pets as a potential reservoir for Clostridium difficile infection.

The purpose of this study was to assess the carriage of Clostridium difficile by household pets to determine their potential as a reservoir of infection. The selective cycloserine-cefoxitin medium was used for C difficile isolation, and tissue culture used for detection of cytotoxin. Carriage of C difficile by household pets was found to be common (23%). The carriage tends to be transient and does not appear to be associated with gastrointestinal disease. Although carriage was higher in animals who had antecedent antibiotic treatment (31%) compared to those which had not (19%), the differences were not statistically significant. In most cases non-cytotoxigenic strains were isolated. Of the cytotoxigenic strains isolated at least one strain was pathogenic in a well documented animal model of human disease. Both cytotoxigenic and non-cytotoxigenic strains of C difficile could be isolated from the environment of the animals studied.

Animals↗