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PubMed2001

Extracolonic manifestations of Clostridium difficile infections. Presentation of 2 cases and review of the literature.

Clostridium difficile is most commonly associated with colonic infection. It may, however, also cause disease in a variety of other organ systems. Small bowel involvement is often associated with previous surgical procedures on the small intestine and is associated with a significant mortality rate (4 of 7 patients). When associated with bacteremia, the infection is, as expected, frequently polymicrobial in association with usual colonic flora. The mortality rate among patients with C. difficile bacteremia is 2 of 10 reported patients. Visceral abscess formation involves mainly the spleen, with 1 reported case of pancreatic abscess formation. Frequently these abscesses are only recognized weeks to months after the onset of diarrhea or other colonic symptoms. C. difficile-related reactive arthritis is frequently polyarticular in nature and is not related to the patient's underlying HLA-B27 status. Fever is not universally present. The most commonly involved joints are the knee and wrist (involved in 18 of 36 cases). Reactive arthritis begins an average of 11.3 days after the onset of diarrhea and is a prolonged illness, taking an average of 68 days to resolve. Other entities, such as cellulitis, necrotizing fasciitis, osteomyelitis, and prosthetic device infections, can also occur. Localized skin and bone infections frequently follow traumatic injury, implying the implantation of either environmental or the patient's own C. difficile spores with the subsequent development of clinical infection. It is noteworthy that except for cases involving the small intestine and reactive arthritis, most of the cases of extracolonic C. difficile disease do not appear to be strongly related to previous antibiotic exposure. The reason for this is unclear. We hope that clinicians will become more aware of these extracolonic manifestations of infection, so that they may be recognized and treated promptly and appropriately. Such early diagnosis may also serve to prevent extensive and perhaps unnecessary patient evaluations, thus improving resource utilization and shortening length of hospital stay.

Adult↗
PubMed1998

Recurrence of symptoms in Clostridium difficile infection--relapse or reinfection?

We have fingerprinted Clostridium difficile isolates from patients with symptomatic recurrences of infection, using random amplified polymorphic DNA (RAPD). The medical records of 55/79 patients were examined, from whom multiple C. difficile-positive faeces were received during hospitalization at least five days, but no more than two months, apart. In 20 of these cases symptoms either did not recur (i.e., absent for at least three days between episodes), or were explainable by other causes, such as laxative administration. Of the remaining 35 patients, 27 sets of C. difficile isolates (23 pairs and four triplicates) were available for RAPD fingerprinting. Differing C. difficile DNA fingerprints (at least three major bands difference) were obtained for 15/27 patients, and hence at least 56% of the clinical recurrences of infection were in fact due to re-infection as opposed to relapse. Since we found that an endemic C. difficile clone was present in 18 out of 27 patients (67%) and accounted for 53% (31/58) of all isolates, it is probable that the majority of symptomatic recurrences are in fact re-infections, with either a different or the same C. difficile strain. We conclude that more attention must be given to preventing the re-infection of C. difficile symptomatic patients. Isolation of symptomatic individuals is the preferred option for the protection of other patients, but measures must be taken to ensure that further strain acquisition by the index cases does not occur.

Adult↗
PubMed1986

An in-vitro model of colonisation resistance to Clostridium difficile infection.

To investigate the importance of the normal gut flora in preventing the establishment of Clostridium difficile in vivo we have developed an in-vitro test system based on growth in faecal emulsions. Growth of C. difficile and cytotoxin production are inhibited in faecal emulsions from healthy adults, but not in sterilised emulsions; the importance of viable bacteria in the inhibitory system is evident. Generally, faecal emulsions derived from infants, children and geriatric patients were less inhibitory than those from healthy adults. Those from bottle-fed infants were significantly less inhibitory than those from breast-fed infants. Decreased levels of cytotoxin in the latter group were attributed to the acidic pH of the stools. With the different patient groups studied, faecal samples not inhibitory to C. difficile in vitro were obtained from 21% of patients with antibiotic-associated diarrhoea, 33% of those taking antibiotics but who did not have diarrhoea, 18.7% of those with diarrhoea unassociated with antibiotics, and 79% of those with C. difficile-mediated diarrhoea. In some cases inhibition was due to low faecal pH, as in some infants, and in others to other filterable substances. The degree of inhibition could not be linked to specific volatile fatty acids or enzymes.

Adolescent↗
PubMed1987

Epidemiology and prevention of Clostridium difficile infections in a leukemia unit.

A 29-month prospective study was carried out in a leukemia unit with the aim of investigating the epidemiology of Clostridium difficile infections and limiting their spread. Systematic cultures of stools and assays for cytotoxin were performed on patient admission and at weekly intervals, yielding 1,355 cultures and assays. The study period was divided in period A, before total unit renovation, and period B, afterwards. During period B all patient carriers of Clostridium difficile received vancomycin. A comparison of the two periods showed that the percentage of positive cultures fell from 16.6% to 3.6% and the positive toxin assays from 9.9% to 1.2%. It was concluded that colonization by Clostridium difficile can be prevented in hospital wards with generally high rates of infection by a combination of decontamination of the environment, introduction of preventive measures and treatment of Clostridium difficile carriage with vancomycin.

Carrier State↗
PubMed1997

Review article: treatment of Clostridium difficile infection.

AIM: A systematic review of controlled trials of therapy of Clostridium difficile intestinal infection using methodology described by the Cochrane Collaboration. METHODS: Trials were identified by searching computer databases over the years 1978-1996. Trials were included if they were (a) prospective randomized, controlled trials and (b) included patients with symptomatic disease. The primary end-point was clinical resolution of diarrhoea. Secondary end-points were clinical relapse and stool clearance of C. difficile and C. difficile toxin. RESULTS: Nine trials (469 patients) satisfying the inclusion criteria were identified. Two trials were placebo controlled. Six trials compared vancomycin to other antibiotics (fusidic acid, bacitracin, teicoplanin and metronidazole). For clinical resolution response rates ranged from 21 (placebo) to 100% (vancomycin). On pooling the trials, no antibiotic showed clear therapeutic superiority. Rates of clinical relapse ranged from 5 to 42%. Only one trial showed significant advantage of one antibiotic over another for prevention of relapse (teicoplanin vs. fusidic acid). CONCLUSION: The published data are limited, and further studies are required.

Anti-Bacterial Agents↗
PubMed2006

Clostridium septicum infections in children: a case report and review of the literature.

Clostridium myonecrosis is a rare and deadly infection that progresses very rapidly; thus, prompt diagnosis and treatment is vital. In adults, clostridial myonecrosis used to be a well-known complication of war wounds. Today, it is usually seen in settings of trauma, surgery, malignancy, skin infections/burns, and septic abortions. More recently, cases of nontraumatic or spontaneous clostridial myonecrosis have been reported in both adults and children. Clostridium perfringens and Clostridium septicum are responsible for the majority of the clinically relevant infections. Higher mortality rates are seen when C septicum is the causative agent. Here we present a child who survived a severe case of C septicum myonecrosis involving both abdominal and thoracic cavities. This rare infection has a high mortality rate and might be easily misdiagnosed in children, even by experienced clinicians, because of its nonspecific presentation. We also review all reported pediatric cases of C septicum infection and myonecrosis and discuss the surgical and medical interventions associated with improved survival. We identified a total of 47 cases of C septicum infection; of these, 22 (47%) were cases of C septicum associated with myonecrosis. Several factors, if available, were analyzed for each case: age, gender, infection location, previous diagnoses, presenting signs and symptoms, neutropenia, gross pathology of the colon, antibiotic use, surgical intervention, and final outcome. We found that conditions related with C septicum infection in children can be grouped into 3 major categories: patients with neutrophil dysfunction; patients with associated bowel ischemia; and patients with a history of trauma. Malignancies were found in 49% of the cases, cyclic or congenital neutropenia in 21%, hemolytic-uremic syndrome in 11%, structural bowel ischemia in 4%, and local extremity trauma in 6%. In addition, 6% of the cases had no known underlying disorder. Abdominal symptoms including vomiting, diarrhea, blood per rectum, abdominal pain, anorexia, and/or acute abdomen, were reported in 85% of the children. Fever was also a common finding. The mainstay of treatment for C septicum infection was parenteral antibiotics and/or surgical intervention. The mortality rate for children with C septicum infection and myonecrosis was 57% and 59%, respectively. Although 82% of all cases received antibiotics, only 43% underwent therapeutic surgical intervention. Several clinical factors were found to be associated with improved survival. Only 35% of the children with gastrointestinal tract involvement survived, compared with 86% of the children without gastrointestinal tract involvement. The survival rates for other conditions ranged from 0% to 50%. One hundred percent survival was reported in patients with no previously diagnosed conditions and those with infections resulting from trauma to the extremities. All survivors received antibiotic treatment, compared with only 68% of the nonsurvivors. Most survivors (84%) underwent therapeutic surgical intervention, compared with only 12% of nonsurvivors. Other treatments were used adjunctively, including hyperbaric oxygen, granulocyte colony-stimulating factor, granulocyte transfusions, and intravenous immunoglobulin. C septicum infections in children are often fatal; thus, one needs to have a high index of suspicion in at-risk patients. This review describes who these patients are, their clinical presentation, and the therapeutic strategies associated with improved survival.

Abdomen↗
PubMed1988

Clostridium septicum infection in neutropenic enterocolitis.

A 36-year-old woman developed neutropenia following chemotherapy for inoperable carcinoma of the cervix. She suffered acute abdominal pain, nausea, vomiting, and peritonitis of rapid onset. The right hemicolon and 15 cm of terminal ileum were resected at laparotomy and this showed marked edema of the cecum and ileo-cecal valve associated with superficial ulceration of the valve. There was necrosis of submucosal tissues and the muscle wall which contained a large number of Gram-positive bacilli. These showed positive membrane immunofluorescence with specific anti-Clostridium septicum antisera. We identify a case of enterocolitis due to Clostridium septicum infection. This is associated with neutropenia and is often fatal due to the rapid course of and failure to recognize the infection.

Adult↗
PubMed2002

[Clostridium difficile infection in a Department of Internal Medicine. A consecutive series of 45 patients].

OBJECTIVES AND METHODS: A retrospective study of 45 patients with Clostridium difficile infection over a 4-year period in a department of Internal Medicine. RESULTS: Mean age was 79 years; sex-ratio (F/M)=1.5; 38% of the patients had neurological or severe psychiatric disorders; 20% had a neoplastic disease. Ninety-three percent of cases had received one or more antibiotics before onset of diarrhea, prescribed mainly for a pulmonary infection. Amoxicillin clavulanic acid and cephalosporins were the most frequently used treatments, respectively in 48% and 40% of cases. For 25 patients (56%) Clostridium difficile-associated diarrhea was considered as a nosocomial infection, and as community-acquired diarrhea in 20 cases (44%). Treatment included isolation of the patient as soon as bacteriological diagnosis was known and specific therapy was instituted by metronidazole or vancomycin for a mean of 18 days. The addition of Saccharomyces boulardii was used in of cases. The clinical course was rapidly favorable for 80% of patients. Five patients died with complications of severe colitis in 2 cases. Mean hospital stay was 49 days (annual mean of the department=10 days). CONCLUSION: Clostridium difficile diarrhea concerns above all elderly patients with one or more underlying pathologies. Amoxicillin clavulanic acid and third-generation cephalosporins are the most frequently prescribed antibiotics in these cases and have the highest correlation with this infectious complication. This medical problem requires greater knowledge as it causes significant morbidity and increases the risk of prolonged hospital stays.

Aged↗