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Pathogenesis of Clostridium difficile infection.

Clostridium difficile produces two major toxins referred to as toxins A and B. These are thought to be primarily responsible for the virulence of the bacterium and the major contributors to the pathogenesis of antibiotic-associated gastrointestinal disease. The molecular organization and control of expression of toxins A and B is now starting to be understood, and the cellular mechanism of action of both toxins, glucosylation of Rho family proteins, has been discovered. Other factors, such as production of proteolytic and hydrolytic enzymes, expression of fimbriae and flagella, chemotaxis and adhesion to gut receptors, and production of capsule, may all play a part in pathogenesis by facilitating colonization or by directly contributing to tissue damage, or both. Differential expression between strains of various combinations of these colonization and virulence factors may explain the apparent variability in virulence of C. difficile strains.

Animals↗

[Clostridium difficile infection].

Clostridium difficile is an anaerobic species consisting of bacilli with large, oval, subterminal spores, normally found in intestines. It uses two toxins, which produce cytopathic changes in the intestinal mucosae, causing diarrhea. Patients can present a spectrum of disease that varies from uncomplicated antibiotic-associated diarrhea to life threatening antibiotic-associated pseudomembranous colitis. C. difficile is the only species. There are no defined sterotypes. Toxigenic and nontoxigenic strains exist. The former produce varying amounts of toxin A (enterotoxin) and toxin B (Cytotoxin). Broad spectrum antiboiotic therapy eliminates much competing normal flora, permitting intestinal overgrowth of toxigenic C. difficile. There are no defined host defenses. Metronidazole and vancomycin should be used therapeutically, however, relapses can occur. Supportive therepy may be needed.

Enterocolitis, Pseudomembranous↗

Severe clostridium infection following perforation of the uterus in a patient with an ectopic pregnancy.

Twenty-eight hours after CO2 insufflation and curettage in a 26 year old, haemolysis, jaundice and anuria developed. As an ectopic pregnancy was also suspected, a diagnostic laparoscopy was done and was followed by a hysterectomy and left salpingo-oophorectomy before Clostridium perfringens was grown on culture. The survival of the patient despite clostridial infection is probably due to immediate surgical treatment and intensive post-operative care.

Adult↗

[Clostridium infections with and without manifest gas gangrene. Report on 77 infections in 76 patients].

Systematic microbiological research and correlation of the histopathological findings obtained from random autopsies revealed 23 hitherto undetected clostridial infections including 11 cases of gas gangrene, 4 of septicemia, 3 of bacteremia, and 5 other clostridial infections. The knowledge gained from this study led to clinical diagnosis of several cases of gas gangrene which were confirmed bacteriologically and histologically. Of 8 hospital patients who were thus diagnosed in this surgical clinic, 7 recovered, including a case of gas gangrene of the abdominal wall. The problem in gas gangrene is timely clinical diagnosis. Little is known about gas edema illnesses which are not traumatically conditioned. Recognition of the local and general symptoms (local, violent, yet inappropriate pain in the wound, "unexplained" postoperative secondary bleeding, appearance of tachycardia wholly unrelated to the patient's temperature, sudden shock, rapid deterioration of patient's general condition, jaundice and rise in CPK) makes it possible to diagnose postoperative gas edema in time. 77 infections with isolation of clostridia, seen in 76 patients, are reported. On the basis of clinical and histopathological criteria they have been classified as follows: 22 cases with gas gangrene (clostridial myonecrosis), 16 cases with anaerobic cellulitis, 20 wound infections, 8 cases of septicemia, 5 of bacteriemia, 1 of tetanus, and 5 other clostridial infections.

Adolescent↗

Clostridium infection resulting in paralysis in a child.

CASE REPORT: We report an 11-year-old boy who fell from an All Terrain Vehicle and sustained multiple minor soft tissue contusions and a small midthoracic laceration. Irrigation and closure of the small wound was performed at another hospital. There was no history of a penetrating wound. Within 48 h of injury, the patient developed profound dysesthesia and paralysis of the lower extremities and was transferred to our hospital. MRI disclosed a paraspinal abnormality without bony involvement. At exploration a portion of a tree branch was removed. Wound cultures were positive for Clostridium botulinum, tetani, and perfringens. CONCLUSIONS: To our knowledge, this is the first case of direct Clostridium intoxication of the spinal cord in man. Moreover, this report demonstrates the invasive manner in which Clostridium toxins may breach both the intact ligamentum flavum and the dura mater to deliver their toxicity to the intradural contents. Although the patient's dysesthesia resolved and paraplegia improved to ambulation he is still left with a significant motor deficit.

Child↗

Is there a relationship between vancomycin-resistant enterococcal infection and Clostridium difficile infection?

The relationship between vancomycin or metronidazole treatment of Clostridium difficile-associated diarrhea (CDAD) and the occurrence of vancomycin-resistant enterococcus (VRE) infection was investigated by review of 18 case-control studies. Fifteen (83%) of 18 studies found vancomycin use, days of use, or grams used to be significantly associated with VRE infection or colonization. Intravenous vancomycin use was a significant risk in nine of 10 studies, and oral vancomycin use was a significant risk in three of four studies that stratified risk by route of administration. Although statistically associated, oral vancomycin use was so infrequent (25% in the study with the most use) that it is likely to have only a minor influence as a risk for VRE infection or colonization when compared with the much more widespread use of intravenous vancomycin. Metronidazole exposure was found to be a significant risk in four of five studies that specifically assessed this variable, but the indication for metronidazole use was not specified. Risk factors for both VRE infection and CDAD include antimicrobial exposure, number of antimicrobials, days of antimicrobial use, specific agents (third-generation cephalosporins, clindamycin, and imipenem), patient age, length of hospitalization, severity of underlying illness, use of electronic rectal thermometers, enteral feedings, environmental contamination, and contamination of the hands of health care workers.

Anti-Bacterial Agents↗

Non-traumatic clostridium infection: report of an unusual case with rapid progression and a paucity of clinical signs in a patient with type 1 diabetes.

The number of cases of non-traumatic, spontaneous clostridial gas gangrene is increasing, and is an area of major concern for awareness by doctors. The disease is associated with high mortality, and survival is directly related to rapid diagnosis and prompt institution of appropriate antibiotics, surgical debridement and hyperbaric oxygen therapy. The dilemma is that early diagnosis cannot be firmly made on clinical findings alone, as these may not appear until very late, as in our patient, jeopardising the chances of the patient's survival. Mortality increases substantially in the absence of surgical treatment. Therefore, it could be suggested here that early surgical evaluation is needed, which could help in timely diagnosis, in patients with pain out of proportion to clinical findings, especially when no other plausible cause could be found.

Aged, 80 and over↗

Clostridium novyi infection: a fatal association with injecting drug users.

Injecting drug users frequently use accident and emergency (A&E) departments to access emergency care for local and systemic infections. Clostridium novyi type A is a bacterium that has recently been associated with a number of fatalities among drug injecting addicts. The clinical course is described of a patient who attended an A&E department with septicaemia who was found at postmortem examination to have been infected with Clostridium novyi type A. Doctors working in A&E departments should be aware of the existence of this infection and be vigilant when treating injecting drug users with localised infection.

Clostridium↗

[Epidemiology, risk factors and prevention of Clostridium difficile nosocomial infections].

Clostridium difficile is responsible for 10-25% of cases of antibiotic-associated diarrhea (AAD) and for virtually all cases of antibiotic-associated pseudo-membranous colitis (PMC). This anaerobic spore-forming bacterium has been identified as the leading cause of nosocomial infectious diarrhea in adults. Pathogenesis relies on a disruption of the normal bacterial flora of the colon, a colonization by C. difficile and the release of toxins A and B that cause mucosal damage and inflammation. Incidence of C. difficile intestinal disorders usually varies from one to 40 per thousand patient admissions. Risk factors for C. difficile-associated diarrhea include antimicrobial therapy, older age (> 65 years), antineoplastic chemotherapy, and length of hospital stay. Nosocomial transmission of C. difficile via oro-fecal route occurs in 3-30% of total patient admissions but it remains asymptomatic in more than 66% of cases. Persistent environmental contamination and carrying of the organism on the hands of hospital staff are common. Measures that are effective in reducing cross-infection consist of an accurate and rapid diagnosis, an appropriate treatment, an implementation of enteric precautions for symptomatic patients, a reinforcement of hand-washing and a daily environmental disinfection. C. difficile is a common cause of infectious diarrhea and should be therefore systematically investigated in patients with nosocomial diarrhea.

Clostridioides difficile↗