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Medical implications of nosocomial infection with Clostridium difficile.

88 patients above the age of 60 years who contracted Clostridium difficile associated diarrhoea (CDAD) between 1979 and 1986, mostly during their stay in hospital were studied retrospectively as regards nursing time and clinical outcome. These patients were compared with 176 control patients who were matched according to diagnosis on admission to hospital, sex, age and underlying disease. Thromboembolic complications occurred in 14% in CDAD patients (controls 4%) (p = 0.0042). The mortality rate was 21% in CDAD and 7% in controls (p = 0.0009). The median time in hospital for CDAD patients was 50 days (14 days for controls).

Clostridium Infections↗

Fatal chemotherapy associated Clostridium difficile infection--a case report.

Clostridium difficile associated diarrhoea or Pseudomembranous colitis occasionally occurs without prior antibiotic usage. While the association of chemotherapy and Clostridium difficile infection has previously been well recorded, the true incidence is unknown. We report a case of Clostridium difficile associated diarrhoea after chemotherapy for lung cancer. The fatal outcome in this case and the increasing use of chemotherapy in this country highlights the need to have a high index of suspicion in any case of unexplained diarrhoea post chemotherapy. A review of the literature is presented.

Aged↗

Comparison of the efficacy of ramoplanin and vancomycin in both in vitro and in vivo models of clindamycin-induced Clostridium difficile infection.

OBJECTIVES: Treatment of Clostridium difficile infection (CDI) is limited primarily to either metronidazole or vancomycin. We compared vancomycin and a novel glycolipodepsipeptide, ramoplanin, in both hamster and in vitro gut models of clindamycin-induced CDI. METHODS: We used an in vitro triple-stage chemostat model that simulates the human gut, and an in vivo hamster model, both primed with clindamycin. RESULTS: Clindamycin exposure elicited symptomatic disease in the hamster model, and promoted C. difficile germination and toxin production in the gut model. C. difficile germination and toxin production were not associated with depletion of gut microflora in the gut model, but were temporarily associated with subinhibitory concentrations of clindamycin. Both ramoplanin and vancomycin were associated with rapid symptom resolution in the hamster model, and rapid toxin titre decrease in the in vitro gut model. In both models of CDI, vancomycin was associated with greater persistence of C. difficile spores. C. difficile spores were recovered significantly more often from the caecal contents of vancomycin-treated (n = 19/23) compared with ramoplanin-treated (n = 6/23) hamsters (P < 0.05). CONCLUSIONS: Results from the in vitro gut and hamster models were concordant. Ramoplanin and vancomycin were similarly effective at reducing cytotoxin production in the gut CDI model and in resolving symptoms in the hamster model. Ramoplanin may be more effective than vancomycin at killing spores and preventing spore recrudescence. These findings suggest a potential therapeutic role for ramoplanin in CDI that requires further clinical investigation.

Animals↗

[Clostridium difficile infections. Current aspects].

Clostridium difficile is a gram-positive anaerobe that forms subterminal spores. It is now one of major nosocomial pathogens, mainly in older patients, because of its ability to persist in the environment and to become established in the gastrointestinal tract once the natural microflora has been modified by antibiotic therapy. Toxigenic strains of C. difficile produce toxin A (enterotoxin) or toxin B (cytotoxin) or both with cause the cytotoxic effect "rounding". C. difficile can spread from patient to patient and, probably, the primary way by which the organism is spread is by health care workers. C. difficile causes intestinal diseases ranging by mild diarrhea (antibiotic associated diarrhea) to fatal pseudomembranous colitis (PMC). The current therapy is based on oral administration of metronidazole or vancomycin . In patients non responders or that continue to relapse can be used other forms of therapy: antibiotic (teicoplanine, bacitracine, rifamixine); anion exchange resin (colestipol, colestiramine); probiotic therapy (S. boulardii, lactobacilli and fecal enemas). New and improved studies will lead to new and better ways of treating patients and better understanding of this unusual pathogen and how it causes diseases.

Anti-Bacterial Agents↗

[Clostridium difficile infection associated with pseudomembranous colitis in district hospitals].

At a regional hospital serving 150,000 inhabitants, the authors were tracking the occurrence of antibiotic-associated diarrhea caused by a nosocomial infection of the Clostridium difficile, especially its most serious form--pseudomembranous colitis. Six cases of the disease were found in a retrospective study in 2001, another 20 cases were diagnosed while actively searching for the disease from January till September of 2002. The patients suffered from many complications, were of an average age of 69.24 years, their hospitalization averaged 34 days and 15 (52%) of them underwent surgery during their hospitalization. It could be demonstrably proved that 25 cases of nosocomial infection occurred during hospitalization and 3 patients were admitted to hospital with the disease. However, 2 of them had been released from hospital less than 20 days before being admitted again. Twenty-five patients (96%) had been treated with antibiotics, often in combined therapy. Most often this involved penicillin with betalactamas activity (50%), clindamycin (42%) and cefalosporins (42%). We used methods for detecting enterotoxin A in the stool, rectoscopy and anaerobic cultivation of the stool in the diagnostic process. Rectoscopy discovered pseudomembranous colitis in 14 of 17 patients examined this way. The sensitivity for proving enterotoxin A in the stool using EIA, for patients with proven pseudomembranous colitis via rectoscopy, was 75%. Anaerobic cultivation of the stool was done in 12 patients and all the results were negative. The mortality rate of 38% for our group of patients testifies to the seriousness of this disease, which we consider to be the results of antibiotic therapy. In conclusion, nosocomial infection caused by Clostridium difficile is quite often a nosocomial disease, a prognosis that especially worsens for seriously ill patients.

Adolescent↗

Demonstration of Clostridium septicum infection in a goose flock.

Clostridium septicum infection causing 5.0 to 5.2% mortality is reported for the first time in the literature from six-week-old growing geese in three flocks comprising 5,200, 5,500 and 5,900 geese, respectively. The affected birds exhibited weakness, uncoordinated movement, ataxia and, frequently, oblique position of the head and neck (torticollis) as well as signs indicative of dysequilibrium. The affected birds died within 18-24 h. Gross pathological examination revealed anaemia, hepatitis with map-like necroses of irregular outline (Fig. 1), acute enteritis, pulmonary oedema and cardiac dilatation. Light and electron-microscopic examination showed that the sinusoids of the liver were markedly dilated (Fig. 2) and filled with serous exudate and gas (Figs 2 and 3), and the hepatocytes surrounding them exhibited severe oedema (Fig. 4). Among the hepatocytes, ciliated bacteria 7-10 mu in length and 1-3 mu in width, bounded by a well-defined cell wall and often showing signs of spore formation were observed (Figs 5 and 6). By bacteriological examination the pathogen was isolated, its properties were studied, and the clinical entity of malignant oedema was experimentally reproduced by intramuscular injection of guinea-pigs and rabbits. The applied antibiotic (oxytetracycline) and furazolidone therapy proved effective.

Animals↗

The effect of an enhanced infection-control policy on the incidence of Clostridium difficile infection and methicillin-resistant Staphyloccocus aureus colonization in acute elderly medical patients.

BACKGROUND: Clostridium difficile (CD) infection and methicillin-resistant Staphylococcus aureus (MRSA) colonization are increasingly common in elderly patients, are associated with cephalosporin or prolonged aminopenicillin courses and can be transmitted by direct contact. Management is by side-room isolation. Ward closure may be required to control outbreaks. METHODS: following prolonged bed closures due to CD and MRSA in an acute age-related geriatric service, an enhanced infection control policy was introduced-emphasis on handwashing, cephalosporin restriction, 7-day time limits on antibiotics and feedback of infection rates. The effect of this policy was evaluated by investigating 2,467 consecutive admissions in the 9 months before and after its introduction. RESULTS: CD infection fell from 36/1,075 admissions (3.35 per 100) to 27/1,392 (1.94 per 100; P < 0.05). MRSA incidence fell from 3.95 per 100 to 1.94 (P < 0.01) whilst that in the rest of the hospital continued to fluctuate. Cephalosporin use fell (and aminopenicillin and trimethoprim use rose) by a factor of three. Unoccupied bed days fell from 1,164 (12.6%) to 513 (5.1%) over the winter, an increase in bed availability of 4.95 a day. CONCLUSIONS: introduction of the policy was associated with significant reductions in CD infection and unoccupied bed-days and helped maintain a lower incidence of MRSA. It is not clear which elements of the policy most influenced outcome. A multi-centre study is needed to determine whether our findings are generally applicable.

Aged↗

Optimal methods for identifying Clostridium difficile infections.

The major controversy in the diagnosis of symptomatic gastrointestinal infection due to Clostridium difficile is whether laboratory evidence of the C. difficile organism in culture is sufficient or if evidence of one of the C. difficile toxins in stool should be required. Cultures performed properly on selective media currently are the most sensitive method for detection of C. difficile, whereas the cell cytotoxin assay for detection of toxin B is the most specific. Stool specimens from patients with clinical diarrhea are sometimes found to be culture-positive for C. difficile but assay-negative for cytotoxin. Samples from these patients can be viewed as false-positive by culture or false-negative by cytotoxin test. Evidence from endoscopy indicates that some patients whose stool is culture-positive for the organism but assay-negative for toxin do have pseudomembranous colitis, but its incidence among such patients (11%) is lower than that among patients whose stool is culture- and assay-positive (51%). Response to treatment with vancomycin or metronidazole is similar in the two groups of patients, and withholding treatment from patients whose stool contains C. difficile but not cytotoxin may result in increased morbidity and mortality. Up to one-third of C. difficile organisms from stool specimens that are culture-positive but assay-negative are incapable of producing cytotoxin in vitro, a finding that suggests these organisms may not be the cause of diarrhea.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Proteins↗

Clostridial population and the intestinal lesions in chickens infected with Clostridium perfringens and Eimeria necatrix.

Chickens infected with Clostridium perfringens and Eimeria necatrix were examined bacteriologically and pathologically. When chickens were inoculated with 1.0 x 10(8) C. perfringens and/or 2 x 10(4) E. necatrix sporulated oocysts, populations of C. perfringens in the intestinal contents were examined on 3, 5 and 7 days after E. necatrix inoculation. In both groups infected with E. necatrix, the mean clostridial counts were significantly higher than those of uninfected controls. The concurrent infection had no enhancing effects on increasing the clostridial population more than E. necatrix-alone. Mortality of 4-day-old chickens inoculated on 5 consecutive days with C.perfringens after receiving E. necatrix was higher than those of chickens inoculated with the both organisms. However, intestinal lesions of the concurrently infected group were not different from E. necatrix-alone-infected group on 5 and 7 days after the coccidial infection. When chickens received a large dose (1.5 x 10(9)) of C. perfringens after the inoculation with E. necatrix, edema in the duodenum through jejunum were observed early after the bacterial broth inoculation. These results suggest that the concurrent infection with E. necatrix and C. perfringens increases clostridial population in the intestine of the chickens and has synergic effects on mortality and edema in the upper intestine.

Animals↗

Clostridium septicum infection in children with cyclic neutropenia.

Atraumatic Clostridium septicum infection is rare in infancy and childhood and is associated with a high mortality rate. Although in adults it has been reported to occur mainly in patients with gastrointestinal malignancy, pediatric cases were always associated with neutropenia. About 70% of the cases were described in children with neutropenia caused by chemotherapy and 30% were found in children with cyclic neutropenia. No case was described in children with other forms of congenital severe neutropenia. We describe three children with cyclic neutropenia and severe Clostridium septicum infection, discuss the various possibilities of causation, and the need for prompt and aggressive treatment of this serious condition.

Abdominal Muscles↗

Clostridium sordelli infection.

A case of human Clostridium sordelli soft tissue infection is presented. Analysis of this patient's course led to the use of a mouse experimental model for examination of this organism's potential for toxin production. Data thus obtained correlated with that seen in this instance of human infection, indicates that the lethal effects of this organism may be related to the ability to Clostridium sordelli to produce a widespread "toxin-mediated" edema with subsequent marked "third-space" sequestration of fluid.

Adult↗

Accuracy of ICD-9 coding for Clostridium difficile infections: a retrospective cohort.

Clostridium difficile (C. diff) is a major nosocomial problem. Epidemiological surveillance of the disease can be accomplished by microbiological or administrative data. Microbiological tracking is problematic since it does not always translate into clinical disease, and it is not always available. Tracking by administrative data is attractive, but ICD-9 code accuracy for C. diff is unknown. By using a large administrative database of hospitalized patients with C. diff (by ICD-9 code or cytotoxic assay), this study found that the sensitivity, specificity, positive, and negative predictive values of ICD-9 coding were 71%, 99%, 87%, and 96% respectively (using micro data as the gold standard). When only using symptomatic patients the sensitivity increased to 82% and when only using symptomatic patients whose test results were available at discharge, the sensitivity increased to 88%. C. diff ICD-9 codes closely approximate true C. diff infection, especially in symptomatic patients whose test results are available at the time of discharge, and can therefore be used as a reasonable alternative to microbiological data for tracking purposes.

Boston↗