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PubMed2003

Prevalence of Clostridium spp. and Clostridium difficile in children with acute diarrhea in São Paulo city, Brazil.

Species of Clostridium are widely distributed in the environment, inhabiting both human and animal gastrointestinal tracts. Clostridium difficile is an important pathogen associated with outbreaks of pseudomembranous colitis and other intestinal disorders, such as diarrhea. In this study, the prevalence of Clostridium spp. and C. difficile, from hospitalized children with acute diarrhea, was examined. These children were admitted to 3 different hospitals for over 12 months. Eighteen (20%) and 19 (21%) stool specimens from children with (90) and without (91) diarrhea respectively, were positive to clostridia. Only 10 C. difficile strains were detected in 5.5% of the stool samples of children with diarrhea. None healthy children (without diarrhea) harbored C. difficile. From these 10 C. difficile, 9 were considered as toxigenic and genotyped as tcdA+/tcdB+ or tcdA-/tcdB+, and 1 strain as nontoxigenic (tcdA-/tdcB-). They were detected by the citotoxicity on VERO cells and by the multiplex-polymerase chain reaction. Thirty clinical fecal extracts produced minor alterations on VERO cells. The presence of C. difficile as a probable agent of acute diarrhea is suggested in several countries, but in this study, the presence of these organisms was not significant. More studies will be necessary to evaluate the role of clostridia or C. difficile in diarrhoeal processes in children.

Acute Disease↗
PubMed2006

Clostridium difficile-associated disease: an emerging threat to patient safety: insights from the Society of Infectious Diseases Pharmacists.

A formerly infrequently isolated strain of Clostridium difficile known as BI/NAP1 has resulted in geographically diverse outbreaks of C. difficile-associated disease. Such rapid dissemination and distribution of an outbreak strain of C. difficile are unprecedented, with many regions across North America, as well as several countries in Europe, being affected, all in such a short period of time. Also of note is that nontraditional hosts (e.g., otherwise healthy, noninstitutionalized persons residing in the community, some without antimicrobial exposure) have been reported to have severe disease. Data suggest that certain virulence characteristics may be responsible for more severe clinical presentations and poor outcomes. These factors (e.g., hypertoxin production, hypersporulation, antimicrobial resistance) possessed by a previously uncommon strain of C. difficile, in conjunction with particular host and environmental factors, may have precipitated the now widespread establishment of this pathogen. Antimicrobial intervention has traditionally been a mainstay of combating C. difficile-associated disease. Efforts to combat BI/NAP1 should include good antimicrobial stewardship in addition to effective infection control and environmental intervention.

Anti-Infective Agents↗
PubMed2001

Fatal pseudomembranous colitis associated with a variant clostridium difficile strain not detected by toxin A immunoassay.

BACKGROUND: Many clinical laboratories use toxin A immunoassays to test for Clostridium difficile. OBJECTIVE: To describe the clinical course of a patient infected with a toxin variant strain of C. difficile that was not detected by toxin A immunoassay; to genetically characterize this strain; and to estimate the number of laboratories that use only toxin A immunoassays. DESIGN: Case report, molecular investigation, and laboratory survey. SETTING: Tertiary care hospital in Chicago, Illinois. PATIENT: An 86-year-old man. MEASUREMENTS: Restriction endonuclease analysis, polymerase chain reaction, and survey of regional clinical laboratories. RESULTS: An elderly hospitalized man died of advanced pseudomembranous colitis. Four stool specimens submitted over a 2-month period had tested negative on toxin A immunoassay, but a strain of C. difficile with a 1.8-kb deletion of the toxin A gene was recovered from each specimen. This strain, identified as restriction endonuclease analysis type CF4, is closely related to a widely disseminated variant, toxinotype VIII. Toxin A immunoassay was the only test being performed for detection of C. difficile at 31 of 67 (46%) regional clinical laboratories. CONCLUSIONS: Toxin A variant strains of C. difficile cause serious disease and are undetectable in clinical laboratories that use only toxin A immunoassays for C. difficile testing.

Aged↗
PubMed2001

Antibiotic susceptibility of Clostridium difficile isolates from adult patients at two Jamaican hospitals. Clinical and epidemiological implications.

The susceptibility of 39 toxin producing Clostridium difficile isolates from stools of hospitalized patients was determined, by disc diffusion, to six antibiotics. All but one isolate (toxin A negative) produced toxin A and toxin B. A wide variation in susceptibility to clindamycin, tetracycline and chloramphenicol was noted. Erythromycin and cotrimoxazole showed a clear-cut discrimination in resistance and susceptibility, while all isolates were sensitive to vancomycin. Erythromycin sensitive isolates demonstrated a significant association with diarrhoea (60.9%, 14/23, p < 0.001). These strains were predominantly found at the University Hospital of the West Indies (UHWI, 94.1%, 16/17). Strains resistant to erythromycin and clindamycin together were commonly found at the National Chest Hospital (NCH, 68.2%, 15/22). All erythromycin sensitive strains found at the NCH were from patients transferred to that hospital. These findings suggest that there is a common strain of C difficile (erythromycin resistant) at the NCH different from that found at the UHWI; the resistant pattern seen with isolates from the NCH was typical of toxigenic serogroup C strain and could be typed by the the disc diffusion method. Patients at the NCH who were colonized with either of the two strains of C difficile were likely to get diarrhoea, once there was suppression of the normal microflora by antibiotics and colonic overgrowth with C difficile.

Adolescent↗
PubMed1995

In vivo and in vitro studies of Clostridium difficile-induced disease in hamsters fed an atherogenic, high-fat diet.

After previous observation of increased susceptibility to Clostridium difficile enterocolitis in hamsters fed an atherogenic, high-fat diet, a study was undertaken to examine experimental reproducibility of this disease. Hamsters were fed either the high-fat diet or a control diet, then orally challenged with a toxigenic strain of C. difficile. Hamsters fed the high-fat diet suffered 80% morbidity, which was statistically significant from the 11% morbidity of the control diet group (P < or = 0.05). The disease presented acutely, the most common presentation being sudden death. The most common lesions in the affected hamsters were necrohemorrhagic cecitis and cecal mucosal hyperplasia. Hepatic lipidosis was consistent in all hamsters fed the high-fat diet. Toxigenic C. difficile could be recovered from the cecum of most affected hamsters, and toxins A and B were detected in these ceca. Hamsters that were fed the high-fat diet and orally inoculated with a nontoxigenic strain of C. difficile before experimental challenge with a toxigenic strain were initially protected against disease. The protection decreased with each exposure to the toxigenic strain. Results of in vitro colonization-resistance studies indicated that the cecal flora from hamsters fed the high-fat diet and control diets inhibited C. difficile growth, suggesting that increased disease susceptibility was not the result of altered cecal flora.

Animals↗
PubMed1996

[Clostridium difficile and diarrhea associated with the use of antibiotics in the origin of nosocomial and community-acquired diarrhea].

BACKGROUND: Clostridium difficile is currently recognized as an important nosocomial enteric pathogen. The significance as etiologic agent of community and nosocomial diarrhea is not well known in Spain. METHODS: Retrospective study of all cases of community diarrhea that required admission in the hospital and all nosocomial diarrhea observed in a period of three months in a 450-bed university hospital. We performed conventional coprocultives and detection of toxin-A of C. difficile with the method ELISA Premier. RESULTS: During the period of study were included 66 patients, 19 pediatrics and 47 adults patients (23 males, 24 females, age: 54.5 +/- 21.8 years). Three cases (15.8%) of pediatrics patients were diagnosticated of antibiotic-associated diarrhea, only one case were of nosocomial origin. Toxin A of C. difficile were detected in 6 cases, all were patients under two years old, represented 60% of these patients. The origin of diarrhea were: community in 32 cases and nosocomial in 15 of adults patients, in 18 cases (38.3%) were diagnosticated antibiotic-associated diarrhea, 11 were nosocomial. Toxin A of C. difficile were detected in 12 patients, 25.5% of adults, and 4 cases had criteria of C. difficile associated diarrhea, representing 8.5% of the diarrhea. None of this cases were suspected during admission. CONCLUSIONS: Antibiotic-associated diarrhea and C. difficile associated diarrhea were not infrequent cause of diarrhea of nosocomial and of community origin in our environment. We recommended culture and/or detection of toxins of C. difficile in patients who were treated with antibiotics and diarrhea of more than 72 hours of evolution.

Adolescent↗
PubMed1998

Reactive oligoarthritis in a patient with Clostridium difficile pseudomembranous colitis. Review of the literature.

A 57-year-old man developed oligoarthritis of the right sacroiliac joint, knee and elbow in the wake of Clostridium difficile pseudomembranous colitis. He was HLA B27-positive and had a history of Reiter's syndrome. His joint manifestations resolved after a course of nonsteroidal antiinflammatory drug therapy and injection of the right knee with triamcinolone acetonide. Clostridium difficile should be recognized as a rare cause of reactive arthritis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Preoperative oral antibiotics in colorectal surgery increase the rate of Clostridium difficile colitis.

HYPOTHESIS: Bowel preparation traditionally consists of cathartics, oral antibiotics, and intravenous antibiotics. We hypothesize that the use of oral antibiotics in bowel preparation results in a higher rate of postoperative Clostridium difficile colitis. DESIGN: Retrospective case-controlled study of elective colon surgery patients; January 1997 to June 2003. SETTING: Tertiary care veterans administration hospital. PATIENTS: Records of patients who underwent elective colorectal surgery (n = 304) were reviewed. Patients with bowel obstruction or emergent operation were excluded. MAIN OUTCOME MEASURE: Detection of C difficile toxin A/B by enzyme-linked immunosorbent assay in a stool specimen within 30 days of surgery. RESULTS: All 304 patients received both cathartics and intravenous antibiotics. Of 304 patients, 107 (35.1%) received oral antibiotics. The rate of postoperative C difficile colitis was 4.2% in the entire study population. The rate of C difficile infection was higher in patients who received oral antibiotics (7.4%) compared with patients who did not receive oral antibiotics (2.6%; P = .03). There were no C difficile-related mortalities. CONCLUSION: Oral nonabsorbable antibiotics in bowel preparation resulted in a higher rate of C difficile infection. This may be due to the additional effect of oral antibiotics on normal bowel flora. We recommend that oral nonabsorbable antibiotics not be used in preoperative bowel preparation regimens since postoperative C difficile infection can lead to additional morbidity, length of stay, and hospital costs.

Administration, Oral↗
PubMed2006

Intravenous immunoglobulin for the treatment of severe, refractory, and recurrent Clostridium difficile diarrhea.

PURPOSE: Clostridium difficile diarrhea is common in elderly patients and leads to prolonged hospitalization. Patients with severe or recurrent Clostridium difficile diarrhea have poor antitoxin antibody responses. Intravenous immunoglobulin has been advocated in these patients. This study was designed to assess the response of patients with refractory, recurrent, or severe Clostridium difficile diarrhea to intravenous immunoglobulin. METHODS: Retrospective review (November 2003-January 2005) of 14 patients with severe, refractory, recurrent Clostridium difficile diarrhea treated with intravenous immunoglobulin (Flebogamma, 150-400 mg/kg) from 264 Clostridium difficile toxin-positive patients. RESULTS: Median age was 79 (range, 54-91) years. Median length of symptoms before intravenous immunoglobulin was 29 (range, 3-90) days. Patients received a median of three (range, 1-5) courses of vancomycin or metronidazole before intravenous immunoglobulin. All had hypoalbuminemia (median, 22 g/l; range, 18-33) and raised C-reactive protein (median, 47 mg/l; range, 25-255) at time of infusion. The median white cell count was 15.3 x 10(9)/liters (range, 4-24). Eight patients had evidence of pancolitis on abdominal imaging, suggesting severe Clostridium difficile diarrhea. All patients tolerated intravenous immunoglobulin without side effects. Nine (64 percent) responded with bowels normalizing in a median of ten (range, 2-26) days; one patient received two doses. One patient had a partial response from two doses but died two months later after a recurrence. The other four patients died of other causes within three weeks of infusion. CONCLUSIONS: Intravenous immunoglobulin may be effective for severe, refractory, or recurrent Clostridium difficile diarrhea after failed conventional treatment.

Aged↗
PubMed2004

The effect of Perasafe and sodium dichloroisocyanurate (NaDCC) against spores of Clostridium difficile and Bacillus atrophaeus on stainless steel and polyvinyl chloride surfaces.

Clostridium difficile is an important cause of nosocomial diarrhoea. The aim of this study was to evaluate the potential for Perasafe, a recently introduced biocide, to contribute to control of C. difficile spores in the patient environment, in comparison with the chlorine-releasing agent sodium dichloroisocyanurate (NaDCC). These agents were evaluated against a water control, in a surface test on stainless steel and polyvinyl chloride (PVC) floor covering, materials commonly found in the hospital environment. The organisms studied were a toxigenic clinical isolate of C. difficile, and Bacillus atrophaeus (formerly B. subtilis var niger). The data indicate that in our in vitro system, Perasafe was significantly more active than NaDCC (1000 ppm available chlorine) against C. difficile spores dried on stainless steel surfaces, and against B. atrophaeus on PVC floor covering material, achieving mean log10 reduction factors in viable counts of 6 and 5.5, respectively, at 10 min exposures. Perasafe appeared to be less lethal in 10 min exposures to C. difficile spores fixed on PVC floor covering material. In general, 1000 ppm chlorine generated from NaDCC showed lower log10 reduction factors in viable counts at 10 min, ranging from 0.7 to 1.5, than Perasafe which ranged from 2.7 to 6.0. The potential efficacy of Perasafe in reducing the density of C. difficile spores in the patient environment in hospitals, nursing homes or other long-stay facilities should be evaluated in field studies.

Acetic Acid↗
PubMed2003

Clostridium difficile toxin B is an inflammatory enterotoxin in human intestine.

BACKGROUND & AIMS: Clostridium difficile causes antibiotic-associated diarrhea and pseudomembranous colitis, diseases afflicting millions of people each year. Although C. difficile releases 2 structurally similar exotoxins, toxin A and toxin B, animal experiments suggest that only toxin A mediates diarrhea and enterocolitis. However, toxin A-negative/toxin B-positive strains of C. difficile recently were isolated from patients with antibiotic-associated diarrhea and colitis, indicating that toxin B also may be pathogenic in humans. METHODS: Here we used subcutaneously transplanted human intestinal xenografts in immunodeficient mice to generate a chimeric animal model for C. difficile toxin-induced pathology of human intestine. RESULTS: We found that intraluminal toxin B, like equivalent concentrations of toxin A, induced intestinal epithelial cell damage, increased mucosal permeability, stimulated interleukin (IL)-8 synthesis, and caused an acute inflammatory response characterized by neutrophil recruitment and tissue damage. Laser capture microdissection and real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) showed that intestinal epithelial cell-specific IL-8 gene expression also was increased significantly after luminal exposure to C. difficile toxins in vivo. CONCLUSIONS: We conclude that C. difficile toxin B, like toxin A, is a potent inflammatory enterotoxin for human intestine. Future therapeutic or vaccine strategies for C. difficile infection therefore need to target both toxins.

Adolescent↗
PubMed1998

Risk factors for Clostridium difficile infection.

A systematic review of the literature to identify risk factors associated with Clostridium difficile infection was conducted. Two main outcomes were considered: C. difficile diarrhoea and C. difficile carriage. A qualitative assessment, based on a set of defined and consistently applied criteria, appeared to be the best approach for risk factors other than antibiotic use, as an approach based on meta-analysis would have utilized only the information provided by a minority of the studies. Risk factors for which there was evidence suggestive or consistent with an association with C. difficile diarrhoea were: increasing age (excluding infancy), severity of underlying diseases, non-surgical gastrointestinal procedures, presence of a nasogastric tube, anti-ulcer medications, stay on ITU, duration of hospital stay, duration of antibiotic course, administration of multiple antibiotics. For malignant haematological disorders there was evidence of an association only with C. difficile carriage, but there were no suitable studies to explore a possible association of this risk factor with symptomatic infection. Antibiotic use lent itself to quantitative assessment with meta-analysis using logistic regression. Exposure to an antibiotic was shown to be statistically significantly associated with both C. difficile diarrhoea and C. difficile carriage. The meta-analysis approach enabled the ranking of individual antibiotics in relation to the risk of C. difficile infection, though the 95% confidence intervals were often wide and overlapping. Antibiotics associated with a lower risk of C. difficile diarrhoea should be considered, especially when attempting to control a C. difficile outbreak or when prescribing for a patient with other C. difficile risk factors. This systematic review of the literature enabled the identification of features it would be desirable to consider in future epidemiological studies.

Anti-Bacterial Agents↗
PubMed1997

Risk of diarrhoea, Clostridium difficile and cefotaxime in the elderly.

Clostridium difficile diarrhoea is an increasingly important nosocomial infection. Clostridium difficile infection is associated with antibiotic use. The elderly are at greatest risk. We reported an outbreak associated with the use of cefotaxime, a third-generation cephalosporin. We review the extent of this association, putative causal mechanisms and suggest an integrated approach to the control of C difficile infection which focuses on both limiting environmental contamination and reducing patient susceptibility. Future developments are also considered, especially the potential for vaccination.

Aged↗
PubMed1993

A molecular characterization of Clostridium difficile isolates from humans, animals and their environments.

It is generally accepted that most patients with Clostridium difficile-associated diarrhoea acquire the organism from the environment. Recently we demonstrated that household pets may constitute a significant reservoir of C. difficile through gastrointestinal carriage in up to 39% of cats and dogs. These findings suggested that direct transmission from household pets, or contamination of the environment by them, may be a factor in the pathogenesis of C. difficile-associated diarrhoea. To investigate this possibility, we examined isolates of C. difficile from humans, pets and the environment by restriction enzyme analysis (REA) and restriction fragment length polymorphism (RFLP) typing using enhanced chemiluminescence. Both REA and RFLP typing methods used Hind III digests of chromosomal DNA. A total of 116 isolates of C. difficile from pets (26), veterinary clinic environmental sites (33), humans (37) and hospital environmental sites (20) was examined. REA was far more discriminatory than RFLP typing and for all isolates there were 34 REA types versus 6 RFLP types. There was good correlation between the REA types found in isolates from pets and from the veterinary clinic environment, and between isolates from humans and from those found in the hospital environment. There was, however, no correlation between REA type of C. difficile found in pets and isolates of human origin. We conclude that there may still be a risk of humans acquiring C. difficile from domestic pets as these findings may be the result of geographical variation.

Animals↗
PubMed2001

The role of Clostridium difficile in childhood nosocomial diarrhea.

The role of Clostridium difficile was investigated in 100 children with nosocomial diarrhea. An etiologic agent was identified in 69 cases, 8 of whom had dual infection. C. difficile-associated diarrhea (Cdad) was defined in 16 children (16%). The mean age of the patients with Cdad was 5.4 y (range 2 months to 13 y) and the male:female ratio was 1.2. All cases with Cdad were on antibiotic therapy. Cdad occurred more frequently in the cases given combined antibiotic treatment than in those given single antibiotic treatment (p < 0.05). One case with neutropenic sepsis died. C. difficile was also investigated in the stool samples of 50 hospitalized children treated with antibiotics who did not develop diarrhea. C. difficile toxins A and B were found in 5 children aged < 2 y in the control group. This study shows that C. difficile is an important cause of nosocomial diarrhea in our hospital population.

Adolescent↗
PubMed1990

Clostridium difficile invasion and toxin circulation in fatal pediatric pseudomembranous colitis.

The direct involvement of Clostridium difficile in the lesional tissue of pseudomembranous colitis has not been demonstrated; the organism's effects have been assumed to be strictly toxin mediated. Because C. difficile cytotoxin may be found incidentally in the intestinal lumina of asymptomatic infants, the role of the organism in a variety of pediatric intestinal diseases is uncertain. The authors studied seven cases of fatal pediatric pseudomembranous colitis in which the presence of C. difficile was uniformly demonstrable in lesional tissues with the use of both an intestinal spore stain and a specific immunostain. The patients had either underlying Hirschsprung's disease or hematologic malignancy; the striking pathologic features peculiar to these patients were altered mucosal mucin and immunologic barriers in the former group and neutropenia in the latter. Two patients had demonstrable circulating cytotoxin in serum or ascitic fluid, and C. difficile was identified invading colonic mucosa or submucosa. Such phenomena did not occur in control pediatric patients with multiple other intestinal lesions. Altered host factors may be responsible for the intestinal invasion of C. difficile and its systemic toxin circulation in cases of fatal pediatric pseudomembranous colitis.

Adolescent↗