A Case of Infant Botulism due to Neurotoxigenic Clostridium butyricum Type E Associated with Clostridium difficile Colitis

Reported here is the sixth case of intestinal toxemia botulism caused by Clostridium butyricum type E in Italy since 1984. In this case, the patient was concomitantly affected with colitis due to Clostridium difficile toxin. A review of previously reported cases revealed that some of these patients may also have had intestinal toxemia botulism associated with Clostridium difficile colitis, based on the reported symptoms. Given that this association has been shown to exist not only in Italy but also in the USA, it is recommended that individuals with intestinal botulism and symptoms of colitis undergo testing for Clostridium difficile and its toxins in fecal samples. Electronic Publication     

Polymicrobial septicemia withClostridium difficile in acute diverticulitis

A case is reported of a patient without previous gastrointestinal symptoms, who presented with polymicrobial septicemia caused byEscherichia coli, Enterococcus faecalis, Clostridium difficile andBacteroides vulgatus. Septicemia occurred during acute diverticulitis. A strain ofClostridium difficile, which was of the same serogroup C as the blood culture isolate and also produced toxin, was recovered from the stools, but the pathogenic role of this organism in the gastrointestinal symptomatology was not clearly established. Other reported cases ofClostridium difficile septicemia are also reviewed.     

Splenic abscess caused byClostridium difficile

Splenic abscess is a previously unreported complication ofClostridium difficile colitis. A case ofClostridium difficile splenic abscess is reported that developed after the patient had been in intensive care for five weeks. A response was seen to radiologically guided drainage and antibiotic therapy with formal laparotomy, and surgical drainage not being required.     

Clostridium difficile-Associated diarrhoea in uremic patients

An outbreak of 94 episodes of Clostridium difficile-associated diarrhoea in 62 patients in a nephrology ward over a two-year period was investigated. Quantitative stool cultures were performed on ten uremic patients not on antibiotics and without diarrhoea and on ten healthy controls. All diarrhoeal episodes were associated with Clostridium difficile,and no other bacterial pathogens were isolated. Thirty-two relapses occurred in 16 patients, fourteen of the relapses without preceding antibiotic exposure.Clostridium difficile could not be isolated from the environment of the patients. Uremic patients, who had a significantly increased number of Clostridium spp. in their stools, are predisposed to Clostridium difficile infections.     

Incidence and significance ofclostridium difficile in hospitalized cancer patients

The aim of the study was to assess the incidence and clinical significance ofClostridium difficile in patients in our cancer center. Over a period of seven consecutive months, 557 stools samples obtained from 156 hospitalized cancer patients (37 leukemic patients receiving oral antimicrobial prophylaxis and 119 patients from whom a stool sample was sent to the laboratory) were analyzed for the presence ofClostridium difficile. Clostridium difficile and/or its toxin was recovered from 13 (35 %) of the 37 patients receiving oral antimicrobial prophylaxis, and from 15 (12 %) of the other 119 patients (p<0.05). Isolation ofClostridium difficile was associated with diarrhoea in 13 (46 %) of 28 patients but specific treatment was initiated only in 7 (25 %) of the 28 patients in whomClostridium difficile was isolated. The wide distribution of the serotypes identified in our patients does not suggest an epidemic situation in our hospital.     

Nosocomial Outbreak of Clostridium difficile-Associated Diarrhoea due to a Clindamycin-Resistant Enterotoxin A-Negative Strain

A clindamycin-resistant toxin A-negative, toxin B-positive Clostridium difficile strain caused an outbreak among 24 hospitalized patients at the Department of Surgery, the Intensive Care unit, and the Department of Internal Medicine of an 800-bed academic hospital. Nineteen patients had undergone a surgical intervention and all 24 patients received at least one dose of antibiotics prior to the development of Clostridium difficile-associated diarrhoea. Twenty-seven episodes of Clostridium difficile-associated diarrhoea in 24 patients were categorized as mild (n=19), severe (n=7), or fatal (n=1). Relapses occurred in three patients. Nineteen of the 27 episodes required anti-Clostridium difficile treatment. Molecular typing performed by arbitrary primer polymerase chain reaction (PCR) and PCR amplification of rRNA intergenic spacer regions revealed that the outbreak strains recovered from culture were identical. The outbreak strain belonged to serogroup F and was resistant to erythromycin, clindamycin, and tetracycline, whereas susceptibility to chloramphenicol varied. No phenotypic activity of enterotoxin A was detected. A deletion of approximately 1.7 kb was found in the toxin A gene. Cytotoxin B had an unusual effect on cell culture assays that, at first, was not recognized as Clostridium difficile specific but could be neutralized with anti-Clostridium difficile B cytotoxin. Electronic Publication     

Septicemia and meningitis due toStreptococcus zooepidemicus

A case of septicemia and meningitis due toStreptococcus zooepidemicus in an immunocompetent patient is reported. This organism is an uncommon human pathogen that sometimes causes severe infection, usually in immunocompromised patients. In the reported case, the patient required to be mechanically ventilated for one week and was treated with intravenous ampicillin and gentamicin. He recovered and was discharged from hospital three weeks after the initial presentation.Streptococcus zooepidemicus sensitive to all penicillins, was isolated from all blood cultures and the cerebrospinal fluid.     

Hepatitis associated with Clostridium difficile in an ostrich chick

A live 19-day-old male ostrich chick was euthanized and necropsied. It was one of 12 chicks in a group in which 8 had died with history of anorexia, diarrhoea and weight loss. The birds had been treated with amikacin, piperacillin and enrofloxacin. Necropsy of the ostrich revealed dehydration, mild ascites and serous atrophy of fat around the heart. The liver had numerous yellow tan foci on the capsular surface as well as on the cut surface. Caecal contents were watery. Microscopic examination of the liver revealed multifocal necrosis of hepatocytes with infiltration of heterophils mixed with fibrin, few lymphocytes, and multinucleated giant cells. A Gram stain of the liver revealed a few gram-positive bacilli scattered within the necrotic foci. Clostridium difficile was isolated from the liver, and toxin A was detected by ELISA. A retrospective examination of approximately 1000 ostriches submitted during a seven year period to the laboratory system revealed seven cases of hepatitis due to Clostridium perfringens, two additional cases due to C. difficile and two cases due to C. sordelli.     

Nosocomial outbreak ofClostridium difficile diarrhea in a pediatric service

An outbreak of nosocomial diarrhea that occurred in a pediatric orthopedic service between 1 December 1993 and 15 April 1994 is reported. A total of 37 patients (mean age, 9.6 years; range, 2 months-19.3 years) were involved in the outbreak, including six patients with bacteriologically documentedClostridium difficile infection. A multivariate analysis identified lincomycin treatment for at least three days as the only significant risk factor. Stool samples from four asymptomatic patients were also positive forClostridium difficile and its cytotoxins. Isolates from all patients belonged to serogroup C, were highly resistant to lincomycin, and exhibited the same restriction pattern by pulsedfield gel electrophoresis. The outbreak ended after treatment with lincomycin was discontinued and hygiene control measures were implemented.     

Epidemiology and prevention ofClostridium 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.     

<Emphasis Type="Italic">Clostridium difficile</Emphasis>-Associated Diarrhoea After Internal Fixation of Intertrochanteric Femoral Fractures

The aim of the study presented here was to record the incidence and outcome of Clostridium difficile-associated diarrhoea in patients undergoing surgery for intertrochanteric femoral fractures. Between January 2000 and June 2001, a total of 239 patients who underwent surgery after sustaining an intertrochanteric femoral fracture were included in the study. Seventeen patients developed Clostridium difficile-associated diarrhoea (incidence risk, 7.1%), and six patients died after developing the condition (case fatality rate, 35%). Thus, Clostridium difficile-associated diarrhoea was found to cause significant morbidity and mortality after surgery for intertrochanteric femoral fractures, and antibiotics should be used judiciously in this group of patients.     

Computer-aided densitometric analysis of protein patterns ofClostridium difficile

The applicability of whole-cell protein patterns obtained by sodium dodecylsulfate-polyacrylamide gel electrophoresis as a typing method forClostridium difficile was examined using a total of 227 strains isolated from 191 patients and their surroundings. Computer-aided densitometric analysis was used to establish a reliable standardization technique with which a large number of protein patterns could be efficiently classified. The normalized tracks could be electronically superimposed and compared to give reproducible results. The influence of sample preparation for electrophoresis was found to be negligible. By this technique 35 subgroups could be differentiated, and further discrimination was possible within each subgroup using minor, even very weak protein bands. Epidemiologically related strains ofClostridium difficile yielded absolutely identical patterns, allowing unequivocal identification. Thus protein electrophoresis combined with densitometric analysis was shown to be useful for typingClostridium difficile isolates.     

Intravenous teicoplanin does not prevent Clostridium difficile associated diarrhea

A 59-year-old man with the diagnosis of endocarditis of the mitral valve due to Streptococcus mitis was treated with penicillin G, gentamicin, and later with clindamycin as inpatient for 3 weeks. Thereafter outpatient therapy with parenteral teicoplanin 3 × per week was initiated. After 17 days of teicoplanin treatment he developed severe diarrhea, and stool samples were positive for Clostridium difficile toxin. In addition to the ongoing parenteral therapy with teicoplanin, oral teicoplanin was administered. On the third day of this regimen the diarrhea and other disabling symptoms subsided, and test results for C. difficile toxin became negative. Oral teicoplanin was continued for 10 days and cleared C. difficile effectively after treatment as assessed by consecutive stool cultures (until 60 days thereafter). The parenteral administration of teicoplanin could not prevent the onset of C. difficile associated diarrhea in this patient, who previously had been treated with clindamycin. Thus, the administration of parenteral teicoplanin does not seem to be a treatment option for C. difficile associated diarrhea in patients in which oral therapy is not possible.     

Intestinal colonization withClostridium difficile in infants up to 18 months of age

The faecal colonization withClostridium difficile was investigated among 343 infants during their first 18 months of life. Rectal swabs were taken at the ages of 6 days, 6 weeks, 6 months, 11 months and 18 months. About 25 % of the children were colonized withClostridium difficile between 6 days and 6 months of age. The colonization rate decreased to 3 % at 18 months of age. The rate of strains producing cytotoxin was low in infants less than 6 months of age, but at that age about half of the strains isolated were toxin-producing. Breast-fed children were significantly less often colonized withClostridium difficile than were bottle-fed infants, both at 6 weeks of age (21 % versus 47 %, p<0.05) and at 6 months of age (19 % versus 39 %, p<0.001). Colonization withClostridium difficile at 6 months of age was associated with a greater frequency of diarrhoeal disease between 6 and 11 months of age (27 % versus 16 %, p<0.05). This association was even more pronounced when the bacteria persisted at 11 months of age (54 %, p<0.01). Antibiotic therapy could not be demonstrated to influence colonization withClostridium difficile at any age.     

Clostridium difficile toxin-induced reactive arthritis in a patient with chronic Reiter's syndrome

The first case ofClostridium difficile toxin-induced reactive arthritis in a patient with chronic Reiter's syndrome is described and compared with previous cases of reactive arthritis associated with this organism. This case demonstrates how distinct clinical manifestations may develop at different times in Reiter's syndrome, according to the infecting organism. Diagnostic terminology is discussed in this context.Clostridium difficile should now be considered a firmly established cause of reactive arthritis.     

Use of pulsed-field gel electrophoresis for investigation of an outbreak ofClostridium difficile infection among geriatric patients

A six-month outbreak ofClostridium difficile infection among elderly residents of a middle-term-care facility was investigated. Pulsed-field gel electrophoresis was used to genotype 22 outbreak strains and 30 epidemiologically unrelated strains. A prospective case-control study was conducted to identify risk factors for epidemicClostridium difficile-associated diarrhea. All epidemiologically unrelatedClostridium difficile strains of the same serogroup could be differentiated by their DNA patterns with two restriction enzymes (Smal andKspl). Among clustered strains, two epidemic serogroups (C and K) were identified. Two different DNA patterns were identified among serogroup C strains and three among serogroup K strains. Multivariate analysis showed that the risk ofClostridium difficile infection increased with antimicrobial chemotherapy (-lactam agents and pristinamycin) and the presence of a feeding tube. This study confirms the high discriminative power of restriction fragment length polymorphism analysis by pulsed-field gel electrophoresis to describeClostridium difficile epidemiology. The typing results confirm that infection was principally exogenous in this outbreak. Furthermore, they indicate the need to improve all measures limiting transmission of infection.     

Rapid polymerase chain reaction method for specific detection of toxigenicClostridium difficile

A rapid polymerase chain reaction (PCR) method for detection of toxigenicClostridium difficile directly from fecal samples by amplification of toxin Agene fragments was investigated. The technique was applied to monitor the spread of the microorganism in a long-term care ward with a relatively high incidence of overt episodes of diarrhea. The PCR approach has several advantages over traditional methods, rapidly allowing the specific detection of toxigenicClostridium difficile strains from stool samples in both symptomatic and asymptomatic subjects with toxigenic strains. This PCR method allows early detection of toxigenicClostridium difficile and could thus represent a powerful tool for the surveillance of epidemics.     

Treatment of relapsingClostridium difficile diarrhoea by administration of a non-toxigenic strain

Two patients with relapsing Clostridium difficile diarrhoea following metronidazole and vancomycin therapy were colonised with a non-toxigenic avirulent Clostridium difficile strain given orally in three doses. Both patients appeared to respond without sideeffects. Oral bacteriotherapy with a defined nontoxigenic strain of Clostridium difficile would appear to represent an acceptable, alternative and novel way to treat hospitalised patients who relapse with Clostridium difficile diarrhoea after specific antibiotic therapy.     

The potential economic value of screening hospital admissions for Clostridium difficile

Asymptomatic Clostridium difficile carriage has a prevalence reported as high as 51–85?%; with up to 84?% of incident hospital-acquired infections linked to carriers. Accurately identifying carriers may limit the spread of Clostridium difficile. Since new technology adoption depends heavily on its economic value, we developed an analytic simulation model to determine the cost-effectiveness screening hospital admissions for Clostridium difficile from the hospital and third party payer perspectives. Isolation precautions were applied to patients testing positive, preventing transmission. Sensitivity analyses varied Clostridium difficile colonization rate, infection probability among secondary cases, contact isolation compliance, and screening cost. Screening was cost-effective (i.e., incremental cost-effectiveness ratio [ICER] ≤?$50,000/QALY) for every scenario tested; all ICER values were?≤?$256/QALY. Screening was economically dominant (i.e., saved costs and provided health benefits) with a ≥10.3?% colonization rate and ≥5.88?% infection probability when contact isolation compliance was ≥25?% (hospital perspective). Under some conditions screening led to cost savings per case averted (range, $53–272). Clostridium difficile screening, coupled with isolation precautions, may be a cost-effective intervention to hospitals and third party payers, based on prevalence. Limiting Clostridium difficile transmission can reduce the number of infections, thereby reducing its economic burden to the healthcare system.     

Evaluation of an oligonucleotide probe and an immunological test for direct detection of toxigenicClostridium difficile in stool samples

A 33 basepair oligonucleotide probe, designed from the sequence of theClostridium difficile toxin B gene, was evaluated for its ability to detect toxigenicClostridium difficile directly in stool samples, without culture or DNA isolation. Two different labelling techniques were investigated: radiolabelling and digoxigenin-labelling. One hundred ninety-six stools were tested, with a good correlation (96 %) obtained between the oligonucleotide probe and the gold standard, the cytotoxicity tissue culture assay. The sensitivity and specificity were 83 % and 100 %, respectively. In parallel, a new commercially available enzyme immunoassay for the detection ofClostridium difficile toxin A in stool specimens was investigated. In 162 samples tested, a sensitivity of 80 % and a specificity of 98 % were obtained.