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The authors describe a particularly serious case of pseudomembranous colitis due to Clostridium difficile that was complicated by toxic megacolon. It was resolved by surgical intervention, and the reasons why subtotal colectomy is preferable to simple ileostomy are discussed.
Infectious diarrhea is a very common, usually self-limited disease. Among travellers to developing countries, diarrhea is by far the most common medical problem. The intake of sufficient glucose-electrolyte solutions is the most important step to prevent dehydration. Loperamide may be prescribed as a valuable antimotility agent: however, this drug should not be used in patients with high fevers, bloody diarrhea and severe abdominal cramps. Stool cultures are recommended in cases without improvement, when clostridium difficile is suspected and when multiple cases occur. Antibiotics are indicated for treatment of certain microorganisms, for patients with immunosuppression and in dysenteric syndromes. They are not recommended for prophylaxis on a routine basis.
In the vast majority of cases, Clostridium difficile-associated diarrhoea and pseudomembranous colitis develop following the use of antibiotics. We report a case in which C. difficile-associated diarrhoea was diagnosed in the absence of previously reported predisposing factors. It transpired that the patient had a colonic carcinoma. We suggest that a diagnosis of C. difficile-associated diarrhoea in the absence of a history of antibiotics or other established causes should prompt a colonoscopy to search for alternative explanations for the alteration in bowel flora which such an infection indicates.
ADP-ribosylation of a protein in human fibroblasts treated with partially purified Clostridium difficile toxin B was previously reported. Here we show that the same protein was ADP-ribosylated also in human fibroblasts exposed to supernatant from a C. difficile strain producing neither toxin A nor toxin B. Furthermore, in Chinese hamster ovary and in Vero cells, showing toxin B-induced cytopathogenic effect, the protein was not significantly ADP-ribosylated. The results indicate that the ADP-ribosylation is unrelated to the cytopathogenic effect of toxin B. It appears to be caused by another unidentified factor from C. difficile, and the substrate may correspond to a protein modified endogenously in cells exposed to stressful situations. Cellular actin was not ADP-ribosylated by toxin B.
OBJECTIVE: To compare two immunoassays for detection of toxins produced in vitro by isolates of Clostridium difficile with the standard tissue culture assay, to help in the diagnosis of C. difficile-associated diarrhoea. METHODS: Toxin production was investigated in 42 strains of C. difficile of various serotypes, ribotypes and S-protein types. These included strains from our laboratory collection, strains freshly isolated from stool specimens of patients suspected of suffering from C. difficile-associated disease or of carrying it asymptomatically, and one reference strain (NCTC 11223). Toxin was assayed by (i) a rapid slide immunoassay (C. difficile toxin A test, Clearview, Oxoid), (ii) an enzyme-linked microplate immunoassay (C. difficile toxin A/B test, Techlab), and (iii) a tissue culture assay. The rapid slide assay and the enzyme immunoassay were performed according to the manufacturers' recommendations. The tissue culture assay was performed using Vero cells. RESULTS: Thirty of the 42 strains (71%) were shown to be positive for toxin A by the slide immunoassay and 34 of the strains (81%) were found to be toxin A/B producers by the enzyme immunoassay. The same 34 strains that were positive in the enzyme immunoassay also produced toxin B (cytotoxin) in the tissue culture assay. The sensitivity, specificity, and positive and negative predictive values for the rapid slide immunoassay method were calculated to be 88.2%, 100.0%, 100.0% and 66.7%, respectively, when compared to tissue culture assay results as the reference method. These values for the enzyme immunoassay method were all 100.0%. In this study eight strains were found to be non-toxin-producing by all methods. It is possible that there were four strains that only produced toxin B (A- B+), and were missed by the rapid A-only assay. CONCLUSIONS: We can recommend the use of the Techlab A + B enzyme immunoassay for the detection of toxin production by C. difficile strains because of its high sensitivity and specificity, its ease of use, and its capability of detecting both A- and B-type toxins.
We conducted a prospective, randomized study to compare the efficacy of oral fusidic acid, oral metronidazole, oral vancomycin, and oral teicoplanin for the treatment of Clostridium difficile-associated diarrhea. Treatment resulted in clinical cure for 94% of the patients who were treated with vancomycin, 96% of those treated with teicoplanin, 93% of those treated with fusidic acid, and 94% of those treated with metronidazole. Clinical symptoms recurred in 16% of patients treated with vancomycin, 7% of those treated with teicoplanin, 28% of those treated with fusidic acid, and 16% of those treated with metronidazole. There was asymptomatic carriage of C. difficile toxin in 13% of patients treated with vancomycin, 4% of those treated with teicoplanin, 24% of those treated with fusidic acid, and 16% of those treated with metronidazole. No adverse effects related to therapy with vancomycin or teicoplanin were observed. Considering the costs of treatment, our findings suggest that metronidazole is the drug of choice for C. difficile-associated diarrhea and that glycopeptides should be reserved for patients who cannot tolerate metronidazole or who do not respond to treatment with this drug.
Clostridium difficile-associated disease continues to be a major problem in hospitals and long-term care facilities throughout the developed world. Administration of certain antibiotics such as amoxycillin, oral cephalosporins and clindamycin is associated with the greatest risk of developing C. difficile disease. The two antibiotics used for treatment of C. difficile disease are vancomycin and metronidazole, to which there is currently very little resistance. Randomly selected isolates (186) from 90 patients being investigated during an 18-month epidemiological study into the disease were tested for their susceptibility to vancomycin, metronidazole, amoxycillin, clindamycin, cefoxitin and ceftriaxone by the NCCLS agar dilution method. There was a narrow range of MIC for the two treatment agents (vancomycin and metronidazole), from 0.5 to 4 microg ml(-1), with no evidence of resistance. All strains were resistant to cefoxitin (MIC 64-256 microg ml(-1)), the antibiotic used in most selective media. All strains were of similar sensitivity to amoxycillin (MIC(90)= 4 microg ml(-1)). Most strains were resistant to ceftriaxone (MIC > or = 64 microg ml(-1)) or of intermediate resistance (MIC > or = 32 microg ml(-1)), with only two sensitive strains (MIC 16 microg ml(-1)). Clindamycin resistance was common, with 67 % of strains resistant (MIC > or = 8 microg ml(-1)), 25 % with intermediate resistance (MIC > or = 4 microg ml(-1)) and only 8 % sensitive (MIC < or = 2 microg ml(-1)). Twelve isolates from six different patients had very high resistance to clindamycin (MIC > or = 128 microg ml(-1)). Multiple isolates from the same patient, taken at different times, showed changes in susceptibility patterns over time. The only major change in susceptibility over the time-period was in clindamycin resistance; some strains appeared to become more resistant while others became less resistant. No differences were seen in the MIC(50) and MIC(90) of the different S-types of C. difficile identified, although some S-types were present in very small numbers. There was no correlation between the antibiotics prescribed and susceptibility.
BACKGROUND: The clinical presentation of Clostridium difficile infection ranges from asymptomatic carriage, colitis with or without pseudomembranes, to fulminant colitis. Although not common, fulminant C. difficile colitis can result in bowel perforation and peritonitis with a high mortality rate. Colectomy is often indicated in these cases. METHODS: We retrospectively analysed the outcome of 14 patients who underwent surgery for fulminant C. difficile colitis in the period 1996-2003 in our Unit. RESULTS: The indications for surgery were systemic toxicity and peritonitis (n = 10), radiological and clinical evidence of progressive toxic colonic dilatation (n = 3) and progressive colonic dilatation with bowel perforation (n = 1). C. difficile infection as the cause of colitis was diagnosed pre-operatively in seven (50%) patients, six of whom underwent a total colectomy and one a right hemicolectomy. Overall mortality in our series was 35.7%. Total colectomy was associated with a lower mortality rate of 11.1% (1/9) when compared with left hemicolectomy was 100% (4/4) (P = 0.01). One patient who underwent a right hemicolectomy (on the basis of deceptively normal external appearance of the rest of the colon intra-operatively) survived after a prolonged hospital stay. CONCLUSIONS: Early or pre-operative microbiological diagnosis of C. difficile infection can be difficult in patients with a fulminant presentation. Those patients with C. difficile colitis, who develop signs of toxicity, peritonitis or perforation, should undergo a total colectomy as the operation of choice.
OBJECTIVE: To determine the period prevalence of Clostridium difficile disease and asymptomatic carriage in the residents of long-term care facilities (LTCF) and to characterize the risk factors for colonization or associated disease. DESIGN: Period prevalence survey. SETTING: Two long-term care facilities in St. Paul, MN. PARTICIPANTS: Specimens were collected from 225 LTCF residents. MEASUREMENTS: The dependent variable was the culture result for C. difficile, which was isolated and identified using selective culture media and a commercial anaerobe identification kit. Tissue culture assay was used to detect the ability of each C. difficile isolate to produce toxin. Independent variables (including gender, age, race, current medical diagnoses, severity of underlying disease, case mix, current clinical symptoms, current medications, antibiotic use within 4 weeks prior to specimen procurement, and other pertinent history) were obtained from the current medical record of each participant. RESULTS: Of 225 stool cultures that were obtained, 16 (7.1%) were positive for C. difficile. None of the residents with a positive culture was symptomatic. History of nosocomial infection and the use of antibiotics in general, cephalosporins, trimethoprim/sulfamethoxazole (TMP/SMX), and histamine-2 blockers were significantly associated with positive C. difficile culture (P < or = 0.05) by univariate analyses. Trends towards significance (0.05 < 0.10) were noted for narcotic use, previous hospitalization, LTCF, and non-insulin-dependent diabetes mellitus. Logistic regression analysis revealed significant, independent predictors of positive culture: antibiotic use in general (P = 0.028; relative risk = 3.31), histamine-2 antagonist use (P = 0.038; relative risk = 3.27), cephalosporin use (P = 0.038; relative risk = 4.66), and TMP/SMX use (P = 0.007; relative risk = 8.45). CONCLUSIONS: The use of antibiotics, particularly cephalosporins and TMP/SMX, is a significant risk factor for asymptomatic carriage of C. difficile in long-term care facilities. The use of H-2 blockers was also a significant risk factor for carriage; however, this finding has not been reported previously and should be confirmed by independent studies. These medications should be used judiciously in the LTCF population. When diarrheal diseases are encountered in LTCF residents, a high index of suspicion for C. difficile infection should be maintained and the appropriate diagnostic and therapeutic measures taken.
Agar dilution anaerobic susceptibility studies using rifampin, vancomycin, metronidazole, and bacitracin individually and in combination were performed with Clostridium difficile. Fifty-five strains of C. difficile were studied. Eighty-five percent of strains tested (29 of 34) were synergistically inhibited by the combination of bacitracin and rifampin (fractional inhibitory concentration, less than or equal to 0.50).
We studied 557 nonduplicate fresh stool specimens from adult patients clinically suspected of having Clostridium difficile-associated diarrhea. All samples were tested in parallel with an in-house cytotoxin B tissue culture assay (CTA), the C DIFFICILE TOX A/B II test (TA/B; TechLab, Blacksburg, VA), and the Triage Micro C DIFFICILE Panel (Biosite Diagnostics, San Diego, CA). The Triage device detects toxin A (TA) and glutamate dehydrogenase (GDH) simultaneously. Of the specimens, 350 were negative and 95 were positive for all markers. Another 112 specimens yielded discrepant results. The CTA found 143 positive specimens. Results of the components of the Triage and TA/B were compared separately with those of CTA. GDH was the most sensitive but least specific marker, whereas TA and TA/B were less sensitive but highly specific. Because of these attributes and a quick turnaround time, GDH would be the best screening test for C difficile-associated diarrhea. CTA detected the highest number of cases of C difficile-associated diarrhea and would be most useful as a confirmatory test for GDH-positive and TA-negative specimens.
A case of nosocomial diarrhea by Clostridium difficile in an older woman with an old history of increasing stool frequency, is reported. Colonoscopy and biopsy was performed due to an incomplete response to vancomicyn, and the diagnosis of underlying ulcerative colitis was made. The incidence of Clostridium difficile infection associated with the relapse of ulcerative colitis is nearly 10%. In patients with ulcerative colitis, macroscopic pseudomembranes and the usual predisposing factors for Clostridium difficile infection, usually, are not present. It seems to exist a significant correlation between the severity of the relapse and Clostridium difficile. The specific treatment of the pseudomembranous colitis, in the majority of the cases, is sufficient for a correct control of relapse of ulcerative colitis.
Four patients had diarrhea due to Clostridium difficile after receiving chemotherapy for cancer. None of the patients had received antibiotics for at least 4 weeks before the onset of diarrhea. At the time of admission of any of these four patients no outbreak of diarrhea was noted on the ward. Each patient was admitted with the acute onset of diarrhea after receiving chemotherapy, at different times of the year. Diarrhea was clinically important and was associated with dehydration, toxemia, and blood in the stool in all cases. Diagnosis of C difficile was confirmed by endoscopic examination, positive biopsy specimen, and positive test for toxin in the stool. All patients recovered after undergoing specific treatment. Drugs not believed to carry serious risk to the bowel mucosa may facilitate proliferation of C difficile. Patients with severe diarrhea after receiving chemotherapy, particularly those with blood in the stool, should be promptly tested for C difficile even in the absence of a history of antibiotic administration. Early and specific treatment can prevent additional morbidity and reduce cost of care.
The thermoresistance of spores of Clostridium difficile strains belonging to the different toxigenicity groups was compared in the study. Among spores of toxigenicity C. difficile strains (26 C. difficile strains produced toxins A and B (TcdA+TcdB+) and 32 C. difficile strains produced only toxin B (TcdA-TcdB+) were high thermoresistant. Between spores of non-toxigenic C. difficile strains much lower thermoresistance was observed. In conclusion, more studies are needed to clarify the importance of spores transmission in the increasing number of AAD cases in Poland.
BACKGROUND & OBJECTIVE: Clostridium perfringens type A (CPA) isolates produce lethal necrotizing antigens and the heat resistant forms of the organism are associated with pathogenic outcome in humans. CPA has also been implicated in antibiotic associated diarrhoea (AAD). We therefore undertook this study to investigate the presence of CPA in stool samples of patients with AAD in a tertiary care setting in north India. METHODS: A total of 285 stool samples obtained from patients suspected for Clostridium difficile aetiology were examined for the presence of CPA antigens. Four sets of reagents (CP-I, CP-II, CP-III and CP- IV) comprising latex beads coated with polyvalent immune sera to 17 serotypes of heat resistant CPA were used in the study. Agglutination reaction was carried out using the reagents with the stool supernatants. RESULTS: Of the 285 stool samples tested, 25 (8.77%) were positive for at least one or more of the four polyvalent sets. Briefly, 48 per cent were positive for all the four sets, 12 per cent for 3 sets, 28 per cent for 2 sets and 12 per cent for only one set, indicating the prevalence of multiple serotypes of CPA. Twenty three (92%) of the 25 positive samples came from patients who were on antibiotics. C. difficile toxin was also present in 9 of 25 (36%) of the samples positive for CPA antigens. INTERPRETATION & CONCLUSION: In our setting, CPA could thus be associated with AAD either by itself or in synergy with C. difficile infection. Assessment of true burden of CPA associated AAD would be required to take appropriate steps for its control in our country.
During a 12-month period, Clostridium difficile was isolated from 38 (11.1%) of 341 hospitalised patients suffering from acute diarrhoea and from five (3%) of 172 patients as control who were admitted with illnesses other than diarrhoea. It was the sole bacterial pathogen in 31 cases. 87% of the isolates obtained from patients with diarrhoea produced neutralisable cytotoxin. None of these patients had any history of previous treatment using antibiotics. No age or gender-specific high incidence was observed. Clinical presentation in these patients revealed no distinctive pattern. Both dysenteric and diarrhoeal presentations were found, the latter being more frequent. The results suggest that Clostridium difficile by itself may be a causal agent of acute diarrhoea.
The current impact of Clostridium difficile will have been noticed by many clinicians, particularly those managing elderly patients. Infection with this bacterium can give rise to a wide range of symptoms, from diarrhoea to fulminating colitis and toxic megacolon. Patients may also be asymptomatically colonized by C. difficile. In this article the epidemiology and aetiology of C.difficile infection will be discussed, followed by an explanation of how diagnosis of cases is best achieved, how the disease is optimally treated and how cross-infection can be minimized.
CONTEXT: Recent reports suggest an increasing occurrence and severity of Clostridium difficile-associated disease. We assessed whether the use of gastric acid-suppressive agents is associated with an increased risk in the community. OBJECTIVE: To determine whether the use of gastric acid-suppressive agents increases the risk of C difficile-associated disease in a community population. DESIGN, SETTING, AND PATIENTS: We conducted 2 population-based case-control studies using the United Kingdom General Practice Research Database (GPRD). In the first study, we identified all 1672 cases of C difficile recorded between 1994 and 2004 among all patients registered for at least 2 years in each practice. Each case was matched to 10 controls on calendar time and the general practice. In the second study, a subset of these cases defined as community-acquired, that is, not hospitalized in the prior year, were matched on practice and age with controls also not hospitalized in the prior year. MAIN OUTCOME MEASURES: The incidence of C difficile and risk associated with gastric acid-suppressive agent use. RESULTS: The incidence of C difficile in patients diagnosed by their general practitioners in the General Practice Research Database increased from less than 1 case per 100,000 in 1994 to 22 per 100,000 in 2004. The adjusted rate ratio of C difficile-associated disease with current use of proton pump inhibitors was 2.9 (95% confidence interval [CI], 2.4-3.4) and with H2-receptor antagonists the rate ratio was 2.0 (95% CI, 1.6-2.7). An elevated rate was also found with the use of nonsteroidal anti-inflammatory drugs (rate ratio, 1.3; 95% CI, 1.2-1.5). CONCLUSIONS: The use of acid-suppressive therapy, particularly proton pump inhibitors, is associated with an increased risk of community-acquired C difficile. The unexpected increase in risk with nonsteroidal anti-inflammatory drug use should be investigated further.