Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic Escherichia coli and Vibrio cholerae

To evaluate the antisecretory activity of berberine sulfate (BS), we studied 165 adult patients with acute diarrhea due to enterotoxigenic Escherichia coli (ETEC) and Vibrio cholerae in randomized controlled trials. In patients with ETEC diarrhea who received 400 mg of BS in a single oral dose, the mean stool volumes were significantly less than those of the controls during three consecutive 8-hr periods after treatment (P less than .05). At 24 hr after treatment, significantly more patients who were treated with BS and had ETEC diarrhea stopped having diarrhea as compared with the controls (42% vs 20%, P less than .05). In patients with cholera who received 400 mg of BS, the mean 8-hr stool volume during the second 8-hr period after treatment declined to 2.22 liters, which was significantly less than the 2.79 liters found in the controls (P less than .05). However, patients with cholera who received 1200 mg of BS plus tetracycline did not have significant reduction in stool output compared with patients who received tetracycline alone. No side effects of BS were noted. These results indicated that BS is an effective and safe antisecretory drug for ETEC diarrhea, whereas the activity against cholera is slight and not additive with tetracycline.     

Is irritable bowel syndrome more common in patients presenting with bacterial gastroenteritis? A community-based,case-control study

OBJECTIVE: Irritable bowel syndrome (IBS) has been reported to follow infectious diarrhea. Food-borne infections affect 76 million people in the United States and 9.4 million in England per year; of these, only a small percentage of patients see their doctor, and even fewer will have stool culture confirmation. We hypothesized that patients who present to their doctor with gastroenteritis and have positive stool samples may be different from the normal population with regard to their pre-existing bowel symptoms. Our aim was to determine if patients with bacterial gastroenteritis were more likely to have prior IBS, functional dyspepsia, or functional diarrhea, compared with a control population. METHODS: Between January, 2000 and January, 2001, subjects with stool positive bacterial gastroenteritis and control subjects from the same primary care practice were invited to participate. The main outcome measure was the presence of IBS, functional dyspepsia, or functional diarrhea diagnosed using self-report Rome II modular questionnaires. RESULTS: A total of 217 people with recent bacterial gastroenteritis and 265 community controls consented to participate in the study. Of these, 89/217 cases and 46/265 controls had one of the functional GI disorders (OR = 3.3; 95% CI = 2.17-5.00). IBS was present in 67 cases (31%) and 26 controls (10%) (OR = 4.1; 95% CI = 2.49-6.72). There was no statistically significant difference in the presence of prior functional dyspepsia or functional diarrhea. CONCLUSIONS: IBS is more frequent before diagnosis in people with bacterial gastroenteritis presenting to their primary care physician than in community controls. Studies that examine the rate of IBS after bacterial gastroenteritis need to carefully exclude people with prior IBS in a systematic way.     

Clostridium difficile Infection is a Treatable Cause of Diarrhea in Patients with Advanced Human Immunodeficiency Virus Infection: A Study of Seven Consecutive Patients Admitted from 1986 to 1992 to a University Teaching Hospital

Of 427 human immunodeficiency virus-seropositive patients admitted to the Robert Wood Johnson University Hospital from January 1986 through August 1992, seven had Clostridium difficile enteric infection documented by the presence of cytotoxin B in the stool, without other enteric infection. All seven patients had AIDS, and all had recently received antibiotics. These patients had a severe clinical presentation of C. difficile infection. All patients had profound watery diarrhea, with a mean of 20 ± 14 (SD) bowel movements per day. Four had fever >38.5°C, and another had hypothermia. Three patients had borderline hypotension, and another was orthostatic. The mean pulse was 119 ± 26 (SD) beats/min. Five patients had abdominal pain and tenderness. Two had occult blood in the stool. Four had metabolic derangements such as hyponatremia, hypokalemia, or prerenal azotemia. Three of four patients undergoing abdominal roentgenography had radiographic findings consistent with severe colitis of colonic dilation, mural thumbprinting, or mural thickening. Sigmoidoscopic findings ranged from diffuse erythema to prominent pseudomembranes. During a mean interval of 14.3 ± 6.2 (SD) days before institution of specific antibiotic therapy, the diarrhea spontaneously resolved in only one of the seven patients. In the others, the diarrhea resolved on average 7.3 ± 4.0 (SD) days after instituting antibiotic therapy. During a mean follow-up of 4.4 ± 6.3 (SD) months, only two patients redeveloped diarrhea. Both patients had recurrent C. difficile colitis; the symptoms again rapidly resolved after repeat antibiotic therapy. We conclude that in patients with AIDS C. difficile may present as a severe enteric infection with profound diarrhea due to immunosuppression, that the diarrhea may be prolonged and not remit spontaneously, and that the diarrhea usually rapidly resolves with specific antibiotic therapy.     

Clostridium difficile. Colonization and toxin production in a cohort of patients with malignant hematologic disorders

We examined 45 (80%) of 56 consecutive adult patients with malignant hematologic disorders who were hospitalized during a 15-week period at Emory University Hospital, Atlanta. Stool samples for Clostridium difficile culture and cytotoxin assay were obtained on admission and then weekly during each patient's hospitalization. On admission, four patients had detectable C difficile in their stool samples, which was associated with prior antimicrobial use but not with prior cancer chemotherapy. One of the four patients with positive stool samples also had toxin present in the stool sample and was the only one with diarrhea. Eight (36%) of 22 patients hospitalized for one or more weeks had C difficile isolated from at least one stool specimen. The positive cultures showed no clustering in time, and no risk factors were identified for colonization. Only seven of 15 culture-positive stool samples and three of seven toxin-positive samples were associated with diarrhea.     

Antimicrobial agents and Clostridium difficile in acute enteric disease: epidemiological data from Sweden, 1980-1982

The carrier rate of Clostridium difficile in an adult Swedish population was found to be 11 (1.9%) of 594. All isolates were toxigenic in vitro, but no healthy individual harbored free cytotoxin in stool. Of 398 patients with acute diarrhea not associated with antibiotic use, cytotoxin was found in stool filtrates of four (1%). In 4,793 patients with antibiotic-associated diarrhea from all parts of Sweden during 1980-1982, C. difficile cytotoxin was demonstrated in 873 (18%). The tissue culture assay was found to be more specific than cultivation for the bacterium. By weighted analysis, in the age group greater than 70 years more women than men were infected. In the age group 21-50 years there was an even greater preponderance of infection in women than in men. Cephalosporins and lincosamides were 10-70 times more often implicated in C. difficile colitis than were narrow-spectrum penicillins.     

Clinical correlation of toxin and common antigen enzyme immunoassay testing in patients with Clostridium difficile disease

OBJECTIVE: The aim of the present study was to assess the correlation of Triage Micro Clostridium difficile Panel and toxin B cytotoxicity assay with the clinical diagnosis of C. difficile diarrhea. METHODS: The subjects evaluated were 98 patients with diarrhea for whom stool was submitted for testing for C. difficile. Clinical symptoms prompting evaluation, laboratory values, comorbid illness, and treatment outcomes that provided clinical insight into the etiology of the diarrhea were recorded. These data were then reviewed by two experienced clinical gastroenterologists who were blinded to the results of the Triage enzyme immunoassay and cytotoxin B assay. The final diagnosis of C. difficile diarrhea was based on the patient's clinical evaluation and symptoms, treatment, and subsequent outcome. RESULTS: Of 98 patients evaluated, 33 were diagnosed with C. difficile diarrhea by clinical criteria. The toxin B assay displayed 88% sensitivity and 100% specificity and positive predictive value. The toxin A component of the Triage Panel displayed 45% sensitivity but 98% specificity and 94% positive predictive value. The common antigen had 97% sensitivity and 95% negative predictive value. Among the 45 patients with only a common antigen detected, the most common diagnoses for diarrhea were chemotherapy-related, antibiotic-related diarrhea, and graft versus host disease. CONCLUSIONS: Our data show that both the Triage Micro C. difficile Panel and cytotoxin B for C. difficile have a high positive predictive value and negative predictive value for C. difficile diarrhea. The Triage Micro C. difficile Panel provides a reasonable alternative to the cytotoxin B assay in the assessment of clinically relevant C. difficile. The Triage Micro C. difficile Panel is less labor intensive and less expensive than cytotoxin B assay. The panel approach improves on the individual assay performances by increasing sensitivity and negative predictive value. When both common antigen and toxin A are positive, the likelihood of C. difficile diarrhea is high; conversely, when both results are negative, the likelihood of C. difficile diarrhea is low.     

Antimicrobial use in children under five years with diarrhea in a central region province, Thailand

This cross-sectional study aimed to estimate the prevalence of appropriate antimicrobial prescribing for treating childhood diarrhea within the public hospital system in a central region province, Thailand. Reported are findings of a prospective clinical audit of 424 cases treated by 38 physicians. Appropriate use of antimicrobials was defined as prescribing antimicrobials for managing an invasive bacterial-type, bloody diarrhea or not prescribing antimicrobials for managing a watery-type or non-bloody diarrhea. Among 424 cases with diarrhea, 12.5% were invasive bacterial-type. Of the 66 diarrheal episodes in which stool samples were cultured, 7 stool specimens were positive, two with Shigella sonnei, two with Vibrio cholerae Ogawa and three with E. coli. Based on the presence of mucus and blood in stools, 27.4% of 424 cases received appropriate antimicrobial drugs. Cotrimoxazole was the most commonly prescribed drug (51%), followed by colistin sulfate (15.3%), norfloxacin (11%), and nalidixic acid (0.5%). The average number of antimicrobials per case of inpatients was higher than outpatients (1.15 vs 0.84, p < 0.001). There was a trend toward prescribing norfloxacin in childhood diarrhea. The Ministry of Public Health should continue providing effective interventions aimed at improving physicians' knowledge of diarrhea treatment. Similar efforts should be directed toward improving caretakers' knowledge about home care for childhood diarrhea and encouraging widespread correct use of oral rehydration therapy (ORT) in the community. Hopefully, such activities will help reduce the inappropriate use of antimicrobial agents in treating diarrheal disease.     

Clostridium difficile Culture-Positive Toxin-Negative Diarrhea

Antibiotic-associated colitis (AAC) is confirmed by the isolation of Clostridium difficile cytotoxin from stool in patients with diarrhea. Culture of the organism has not been required to confirm the diagnosis. A review of cases of C. difficile culture-positive patients was performed in an attempt to clarify the significance of culture-positive toxin-negative (CPTN) compared to culture-positive toxin-positive (CPTP) disease. During an 11-month period, 45 patients were identified who had stool cultures positive for C. difficile. Sixteen of the patients studied were CPTP and 29 were CPTN. There were no major differences between the two groups for underlying diseases, antibiotic exposure, or diagnostic testing. Of the CPTP patients, 10 were treated for AAC and all responded. Two untreated patients resolved spontaneously. Of the CPTN patients, none was given specific antibiotic therapy, symptoms spontaneously resolved in 17, and symptoms were unresolved in five (colectomy or expired before resolution). A prospective analysis was performed of all C. difficile isolated from stool samples by the microbiology laboratory. Isolates were incubated in vitro and cytotoxin production was measured. Of isolates from CPTP patients 97% produced cytotoxin compared to 67% of isolates from CPTN patients (p less than 0.005). The results suggest that C. difficile, despite the absence of cytotoxin, may be an etiological factor in certain diarrheal syndromes. Until a randomized therapeutic trial for CPTN patients is conclusive, a positive culture should be considered evidence for treatment of patients with persistent diarrhea.     

Evaluation of Antibiotic–Associated Diarrhea with a Latex Agglutination Test and Cell Culture Cytotoxicity Assay for Clostridium difficile

Diagnosis of Clostridium difficile (C. difficile) by its antigen or toxin has improved treatment for patients who have antibiotic-associated diarrhea and opportunistic colonization of the colon with C. difficile. Unfortunately, results from the tissue culture cytotoxicity assay are not available for 48 h. We prospectively compared a latex agglutination test with the tissue culture cytotoxicity assay in 83 patients (15 with antibiotic-associated diarrhea, 23 with non-antibiotic-associated diarrhea, and 45 without diarrhea). In the antibiotic-associated diarrhea group, 43% of patients with pseudomembranes and 25% without pseudomembranes tested positive with both tests. In the non-antibiotic groups 92% with diarrhea and 90% without diarrhea were negative with both tests. The number of discordant results illustrates the value of using two tests to identify C. difficile, since additional patients can be identified by using two tests. We found false positives were rare, and C. difficile toxin or antigen could not be detected in more than half the patients with pseudomembranes. The latex agglutination test for C. difficile is reliable, specific, and faster than the tissue culture cytotoxicity assay. The data suggest that other organisms may also be responsible for pseudomembranous colitis, and that negative tests do not obviate the need for visual evaluation of colonic mucosa in suspected cases of antibiotic-associated diarrhea.     

Enteropathogens associated with acute and persistent diarrhea in Bangladeshi children less than 5 years of age.

A longitudinal study of diarrhea was carried out from May 1988 to April 1989 by household surveillance of 705 children less than 5 years old in rural Bangladesh. Stool samples were examined for enteric pathogens at the beginning of each diarrheal episode. For persistent episodes, stool examination was repeated on days 15-17 of the illness. For each case of persistent diarrhea, stool samples from age-matched acute diarrheal and healthy controls were examined. Compared with healthy controls, cases of diarrhea were associated with Shigella species (P = .07) and rotavirus (P less than .05). Diffusely adherent Escherichia coli (P less than .05) and cryptosporidia (P = .07) were the only enteropathogens associated with persistent diarrhea in comparison with acute diarrhea. No more than 15% of children had the same class of pathogen identified from stool on both days 1-3 and days 15-17, indicating that persistent infection was uncommon. However, a different enteropathogen was frequently found on days 15-17, suggesting that sequential infection may be a cause of persistent diarrhea.     

Does bacterial gastroenteritis predispose people to functional gastrointestinal disorders? A prospective, community-based, case-control study

OBJECTIVES: Irritable bowel syndrome (IBS) might develop after gastroenteritis. Most previous studies of this relationship have been uncontrolled, and little is known regarding other functional gastrointestinal disorders (FGIDs) after gastroenteritis. The primary aim of this study was to determine the frequency of IBS, functional dyspepsia, or functional diarrhea 6 months after bacterial gastroenteritis. METHODS: This was a prospective, community-based, case-control study. Cases had proven bacterial gastroenteritis, and controls were community-based. FGIDs were diagnosed with the use of self-completed Rome II modular questionnaires administered at baseline, 3, and 6 months. Subjects with prior FGIDs were excluded. The primary endpoint was the presence of one of the three specific FGIDs at 6 months. RESULTS: A total of 500 cases and 705 controls were identified. Of the 500 cases, 265 (53%) consented, but only 128 cases and 219 community controls who consented were eligible. At 6 months, 108 cases and 206 controls returned the questionnaire. FGIDs were diagnosed in significantly more cases (n = 27, 25%) than controls (n = 6, 2.9%) (OR = 11.11, 95% CI = 4.42-27.92). IBS was diagnosed in 18 cases (16.7%) and four controls (1.9%) (OR = 10.1, 95% CI = 3.32-30.69); functional diarrhea in six cases (5.6%) and no controls. Functional dyspepsia was uncommon in both cases and controls. Similar findings were found at 3 months, with 29% of cases and 2.9% of controls having an FGID. CONCLUSIONS: Symptoms consistent with IBS and functional diarrhea occur more frequently in people after bacterial gastroenteritis compared with controls, even after careful exclusion of people with pre-existing FGIDs. The frequency is similar at 3 and 6 months. Our findings support the existence of postinfectious IBS and give an accurate estimate of its frequency.     

Diarrhea in tube-fed patients: feeding formula not necessarily the cause

PURPOSE: This study of diarrhea in tube-fed patients was undertaken to determine the proportion of cases in which feeding formula is not responsible for the diarrhea, the causes other than the feeding formula, and the diagnostic approach to diarrhea in tube-fed patients. PATIENTS AND METHODS: Inpatients at the Truman Memorial Veterans Hospital who received nasoenteric feeding during the time period from October 1986 through May 1988 were eligible for this study. Of 123 patients who received nasoenteric feeding, 32 patients had documented diarrhea (greater than 500 mL per day for at least two consecutive days) and were enrolled. Three of these patients received hypertonic feeding formula, whereas the remaining 29 received isotonic feeding formula. Prospective determinations of the causes of diarrhea were performed. Laboratory tests included fecal leukocytes, stool osmolality, stool electrolytes, and Clostridium difficile toxin assay. Diarrhea was considered osmotic if the stool osmotic gap was greater than 100 mmol/L. Clinical management involved reducing or stopping the feeding formula, stopping suspected medications, or administering appropriate antibiotics. RESULTS: There were 32 episodes of diarrhea in tube-fed patients during the study period. A single cause could be specified in 29 cases. The tube feeding formula was responsible for diarrhea in only 21% of these cases. Medications were directly responsible in 61% and C. difficile in 17% of cases. Stool osmotic gap correctly distinguished osmotic from non-osmotic diarrhea in all cases. CONCLUSION: When diarrhea develops in properly tube-fed patients, the feeding formula is usually not responsible for the diarrhea. Patients receiving nasoenteric tube feeding are frequently placed on liquid forms of medications. Many medicinal elixirs contain sorbitol, which is often the cause of diarrhea in tube-fed patients. Review of the medications and determination of the stool osmotic gap are the initial diagnostic steps of highest yield.     

Successful treatment with rifampin for fulminant antibiotics-associated colitis in a patient with non-Hodgkin＇s lymphoma

A 74-year-old man was admitted to the hospital because of chemotherapy for relapsed non-Hodgkin‘s lymphoma (NHL).The patient became febrile and experienced diarrhea after chemotherapy. Although ceftazidime and amikacin sulfate were administered as empiric therapy, diarrhea was continued.After several days, stool cytotoxin assay for clostridium difficile (C. difficile) was positive and he was diagnosed as having antibiotics-associated colitis (AAC). Although antibiotics were discontinued and both oral vancomycin and metronidazole were administrated, disease was not improved. To rule out the presence of an additional cause of diarrhea, colon fiberoscopic examination was performed. It revealed multiple deep ulcerative lesions at right side colon, surface erosive and minute erosive lesions in all continuous colon.Pseudomembranes were not seen. These findings are compatible with AAC without pseudomembranes. There are no reports that the rifampin is effective on refractory AAC.However, we administered oral rifampin for the current patient.The reasons are 1) conventional antibiotics were not effective,2) rifampin has excellent in vitro activity against C. difficile,and 3) the efficacy of rifampin on relapsing colitis due to C.difficile is established. After administration of rifampin, fever alleviated and diarrhea was improved. Because AAC may result in significant mortality, patients with refractory or fulminant AAC should be treated with oral rifampin from outset.     

Hemolytic uremic syndrome and diarrhea in Argentine children: the role of Shiga-like toxins

Shiga-like toxin-producing Escherichia coli have been associated with hemorrhagic colitis and the hemolytic uremic syndrome (HUS). Because Argentina has the highest reported frequency of HUS in the world, Argentine children were prospectively studied during the HUS seasons for evidence of Shiga-like toxin-related diseases. On the basis of serology, fecal cytotoxin neutralization, stool cultures, and DNA hybridization of colony lysates, most children with HUS had evidence of infection with Shiga-like toxin-producing organisms. Children with spring-summer diarrhea also commonly (32%, confidence interval 18%-46%) had clear-cut evidence of such infection. No controls (children without gastrointestinal, renal, or hemolytic disease) had free fecal cytotoxin, positive cultures for E. coli O157:H7, or DNA probe-positive organisms; 20% of them had low serum titers of antibodies to Shiga-like toxins. E. coli O157:H7 was not common in either HUS or diarrhea patients. The high frequency of Shiga-like toxin-induced diarrhea in young children in Argentina probably explains the high incidence of HUS in this country and suggests that HUS is a relatively uncommon complication of Shiga-like toxin-related disease.     

Sporadic cases of hemorrhagic colitis associated with Escherichia coli O157:H7. Clinical, epidemiologic, and bacteriologic features

During a 6-month period in 1983, Escherichia coli O157:H7 was isolated from 19 (15%) of 125 patients with grossly bloody diarrhea and 1 sibling with non-bloody diarrhea in the Calgary area. There was no clustering of the cases geographically or in time. All but 1 had clinical manifestations typical of hemorrhagic colitis associated with E. coli O157:H7. The illness appeared to be associated with consumption of hamburgers by 15 patients. The diarrheal illness was usually self-limited, but 3 children developed the hemolytic-uremic syndrome shortly after onset of illness. The organism was excreted in the stools very briefly in adults, although bacterial shedding continued for a longer period in children. All isolates produced verotoxin, and cytotoxic activities were present in stool filtrates. The results suggest that the incidence of sporadic cases of hemorrhagic colitis due to E. coli O157:H7 may be higher than has been suspected, and that patients with grossly bloody diarrhea should be studied promptly for E. coli O157:H7 infection. Specific techniques for identifying this serotype must be applied to the stool cultures. Detection of free cytotoxin in stool filtrates may be an effective diagnostic procedure.     

Rotavirus in travelers' diarrhea: study of an adult student population in Mexico.

The role of rotavirus in adult diarrhea was evaluated in 165 students attending a Mexican university. Students were divided into three groups: newly arrived summer students from the United Sttes, regular students from the United States, and Mexican and Venezuelan students. Ninety-one students with diarrhea and 74 corresponding, matched, asymptomatic control students were included in the study. The frequency of rotavirus in stools was determined by electron microscopy with use of the pseudoreplica technique. Twenty-five percent of those who were ill and 12% of the controls had rotavirus in their stools. A significantly (P less than 0.05) greater number of newly arrived United States summer students with diarrhea had rotavirus in their stool than did matched controls (26% vs. 3%). There was no significant difference in rate of recovery of bacterial pathogens from rotavirus-positive and rotavirus-negative stools (52% vs. 53%) from students with diarrhea. Although significantly more rotavirus was identified from ill American summer students than from controls, the role of rotavirus as a cause of diarrhea in these students could not be established in all cases since bacterial pathogens were also commonly found in stool.     

Clostridium difficile toxin in acute diarrhoea complicating inflammatory bowel disease.

The incidence of Clostridium difficile cytotoxin has been studied in 69 consecutive patients with inflammatory bowel disease complicated by severe diarrhoea or ileostomy flux during 74 admissions to hospital. The cytotoxin was identified in only four patients, all of whom had received antimicrobials. Clostridium difficle, but not cytotoxin, was identified in 10 of 43 admissions. This followed antimicrobial prophylaxis to cover a recent operation in two patients, and five were on long-term sulphasalazine. Only three patients with Clostridium difficile had not received an antimicrobial within one month of the study. Isolation of Clostridium difficile alone is of doubtful pathological significance, as it spontaneously disappeared without treatment in all patients.     

Usefulness of immunological detection of both toxin A and toxin B in stool samples for rapid diagnosis of Clostridium difficile-associated diarrhea

Toxin detection from stool specimens is critical for the diagnosis of Clostridium difficile-associated diarrhea (CDAD). In Japan, only two toxin detection kits targeting toxin A alone are commercially available. We evaluated ImmunoCard Toxin A & B (ImmunoCard), based on enzyme immunoassay for the rapid detection of both C. difficile toxins A and B in stool specimens, compared to a toxin A detection kit (Uniquick) and cytotoxin assay. C. difficile was also cultured from stool specimens and the toxin production type of C. difficile isolates was identified by PCR analysis. Compared to cytotoxin assay, ImmunoCard sensitivity was 86.2%, specificity 93.8%, positive predictive value 91.8%, and negative predictive value 89.4% (n = 146). Sensitivity was significantly higher than that of Uniquick (60.0%, p = 0.0016). ImmunoCard detected 90.6% of cytotoxin positive specimens with isolated toxin A-positive, toxin B-positive C. difficile strains (Uniquick; 67.9%, p = 0.008) and 70.0% of these with isolated toxin A-negative, toxin B-positive C. difficile strains. Although ImmunoCard was slightly less sensitive than cytotoxin assay, it requires no special equipment and completes the entire test in up to 20 min. ImmunoCard thus appears very useful in the rapid diagnosis of CDAD in the clinical laboratory. Kits for the detection of both C. difficile toxins A and B should be immediately introduced into Japan to ensure the correct diagnosis of CDAD and infection control.     

Escherichia coli O157:H7 and the hemolytic uremic syndrome: importance of early cultures in establishing the etiology

Fifty-two patients were studied prospectively to determine the etiology of postdiarrheal hemolytic uremic syndrome (HUS). Escherichia coli O157:H7 was isolated from 33 patients (63.4%). If stool obtained within 2 days of the onset of diarrhea was cultured for E. coli O157:H7, the recovery rate was 100%. This rate decreased to 91.7% and 33.3% if stool was cultured for this pathogen 3-6 or greater than or equal to 7 days, respectively, after diarrhea began. The culture-positive group was more likely to have had bloody diarrhea and fecal leukocytes and to have received transfusions than the culture-negative group but was otherwise similar in clinical characteristics. E. coli O157:H7 is the predominant pathogen associated with HUS in western Washington. Recovery of this pathogen is highly dependent on obtaining stool cultures within 6 days of onset of diarrhea.     

A role for colonic stasis in the pathogenesis of disease related toClostridium difficile

The records of 133 consecutive patients (65 men, 68 women; age range, 15 months to 88 years; median, 57 years) with either a positive Clostridium difficile stool culture or toxin assay from 1982 to 1984 were reviewed in order to assess the pattern of this disease in a large hospital and to examine the type of patient at risk. All patients had diarrhea and/or bloody stools (121 and 36, respectively). Less specific symptoms were common. Most patients had been exposed to multiple antibiotics, but of those who had received only one agent, cephalosporins were most common (21/43). Nineteen patients had cancer chemotherapy. C. difficile toxin assay was positive in 106, culture was positive in 74, and pseudomembranes were seen in six of the 39 patients who underwent endoscopy. Treatment consisted of stopping antibiotic therapy alone (86 percent response), oral vancomycin (88 percent response) or metronidazole (82 percent response). The overall mortality rate was 23 percent, due to C. difficile colitis in three of 31 cases. Many patients were receiving medications or had other diseases associated with fecal stasis. There is much circumstantial evidence to support a role for fecal stasis in the pathogenesis of C. difficile disease. Patients predisposed to colonic stasis who are receiving antibiotics should be considered at risk for this disease, and preventative measures should be taken to decrease stool transit times.