Intravenous metronidazole for the treatment of Clostridium difficile colitis

PURPOSE: SevereClostridium difficile colitis may produce abdominal distention and ileus, precluding oral antibiotic therapy. Stimulated by several case reports in which intravenous metronidazole was used, we reviewed our experience. METHODS: Using pharmacy and microbiology laboratory records, we retrospectively identified patients withC. difficile colitis who received intravenous metronidazole as initial monotherapy. To be included, patients had to fulfill the following criteria: 1) at least six doses (equivalent to two days of therapy) of intravenous metronidazole were administered, 2) no other potential cause for colitis was found, and 3) the diagnosis ofC. difficile colitis was firmly established. For eligible patients, five clinical parameters were assessed before and after intravenous metronidazole. RESULTS: Our patient group (n=10) received an average of 13.7 (range, 6–24) doses of intravenous metronidazole as initial therapy forC. difficile colitis. All received a dose of 500 mg three times daily. The majority of patients with vomiting, fever, and/or abdominal pain present at the beginning of therapy had resolution with intravenous metronidazole. Only one patient developed a symptom (vomiting) while on therapy; however, this eventually resolved when oral metronidazole was instituted. No patient required colectomy for refractory colitis or developed toxic megacolon. No patient, including those on prolonged courses, developed toxicity related to intravenous metronidazole such as peripheral neuropathy. CONCLUSIONS: Intravenous metronidazole may be effective therapy in patients withC. difficile colitis. A randomized, prospective study appears warranted.     

Prevention of further recurrences ofClostridium difficile colitis withSaccharomyces boulardii

Summary A patient with six documented episodes of recurrentClostridium difficile colitis over an eight-month period is described. Relapses of colitis occurred despite treatment with vancomycin, metronidazole, bacitracin, and cholestyramine. Each recurrence appeared to begin successively closer to the end of the previous course of treatment. Four episodes were sufficiently severe to require hospitalization for rehydration.Saccharomyces boulardii, a nonpathogenic yeast, was begun prior to discontinuing vancomycin therapy for the last recurrence and was continued for three months. Serial stool cultures and assays forC. difficile showed persistence of the organism but rapid reduction of high titers of cytotoxin. No further recurrences of diarrhea or colitis were encountered while the patient was takingSaccharomyces boulardii and for 18 months of follow-up after the yeast was discontinued.     

Outcome After Colectomy for <Emphasis Type="Italic">Clostridium Difficile</Emphasis> Colitis

PURPOSE Clostridium difficile colitis is a relatively common entity, yet large series of patients with fulminant C. difficile colitis are infrequently reported. This study was designed to identify risk factors, clinical characteristics, and outcome of patients who required colectomy for fulminant C. difficile colitis.METHODS A population-based study on all patients in 159 hospitals of the Department of Veterans Affairs from 1997 to 2001 was performed. Data were compiled from several national computerized Department of Veterans Affairs data sets. Supplementary information including demographic information, discharge summaries, operative reports, and pathology reports were obtained from local medical records. Patient variables were entered into a computerized database and analyzed using the Pearson chi-squared and Fishers exact tests. Statistical significance was designated as P < 0.05.RESULTS Sixty-seven patients (mean age, 69 (range, 40–86) years; 99 percent males) were identified. All 67 patients had C. difficile verified in the colectomy specimens. Thirty-six of 67 patients (54 percent) developed C. difficile colitis during a hospitalization for an unrelated illness, and 30 of 36 patients (87 percent) after a surgical procedure. Thirty-one of 67 (46 percent) developed C. difficile colitis at home. There was no history of diarrhea in 25 of 67 patients (37 percent). Thirty of 67 patients (45 percent) presented in shock (blood pressure, <90 mmHg). Forty-three of 67 patients (64 percent) presented with an acute surgical abdomen. Mean white blood cell count was 27.2; mean percent bands was 12. Twelve of 67 patients (18 percent) had a negative C. difficile colitis stool assay. Abdominal computed tomography correctly diagnosed 45 of 46 patients (98 percent) who were imaged. Twenty-six of 67 patients (39 percent) underwent colonoscopy; all 26 were found to have severe inflammation or pseudomembranes. Fifty-three of 67 patients (80 percent) underwent total colectomy; 14 of 67 underwent segmental colonic resection. Perforation and infarction were found in 59 of 67 patients (58 percent) at surgery. Overall mortality was 48 percent (32/67). Mean hospitalization was 36 (range, 2–297) days.CONCLUSIONS Patients with fulminant C. difficile colitis often present with an unexplained abdominal illness with a marked leukocytosis that rapidly progresses to shock and peritonitis. Although frequently developed during a hospitalization and often after a surgical procedure, it may develop outside of a hospital setting. Diarrhea may be absent and stool cytology may be negative for C. difficile toxin. Perforation and infarction are frequently found at surgery. In those patients who survive, a prolonged hospitalization is common. Mortality from fulminant C. difficile colitis remains high despite surgical intervention.Read at the meeting of The American Society of Colorectal Surgeons, New Orleans, Louisiana, June 21 to 26, 2003.     

Pseudomembranous enteritis after proctocolectomy

Intestinal pseudomembrane formation, sometimes a manifestation of antibiotic-associated diarrheal illnesses, is typically limited to the colon but rarely may affect the small bowel. A 56-year-old female taking antibiotics, who had undergone proctocolectomy for idiopathic inflammatory bowel disease, presented with septic shock and hypotension. A partial small-bowel resection revealed extensive mucosal pseudomembranes, which were cultured positive forClostridium difficile. Intestinal drainage contents from an ileostomy were enzyme immunoassay positive forC. difficile toxin A. Gross and histopathologic features of the small-bowel resection specimen were similar to those characteristic of pseudomembranous colitis. The patient was treated successfully with metronidazole. These findings suggest a reservoir forC. difficile also exists in the small intestine and that conditions for enhanced mucosal susceptibility toC. difficile overgrowth may occur in the small-bowel environment of antibiotic-treated patients after colectomy. Pseudomembranous enteritis should be a consideration in those patients who present with purulent ostomy drainage, abdominal pain, fever, leukocytosis, or symptoms of septic shock.     

Clostridium difficile-associated Enteric Disease

Clostridium difficile was identified as the putative agent of antibiotic-associated pseudomembranous colitis in 1978 and is now recognized as the major identifiable cause of antibioticassociated diarrhea. This microbe causes a spectrum of enteric disease ranging from nuisance diarrhea to life-threatening colitis. Risk factors include increasing age, exposure to antibiotics, colonization or acquisition of toxin-producing strains of C. difficile, and lack of circulating antibody to C. difficile toxin A. Detection is relatively simple by stool assay for C. difficile toxin—usually an enzyme immunoassay that will detect toxin A and B. Most nonsevere cases will respond with discontinuation of the implicated antibiotic. More severe cases require metronidazole and supportive care. The major complications include ileus, toxic megacolon, relapsing disease after antibiotic treatment, and nosocomial epidemics.     

Bacitracin therapy in antibiotic-associated pseudomembranous colitis

Two patients with antibiotic-associated pseudomembranous colitis and stool positive forClostridium difficile cytotoxin were successfully treated with oral bacitracin. One patient had previously suffered two relapses of pseudomembranous colitis following successful treatment with vancomycin and one patient was allergic to vancomycin. Bacitracin appears to be a reasonable choice to treat patients with antibiotic-associated colitis who are allergic to vancomycin. Further studies comparing vancomycin and bacitracin are needed.     

Clostridium difficile colitis secondary to intravenous vancomycin

Summary Nearly every known antibiotic has been implicated as a cause ofClostridium difficile colitis. We report the first case resulting from monotherapy with intravenous vancomycin. The patient was on chronic hemodialysis and was treated with intravenous vancomycin for presumed cervical osteomyelitis. After 29 days of therapy he developed abdominal pain and diarrhea and his stool was found to contain bothC. difficile and cytotoxin. The patient responded with symptomatic and microbiological recovery to withdrawal of the drug and treatment with oral metronidazole. The prolonged elevation of serum vancomycin levels in patients with renal failure may predispose them to the development ofC. difficile colitis.     

Who are Susceptible to Pseudomembranous Colitis Among Patients with Presumed Antibiotic-Associated Diarrhea?

Purpose Pseudomembranous colitis is a severe form of antibiotic-associated diarrhea. However, there have been no reports about the factors that make patients with presumed antibiotic-associated diarrhea susceptible to pseudomembranous colitis. This study was designed to determine the clinical risk factors for pseudomembranous colitis among the patients with presumed antibiotic-associated diarrhea. Methods This was a retrospective study of 150 consecutive patients admitted to our institution between January 2000 and December 2004 with a diagnosis of presumed antibiotic-associated diarrhea. All patients underwent sigmoidoscopy or colonoscopy because of diarrhea after administration of antibiotics. Pseudomembranous colitis was confirmed both endoscopically and histologically. Various clinical parameters were compared between the pseudomembranous colitis group and non-pseudomembranous colitis group. Results The mean age of patients was 61 years, and 60 percent (90/150) was female. Pseudomembranous colitis was diagnosed in 53 percent (80/150). On univariate analysis, older than aged 70 years (P = 0.014), antibiotic therapy for more than 15 days (P < 0.0001), hospital stay for more than 20 days (P < 0.0001), number of antibiotics used more than one (P = 0.01), and surgical procedures (P = 0.029) were significant parameters for pseudomembranous colitis. On multivariate analysis, the important clinical risk factors were advanced age (older than aged 70 years; adjusted odds ratio, 2.7; 95 percent confidence interval, 1.208–6.131; P < 0.016) and long hospital stay (more than 20 days; adjusted odds ratio, 5.1; 95 percent confidence interval, 2.1–12.259; P < 0.0001). When both risk factors were present, the positive predictive value of pseudomembranous colitis was 0.86. Conclusions Advanced age and long hospital stay may make patients with presumed antibiotic-associated diarrhea susceptible to pseudomembranous colitis. Therefore, pseudomembranous colitis should be first suspected in cases with presumed antibiotic-associated diarrhea having such risk factors. Poster presentation at the meeting of the Asian-Pacific Digestive Week 2005, Seoul, Republic of Korea, September 25 to 28, 2005.     

Effect of yogurt on clindamycin-inducedClostridium difficile colitis in hamsters

Yogurt exhibitsin vitro bactericidal activity against a variety of pathogenic microorganisms, includingClostridium difficile. In the present studies, we tested whether yogurt ingestion could prevent or ameliorate antibiotic associated colitis in the clindamycin-treated hamster model. Male golden Syrian hamsters were given 5 mg/kg clindamycin subcutaneously 24 hr before and 6 hr following inoculation with 0.5 ml of <10, 10³, 10⁵, or 10⁶ CFU/ml ofC. difficile. Hamsters in the control group ingested chow and waterad libitum, whereas the experimental group ingested chow and a 11 (v/v) mixture of yogurt and waterad libitum, beginning 24 hr before the first injection of clindamycin and continuing throughout the course of the study. Animals were monitored for colonization withC. difficile, pathological evidence of colitis, and death. Mortality was 100% in yogurt-treated animals, and all animals showed histological changes of severe colitis. Fecal and intestinal segment cultures were positive forC. difficile in all animals. Thus, in the hamster model, we found no evidence to support the possible efficacy of yogurt in the prevention ofC. difficile colitis.This work was supported in part by Veterans Affairs Merit Review funding and the National Yogurt Association.     

Yersinia colitis masquerading as pseudomembranous colitis

Summary We describe a 15-month-old male who presented with fever and diarrhea 24 hr after receiving antibiotics for otitis media. A flexible sigmoidoscopy was initially interpreted endoscopically as antibiotic-associated pseudomembranous colitis, and the patient was treated with vancomycin. The diagnosis of antibiotic-associated colitis was excluded in our patient by the negative stool examination forClostridium difficile toxin, the failure to obtain supportive features on rectal biopsy, and the failure to demonstrate sigmoidoscopic improvement with vancomycin therapy. Thirteen days later,Y. enterocolitica was cultured from the initial stool specimens. In this case, the raised central whitish area on an erythematous base was misinterpreted as pseudomembranous colitis.     

Antibiotic-Associated Diarrhoea,Clostridium difficile,and Short-Chain Fatty Acids

Background: It has been hypothesized that Clostridium difficile and decreased colonic production of short-chain fatty acids (SCFAs) cause the development of antibiotic-associated diarrhoea. We therefore wanted to investigate the effects of an intensive and uniform antibiotic therapy on faecal SCFAs concentrations, C. difficile, and extent of diarrhoea. Methods: Fifteen liver-transplanted patients who received oral bowel flora suppression therapy (6.3 g cefuroxime, 0.6 g tobramycin, and 0.5 g nystatin three times daily) were studied for 12 days before and 12 days after discontinuation of therapy. Results: Thirteen of the 15 patients (87%) developed diarrhoea. Colonic fermentation was negligible in all patients, judged by very low levels of faecal SCFAs (<10 mmol/l). Diarrhoea lessened as suppression therapy proceeded despite continuous low levels of SCFAs. Initial stool frequency of 4.1 ± 0.6 and viscosity of 2.5 ± 0.2 per day (on a scale of 1-3; mean ± SE) decreased to 2.2 ± 0.5 (p = 0.0009) and 1.6 ± 0.2 (p = 0.003) per day, respectively, just before cessation of suppression therapy. Both SCFAs and stool habits normalized within days after discontinuation of antibiotics. Only a few samples from 2 patients were culture-positive for C. difficile during therapy, whereas 9 of the 15 patients (60%) became culture-positive (6 cytotoxin-positive) after cessation of suppression therapy at a time when none had diarrhoea. Conclusions: Intensive treatment with antibiotics directed against the colonic flora resulted in diarrhoea in the vast majority of patients, but the diarrhoea was self-limiting despite continual antibiotic treatment and very low faecal concentrations of SCFAs. C. difficile was not associated with antibiotic-associated diarrhoea but was a common finding after treatment with antibiotics was stopped at the time when diarrhoea had ceased.     

Diagnosis,Management, and Prevention of Clostridium difficile Infection in Long‐Term Care Facilities: A Review

Clostridium difficile is a significant healthcare‐associated pathogen and the major cause of antibiotic‐associated diarrhea. The incidence and severity of C. difficile infection have increased in many parts of North America and Europe in the past few years with the widespread dissemination of a hypervirulent strain of C. difficile, referred to as North American pulsed‐field type 1, polymerase chain reaction ribotype 027 (NAP1/027). C. difficile infection appears to affect older adults disproportionately. Long‐term care facility (LTCF) residents are at greater risk because of advanced age, the frequent need for hospitalization, and recurrent exposures to antimicrobial agents. Early identification of C. difficile infection and prompt initiation of appropriate therapy are required to reduce morbidity and mortality. Diagnosis is based on the detection of C. difficile toxins A or B in diarrheal stool specimens. The treatment of choice for moderate or severe C. difficile infection (defined as the presence of pseudomembranous colitis, treatment in an intensive care unit, or two of (i) aged 60 and older, (ii) fever greater than 38.3°C, (iii) peripheral leukocytosis (>15,000 cells/mm³), or (iv) hypoalbuminemia (<2.5 mg/dL) should be with oral vancomycin (125 mg four times a day for 10–14 days). Treatment with oral metronidazole should be reserved for those with milder disease. Measures to prevent outbreaks and reduce the risk of C. difficile infection in LCTFs should include antimicrobial stewardship to ensure judicious use of antibiotics, C. difficile infection surveillance, appropriate use of contact or barrier precautions, and careful environmental cleaning and disinfection using sporicidal agents.     

Epidemiology of Clostridium difficile Infection in a Large Population of Hospitalized US Military Veterans

The Patient Treatment File (PTF) of the Department of Veterans Affairs (VA) comprises the computerized records of all inpatients treated at all VA hospitals throughout the United States. The database was utilized to study the clinical epidemiology and impact of C. difficile colitis on health care among hospitalized US military veterans. The computerized medical records of 15,091 cases with C. difficile colitis and 61,931 controls without the diagnosis were extracted from the annual files between 1993 and 1998. Of all patients admitted to the hospital, 1% were diagnosed with C. difficile colitis, in 16% of whom it was listed as the primary discharge diagnosis. C. difficile colitis was more likely to occur in elderly white patients with multiple comorbid conditions. Compared with a control population of hospitalized patients without C. difficile colitis, the case population was subjected to more medical and surgical procedures and experienced longer hospital stays. The diagnosis of C. difficile colitis was associated with more frequent admissions to the intensive care unit and higher hospital-related and subsequent mortality. Eleven percent of the cases were admitted to hospital a second time after a mean of 202 days, 2.5% were readmitted a third time after an additional 182 days, and 0.8% were readmitted a fourth time after an additional 194 days. In conclusion, as old age, multiple comorbid conditions, a high number of medical and surgical intervention, and long hospitalization constitute the main risk factors for the development of C. difficile colitis, efforts at prevention should be directed primarily towards patients who present with these characteristics.     

Cefoperazone-treated mice as an experimental platform to assess differential virulence of Clostridium difficile strains

The toxin-producing bacterium C. difficile is the leading cause of antibiotic-associated colitis, with an estimated 500,000 cases C. difficile infection (CDI) each year in the US with a cost approaching 3 billion dollars. Despite the significance of CDI, the pathogenesis of this infection is still being defined. The recent development of tractable murine models of CDI will help define the determinants of C. difficile pathogenesis in vivo. To determine if cefoperazone-treated mice could be utilized to reveal differential pathogenicity of C. difficile strains, 5–8 week old C57BL/6 mice were pretreated with a 10 d course of cefoperazone administered in the drinking water. Following a 2-d recovery period without antibiotics, the animals were orally challenged with C. difficile strains chosen to represent the potential range of virulence of this organism from rapidly fatal to nonpathogenic. Animals were monitored for loss of weight and clinical signs of colitis. At the time of harvest, C. difficile strains were isolated from cecal contents and the severity of colitis was determined by histopathologic examination of the cecum and colon. Cefoperazone treated mice challenged with C. difficile strains VPI 10463 and BI1 exhibited signs of severe colitis while infection with 630 and F200 was subclinical. This increased clinical severity was correlated with more severe histopathology with significantly more edema, inflammation and epithelial damage encountered in the colons of animals infected with VPI 10463 and BI1. Disease severity also correlated with levels of C. difficile cytotoxic activity in intestinal tissues and elevated blood neutrophil counts. Cefoperazone treated mice represent a useful model of C. difficile infection that will help us better understand the pathogenesis and virulence of this re-emerging pathogen.     

The potential for emerging therapeutic options for Clostridium difficile infection

Clostridium difficile is mainly a nosocomial pathogen and is a significant cause of antibiotic-associated diarrhea. It is also implicated in the majority of cases of pseudomembranous colitis. Recently, advancements in next generation sequencing technology (NGS) have highlighted the extent of damage to the gut microbiota caused by broad-spectrum antibiotics, often resulting in C. difficile infection (CDI). Currently the treatment of choice for CDI involves the use of metronidazole and vancomycin. However, recurrence and relapse of CDI, even after rounds of metronidazole/vancomycin administration is a problem that must be addressed. The efficacy of alternative antibiotics such as fidaxomicin, rifaximin, nitazoxanide, ramoplanin and tigecycline, as well as faecal microbiota transplantation has been assessed and some have yielded positive outcomes against C. difficile. Some bacteriocins have also shown promising effects against C. difficile in recent years. In light of this, the potential for emerging treatment options and efficacy of anti-C. difficile vaccines are discussed in this review.     

Clostridium difficile-associated diarrhea: current strategies for diagnosis and therapy

Clostridium difficile, a spore-forming toxigenic bacterium, is one of the most common causes of infectious diarrhea and colitis in the United States. Most patients with C. difficile infection have recently received antimicrobial therapy — usually clindamycin, cephalosporins, or the extended-spectrum penicillins. Clinical presentation varies from asymptomatic colonization to mild diarrhea to severe colitis. The mainstay of diagnosis is detection of C. difficile toxin A, toxin B, or both with a cytotoxin test or enzyme immunoassay of the stool of patients who have received antibiotic therapy and have features of C. difficile-associated diarrhea. Enzyme immunoassays that detect both toxins are preferred because of their higher diagnostic accuracy. If the first assay is negative and C. difficile-associated diarrhea is strongly suspected, a second assay may be performed. Ten days of oral metronidazole is the preferred therapy for most initial infections. Vancomycin is considered secondline therapy because of its cost and potential to select for vancomycin resistance. About 20% to 25% of patients experience reinfection or relapse after initial therapy and require retreatment. The disease can best be prevented by limiting the use of broad-spectrum antibiotics and adhering to control techniques.     

Association Between Fecal Hydrogen Sulfide Production and Pouchitis

PURPOSE The beneficial effect of antibiotics in pouchitis suggests that an unidentified fecal bacterial product causes this condition. A candidate compound is hydrogen sulfide, a highly toxic gas produced by certain fecal bacteria, which causes tissue injury in experimental models. We investigated hydrogen sulfide release and sulfate-reducing bac-terial counts in pouch contents to determine whether hy-drogen sulfide production correlates with pouchitis.METHODS During incubation at 37°C, the production of hydrogen sulfide, methylmercaptan, carbon dioxide, and hydrogen were studied using fresh fecal specimens obtained from 50 patients with ileoanal pouches constructed after total proctocolectomy for ulcerative colitis (n = 45) or for familial adenomatous polyposis (n = 5). Patients with ulcerative colitis were divided into five groups: a) no history of pouchitis (pouch for at least 2 years; n = 8); b) past episode(s) of pouchitis but no active disease for the previous year (n = 9); c) pouchitis in the past year but presently inactive (n = 9); d) ongoing antibiotic treatment (metronidazole or ciprofloxacin) for pouchitis (n = 11); e) currently suffering from pouchitis (n = 8).RESULTS Release of hydrogen sulfide when pouchitis was active (6.06 ± 1.03 mol g^–1 4 h^–1) or had occurred in the past year (4.71 ± 0.41 mol g^–1 4 h^–1) was significantly higher (P < 0.05) than when pouchitis had never occurred (1.71 ± 0.43 mol g^–1 4 h^–1) or had been inactive in the past year (2.62 ± 0.49 mol g^–1 4 h^–1). Antibiotic therapy was associated with very low hydrogen sulfide release (0.68 ± 0.29 mol g^–1 4 h^–1). Pouch contents from familial adenomatous polyposis patients produced significantly less hydrogen sulfide (0.75 ± 0.09 mol g^–1 4 h^–1) than did any group of nonantibiotic-treated ulcerative colitis patients. Sulfate-reducing bacterial counts in active pouchitis (9.5 ± 0.5 log₁₀/g) were significantly higher than in those who never experienced pouchitis (7.38 ± 0.32 log₁₀/g), and these counts fell dramatically with antibiotic treatment. No statistically significant differences in carbon dioxide and hydrogen were observed among the groups not receiving antibiotics.CONCLUSIONS Pouch contents of patients with ongoing pouchitis or an episode within the previous year released significantly more hydrogen sulfide than did the contents of patients who never had an attack of pouchitis and those with longstanding inactive disease. The response to therapy with metronidazole or ciprofloxacin was associated with marked reductions in hydrogen sulfide release and sulfate-reducing bacteria. These results provide a rationale for additional studies to determine whether the high sulfide production is a cause or effect of pouchitis. The lower hydrogen sulfide production by pouch contents of familial adenomatous polyposis vs. patients with ulcerative colitis suggests a fundamental difference in gut sulfide metabolism that could have implications for the etiology of ulcerative colitis as well as the pouchitis of patients with ulcerative colitis.Supported by The International Research Scholarship of the Research Foundation, The American Society of Colon and Rectal Surgeons, and Minnesota Colon and Rectal Foundation.Read at the meeting of The American Society of Colon and Rectal Surgeons, Dallas, Texas, May 8 to 13, 2004.     

Clostridium difficile infection

Summary Considering the current wide use of antimicrobial agents, the general internist is commonly faced with the patient at risk for diarrhea due toC. difficile. The diagnosis should be considered for any patient with diarrhea who has received any type of antibiotic therapy in the preceding 4–6 weeks. Symptoms may range from a minor bout of diarrhea to fulminant and fatal colitis. Diagnosis usually requires demonstration of the toxin in stool; culture of the organism and fiberoptic endoscopy may play an adjunctive role in selected clinical settings. The ultimate goal in the treatment forC. difficile infection is to repopulate the normal colonic flora in the most efficacious manner. Minimally symptomatic patients may respond to discontinuing the offending antimicrobial agent or using nonspecific binding agents. Oral vancomycin continues to be the “gold standard” for specific treatment, while metronidazole therapy is considered the first-line agent for individuals with milder infection. Oral bacitracin shows promise, though large studies are lacking. Patients with multiple relapses ofC. difficile diarrhea can be treated with prolonged courses of vancomycin or a combination of vancomycin and rifampin. Intensive care unit patients who are NPO have few therapeutic options besides intravenous administration of metronidazole and oral administration of vancomycin via clamped nasogastric tube. Preventive efforts are directed at cautious use of antibiotics and the use of vinyl gloves when caring for patients with known infection.     

“Diversion” Colitis Caused by Clostridium difficile Infection: Report of a Case

Recurrent ulcerative colitis and/or diversion colitis occur commonly in the rectal remnant after colectomy for ulcerative colitis. We report a case in which such a patient's symptoms of rectal discharge were initially thought to be the result of one or both of these diagnoses, on both clinical and histologic grounds. However, examination of the discharge revealed Clostridium difficile infection. Treatment with metronidazole suppositories improved his symptoms and avoided further inappropriate intervention. Effie Tsironi, M.D. is supported by the Hellenic Society of Gastroenterology, Greece. Reprints are not available.     

Double-blind crossover trial of metronidazole versus placebo in chronic unremitting pouchitis

Metronidazole has been used to treat pouchitis, but there are no controlled data that show it is effective. Chronic unremitting pouchitis is a form of the disorder particularly difficult to manage. Diarrhea is the main symptom of pouchitis, which results from acute inflammation of the mucosa of an ileal reservoir. To test the hypothesis that metronidazole (400 mg thrice daily for seven days) is no better than placebo at reducing stool frequency in chronic unremitting pouchitis, a double-blind placebo-controlled crossover study has been performed. Thirteen patients who had undergone restorative proctocolectomy for ulcerative colitis were studied. The diagnosis of pouchitis was based on clinical, endoscopic, and histological criteria. At entry all patients had symptomatic pouchitis and were passing more than six stools/24 hr or had consistently bloody stools with at least four of six endoscopic criteria of mucosal inflammation. The median frequency of defecation decreased by 3 bowel action/24 hr (conservative 95% confidence intervals 0–4/24 hr) on metronidazole but increased by a median of 1/24 hr on placebo. The difference between the median number of bowel motions, when treatment with metronidazole was compared to placebo, was 4 motions/24 hr (P<0.05) in favor of metronidazole. There was no significant change in the endoscopic or histological grade of inflammation, in the serum C-reactive protein level, or symptomatic scores. In a parallel study, metronidazole did not alter stool frequency in asymptomatic patients without pouchitis who had endoscopically normal reservoirs (six polyposis, six colitis). Metronidazole significantly reduces the frequency of defecation when compared with placebo in chronic pouchitis. The reduction in stool frequency is, however, of limited symptomatic benefit to the patient.These data were presented to the British Society of Gastroenterology in March 1992 (Gut 33:539, 1992).