Clinical Predictors of Fulminant Colitis in Patients with Clostridium difficile Infection

Background/Aim:

Clostridium difficile infection (CDI) can affect up to 8% of hospitalized patients. Twenty-five percent CDI patients may develop C. difficile associated diarrhea (CDAD) and 1–3% may progress to fulminant C. difficile colitis (FCDC). Once developed, FCDC has higher rates of complications and mortality.

Patients and Methods:

A 10-year retrospective review of FCDC patients who underwent colectomy was performed and compared with randomly selected age- and sex-matched non-fulminant CDAD patients at our institution. FCDC (n=18) and CDAD (n=49) groups were defined clinically, radiologically, and pathologically. Univariate analysis was performed using Chi-square and Student''s t test followed by multivariate logistic regression to compute independent predictors.

Results:

FCDC patients were significantly older (77 ± 13 years), presented with triad of abdominal pain (89%), diarrhea (72%), and distention (39%); 28% had prior CDI and had greater hemodynamic instability. In contrast, CDAD patients were comparatively younger (65 ± 20 years), presented with only 1 or 2 of these 3 symptoms and only 5% had prior CDI. No significant difference was noted between the 2 groups in terms of comorbid conditions, use of antibiotics, or proton pump inhibitor. Leukocytosis was significantly higher in FCDC patients (18.6 ± 15.8/mm³ vs 10.7 ± 5.2/mm³; P=0.04) and further increased until the point of surgery. Use of antiperistaltic medications was higher in FCDC than CDAD group (56% vs 22%; P=0.01).

Conclusions:

Our data suggest several clinical and laboratory features in CDI patients, which may be indicative of FCDC. These include old age (>70 years), prior CDI, clinical triad of increasing abdominal pain, distention and diarrhea, profound leukocytosis (>18,000/mm³), hemodynamic instability, and use of antiperistaltic medications.     

Incidence and Clinical Outcomes of Clostridium difficile Infection after Treatment with Tuberculosis Medication

Background/Aims

To determine the incidence and clinical characteristics of tuberculosis (TB) medication-associated Clostridium difficile infection.

Methods

This multicenter study included patients from eight tertiary hospitals enrolled from 2008 to 2013. A retrospective analysis was conducted to identify the clinical features of C. difficile infection in patients who received TB medication.

Results

C. difficile infection developed in 54 of the 19,080 patients prescribed TB medication, representing a total incidence of infection of 2.83 cases per 1,000 adults. Fifty-one of the 54 patients (94.4%) were treated with rifampin. The patients were usually treated with oral metronidazole, which produced improvement in 47 of the 54 patients (87%). Twenty-three patients clinically improved with continuous rifampin therapy for C. difficile infection. There were no significant differences in improvement between patients treated continuously (n=21) and patients in whom treatment was discontinued (n=26).

Conclusions

The incidence of C. difficile infection after TB medication was not low considering the relatively low TB medication dosage compared to other antibiotics. It may not be always necessary to discontinue TB medication. Instead, decisions concerning discontinuation of TB medication should be based on TB status.     

Pseudomembranous colitis associated with a triple therapy for Helicobacter pylori eradication

Helicobacter pylori(H.pylori)is one of the most common chronic bacterial infections in humans,affecting half of world’s population.Therapy for H.pylori infection has proven to be both effective and safe.The oneweek triple therapy including proton pump inhibitor,clarithromycin,and amoxicillin or metronidazole is still recommended as a first-line treatment to eradicate H.pylori infection in countries with low clarithromycin resistance.Generally,this therapy is well-tolerated,with only a few and usually minor side effects.However,rare but severe adverse effects such as pseudomembranous colitis have been reported,Clostridium difficile(C.difficile)infection being the main causative factor in all cases.We report the cases of two women who developed pseudomembranous colitis after a 1-wk triple therapy consisting of pantoprazole 20 mg bid,clarithromycin 500 mg bid,and amoxicillin 1 g bid to eradicate H.pylori infection.A limited colonoscopy showed typical appearance of pseudomembranous colitis,and the stool test for C.difficile toxins was positive.Rapid resolution of symptoms and negative C.difficile toxins were obtained in both patients with oral vancomycin.No relapse occurred during a four and eleven-month,respectively,follow up.These cases suggest that physicians should have a high index of suspicion for pseudomembranous colitis when evaluate patients with diarrhea following H.pylori eradication therapy.     

Reducing the risk of severe complications among patients with Clostridium difficile infection

BACKGROUND:

The incidence and severity of Clostridium difficile infections are increasing, and there is a need to optimize the prevention of complicated disease.

OBJECTIVE:

To identify modifiable processes of care associated with an altered risk of C difficile complications.

METHODS:

A retrospective cohort study (with prospective case ascertainment) of all C difficile infections during 2007/2008 at a tertiary care hospital was conducted.

RESULTS:

Severe complications were frequent (occurring in 97 of 365 [27%] C difficile episodes), with rapid onset (median three days postdiagnosis). On multivariable analysis, nonmodifiable predictors of complications included repeat infection (OR 2.67), confusion (OR 2.01), hypotension (OR 0.97 per increased mmHg) and elevated white blood cell count (OR 1.04 per 10⁹ cells/L). Protection from complications was associated with initial use of vancomycin (OR 0.24); harm was associated with ongoing use of exacerbating antibiotics (OR 3.02).

CONCLUSION:

C difficile infections often occur early in the disease course and are associated with high complication rates. Clinical factors that predicted a higher risk of complications included confusion, hypotension and leukocytosis. The most effective ways to improve outcomes for patients with C difficile colitis are consideration of vancomycin as first-line treatment for moderate to severe cases, and the avoidance of unnecessary antibiotics.     

Effect of Treatment Variation on Outcomes in Patients with Clostridium difficile

Purpose

New guidelines for the treatment of Clostridium difficile-associated diarrhea were published by the Infectious Disease Society of America (IDSA) in 2010, however, there has been no literature evaluating the effectiveness of these guidelines. The purpose of this study was to examine the clinical outcomes of Clostridium difficile infection including death, C difficile infection recurrence, toxic megacolon, and surgery between patients who received guideline-concordant therapy vs guideline-discordant therapy.

Methods

Retrospective case-control study of hospitalized adults with C difficile infection presenting to a 420-bed tertiary care referral county teaching hospital. Patients were identified by International Classification of Diseases-9th Revision codes, and included if they were ≥18 years of age and treated for C difficile infection during their hospital visit. Complication rates (death, infection recurrence, toxic megacolon, and surgery) of patients with C difficile infection were measured to determine if following the IDSA guidelines improves outcomes.

Results

Only 51.7% of the patients' prescribers followed the 2010 IDSA guidelines. Patients whose prescribers followed the IDSA guidelines experienced fewer complications than patients whose prescribers strayed from the guidelines (17.2% vs 56.3%, P <.0001). This difference was mainly due to a reduction in mortality (5.4% vs 21.8%, P = .0012) and infection recurrence (14% vs 35.6%, P = .0007). Patients who presented with severe and complicated disease received guideline-based therapy significantly less often than patients with mild disease (19.7%, 35.3%, and 81.2%, respectively, P <.0001).

Conclusions

There was a significant reduction in C difficile infection recurrence and mortality when prescribers followed the IDSA/Society for Healthcare Epidemiology of America guidelines for treatment of C difficile infection.     

Stool therapy may become a preferred treatment of recurrent Clostridium difficile?

Fecal enemas were first reported to successfully treat life threatening enterocolitis in 1958, but fecal therapy to treat Clostridium difficile (C. difficile ) infection has remained esoteric and not well investigated until recently. In the past few years, systematic reviews of case series and case reports of fecal microbiota transplant for recurrent C. difficile infection have become available and validate use of fecal transplant for C. difficile enterocolitis. Methods of fecal transplant reported in the literature include: nasogastric tube, gastroscope, duodenal tube, colonoscopy, rectal tube, and fecal enemas administered at home; no method has been shown to be superior. A recent randomized study published in New England Journal of Medicine found fecal transplant to be superior to oral vancomycin alone in treatment of recurrent C. difficile enterocolitis. The significance of this trial cannot be underestimated as it lends credibility to the idea of intentionally using microbes to combat disease, providing an alternative to the older paradigm of disease eradication through use of antimicrobials.     

The Impact of Clostridum Difficile on Surgical Rate Among Ulcerative Colitis Patients: A Systemic Review and Meta-analysis

There is growing recognition of the impact of Clostridum difficile infection (CDI) on patients with inflammatory bowel disease. Clostridium difficile infection causes greater morbidity and mortality. This study aimed to evaluate the impact of C. difficile on surgical risk among ulcerative colitis (UC) patients. We searched the following databases: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, ACP Journal Club, DARE, CMR, and HTA. Studies were included if fulfilled the following criteria: (1) Cohort or case–control studies, which involved a comparison group that lacked CDI, (2) Patients were given a primary diagnosis of UC, (3) Comorbidity of CDI was evaluated by enzyme immunoassay of stool for C. difficile toxin A and B or C. difficile stool culture, (4) Studies evaluated surgical rate, and (5) Studies reported an estimate of odds ratio, accompanied by a corresponding measure of uncertainty. Five studies with 2380 patients fulfilled the inclusion criteria. Overall, meta-analysis showed that UC with CDI patients had a significant higher surgical rate than patients with UC alone. (OR=1.76, 95% CI=1.36–2.28). C. difficile infection increased the surgical rate in UC patients. However, results should be interpreted with caution, given the limitations of this stud.     

Recurrent Clostridium difficile infections: The importance of the intestinal microbiota

Clostridium difficile infections (CDI) are a leading cause of antibiotic-associated and nosocomial diarrhea. Despite effective antibiotic treatments, recurrent infections are common. With the recent emergence of hypervirulent isolates of C. difficile, CDI is a growing epidemic with higher rates of recurrence, increasing severity and mortality. Fecal microbiota transplantation (FMT) is an alternative treatment for recurrent CDI. A better understanding of intestinal microbiota and its role in CDI has opened the door to this promising therapeutic approach. FMT is thought to resolve dysbiosis by restoring gut microbiota diversity thereby breaking the cycle of recurrent CDI. Since the first reported use of FMT for recurrent CDI in 1958, systematic reviews of case series and case report have shown its effectiveness with high resolution rates compared to standard antibiotic treatment. This article focuses on current guidelines for CDI treatment, the role of intestinal microbiota in CDI recurrence and current evidence about FMT efficacy, adverse effects and acceptability.     

Proton pump inhibitors as a risk factor for recurrence of Clostridium-difficile-associated diarrhea

AIM:To investigate the risk factors for Clostridiumdifficile-associated diarrhea(CDAD)recurrence,and its relationship with proton pump inhibitors(PPIs). METHODS:Retrospective data of 125 consecutive hospitalized patients diagnosed with CDAD between January 2006 and December 2007 were collected by medical chart review.Collected data included patient characteristics at baseline,underlying medical disease, antibiotic history before receiving a diagnosis of CDAD, duration of hospital stay,severity of CDAD,concu...     

Clostridium difficile Infection: A Worldwide Disease

Clostridium difficile, an anaerobic toxigenic bacterium, causes a severe infectious colitis that leads to significant morbidity and mortality worldwide. Both enhanced bacterial toxins and diminished host immune response contribute to symptomatic disease. C. difficile has been a well-established pathogen in North America and Europe for decades, but is just emerging in Asia. This article reviews the epidemiology, microbiology, pathophysiology, and clinical management of C. difficile. Prompt recognition of C. difficile is necessary to implement appropriate infection control practices.     

Biological and Histological Parameters as Predictors of Relapse in Ulcerative Colitis: A Prospective Study

Background/Aim:

Ulcerative colitis is a chronic inflammatory disease of unknown etiology characterized by periods of remission and relapses. This study has been carried out in a group of North Indian patients, where the disease has shown an increasing prevalence and frequent relapses. Hence, there is a need to predict relapse for better management and to reduce morbidity. To assess the importance of biological and histological parameters in predicting relapse when the disease is in quiescent phase.

Materials and Methods:

A prospective study of twenty-six patients with quiescent ulcerative colitis was carried out in Dayanand Medical College and Hospital, Punjab. Only patients with clinical and endoscopic remission at the time of screening visit were included. Hemoglobin, erythrocyte sedimentation rate (ESR), C- reactive protein (CRP) and serum Interleukin-6 (IL-6) levels were measured. The baseline colonoscopic mucosal biopsies were retrieved and studied. Follow-up was conducted for one year at monthly interval or earlier if relapse occurred.

Results:

Fifteen out of twenty-six patients (57.69%) had evidence of clinical relapse during the follow-up. Hemoglobin, ESR, CRP and IL-6 levels were not found to be significant predictors of relapse. Increased number of eosinophils and neutrophils in the lamina propria were observed to be associated with significantly higher relapse rate.

Conclusion:

A higher risk of relapse in patients with quiescent colitis can be predicted by the presence of increased number of eosinophils and neutrophils in the lamina propria.     

The value of repeat Clostridium difficile toxin testing during and after an outbreak of C difficile-associated diarrhea

BACKGROUND:

The recent increase in Clostridium difficile-associated diarrhea (CDAD) has led to questions about the reproducibility and sensitivity of C difficile toxin testing (CDTT). While there have been recommendations to repeat CDTT following a negative result, previous studies have failed to show a benefit. However, no studies were performed during an outbreak of CDAD. The value of repeat CDTT after an initial negative result in patients tested during and after an outbreak of CDAD is reported in the present study, as well as the reproducibility of CDTT when multiple samples are received and tested on the same day.

METHODS:

The results of CDTT, performed using a cell cytotoxicity assay between April 1, 2001, and March 31, 2008, were retrieved and searched for patients who had repeat samples tested after an initial negative result. The result and the number of days after a negative result were determined using the date of the most recent negative test. The cumulative positivity rate was calculated by adding all of the repeat positive test results for the days in question and dividing by the total number of tests performed during that time.

RESULTS:

A total of 8661 patients submitted 14,991 stool specimens for CDTT during the study period. There were 3095 samples that tested positive (20.6%) for the toxin. The results were divided into two time periods to reflect the CDAD outbreak, which began in April 2002: period 1 (outbreak) was from April 1, 2002, to March 31, 2006, and period 2 was from April 1, 2006, to March 31, 2008. The rate of positivity was 24.2% during period 1, and 11.6% during period 2 (P<0.001). Repeat CDTT was performed 619 times on samples received on the same day as the initial specimen, and only three (0.5%) were discordant. A total of 1630 samples were retested within one to seven days of a negative result, and 103 (6.3%) tested positive (7.8% period 1 and 2.9% period 2; P=0.002). The likelihood of a positive result on repeat testing in the first three days after a negative result was low (0.9%, 7% and 4%, respectively). The cumulative positivity for repeat testing performed in the first three days was 0.9%, 3.3% and 3.5%, respectively, and did not differ significantly at day 3 during the period of high CDTT positivity (P=0.110).

CONCLUSIONS:

The value of repeat CDTT, performed using a cell cytotoxicity assay, was low in the first three days after an initial negative result and was unchanged during a CDAD outbreak.     

A Canadian Working Group report on fecal microbial therapy: microbial ecosystems therapeutics

A working group from across Canada comprised of clinician and basic scientists, epidemiologists, ethicists, Health Canada regulatory authorities and representatives of major funding agencies (Canadian Institutes of Health Research and the Crohn's and Colitis Foundation of Canada) met to review the current experience with fecal microbial therapy and to identify the key areas of study required to move this field forward. The report highlights the promise of fecal microbial therapy and related synthetic stool therapy (together called 'microbial ecosystems therapeutics') for the treatment of Clostridium difficile colitis and, possibly, other disorders. It identifies pressing clinical issues that need to be addressed as well as social, ethical and regulatory barriers to the use of these important therapies.     

Clostridium difficile in children: colonisation and disease

Clostridium difficile is the commonest cause of hospital acquired diarrhoea in adults and is associated with significant mortality and morbidity. The clinical significance of C. difficile in children, however, is less certain. In this article we discuss colonisation and infection and describe C. difficile in childhood in terms of risk factors, epidemiology and management.