Non-clostridium difficile induced pseudomembranous colitis

Pseudomembranous colitis is severe inflammation of the inner lining of the colon due to anoxia,ischemia,endothelial damage,and toxin production.The majority of cases of pseudomembranous colitis are due to Clostridium difficile.However,other causative pathogens and agents have been responsible for causing a similar pattern of injury to the bowel with the endoscopic appearance of yellow-white plaques and membranes on the mucosal surface of the colon.Common presenting symptoms and signs include crampy abdominal pain,nausea,watery diarrhea that can progress to bloody diarrhea,fever,leukocytosis,and dehydration.Negative testing for Clostridium difficile or failure to improve on treatment should prompt evaluation for other causes of pseudomembranous colitis.Bacterial infections other than Clostridium difficile,Viruses such as cytomegalovirus,parasitic infections,medications,drugs,chemicals,inflammatory diseases,and ischemia are other differential diagnoses to look out for in pseudomembranous colitis.Complications of pseudomembranous colitis include toxic megacolon,hypotension,colonic perforation with peritonitis,and septic shock with organ failure.Early diagnosis and treatment to prevent progression are important.The central perspective of this paper is to provide a concise review of the various etiologies for pseudomembranous colitis and management per prior literature.

Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis

AIM To perform a systematic review and meta-analysis on proton pump inhibitors(PPIs) therapy and the risk of Clostridium difficile infection(CDI). METHODS We conducted a systematic search of MEDLINE/Pub Med and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios(ORs) estimates with 95% confidence intervals(CIs) were calculated using the random effect. Heterogeneity was assessed by I^2 test and Cochran's Q statistic.Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale(NOS). RESULTS Fifty-six studies(40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI(pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control(OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort(OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted(OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted(OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter(OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter(OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years(OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years(OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses(test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies(I^2 = 85.4%, P < 0.001) as well as evidence of publication bias(funnel plot asymmetry test, P = 0.002). CONCLUSION This meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal.

Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections

Antibiotic-associated diarrhea(AAD) and Clostridum difficile infections(CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. A systematic review of the literature using databases Pub Med(June 3, 1978-2015) was conducted to compare AAD and CDI in pediatric and adult populations and determine significant differences and similarities that might impact clinical decisions. In general, pediatric AAD and CDI have a more rapid onset of symptoms, a shorter duration of disease and fewer CDI complications(required surgeries and extended hospitalizations) than in adults. Children experience more community-associated CDI and are associated with smaller outbreaks than adult cases of CDI. The ribotype NAP1/027/BI is more common in adults than children. Children and adults share some similar risk factors, but adults have more complex risk factor profiles associated with more co-morbidities, types of disruptive factors and a wider range of exposures to C. difficile in the healthcare environment. The treatment of pediatric and adult AAD is similar(discontinuing or switching the inciting antibiotic), but other treatment strategies for AAD have not been established. Pediatric CDI responds better to metronidazole, while adult CDI responds better to vancomycin. Recurrent CDI is not commonly reported for children. Prevention for both pediatric and adult AAD and CDI relies upon integrated infection control programs, antibiotic stewardship and may include the use of adjunctive probiotics. Clinical presentation of pediatric AAD and CDI are different than adult AAD and CDI symptoms. These differences should be taken into account when rating severity of disease and prescribing antibiotics.

Impact of Clostridium difficile infection on inflammatory bowel disease outcome: A review

Although a considerable number of studies support a substantial increase in incidence, severity, and healthcare costs for Clostridium difficile infection(CDI) in inflammatory bowel disease(IBD), only few evaluate its impact on IBD outcome. Medline and several other electronic databases from January 1993 to October 2013 were searched in order to identify potentially relevant literature. Most of the studies showed that IBD patients with CDI present a greater proportion of worse outcomes than those without CDI. These patients have longer length of hospital stay, higher rates of colectomies, and increased mortality. Patients with ulcerative colitis are more susceptible to CDI and have more severe outcomes than those with Crohn's disease. However, studies reported variable results in both short-and long-term outcomes. Contrasting results were also found between studies using nationwide data and those reporting from single-center, or between some NorthAmerican and European studies. An important limitation of all studies analyzed was their retrospective design. Due to contrasting data often provided by retrospective studies, further prospective multi-center studies are necessary to evaluate CDI impact on IBD outcome. Until then, a rapid diagnosis and adequate therapy of infection are of paramount importance to improve IBD patients' outcome. The aim of this article is to provide up to date information regarding CDI impact on outcome in IBD patients.

Clostridium difficile infection and inflammatory bowel disease:Understanding the evolving relationship

Clostridium difficile(C.difficile)infection(CDI)is the leading identifiable cause of antibiotic-associated diarrhea.While there is an alarming trend of increasing incidence and severity of CDI in the United States and Europe,superimposed CDI in patients with inflammatory bowel disease(IBD)has drawn considerable attention in the gastrointestinal community.The majority of IBD patients appear to contract CDI as outpatients.C.difficile affects disease course of IBD in several ways,including triggering disease flares,sustaining activity,and in some cases,acting as an"innocent"bystander.Despite its wide spectrum of presentations,CDI has been reported to be associated with a longer duration of hospitalization and a higher mortality in IBD patients.IBD patients with restorative proctocolectomy or with diverting ileostomy are not immune to CDI of the small bowel or ileal pouch.Whether immunomodulator or corticosteroid therapy for IBD should be continued in patients with superimposed CDI is controversial.It appears that more adverse outcomes was observed among patients treated by a combination of immunomodulators and antibiotics than those treated by antibiotics alone.The use of biologic agents does not appear to increase the risk of acquisition of CDI.For CDI in the setting of underlying IBD,vancomycin appears to be more efficacious than metronidazole.Randomized controlled trials are required to clearly define the appropriate management for CDI in patients with IBD.

Clostridium difficile infections in China

Clostridium difficile （C.difficile） infection has become one of the major hospital-associated infections in Western countries in the last two decades.However,there is limited information on the status of C.difficile infection in Chinese healthcare settings.Given the large and increasing elderly population and the well-recognized problem of over-prescribing of broad spectrum antibiotics in China,it is critical to understand the epidemiology and potential risk factors that may contribute to C.difficile infection in China.A literature review of available published studies,including those in Chinese language-based journals,was conducted.A review of the currently available literature suggested the presence of C.difficile infections in China,but also suggested that these infections were not particularly endemic.This finding should lead to better designed and greatly expanded studies to provide a more reliable epidemiologically-based conclusion on the actual status of C.difficile infection in China,including the identification of any associated risk factors.Such information is ultimately valuable to develop appropriate strategies to prevent C.difficile infection and the vast negative impact of such infections in China and other developing countries.

Burden of Clostridium difficile infection between 2010 and 2013:Trends and outcomes from an academic center in Eastern Europe

AIM:To analyze the incidence and possible risk factors in hospitalized patients treated with Clostridium difficile infection(CDI).METHODS:A total of 11751 patients were admitted to our clinic between 1 January 2010 and 1 May2013.Two hundred and forty-seven inpatients were prospectively diagnosed with CDI.For the risk analysis a 1:3 matching was used.Data of 732 patients matched for age,sex,and inpatient care period and unit were compared to those of the CDI population.Inpatient records were collected from an electronic hospital database and comprehensively reviewed.RESULTS:Incidence of CDI was 21.0/1000 admissions(2.1%of all-cause hospitalizations and 4.45%of total inpatient days).The incidence of severe CDI was 12.6%(2.63/1000 of all-cause hospitalizations).Distribution of CDI cases was different according to the unit type,with highest incidence rates in hematology,gastroenterology and nephrology units(32.9,25 and24.6/1000 admissions,respectively) and lowest rates in 1.4%(33/2312) in endocrinology and general internal medicine(14.2 and 16.9/1000 admissions)units.Recurrence of CDI was 11.3%within 12 wk after discharge.Duration of hospital stay was longer in patients with CDI compared to controls(17.6 ± 10.8d vs 12.4 ± 7.71 d).CDI accounted for 6.3%of allinpatient deaths,and 30-d mortality rate was 21.9%(54/247 cases).Risk factors for CDI were antibiotic therapy[including third-generation cephalosporins or fluoroquinolones,odds ratio(OR) = 4.559;P < 0.001],use of proton pump inhibitors(OR = 2.082,P< 0.001),previous hospitaiization within 12 mo(OR = 3.167,P < 0.001),previous CDI(OR = 15.32;P < 0.001),while presence of diabetes mellitus was associated with a decreased risk for CDI(OR = 0.484;P< 0.001).Treatment of recurrent cases was significantly different from primary infections with more frequent use of vancomycin alone or in combination(P < 0.001),and antibiotic therapy duration was longer(P < 0.02).Severity,mortality and outcome of primary infections and relapsing cases did not significantly differ.CONCLUSION:CDI was accounted for significant burden with longer hospitaiization and adverse outcomes.Antibiotic,PPI therapy and previous hospitaiization or CDI were risk factors for CDI.

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.

Complicated fecal microbiota transplantation in a tetraplegic patient with severe Clostridium difficile infection

A 65-year-old male suffering from acute spinal cord injury leading to incomplete tetraplegia presented with severe recurrent Clostridium difficile(C. difficile) infection subsequent to antibiotic treatment for pneumonia. After a history of ineffective antimicrobial therapies, including metronidazole, vancomycin, fidaxomicin, rifaximin and tigecycline, leading to several relapses, the patient underwent colonoscopic fecal microbiota transplantation from his healthy son. Four days subsequent to the procedure, the patient showed a systemic inflammation response syndrome. Without detecting an infectious cause, the patient received antimicrobial treatment, including tigecycline, metronidazole, vancomycin via polyethylene glycol and an additional enema for a period of seven days, leading to a prompt recovery and no reported C. difficile infection relapse during a 12 wk follow up.

Risk factors for Clostridium difficile infection in cirrhotic patients

Background: Cirrhotic patients are susceptible to Clostridium difficile infection(CDI), however, the high risk factors are not clear. The present study aimed to identify the risk factors in cirrhotic patients with CDI. Methods: A total of 526 cirrhotic patients admitted to our hospital between May 2015 and October 2015 were included in this study. Stool samples were collected upon admission for the detection of CDI and toxin. CDI was monitored during the hospital stay. In total, 34 cases showed CDI. Then we analyzed the effects of age, sex, C. difficile colonization(CDC), multiple hospitalization, extended hospital stay, elevation of total bilirubin(TBIL), creatinine(Cr), Child-Pugh grade C, hepatic encephalopathy, hepatorenal syndrome, upper gastrointestinal hemorrhage, and exposure of antibiotics and proton pump inhibitor(PPI) on the CDI in cirrhotic patients. Results: Patients in the CDI group had more frequent CDC, multiple hospitalization, and extended hospital stay compared to those in the non-C. difficile infection(NCDI) group. Patients in the CDI group had higher TBIL and Cr, and higher frequency of Child-Pugh grade C, hepatic encephalopathy, upper gastrointestinal hemorrhage compared with those in the NCDI group. Multiple logistic regression analysis indicated that age > 60 years(OR = 1.689;95% CI: 1.135–3.128), multiple hospitalization(OR = 3.346;95% CI: 1.392–8.043), length of hospital stay > 20 days(OR = 1.564;95% CI: 1.113–2.563), hypoproteinemia(OR = 4.962;95% CI: 2.053–11.996), CDC(OR = 18.410;95% CI: 6.898–49.136), hepatic encephalopathy(OR = 1.357;95% CI: 1.154–2.368), and exposure of antibiotics(OR = 1.865;95% CI: 1.213–2.863) and PPI(OR = 3.125;95% CI: 1.818–7.548) were risk factors of CDI. Conclusions: Age > 60 years, multiple hospitalization, length of hospital stay > 20 days, hypoproteinemia, CDC, hepatic encephalopathy, and exposure of antibiotics and PPI were risk factors for CDI in cirrhotic patients. These may contribute to the early diagnosis and monitoring of CDI in clinical practice.

A case of Clostridium difficile infection complicated by acute respiratory distress syndrome treated with fecal microbiota transplantation

Acute respiratory distress syndrome is a life-threatening disorder caused mainly by pneumonia.Clostridium difficile infection(CDI)is a common nosocomial diarrheal disease.Disruption of normal intestinal flora by antibiotics is the main risk factor for CDI.The use of broadspectrum antibiotics for serious medical conditions can make it difficult to treat CDI complicated by acute respiratory distress syndrome.Fecal microbiota transplantation is a highly effective treatment in patients with refractory CDI.Here we report on a patient with refractory CDI and acute respiratory distress syndrome caused by pneumonia who was treated with fecal microbiota transplantation.

Predictors of Clostridium difficile infection severity in patients hospitalised in medical intensive care

AIM:To describe and analyse factors associated with Clostridium difficile infection(CDI)severity in hospitalised medical intensive care unit patients.METHODS:We performed a retrospective cohort study of 40 patients with CDI in a medical intensive care unit(MICU)at a French university hospital.We include patients hospitalised between January 1,2007and December 31,2011.Data on demographics characteristics,past medical history,CDI description was collected.Exposure to risk factors associated with CDI within 8 wk before CDI was recorded,including previous hospitalisation,nursing home residency,antibiotics,antisecretory drugs,and surgical procedures.RESULTS:All included cases had their first episode of CDI.The mean incidence rate was 12.94 cases/1000admitted patients,and 14.93,8.52,13.24,19.70,and8.31 respectively per 1000 admitted patients annually from 2007 to 2011.Median age was 62.9[interquartile range(IQR)55.4-72.40]years,and 13(32.5%)were women.Median length of MICU stay was 14.0d(IQR 5.0-22.8).In addition to diarrhoea,the clinical symptoms of CDI were fever(>38℃)in 23 patients,abdominal pain in 15 patients,and ileus in 1 patient.The duration of diarrhoea was 13.0(8.0-19.5)d.In addition to diarrhoea,the clinical symptoms of CDI were fever(>38℃)in 23 patients,abdominal pain in 15 patients,and ileus in 1 patient.Prior to CDI,38patients(95.0%)were exposed to antibiotics,and 12(30%)received at least 4 antibiotics.Fluoroquinolones,3rdgeneration cephalosporins,coamoxiclav and tazocillin were prescribed most frequently(65%,55%,40%and 37.5%,respectively).The majority of cases were hospital-acquired(n=36,90%),with 5 cases(13.9%)being MICU-acquired.Fifteen patients had severe CDI.The crude mortality rate within 30 d after diagnosis was 40%(n=16),with 9 deaths(9 over 16;56.3%)related to CDI.Of our 40 patients,15(37.5%)had severe CDI.Multivariate logistic regression showed that male gender[odds ratio(OR):8.45;95%CI:1.06-67.16,P=0.044],rising serum C-reactive protein levels(OR=1.11;95%CI:1.02-1.21,P=0.021),and previous exposure to fluoroquinolones(OR=9.29;95%CI:1.16-74.284,P=0.036)were independently associated with severe CDI.CONCLUSION:We report predictors of severe CDI not dependent on time of assessment.Such factors could help in the development of a quantitative score in ICU’s patients.

Clinical update for the diagnosis and treatment of Clostridium difficile infection

Clostridium difficile infection(CDI)presents a rapidly evolving challenge in the battle against hospitalacquired infections.Recent advances in CDI diagnosis and management include rapid changes in diagnostic approach with the introduction of newer tests,such as detection of glutamate dehydrogenase in stool and polymerase chain reaction to detect the gene for toxin production,which will soon revolutionize the diagnostic approach to CDI.New medications and multiple medical society guidelines have introduced changing concepts in the definitions of severity of CDI and the choice of therapeutic agents,while rapid expansion of data on the efficacy of fecal microbiota transplantation heralds a revolutionary change in the management of patients suffering multiple relapses of CDI.Through a comprehensive review of current medical literature,this article aims to offer an intensive review of the current state of CDI diagnosis,discuss the strengths and limitations of available laboratory tests,compare both current and future treatments options and offer recommendations for best practice strategies.

Characteristics of Clostridium difficile infection in patients hospitalized with myelodysplastic syndrome or acute myelogenous leukemia

AIM To evaluate factors associated with Clostridium difficile infection (CDI) and outcomes of CDI in the myelodysplastic syndrome(MDS) and acute myeloid leukemia (AML) population.METHODS After IRB approval,all MDS/AML patients hospitalized at the University of Maryland Greenebaum Comprehensive Cancer Center between August 2011 and December 2013 were identified.Medical charts were reviewed for demographics,clinical information,development of CDI,complications of CDI,and mortality.Patients with CDI,defined as having a positive stool PCR done for clinical suspicion of CDI,were compared to those without CDI in order to identify predictors of disease.A t-test was used for comparison of continuous variables and chisquare or Fisher's exact tests were used for categorical variables,as appropriate.RESULTS Two hundred and twenty-three patients (60.1% male,mean age 61.3 years,13% MDS,87% AML) had 594 unique hospitalizations during the study period.Thirtyfour patients (15.2%) were diagnosed with CDI.Factors significantly associated with CDI included lower albumin at time of hospitalization (P < 0.0001),prior diagnosis of CDI (P < 0.0001),receipt of cytarabine-based chemotherapy (P = 0.015),total days of neutropenia (P = 0.014),and total days of hospitalization (P = 0.005).Gender (P = 0.10),age (P = 0.77),proton-pump inhibitor use (P = 0.73),receipt of antibiotics (P = 0.66),and receipt of DNA hypomethylating agent-based chemotherapy (P = 0.92) were not significantly associated with CDI.CONCLUSION CDI is common in the MDS/AML population.Factors significantly associated with CDI in this population include low albumin,prior CDI,use of cytarabine-based chemotherapy,and prolonged neutropenia.In this study,we have identified a subset of patients in which prophylaxis studies could be targeted.

Preventing pediatric antibiotic-associated diarrhea and Clostridium difficile infections with probiotics: A metaanalysis

AIM: To assess the efficacy and safety of probiotics for preventing pediatric:(1) antibiotic associated diarrhea and(2) Clostridium difficile(C. difficile) infections.METHODS: On June 3, 2013, we searched Pub Med(1960-2013), EMBASE(1974-2013), Cochrane Database of Systematic Reviews(1990-2013), CINAHL(1981-2013), AMED(1985-2013), and ISI Web of Science(2000-2013). Additionally, we conducted an extensive grey literature search including contact with National Institutes of Health Clinical Trials Registry, abstracts from annual infectious disease and gastroenterology meetings, experts in the field and correspondence with authors. The primary outcomes were the incidence of antibiotic-associated diarrhea(AAD) and C. difficile infections(CDI). Dichotomous outcomes(e.g., incidence of AAD or CDI) were pooled using a random-effects model to calculate the relative risk and corresponding 95% confidence interval(95%CI) and weighted on study quality. To explore possible explanations for heterogeneity, a priori subgroup analysis were conducted on probiotic strain type, daily dose, quality of study and safety of probiotics. The overall quality of the evidence supporting each outcome was assessed using the grading of recommendations, assessment, development and evaluation criteria.RESULTS: A total of 1329 studies were identified with 22 trials(23 treatment arms and 4155 participants) meeting eligibility requirements for our review of prevention of AAD and 5 trials(1211 participants) for the prevention of CDI. Trials in adult populations, trials of uncertain antibiotic exposure or studies which did not provide incidence of AAD were excluded. We found 12 trials testing a single strain of probiotic and 10 trials testing a mixture of probiotic strains. Probiotics(all strains combined) significantly reduced the incidence of pediatric AAD(pooled RR = 0.42, 95%CI: 0.33-0.53) and significantly reduced pediatric CDI(pooled RR = 0.35, 95%CI: 0.13-0.92). Of the two strains with multiple trials, both significantly reduced pediatric AAD: Saccharomyces boulardii lyo(pooled RR = 0.43, 95%CI: 0.32-0.60) and Lactobacillus rhamnosus GG(pooled RR = 0.36, 95%CI: 0.19-0.69). There was no significant effect by type of antibiotic, or by duration or dose of probiotic. No adverse events associated were found in the 22 controlled trials relating to the use of probiotics.CONCLUSION: This meta-analysis found that probiotics significantly prevented pediatric antibiotic associated diarrhea and pediatric CDI, but the efficacy varies significantly by the strain of the probiotic.

Management of inflammatory bowel disease with Clostridium difficile infection

AIM To address the management of Clostridium difficile(C. difficile) infection(CDI) in the setting of suspected inflammatory bowel disease(IBD)-flare.METHODS A systematic search of the Ovid MEDLINE and EMBASE databases by independent reviewers identified 70 articles including a total of 932141 IBD patients or IBDrelated hospitalizations. RESULTS In those with IBD,CDI is associated with increased morbidity,including subsequent escalation in IBD medical therapy,urgent colectomy and increased hospitalization,as well as excess mortality. Vancomycincontaining regimens are effective first-line therapies for CDI in IBD inpatients. No prospective data exists with regards to the safety or efficacy of initiating or maintaining corticosteroid,immunomodulator,or biologic therapy to treat IBD in the setting of CDI. Corticosteroid use is a risk factor for the development of CDI,while immunomodulators and biologics are not. CONCLUSION Strong recommendations regarding when to initiate IBD specific therapy in those with CDI are precluded by a lack of evidence. However,based on expert opinion and observational data,initiation or resumption of immunosuppressive therapy after 48-72 h of targeted antibiotic treatment for CDI may be considered.

Fecal microbiota transplantation as an effective initial therapy for pancreatitis complicated with severe Clostridium difficile infection:A case report

BACKGROUND Moderately severe acute pancreatitis (MSAP) is a critical form of acute pancreatitis that is related with high morbidity and mortality.Severe Clostridium difficile infection (sCDI) is a serious and rare nosocomial diarrheal complication,especially in MSAP patients.Fecal microbiota transplantation (FMT) is a highly effective treatment for refractory and recurrent CDI (rCDI).However,knowledge regarding the initial use of FMT in patients suffering from sCDI is limited.CASE SUMMARY Here,we report an MSAP patient complicated with sCDI who was treated by FMT as a first-line therapy.The patient was a 51-year-old man who suffered from diarrhea in his course of acute pancreatitis.An enzyme immunoassay was performed to detect toxins,and the result was positive for toxin-producing C.difficile and toxin B and negative for C.difficile ribotype 027.The colonoscopy revealed pseudomembranous colitis.Due to these findings,sCDI was our primary consideration.Because the patient provided informed consent for FMT treatment,we initially treated the patient by FMT rather than metronidazole.Diarrhea resolved within 5 d after FMT.The patient remained asymptomatic,and the follow-up colonoscopy performed 40 d after discharge showed a complete recovery.Our case is the first reported in China.CONCLUSION This case explores the possibilities of initially using FMT to treat severe CDI.Moreover,FMT may become a critical component of the treatment for severe CDI in MSAP patients.

Clostridium difficile infection aggravates colitis in interleukin 10-deficient mice

AIM:To investigate the effect of Clostridium difficile(C.difficile)infection in an interleukin 10-deficient(IL-10-/-)mouse model of inflammatory bowel disease.METHODS:Bone marrow-derived dendritic cells isolated from wild type(WT)and IL-10-/-mice were stimulated for 4 h with C.difficile toxin A(200μg/m L),and gene expression of interferon(IFN)-γ,IL-12 and IL-23was determined by real-time reverse transcription polymerase chain reaction.WT and IL-10-/-mice(n=20each)were exposed to an antibiotic cocktail for three days and then were injected with clindamycin(i.p.).Mice(n=10 WT,10 IL-10-/-)were then challenged with oral administration of C.difficile(1×105 colony forming units of strain VPI 10463).Animals were monitored daily for 7 d for signs of colitis.Colonic tissue samples were evaluated for cytokine gene expression and histopathologic analysis.RESULTS:C.difficile toxin A treatment induced IFN-γgene expression to a level that was significantly higher in BDMCs from IL-10-/-compared to those from WT mice(P<0.05).However,expression of IL-12 and IL-23 was not different among the groups.Following C.difficile administration,mice developed diarrhea and lost weight within 2-3 d.Weight loss was significantly greater in IL-10-/-compared to WT mice(P<0.05).C.difficile infection induced histopathologic features typical of colitis in both IL-10-/-and WT mice.The histopathologic severity score was significantly higher in the IL-10-/-than in WT mice(mean±standard error;5.50±0.53 vs 2.44±0.46;P<0.05).This was accompanied by a significantly greater increase in IFN-γgene expression in colonic tissues from IL-10-/-than from WT mice challenged with C.difficile(P<0.05).CONCLUSION:These results indicate that colitis is more severe after C.difficile infection in IL-10-/-mice,and that IFN-γexpression is involved in this process.

Ulcerative colitis worsened after Clostridium difficile infection:Efficacy of infliximab

The incidence of Clostridium difficile(C.difficile)infection(CDI)is 1.8%-5.7%in admitted patients with ulcerative colitis(UC).CDI can worsen UC and increase the risk for colectomy or even death,thus necessitating therapy escalation,such as increasing the corticoid therapy or starting a biologic treatment.Several reported cases with infliximab therapy have provided favorable outcomes in UC patients with CDI,suggesting that infliximab treatment may be protective;however,the optimal infliximab treatment regimen for UC patients with CDI remains to be established.Here,we report a case of worsening UC in the presence of recurrent CDI.The patient had received prior ciprofloxacin and immunosuppressive therapy during a prolonged hospital stay.The deterioration in the patient’s condition likely resulted from the ability of C.difficile to promote relapsing of UC by activating the immune response.Ultimately,the patient was treated with a high dose of infliximab after a low trough level of infliximab at week 8was identified,yielding better clinical results.Infliximab was found to be safe after repetitive episodes of CDI.The trough level of infliximab was therefore a useful indicator to guide therapy and correlated well with the patient’s outcome.

Clostridioides difficile infection in patients with nonalcoholic fatty liver disease-current status

Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,leading to fibrosis,cirrhosis and hepatocellular carcinoma and also associated with increased cardiovascular disease mortality.The pathogenesis of NAFLD is not fully understood,although NAFLD is thought to be a hepatic form of metabolic syndrome.There is an increasing understanding of the role of microbiota disturbances in NAFLD pathogenesis,and as with many other conditions affecting the microbiota,NAFLD may be a novel risk factor for Clostridioides difficile(C.difficile)colonization(CDC)and C.difficile infection(CDI).CDI is an emerging nosocomial disease,and community-acquired cases of infection are growing,probably due to an increase in CDC rates.The association of NAFLD with CDI has been shown in only 4 studies to date,three of which included less than 1000 patients,although the frequency of NAFLD in these studies was observed in almost 20%of the total patient cohort.These data revealed that NAFLD is a risk factor for CDI development and,moreover,is a risk factor for intestinal complications of CDI.More studies are needed to investigate this association and move forward CDC and CDI screening efforts for this group of patients.