Clostridium Difficile Disease Research Articles

Humanized microbiota mice as a model of recurrent Clostridium difficile disease.

BackgroundClostridium difficile disease is the leading antibiotic-associated cause of diarrhea and nosocomial acquired infection in the western world. The per annum burden in the USA alone amounts to 250,000 cases with 14,000 ascribed deaths and medical costs in excess of a billion dollars. Novel models for the study of C. difficile infection are therefore pertinent.ResultsGerm free C57BL/6 mice gavaged with a healthy human fecal microbiota maintained a stable “humanized” microbiota over multiple generations when housed under specific pathogen-free (SPF) conditions. As with mice containing a conventional microbiota, treatment with a five-antibiotic cocktail followed by a single dose of clindamycin renders the animals susceptible to C. difficile infection (CDI). Interestingly, after recovery from the initial CDI infection, a single intraperitoneal injection of clindamycin is sufficient to induce CDI relapse. Relapse of CDI can be induced up to 35 days postinfection after recovery from the initial infection, and multiple episodes of relapse can be induced.ConclusionsThis model enables the study of recurrent C. difficile disease in a host containing a human-derived microbiota. Probiotic treatments using human-derived microbes, either prophylactic or curative, can be tested within the model. The identification and testing of human-derived microbial communities within a humanized microbiota mouse model may enable a higher rate of successful transfer of bacteria-based treatments from the lab to human patients due to the microbes involved initiating from, and being adapted to, the human GI tract.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-015-0097-2) contains supplementary material, which is available to authorized users.

Waiting for test results before isolating patients with Clostridium difficiledisease may be associated with increased transmission

Clostridium difficile is an infection that is associated with environmental contamination. Rapid isolation is recommended to prevent transmission. UK Guidelines state that patients with suspected infection should be isolated within two hours of the onset of symptoms [1], however they also state that the diarrhoea should not be clearly attributable to another cause. This can cause confusion and in busy clinical settings diarrhoea can be attributed to the administration of laxatives and other causes, meaning that patients may not be isolated until after a positive test result is received.

What's trending in the infection prevention and control literature? From HIS 2012 to HIS 2014, and beyond

SummaryThis is an informal review of some of the trends in the infection prevention and control literature since the last Healthcare Infection Society (HIS) conference in late 2012. Google Trends was used to investigate how the volume of interest in various infection control topics had changed over time. Ebola trumped all the others in Google searches, reflecting a surge of publications in the literature. Aside from Ebola, other trends in the infection prevention and control literature covered in this article include Middle East Respiratory Syndrome (MERS) coronavirus, universal versus targeted interventions, faecal microbiota transplantation, whole genome sequencing, carbapenem-resistant Enterobacteriaceae, and some aspects of environmental science. The review ends with an attempt to predict some of the trends in the infection prevention and control literature between now and the next HIS conference in 2016.

The molecular basis of Clostridium difficile disease and host response.

Clostridium difficile infection (CDI) ranges from asymptomatic colonization to severe colitis and death. The physiologic and molecular mechanisms determining disease outcome are thus far poorly understood. Here, we review recent advances in the relationship between host response to infection and disease outcome. Furthermore, we review recent studies on the relationship between intestinal microbial ecology and pathogenesis of CDI. Severe CDI is characterized by toxin-induced epithelial injury and marked intestinal inflammation. Recent studies demonstrate that systemic markers of inflammation correlate with disease outcome. Peripheral neutrophil count, C-reactive protein, and proinflammatory cytokines are elevated in patients with severe disease as compared with asymptomatic controls. Furthermore, fecal inflammatory biomarkers are better predictors of disease severity and diarrhea persistence than C. difficile abundance. A landmark study reported higher than 80% success rate of fecal microbiota transplantation for treatment of recurrent CDI. The commensal microbes responsible for C. difficile protection, and the molecular basis by which microbial ecology impacts disease outcome, are under active investigation. Under conditions of altered microbial ecology, C. difficile incites epithelial injury and marked intestinal inflammation, the primary determinant of disease outcome. Restoration of a diverse intestinal microbial population by fecal microbiota transplantation attenuates disease and prevents recurrence by mechanisms that are yet to be fully elucidated.

A New, Virulent Strain of

Over the past decade, the incidence and severity of Clostridium difficile disease have been increasing in North America and Europe in conjunction with

Use and Outcomes of Extended Antibiotic Prophylaxis in Urological Cancer Surgery

Although perioperative antibiotic prophylaxis prevents postoperative infectious complications, national guidelines recommend cessation of antibiotics within 24 hours after the procedure. Extended antibiotic prophylaxis beyond 24 hours may contribute to hospital acquired infections such as Clostridium difficile colitis. We evaluated practice patterns of antibiotic prophylaxis in genitourinary cancer surgery and assessed the impact of antibiotic prophylaxis on hospital acquired C. difficile infections. We identified 59,184 patients treated with radical prostatectomy, 27,921 who underwent partial or radical nephrectomy, and 5,425 treated with radical cystectomy for prostate, kidney and bladder cancers, respectively, from the Premier Perspective Database (Premier Inc., Charlotte, North Carolina) from 2007 to 2012. We constructed hierarchical linear regression models to identify patient and hospital factors associated with extended antibiotic prophylaxis. We evaluated the association between extended antibiotic prophylaxis and C. difficile infections for patients who underwent partial or radical nephrectomy and radical cystectomy with multivariate logistic regression. Surgery specific models demonstrated that hospital identity was associated with a substantial proportion of the variation in extended antibiotic prophylaxis (20% to 35% for radical prostatectomy, partial or radical nephrectomy, and radical cystectomy). Postoperative C. difficile colitis occurred in 0.02% of patients treated with radical prostatectomy, 0.23% of those treated with partial or radical nephrectomy and 1.7% of those treated with radical cystectomy. On multivariate analysis extended antibiotic prophylaxis was associated with higher odds of C. difficile infection after partial or radical nephrectomy (OR 3.79, 95% CI 2.46-5.84) and radical cystectomy (OR 1.64, 95% CI 1.12-2.39). Antibiotics may be overused after genitourinary cancer surgery and this overuse is associated with hospital acquired C. difficile colitis. Efforts are needed to encourage greater compliance with evidence-based approaches to postoperative care.

Faecal microbiota transplantation for Clostridium difficile infection

To review the current clinical literature regarding the use of fecal microbiota transplantation (FMT) for severe and recurrent Clostridium difficile disease (CDAD). Clostridium difficile (C. difficile) is a gram positive, spore forming bacteria, and an important nosocomial pathogen causing healthcare associated diarrhoea in hospitalized patients in developed and developing countries. During the past several years, CDAD has become more frequent, severe, refractory, and more likely to relapse. It has become apparent that C. difficile is no longer just a nosocomial infection, with a rising rate of infection in populations not previously affected. Standard treatment regimens and new medications exist, but recurrence rates are high. Using PubMed, we conducted a Boolean search with the following medical subject headings (MeSH): Clostridium difficile infection and fecal transplantation or recurrent C. difficile infection. We restricted the search to human studies, published in English, between 2011 through June 1, 2013. There were 104 publications identified. Of those related to FMT, there were 20 clinical reviews, 6 case reports, 3 clinical trials (one, a randomized control trial), and 1 meta-analysis. Since 1958 there have been 36 published reports of FMT for C. difficile infection (CDI) representing 583 patients. Success rates were higher when FMT was administered via colonoscopy (representing the majority of patients, 79.2%). The overall success rate for FMT, regardless of administration method, was 80-98%. Fecal microbiota transplantation attempts to restore the normal microbiome of the colon, and has achieved a cure rate reaching more than 90%. Mounting evidence supports the utility of FMT for severe and recurrent cases of CDI. Barriers that will need to be addressed are patient perceptions and fears, standard protocol development, and further clinical trials.

Characterization of the SigD Regulon of C. difficile and Its Positive Control of Toxin Production through the Regulation of tcdR

Clostridium difficile intestinal disease is mediated largely by the actions of toxins A (TcdA) and B (TcdB), whose production occurs after the initial steps of colonization involving different surface or flagellar proteins. In B. subtilis, the sigma factor SigD controls flagellar synthesis, motility, and vegetative autolysins. A homolog of SigD encoding gene is present in the C.difficile 630 genome. We constructed a sigD mutant in C. difficile 630 ∆erm to analyze the regulon of SigD using a global transcriptomic approach. A total of 103 genes were differentially expressed between the wild-type and the sigD mutant, including genes involved in motility, metabolism and regulation. In addition, the sigD mutant displayed decreased expression of genes involved in flagellar biosynthesis, and also of genes encoding TcdA and TcdB as well as TcdR, the positive regulator of the toxins. Genomic analysis and RACE-PCR experiments allowed us to characterize promoter sequences of direct target genes of SigD including tcdR and to identify the SigD consensus. We then established that SigD positively regulates toxin expression via direct control of tcdR transcription. Interestingly, the overexpression of FlgM, a putative anti-SigD factor, inhibited the positive regulation of motility and toxin synthesis by SigD. Thus, SigD appears to be the first positive regulator of the toxin synthesis in C. difficile.

Elevated lactoferrin is associated with moderate to severe Clostridium difficile disease, stool toxin, and 027 infection

We evaluated blood and fecal biomarkers as indicators of severity in symptomatic patients with confirmed Clostridium difficile infection (CDI). Recruitment included patients with CDI based on clinical symptoms and supporting laboratory findings. Disease severity was defined by physician’s assessment and blood and fecal biomarkers were measured. Toxigenic culture done using spore enrichment and toxin B detected by tissue culture were done as confirmatory tests. Polymerase chain reaction (PCR) ribotyping was performed on each isolate. There were 98 patients recruited, with 85 (87 %) confirmed cases of toxigenic CDI (21 severe, 57 moderate, and seven mild), of which 68 (80 %) were also stool toxin-positive. Elevated lactoferrin (p = 0.01), increased white blood cell (WBC) count (p = 0.08), and low serum albumin (p = 0.03) were all associated with the more severe cases of CDI. Ribotype 027 infection accounted for 71 % of severe cases (p < 0.01) and patients with stool toxin had significantly higher lactoferrin levels and WBC counts (p < 0.05). Our findings show that elevated fecal lactoferrin, along with increased WBC count and low serum albumin, were associated with more severe CDI. In addition, patients infected with ribotype 027 and those with stool toxin had significantly higher fecal lactoferrin and WBC counts.

Mortality in patients with Clostridium difficile infection correlates with host pro-inflammatory and humoral immune responses

Host anti-toxin immune responses play important roles in Clostridium difficile disease and outcome. The relationship between host immune and inflammatory responses during severe C. difficile infection (CDI) and the risk of mortality has yet to be defined. We aimed to investigate the host systemic IgG anti-toxin immune responses, the in vitro cytotoxicity of the infecting C. difficile ribotyped strain, and the host inflammatory markers and their relationship to CDI disease severity and risk of mortality. Inflammatory markers, co-morbidities and CDI outcomes were recorded in a prospective cohort of 150 CDI cases. Serum anti-cytotoxin A (TcdA) and anti-TcdB IgG titres were measured by ELISA and the infecting C. difficile isolate was ribotyped and the in vitro cytotoxin titre assessed. A low median anti-TcdA IgG titre was significantly associated with 30-day all-cause mortality (P<0.05). Ribotype 027 isolates were significantly more toxinogenic than other ribotypes (P<0.00001). High cytotoxin titres correlated with increased inflammatory markers but also higher anti-TcdA and -TcdB (P<0.05) IgG responses resulting in a lower risk of mortality. On multivariate analysis, predictors of mortality were peak white cell count >20 × 10(9) l(-1) [odds ratio (OR) 11.53; 95 % confidence interval (CI) 2.38-55.92], creatinine concentration >133 µmol l(-1) (OR 6.54; 95 % CI 1.47-29.07), Horn's index >3 (OR 4.09; 95 % CI 0.76-22.18) and low anti-TcdA IgG (OR 0.97; 95 % CI 0.95-0.99), but not ribotype, cytotoxin titre or anti-TcdB IgG. Thus, host pro-inflammatory and humoral responses correlate with the cytotoxin titre of the infecting strain and effective anti-toxin immune responses reduce the risk of mortality.

Counterpoint: Is Clostridium difficile a food-borne disease?

The increase in community associated Clostridium difficile disease paired with recent data on C. difficile in retail foods has led to speculation that C. difficile is a food-borne pathogen. However, there is no current epidemiologic evidence (i.e. restaurant or food-associated outbreaks) to support this hypothesis. Rates of C. difficile recovery from food vary widely across laboratories and may be due to a number of confounding factors. This commentary discusses the results of two published investigations and suggests that higher prevalence rates observed in some food studies may be due to laboratory contamination. The conclusions are that prevalence of C. difficile in retail foods is relatively low and further investigations are required to determine if C. difficile is food-borne.

Letter: should colectomy be the end‐point to evaluate the effectiveness of drug therapies in severe ulcerative colitis?

SIRS, We read with interest the study of Saito et al. in which predictors of response to i.v. ciclosporin in steroid-refractory, severe, ulcerative colitis (UC) were evaluated. The study provides additional data strengthening the idea that the more severe is disease activity at baseline or soon after starting ciclosporin therapy (as reflected by a persistently high Lichtiger score or a decrease in total serum protein concentration) the poorer is the outcome. 3 However, some methodological issues might limit the application of their proposed score and decision tree. First, the study deals with a highly selected population with severe disease activity, despite i.v. corticosteroids (Lichtiger score >9), which is not the usual clinical scenario when rescue therapies, such as ciclosporin or infliximab, are used in UC patients. In addition, an outstanding proportion of patients in the study presented additional factors for unresponsive disease, such as cytomegalovirus reactivation, Clostridium difficile disease or unsuccessful attempts with other rescue therapies (infliximab or leukocytoapheresis) prior to ciclosporin therapy. Second, all patients were treated with i.v corticosteroids for at least 5 days; despite they all had persistent severe activity. Finally, the authors chose to define response to ciclosporin as the avoidance of colectomy within the following 3 months. Nowadays, when clinical experience with calcineurinic antagonists and anti-TNF agents in UC is wide, 5 therapeutic decisions should be taken in a timely manner to improve drug efficacy and clinical outcomes. Two prospective studies showed that response to corticosteroid therapy in UC is accurately predicted after third day 8 and, therefore, corticosteroid therapy should not be further prolonged, particularly, in severely ill patients. Early introduction of rescue therapies not only may improve their efficacy, but also could allow administering sequential therapies in safer conditions. In this sense, not the need of colectomy, but rather the need for rescue therapies should be the end-point for predictive studies in steroid-refractory UC. In fact, 35% of the patients in the study by Saito et al. achieved a partial response after 14 days of ciclosporin therapy, and some of them were not colectomised, but had to prolong ciclosporin treatment or were switched to leukocytoapheresis, meaning that ciclosporin failed, although colectomy was not performed.

Targeted Restoration of the Intestinal Microbiota with a Simple, Defined Bacteriotherapy Resolves Relapsing Clostridium difficile Disease in Mice

Relapsing C. difficile disease in humans is linked to a pathological imbalance within the intestinal microbiota, termed dysbiosis, which remains poorly understood. We show that mice infected with epidemic C. difficile (genotype 027/BI) develop highly contagious, chronic intestinal disease and persistent dysbiosis characterized by a distinct, simplified microbiota containing opportunistic pathogens and altered metabolite production. Chronic C. difficile 027/BI infection was refractory to vancomycin treatment leading to relapsing disease. In contrast, treatment of C. difficile 027/BI infected mice with feces from healthy mice rapidly restored a diverse, healthy microbiota and resolved C. difficile disease and contagiousness. We used this model to identify a simple mixture of six phylogenetically diverse intestinal bacteria, including novel species, which can re-establish a health-associated microbiota and clear C. difficile 027/BI infection from mice. Thus, targeting a dysbiotic microbiota with a defined mixture of phylogenetically diverse bacteria can trigger major shifts in the microbial community structure that displaces C. difficile and, as a result, resolves disease and contagiousness. Further, we demonstrate a rational approach to harness the therapeutic potential of health-associated microbial communities to treat C. difficile disease and potentially other forms of intestinal dysbiosis.

Fighting Fire with Fire: Is it Time to Use Probiotics to Manage Pathogenic Bacterial Diseases?

Probiotics, when considered in clinical practice, have traditionally been used for prophylaxis; however, there is growing data suggesting treatment benefits in numerous disease states. In this review, we focus on probiotics as treatment for and prevention of several acute and chronic infectious processes including Helicobacter pylori, Clostridium difficile, necrotizing enterocolitis, ventilator-associated pneumonia, vancomycin-resistant enterococci, and nonalcoholic fatty liver disease. It is inaccurate to generalize findings observed in a single probiotic species to all probiotics. This reasoning is due to the variability of colonizing abilities of native intestinal floras, probiotic or otherwise, secondary to different combinations, doses, and duration of treatments. Given these limitations, multiple animal and human studies have shown anti-inflammatory and selective antimicrobial effects of specific probiotics. Some studies suggest a role for probiotics as supplemental treatment, in combination with antibiotics, for the aforementioned disease processes. It is apparent from this review that the efficacy of probiotics is widely variable and multifaceted. More focused clinical and basic science research is necessary to better understand the treatment potential of various probiotics.

A Meta-Analysis of Probiotic Efficacy for Gastrointestinal Diseases

BackgroundMeta-analyses on the effects of probiotics on specific gastrointestinal diseases have generally shown positive effects on disease prevention and treatment; however, the relative efficacy of probiotic use for treatment and prevention across different gastrointestinal diseases, with differing etiology and mechanisms of action, has not been addressed.Methods/Principal FindingsWe included randomized controlled trials in humans that used a specified probiotic in the treatment or prevention of Pouchitis, Infectious diarrhea, Irritable Bowel Syndrome, Helicobacter pylori, Clostridium difficile Disease, Antibiotic Associated Diarrhea, Traveler's Diarrhea, or Necrotizing Enterocolitis. Random effects models were used to evaluate efficacy as pooled relative risks across the eight diseases as well as across probiotic species, single vs. multiple species, patient ages, dosages, and length of treatment. Probiotics had a positive significant effect across all eight gastrointestinal diseases with a relative risk of 0.58 (95% (CI) 0.51–0.65). Six of the eight diseases: Pouchitis, Infectious diarrhea, Irritable Bowel Syndrome, Helicobacter pylori, Clostridium difficile Disease, and Antibiotic Associated Diarrhea, showed positive significant effects. Traveler's Diarrhea and Necrotizing Enterocolitis did not show significant effects of probiotcs. Of the 11 species and species mixtures, all showed positive significant effects except for Lactobacillus acidophilus, Lactobacillus plantarum, and Bifidobacterium infantis. Across all diseases and probiotic species, positive significant effects of probiotics were observed for all age groups, single vs. multiple species, and treatment lengths.Conclusions/SignificanceProbiotics are generally beneficial in treatment and prevention of gastrointestinal diseases. Efficacy was not observed for Traveler's Diarrhea or Necrotizing Enterocolitis or for the probiotic species L. acidophilus, L. plantarum, and B. infantis. When choosing to use probiotics in the treatment or prevention of gastrointestinal disease, the type of disease and probiotic species (strain) are the most important factors to take into consideration.

Initial study on the relationship between Clostridium difficile and inflammatory bowel disease

Objective Through the examination of Clostridium difficile (Cd) in the stool of inflammatory bowel disease (IBD) patients to investigate its infection status in IBD patients and the relationship with IBD.Methods From December 2009 to January 2011,a total of 130 diagnosed IBD patients were collected in the Department of Gastroenterology,Ruijin Hospital,Shanghai Jiaotong University School of medicine,including 60 ulcerative colitis (UC) patients and 70 Crohn's disease (CD) patients.At same time.60 irritable bowel syndrome patients and 60 healthy volunteers were collected as control.Stool samples were tested by PCR and Cd toxin A/B test kit (CDTK).SPSS statistical software was used for statistical analysis.Results In 130 enrolled IBD patients,16 cases (12.3％) were Cd infected,of which 10 were UC cases (16.7％) and 6 were CD cases (8.6％).No Cd infection was found positive in control group (x2 =15.779,P=0.000).The infection rate of Cd in the patients of active stage was higher than that in the patients of inactive stage (x2 =10.092,P=0.001).The infection rate of coion-type CD patients was 4/14,which was significantly higher than those of other types CD patients (x2 =13.125,P=0.001).The infection rate of Cd was 4.5％ in mild UC patients,14.3％ in moderate and 6/17 in severe (x2 =6.667,P=0.037) ; the infection rate were 0％ in mild CD patients,4.2％ in moderate and 5/16 in severe.The infection rate increased along with the increase of The disease severity (x2 =13.907,P=0.000).There was no significant difference in the infection rate of Cd between broad-spectrum antibiotics used and not used patients (x2 =1.414,P =0.378), or between patients with broad-spectrum antibiotics used alone and combined with immunosuppressant (x2 =0.330,P=0.962).Conclusions There was certain infection rate of Cd in IBD patients,especially the patients in active stage. The infection rate increased along with the increase of the IBD severity. Key words: Bacillus; Colitis,ulcerative; Crohn disease; Irritable bowel syndrome; Polymerase chain reaction; Feces

War on the Spore: Clostridium difficile Disease Among Patients in a Long-Term Acute Care Hospital

The transmission of Clostridium difficile infection (CDI) is evident in healthcare facilities across the country and poses a risk for patients and communities. A comprehensive infection control program along with an active surveillance process was developed and implemented in a 50-bed long-term acute care hospital (LTACH) in the southeastern United States. Patients are admitted from surrounding hospitals, have an expected stay of at least 25 days, and are acutely ill. The majority of the patient population is ventilator dependent, immunocompromised, and treated with antimicrobials. The program, implemented in December 2009, utilized a tiered approach that included environmental cleaning and disinfection, diagnostics and surveillance, and infection control measures including antibiotic stewardship. The goal of this study was to decrease the incidence rate of CDI 15% by June 2010. Based upon year-end results, the facility achieved a 27.61% decrease in the CDI rate. During the following 12 months, the program continued to demonstrate sustainability resulting in a 23.0% decrease in the CDI rate. This program was successful in decreasing the incidence of CDI in the LTACH creating a safe and cost-effective environment for patients, families, and the community.

Time to Consider Clostridium Probiotics?

Time to Consider <i>Clostridium</i> Probiotics?

Proton pump inhibitor-associated pneumonia: Not a breath of fresh air after all?

Over the past two decades, proton pump inhibitors (PPIs) have emerged as highly effective and relatively safe agents for the treatment of a variety of gastrointestinal disorders. Unfortunately, this desirable pharmacological profile has also contributed to superfluous and widespread use in both the inpatient and outpatient settings. While generally well-tolerated, research published over the last decade has associated these agents with increased risks of Clostridium difficile disease, fractures likely due to calcium malabsorption and both community-acquired (CAP) and hospital-acquired pneumonias (HAP). The mechanism behind PPI-associated pneumonia may be multifactorial, but is thought to stem from compromising the stomach's "acid mantle" against gastric colonization of acid-labile pathogenic bacteria which then may be aspirated. A secondary postulate is that PPIs, through their inhibition of extra-gastric H(+)/K(+)-ATPase enzymes, may reduce the acidity of the upper aerodigestive tract, thus resulting in increased bacterial colonization of the larynx, esophagus and lungs. To date, several retrospective case control studies have been published looking at the association between PPI use and CAP. Some studies found a temporal relationship between PPI exposure and the incidence of pneumonia, but only two could define a dose-response relationship. Furthermore, other studies found an inverse correlation between duration of PPI use and risk of CAP. In terms of HAP, we reviewed two retrospective cohort studies and one prospective study. One retrospective study in a medical ICU found no increased association of HAP in PPI-exposed patients compared to no acid-lowering therapy, while the other in cardiothoracic surgery patients showed a markedly increased risk compared to those receiving H(2)RAs. The one prospective study in ICU patients showed an increased risk of HAP with PPIs, but not with H(2)RAs. In conclusion, the current literature shows a slight trend toward an association between PPI use and pneumonia and an increased risk with PPIs over H(2)RAs, but the findings are not consistent across all studies. Larger controlled trials still need to be done to better identify the risk that PPIs impart towards patients contracting CAP or HAP. Until these are completed, we will have to continue to extrapolate across smaller controlled trials to predict the associated risks in our respective patient populations. In the interim, it appears prudent to limit the use of PPIs to situations where they are clinically indicated and, in such cases, use them at the lowest effective dose. In the case of prescribing for stress ulcer prophylaxis in ICU patients, perhaps H(2)RAs should be used as the preferred agents over PPIs.

Systematic review: Clostridium difficile and inflammatory bowel disease

There is increasing concern about the apparently rising incidence and worsening outcome of Clostridium difficile infection (CDI) associated with inflammatory bowel disease (IBD). We have systematically reviewed the literature to evaluate the incidence, risk factors, endoscopic features, treatment and outcome of CDI complicating IBD. To systematically review: clostridium difficile & inflammatory bowel disease. Structured searches of Pubmed up to September 2010 for original, cross-sectional, cohort and case-controlled studies were undertaken. Of 407 studies, 42 met the inclusion criteria: their heterogeneity precluded formal meta-analysis. CDI is commoner in active IBD, particularly ulcerative colitis, than in controls. Certainty about a temporal trend to its increasing incidence in IBD is compromised by possible detection bias and miscoding. Risk factors include immunosuppressants and antibiotics, the latter less commonly than in controls. Endoscopy rarely shows pseudomembranes and is unhelpful for diagnosing CDI in IBD. There are no controlled therapeutic trials of CDI in IBD. In large studies, outcome of CDI in hospitalised IBD patients appears worse than in controls. The complication of IBD by Clostridium difficile infection has received increasing attention in the past decade, but whether its incidence is really increasing or its outcome worsening remains unproven. Therapeutic trials of Clostridium difficile infection in IBD are lacking and are needed urgently.