European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Vancomycin for the treatment of Clostridium difficile Infection: for whom is this expensive bullet really magic? Lymphopenia as a novel marker of Clostridium difficile infection recurrence. Clostridium difficile infection in the "oldest" old: clinical outcomes in patients aged 80 and older. Hospital-acquired Clostridium difficile infection: determinants for severe disease A common polymorphism in the interleukin-8 gene promoter is associated with an increased risk for recurrent Clostridium difficile infection. Primary Outcomes From a Phase 3, Randomized, Double-Blind, Active-Controlled Trial of Surotomycin in Subjects With Clostridium difficile Infection Systematic reviews in endodontics--examples of GIGO? Effect of age on treatment outcomes in Clostridium difficile infection. Lack of association of outcomes with treatment duration and microbiologic susceptibility data in Clostridium difficile infections in a non-NAP1/BI/027 setting Clostridium difficile infection in an endemic setting in the Netherlands Fidaxomicin Preserves the Intestinal Microbiome During and After Treatment of Clostridium difficile Infection (CDI) and Reduces Both Toxin Reexpression and Recurrence of CDI Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection: A Randomized Clinical Trial. Treatment of First Recurrence of Clostridium difficile Infection: Fidaxomicin Versus Vancomycin A new macrocyclic antibiotic, fidaxomicin (OPT-80), causes less alteration to the bowel microbiota of Clostridium difficile-infected patients than does vancomycin. Surotomycin versus vancomycin in adults with Clostridium difficile infection: primary clinical outcomes from the second pivotal, randomized, double-blind, Phase 3 trial A case-control study of community-associated Clostridium difficile infection. Fecal Microbiota Transplantation: From Clostridium difficile to Inflammatory Bowel Disease. Clinical and laboratory features of the most common Clostridium difficile ribotypes isolated in Belgium. Impact of the type of diagnostic assay on Clostridium difficile infection and complication rates in a mandatory reporting program. Mortality in patients with Clostridium difficile infection correlates with host pro-inflammatory and humoral immune responses. Impact of adding prophylactic probiotics to a bundle of standard preventative measures for Clostridium difficile infections: enhanced and sustained decrease in the incidence and severity of infection at a community hospital Confocal Laser Endomicroscopy for In Vivo Diagnosis of Clostridium difficile Associated Colitis — A Pilot Study
In 2009 the first European Society of Clinical Microbiology and Infection ( ESCMID ) treatment guidance document for  Clostridium difficile infection ( CDI ) was published . The guideline has been applied widely in clinical practice . In this document an up date and review on the comparative effectiveness of the currently available treatment modalities of CDI is given , thereby providing evidence -based recommendations on this issue . A computerized literature search was carried out to investigate r and omized and non-r and omized trials investigating the effect of an intervention on the clinical outcome of CDI . The Grade s of Recommendation Assessment , Development and Evaluation ( GRADE ) system was used to grade the strength of our recommendations and the quality of the evidence . The ESCMID and an international team of experts from 11 European countries supported the process . To improve clinical guidance in the treatment of CDI , recommendations are specified for various patient groups , e.g. initial non-severe disease , severe CDI , first recurrence or risk for recurrent disease , multiple recurrences and treatment of CDI when oral administration is not possible . Treatment options that are review ed include : antibiotics , toxin-binding resins and polymers , immunotherapy , probiotics , and faecal or bacterial intestinal transplantation . Except for very mild CDI that is clearly induced by antibiotic usage antibiotic treatment is advised . The main antibiotics that are recommended are metronidazole , vancomycin and fidaxomicin . Faecal transplantation is strongly recommended for multiple recurrent CDI . In case of perforation of the colon and /or systemic inflammation and deteriorating clinical condition despite antibiotic therapy , total abdominal colectomy or diverting loop ileostomy combined with colonic lavage is recommended The epidemiology , clinical severity , and case-fatality ratio of Clostridium difficile infection ( CDI ) changed dramatically with the emergence of a toxin hyperproducing strain ( BI/NAP1/027 ) in North America and Europe in 2000 . For the treatment of CDI , metronidazole and vancomycin remain the 2 most commonly used drugs . The 3 r and omized controlled trials published thus far , as well as the upcoming tolevamer trial , use intermediate outcomes , rather than the outcomes that now preoccupy clinicians : the frequency of complications or recurrence . The major advantage of metronidazole is its low price . The major advantage of orally administered vancomycin is its more favorable pharmacokinetics . Facilitating vancomycin-resistant enterococci colonization and /or infection is a potential drawback of both drugs . Pending the development of a prospect ively vali date d scoring system , members of the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America expert committee will define severe CDI as present in any patient with a  leukocyte count  > or = 15,000 cells/mm(3 ) or a creatinine level increased by > or = 50 % from baseline . For patients with mild-to-moderate CDI ( defined by a leukocyte count < 15000 cells/mm(3 ) and a creatinine level < 1.5 times the baseline value ) , there is no evidence that treatment with vancomycin is superior to treatment with metronidazole ( even for intermediate outcomes ) , and metronidazole therapy should be preferred . For patients with severe CDI who are not infected with BI/NAP1/027 , there is reasonable evidence that the better pharmacokinetics of vancomycin translate into a lower probability of complications . For those patients who are infected with BI/NAP1/027 , the superiority of vancomycin therapy remains to be proven . In practice , because it is not yet possible to rapidly type the strains , all patients with severe CDI should be treated with  vancomycin .  Future trials should use complicated CDI and recurrences as their primary outcomes BACKGROUND Treatment of Clostridium difficile infection ( CDI ) is often limited by recurrence in 25 % of cases . The objective of this study was to determine risk factors of CDI recurrence during a provincial endemic . METHODS Data was prospect ively collected for 1 year in a Montréal hospital . Inclusion criteria were : age ≥ 18 years ; admission for ≥ 72 h ; CDI diagnosis during current admission ; no CDI diagnosis in the previous 3 months . RESULTS A total of 121 patients were included , of which 42 % were female . Mean age was 77 years , with a median Charlson comorbidity index of 5 . Forty patients ( 33 % ) had recurrent disease within 2 months of initial CDI treatment . There were 20 deaths ( 17 % ) within the 2-month follow-up period . Higher risk of CDI recurrence was independently associated with older age ( HR=2.26 for each decade ) , female gender ( HR=1.56 ) , and lymphopenia at completion of CDI treatment ( HR=2.18 ) , while a positive C. difficile antitoxin serology was protective ( HR=0.17 ) . CDI recurrence was not associated with either lymphopenia at time of diagnosis , underlying comorbidities , severity or treatment of the initial CDI episode , or re-exposure to antibiotics during the follow-up period . CONCLUSION Lymphopenia at the end of CDI treatment appears to be a strong marker for CDI recurrence . This available and inexpensive test may identify patients who are at higher risk of CDI recurrence OBJECTIVES Clostridium difficile infection ( CDI ) represents a cause of substantial morbidity , particularly for older adults . Although older age is a risk factor for CDI , few studies have specifically focused on clinical outcomes in older adults , particularly the " oldest " old . DESIGN Retrospective review . SETTING University of Michigan Health System . PARTICIPANTS All patients aged 80 and older with a positive cytotoxin assay for C. difficile and a clinical course consistent with CDI during 2006 . MEASUREMENTS Clinical data were recorded , including comorbid conditions and treatment regimens , as well as outcomes , including treatment failure , infection relapse , and 90-day mortality . RESULTS Seventy patients aged 80 and older ( mean 84.0+/-4.1 ) with CDI were identified .  Metronidazole was given as initial therapy in 65 ( 92.8 % ) ; 18 of these 65 ( 27.7 % ) experienced treatment failure , requiring subsequent use of oral vancomycin .  Serious adverse events included three episodes of toxic megacolon , two requiring colectomy . One death was directly attributable to CDI . All-cause mortality was 8.6 % at 30 days and 17.1 % at 90 days . Higher white blood cell ( WBC ) counts were independently associated with treatment failure ( P=.02 ) and coronary artery disease with 90-day mortality ( P=.02 ) . CONCLUSION In older adults with CDI , treatment failure on metronidazole occurred frequently and was associated with higher WBC count . Larger prospect i ve studies are needed to determine risk factors for treatment failure and relapse in order to develop better paradigms for CDI treatment in older adults . Initial therapy with vancomycin may be appropriate for elderly patients , especially those with elevated WBC counts Risk factors of severity ( need for surgical intervention , intensive care or fatal outcome ) were analysed in hospital-acquired Clostridium difficile infection ( CDI ) in a 777-bed community hospital . In a prospect i ve analytical cross-sectional study , age ( ≥65 years ) , sex , CDI characteristics , underlying diseases , severity of comorbidity and PCR ribotypes were tested for associations with severe CDI . In total , 133 cases of hospital-acquired CDI ( mean age 74.4 years ) were identified , result ing in an incidence rate of 5.7/10,000 hospital-days . A recurrent episode of diarrhoea occurred in 25 cases ( 18.8 % ) and complications including toxic megacolon , dehydration and septicaemia in 69 cases ( 51.9 % ) . Four cases ( 3.0 % ) required ICU admission , one case ( 0.8 % ) surgical intervention and 22 cases ( 16.5 % ) died within the 30-day follow-up period . Variables identified to be independently associated with severe CDI were severe diarrhoea ( odds ratio [ OR ] 3.64 , 95 % confidence interval [ CI ] 1.19–11.11 , p = 0.02 ) , chronic pulmonary disease ( OR 3.0 , 95 % CI 1.08–8.40 , p = 0.04 ) , chronic renal disease ( OR 2.9 , 95 % CI 1.07–7.81 , p = 0.04 ) and diabetes mellitus ( OR 4.30 , 95 % CI 1.57–11.76 , p = 0.004 ) . The case fatality of 16.5 % underlines the importance of increased efforts in CDI prevention , in particular for patients with underlying diseases BACKGROUND Neutrophil recruitment coordinated by intestinal interleukin (IL)-8 secretion is a key component in the pathogenesis of Clostridium difficile infection ( CDI ) . We hypothesized that a common single-nucleotide polymorphism ( SNP ) in the -251 region of the IL-8 gene promoter may be predictive of recurrent CDI . METHODS This was a prospect i ve cohort study of hospitalized adult patients with CDI who were admitted to a large , university-affiliated medical center from 2007 through 2008 . Patients were monitored for 3 months after diagnosis of CDI and assessed for recurrent CDI ( defined as a return of diarrhea that required treatment after initial symptom resolution ) . DNA was isolated from blood sample s , and genetic sequencing was performed using polymerase chain reaction and pyrosequencing . The association between IL-8 genotype and recurrent CDI was assessed using univariate and multivariate statistics . RESULTS Ninety-six patients with a mean ( ± st and ard deviation ) age of 61 ± 16 years ( 54 % of whom were female and 63 % of whom were white ) were identified .  The overall incidence of recurrent CDI was 24 % . IL-8 allele frequency was similar to previously reported findings ( for A/A , 27 % ; for A/T , 53 % ; and for T/T , 20 % ) . The incidence of recurrent CDI was 38 % in patients with the A/A allele and 19 % in all other patients ( relative risk , 2.1 ; 95 % confidence interval , 1.04 - 4.13 ) ( P = .043 ) . CONCLUSIONS This study indicates that a common SNP in the IL-8 gene promoter is an independent predictor of recurrent CDI . Our results could offer risk stratification for patients at high risk for recurrent CDI Abstract Background Although the incidence of Clostridium difficile infection ( CDI ) is increasing , available CDI treatment options are limited in terms of sustained response after treatment . This phase 3 trial assessed the efficacy and safety of surotomycin , a novel bactericidal cyclic lipopeptide , versus oral vancomycin in subjects with CDI . Methods In this r and omized , double-blind , active-controlled , multicenter , international trial , subjects with CDI confirmed by a positive toxin result were r and omized to receive surotomycin ( 250 mg twice daily ) or vancomycin ( 125 mg 4 times daily ) orally for 10 days . The primary endpoints were clinical response at end of treatment and evaluation of surotomycin safety . The key secondary endpoints were clinical response over time and sustained clinical response through a 30- to 40-day follow-up period . Clostridium difficile infection recurrence during follow-up and time to diarrhea resolution were also analyzed . Results In total , 570 subjects were r and omized and had confirmed CDI ; 290 subjects received surotomycin and 280 subjects received vancomycin . Surotomycin clinical cure rates at end of treatment ( surotomycin/vancomycin : 79.0%/83.6 % ; difference of −4.6 % ; 95 % confidence interval , −11.0 to 1.9 ] ) , clinical response over time ( stratified log-rank test , P = .832 ) , and sustained clinical response at end of trial ( Day 40–50 ) ( 60.6%/61.4 % ; difference of −0.8 % ; 95 % CI , −8.8 to 7.1 ) in the microbiological modified intent to treat population did not meet noninferiority or superiority criteria versus vancomycin . Both treatments were generally well tolerated . Conclusions Surotomycin failed to meet the criteria for noninferiority versus vancomycin for the primary and key secondary endpoints in this trial In many areas of medicine the amount of published information is increasing at an exponential rate , making it difficult for the clinician to condense the data to a manageable amount of valuable and useful information . Systematic review s have been suggested as a remedy for this information overload . Such review s are regarded as the highest level of evidence . Certain statistical methods , e.g. , meta- analysis , have also been introduced for the calculation of a more comprehensive summation of the compiled results from studies with small sample sizes . These findings would then serve as an authoritarian guide for evidence -based practice . Endodontists have lately jumped on the b and wagon of systematic review s and meta-analyses , and papers on various topics are being published . Well done , such comprehensive information would be very useful and authoritative for the practitioner . Alarmingly , the quality of these recent publications is negatively correlated to the frequency . This can have serious consequences in the clinical arena if spurious information is given a seal of approval when communicated as facts in refereed journals . A systematic literature review is design ed to focus on a single question and to synthesize all high- quality research reports relevant to the question . In these studies , however , sources of bias are often not controlled . Therefore , even the best review and meta- analysis becomes useless if it is based on poorly design ed research . Furthermore , these review s are mostly based on published data which are too often biased toward studies that show significant differences in results and /or outcome . “ Uninteresting ” conclusions tend not to be published . Endodontic literature , thus far , is short on well design ed and executed r and omized clinical trials . Furthermore , clinical protocol s often have many important “ proprietary ” modifications that make comparison difficult . This makes it very hard to undertake a systematic review to answer a narrow question . Such GIGO ( garbage in , garbage out ) can easily lead to biased conclusions and reinforce already existing biased comclusions . An example of such bias can be illustrated by a meta- analysis recently published . The study focused on assessing if there were differences in outcome between 1 and 2 treatment visits when treating teeth with apical periodontitis . Relevant publications on this topic are rare , and with the narrow inclusion criteria only 3 investigations were available for the review . However , the only factors connecting these 3 studies was the words “ single ” and “ two visits ” in the title . Beyond that , the selected studies are too different and inadequate for the study . Only 1 study is somewhat demonstrably r and omized , and outcome assessment s are based on 3 vastly different criteria . Two of the studies use calcium hydroxide as intracanal dressing , whereas the third uses no intervisit medication . Complexity of initial pathology and healing time are also clearly factors of great importance but not controlled . In addition , sample sizes in the component studies as well as the final cohort are all too small for the conclusions that there was no significant difference between 1or 2-visit treatment protocol s. To undertake and publish a meta- analysis on such an incomplete sample is counterproductive . Although the publication noted its numerous limitations , it will still communicate erroneous conclusions with a poor scientific foundation to the less informed reader . There are other examples of recently published systematic review s that are very ambiguous and tend to communicate spurious facts . One of these studies looks at the effect of smear-layer removal on sealing ability of root canal obturation . The study is entirely limited to laboratory experiments , with the majority of evaluations using dye leakage which is generally considered to be unreliable . This is an example of review ers lacking content expertise . The authors draw the conclusion , using defective review material , that removal of smear layer enhances the seal of the root filling . We may generally believe that this is the truth OBJECTIVES To determine the effect of advancing age on the clinical outcomes of Clostridium difficile ( CDI ) treatment .  DESIGN Regression modeling of results from two double-blind r and omized multicenter studies on the treatment of primary and first recurrent cases of CDI to examine for effects of age and study drug on outcomes of cure ( resolution of diarrhea ) , recurrence within 4 weeks of completing successful therapy , and cure without recurrence . SETTING Participants were r and omized into studies in the United States , Canada , and Europe . PARTICIPANTS Nine hundred ninety-nine individuals with toxin-positive CDI were r and omized to receive vancomycin ( 125 mg 4 times daily ) or fidaxomicin ( 200 mg twice daily ) for 10 days . MEASUREMENTS The effect of advancing age  in those aged 18 to 40 years and in 10-year increments thereafter was examined . RESULTS The model predicts a 17 % lower clinical cure , 17 % greater recurrence , and 13 % lower sustained clinical response by advancing decade than in those younger than 40 ( P < .01 each ) . Clinical cure was similar in the fidaxomicin and vancomycin treatment groups , although fidaxomicin was associated with a more than 50 % lower relative risk for recurrence than vancomycin ( P < .001 ) . Multivariate regression modeling showed that risk factors accounting for poorer outcomes with advancing age include infection with the BI strain type , inpatient status , renal insufficiency , leukocytosis , hypoalbuminemia , and concomitant medication exposure . CONCLUSION Measurable and progressive deterioration in CDI treatment outcomes occurred with advancing age in those aged 40 and older , highlighting the need for prevention and treatment strategies . Fidaxomicin treatment was associated with a 60 % lower risk of recurrence than vancomycin after adjusting for age , concomitant antibiotics , and C. difficile strain Abstract Background : Concerns regarding the poor response of severe Clostridium difficile infection ( CDI ) treated with metronidazole have arisen over the last 5 y. Methods : We conducted a prospect i ve , non-interventional study of CDI cases at our institution to evaluate the role of drug resistance , co-morbidities , and the emergence of hypervirulent strains on patient outcomes . A total of 118 adult in patients with diarrhea and a positive stool for C. difficile toxin immunoassay had positive stool cultures and were included in the study . All 118 isolates had  vancomycin and metronidazole susceptibility testing via the E-test method ; rep-PCR was performed on 47 isolates . Of the 118 study patients , 107 were treated with either metronidazole or vancomycin .  Results : Initial therapy was metronidazole in 98.1 % ( n = 105 ) and vancomycin in 1.9 % ( n = 2 ) patients . Evaluable clinical response within 5 days of treatment was noted in 52.5 % ( 52/99 ) of cases . The mean duration of treatment was 11.7 ± 7.2 days . The 30-day all-cause mortality rate was 24.6 % ( 29/118 ) . Recurrence occurred in 23.6 % ( 21/89 ) . A recent stay in the intensive care unit was associated with increased 30-day mortality ( odds ratio 3.58 , p = 0.012 ) . There were no isolates resistant to metronidazole or vancomycin . Only 1 isolate was possibly related to the NAP1/BI/027 reference strain . No strain-related differences in deaths or recurrence were noted . Conclusions : Deaths related to CDI in our study appear to be related to multiple factors and did not appear to be independently related to antibiotic susceptibility , strain type , or treatment duration The purpose of this investigation was to study risk factors for  Clostridium difficile infection ( CDI ) in an endemic setting . In a 34-month prospect i ve case – control study , we compared the risk factors and clinical characteristics of all consecutively diagnosed hospitalised CDI patients ( n = 93 ) with those of patients without diarrhoea ( n = 76 ) and patients with non-CDI diarrhoea ( n = 64 ) . The incidence of CDI was 17.5 per 10,000 hospital admissions .  C. difficile polymerase chain reaction ( PCR ) ribotype 014 was the most frequently found type ( 15.9 % ) , followed by types 078 ( 12.7 % ) and 015 ( 7.9 % ) . Independent risk factors for endemic CDI were the use of second-generation cephalosporins , previous hospital admission and previous stay at the intensive care unit ( ICU ) . The use of third-generation cephalosporins was a risk factor for diarrhoea in general . We found no association of CDI with the use of fluoroquinolones or proton pump inhibitors ( PPIs ) . The overall 30-day mortality among CDI patients , patients without diarrhoea and patients with non-CDI diarrhoea was 7.5 % , 0 % and 1.6 % , respectively . In this endemic setting , risk factors for CDI differed from those in outbreak situations . Some risk factors that have been ascribed to CDI earlier were , in this study , not specific for CDI , but for diarrhoea in general . The 30-day mortality among CDI patients was relatively high The microflora-sparing properties of fidaxomicin were examined during the conduct of a r and omized clinical trial comparing vancomycin 125 mg 4 times per day versus fidaxomicin 200 mg twice per day for 10 days as treatment of Clostridium difficile infection ( CDI ) . Fecal sample s were obtained from 89 patients ( 45 received fidaxomicin , and 44 received vancomycin ) at study entry and on days 4 , 10 , 14 , 21 , 28 , and 38 for quantitative cultures for C. difficile and cytotoxin B fecal filtrate concentrations . Additionally , sample s from 10 patients , each receiving vancomycin or fidaxomicin , and 10 sample s from healthy controls were analyzed by quantitative real-time polymerase chain reaction with multiple group-specific primers to evaluate the impact of antibiotic treatment on the microbiome . Compared with controls , patients with CDI at study entry had counts of major microbiome components that were 2–3-log10 colony-forming units (CFU)/g lower . In patients with CDI , fidaxomicin allowed the major components to persist , whereas vancomycin was associated with a further 2–4-log10 CFU reduction of Bacteroides/Prevotella group organisms , which persisted to day 28 of the study , and shorter term and temporary suppression of both Clostridium coccoides and Clostridium leptum group organisms . In the posttreatment period , C. difficile counts similarly persisted in both study population s , but reappearance of toxin in fecal filtrates was observed in 28 % of vancomycin-treated patient sample s ( 29 of 94 ) , compared with 14 % of fidaxomicin-treated patient sample s ( 13 of 91 ; P = .03 ) . Similarly , 23 % of vancomycin-treated patients ( 10 of 44 ) and 11 % of fidaxomicin-treated patients ( 5 of 44 ) had recurrence of CDI . Whereas vancomycin and fidaxomicin are equally effective in resolving CDI symptoms , preservation of the microflora by fidaxomicin is associated with a lower likelihood of CDI recurrence . Clinical Trials Registration . NTC00314951 IMPORTANCE Clostridium difficile infection ( CDI ) is a major burden in health care and community setting s. CDI recurrence is of particular concern because of limited treatment options and associated clinical and infection control issues . Fecal microbiota transplantation ( FMT ) is a promising , but not readily available , intervention . OBJECTIVE To determine whether frozen- and -thawed ( frozen , experimental ) FMT is noninferior to fresh ( st and ard ) FMT in terms of clinical efficacy among patients with recurrent or refractory CDI and to assess the safety of both types of FMT . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , noninferiority trial enrolling 232 adults with recurrent or refractory CDI , conducted between July 2012 and September 2014 at 6 academic medical centers in Canada . INTERVENTIONS Patients were r and omly allocated to receive frozen ( n = 114 ) or fresh ( n = 118 ) FMT via enema . MAIN OUTCOMES AND MEASURES The primary outcome measures were clinical resolution of diarrhea without relapse at 13 weeks and adverse events . Noninferiority margin was set at 15 % . RESULTS A total of 219 patients ( n = 108 in the frozen FMT group and n = 111 in the fresh FMT group ) were included in the modified intention-to-treat ( mITT ) population and 178 ( frozen FMT : n = 91 , fresh FMT : n = 87 ) in the per- protocol population . In the per- protocol population , the proportion of patients with clinical resolution was 83.5 % for the frozen FMT group and 85.1 % for the fresh FMT group ( difference , -1.6 % [ 95 % CI , -10.5 % to ∞ ] ; P = .01 for noninferiority ) . In the mITT population the clinical resolution was 75.0 % for the frozen FMT group and 70.3 % for the fresh FMT group ( difference , 4.7 % [ 95 % CI , -5.2 % to ∞ ] ; P < .001 for noninferiority ) . There were no differences in the proportion of adverse or serious adverse events between the treatment groups . CONCLUSIONS AND RELEVANCE Among adults with recurrent or refractory CDI , the use of frozen compared with fresh FMT did not result in worse proportion of clinical resolution of diarrhea . Given the potential advantages of providing frozen FMT , its use is a reasonable option in this setting . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01398969 Recurrence of Clostridium difficile infection ( CDI ) occurs in approximately 25 % of successfully treated patients . Two phase 3 r and omized , double-blind trials were conducted at 154 sites in the United States , Canada , and Europe to compare fidaxomicin vs vancomycin in treating CDI . Patients with CDI received fidaxomicin 200 mg twice daily or vancomycin 125 mg 4 times daily for 10 days . The primary end point was clinical cure of CDI at end of treatment , and a secondary end point was recurrence during the 28 days following clinical cure . In all , 1164 subjects were enrolled , of which a subgroup of 128 in the per- protocol population had another recent episode of CDI prior to the CDI diagnosis at study enrollment . In the analysis of this subgroup , initial response to therapy was similar for both drugs ( > 90 % cure ) . However , recurrence within 28 days occurred in 35.5 % of patients treated with vancomycin and 19.7 % of patients treated with fidaxomicin ( −15.8 % difference ; 95 % confidence interval , −30.4 % to −0.3 % ; P = .045 ) . Early recurrence ( within 14 days ) was reported in 27 % of patients treated with vancomycin and 8 % of patients treated with fidaxomicin ( P = .003 ) . In patients with a first recurrence of CDI , fidaxomicin was similar to vancomycin in achieving a clinical response at end of therapy but superior in preventing a second recurrence within 28 days . Clinical Trials Registration . NCT00314951 and NCT00468728 Clostridium difficile infection ( CDI ) is the most common identifiable cause of diarrhoea in hospitalized patients . Current therapies rely on the administration of metronidazole or vancomycin , which reduce vegetative population s of C. difficile in the bowel . Recurrence of the disease when treatment with these antibiotics ceases indicates that metronidazole and vancomycin affect not only C. difficile but also commensal population s that normally mediate competitive exclusion . Fidaxomicin is a new antibiotic that inhibits C. difficile . Our study shows that fidaxomicin had little effect on the composition of the faecal microbiota in terms of its major phylogenetic clusters . Notably , clostridial clusters XIVa and IV , and Bifidobacterium , were much less affected by fidaxomicin compared to vancomycin treatment . These findings help to explain the substantially reduced rates of relapse following treatment of CDI with fidaxomicin in recent clinical trials Background The available treatment options for Clostridium difficile infection ( CDI ) are limited by high recurrence rates . Surotomycin was a novel bactericidal cyclic lipopeptide in development to treat CDI that demonstrated non-inferiority to vancomycin in a Phase 2 trial . Objectives To assess surotomycin  safety and clinical response ( non-inferiority versus vancomycin ) at the end of treatment ( EOT ) of CDI . Additionally , to assess surotomycin  response over time and sustained response at 30 - 40 days post-EOT ( superiority versus vancomycin ) . Patients and methods Patients with CDI were r and omized ( 1:1 ) to receive twice-daily oral surotomycin 250 mg alternating with twice-daily placebo or four-times-daily oral vancomycin 125 mg for 10 days in this Phase 3 , double-blind , multicentre , international trial . Clinical response over time and sustained clinical response were monitored until the end of the trial , through a follow-up period of 30 - 40 days . Clinical Trial Registration : NCT01598311 . Results A total of 285 and 292 patients with confirmed CDI were r and omized to receive surotomycin and vancomycin , respectively .  Surotomycin-associated clinical response at EOT was non-inferior to vancomycin ( surotomycin/vancomycin : 83.4%/82.1 % ; difference 1.4 % , 95 % CI - 4.9 , 7.6 ) . Following treatment with surotomycin , both clinical response over time ( stratified log-rank test , P = 0.277 ) and sustained clinical response ( 63.3%/59.0 % ; difference 4.3 % , 95 % CI - 3.6 , 12.2 ) did not demonstrate superiority versus vancomycin at end of trial . Both treatments were generally well tolerated . Conclusions Surotomycin demonstrated non-inferiority to vancomycin for CDI clinical response at EOT . Surotomycin did not demonstrate superiority to  vancomycin  for clinical response over time or sustained clinical response rate OBJECTIVES The aim of this study was to determine the incidence of and risk factors for  community-associated Clostridium difficile infection ( CDI )  . METHODS Prospect i ve surveillance of community-derived faecal sample s for C. difficile cytotoxin , followed by a question naire-based case-control study in two distinct patient cohorts ( one semi-rural and the other urban ) . RESULTS The proportion of r and omly selected faecal sample s positive for C. difficile cytotoxin was 2.1 % in both patient cohorts ( median ages 73 and 45 years for the urban and semi-rural cohorts , respectively ) .  Exposure to antibiotics  in the previous 4 weeks , particularly multiple agents ( P < 0.001 ) , aminopenicillins ( P < 0.05 ) and oral cephalosporins ( P < 0.05 ) , was significantly more frequent among cases than controls . Hospitalization in the preceding 6 months was significantly associated with CDI ( 45 % versus 23 % ; P = 0.022 ) . However , almost half the cases had not received antibiotic therapy in the month before C. difficile detection , and approximately one-third neither had exposure to antibiotics nor recent hospitalization . Contact with infants aged < or = 2 years was significantly associated with CDI ( 14 % versus 2 % ; P = 0.02 ) . Prior exposure to gastrointestinal-acting drugs ( proton pump inhibitor , H2 antagonist or non-steroidal anti-inflammatory ) was not significantly more common in CDI cases . C. difficile PCR ribotype 001 caused 60 % and 13 % of urban and semi-rural community-associated CDI cases , respectively . CONCLUSIONS Reliance on antibiotic history and age ( > or = 65 years ) will contribute to missed diagnoses of community-associated CDI . Potential risk factors for community-associated CDI should be explored further to explain the large proportion of cases not linked to recent antibiotic therapy or hospitalization Fecal microbiota transplantation ( FMT ) has evolved from a case report in the medical literature to the basis of major innovations in the treatment of Clostridium difficile infection ( CDI ) and , potentially , inflammatory bowel disease ( IBD ) . In the clinical setting , FMT was noted to significantly lower the risk of recurrent CDI , likely by increasing microbial diversity and altering the metabolic environment in the intestinal tract of recipients . In parallel , advances in the ability to quantify and characterize microbial communities in fecal sample s led to the association of IBD with a state of intestinal dysbiosis . Consequently , a number of case series and r and omized , controlled trials have evaluated FMT in treating active ulcerative colitis or Crohn 's disease . Unlike in CDI , the efficacy of  FMT  in the treatment of IBD appears to be influenced by a number of factors , including donor microbial profiles , inflammatory burden , and the microbial diversity of the recipient . The therapeutic potential of the microbiome has led to a number of biotechnology and pharmaceutical companies isolating specific strains from healthy stool for use as targeted therapies for IBD in clinical trials . Ongoing studies are likely to determine the missing link between the efficacy of FMT  and its impact on microbial communities and mucosal inflammation BACKGROUND Previous studies comparing Clostridium difficile infection ( CDI ) due to different ribotypes have been conflicting , and many have only compared small numbers of cases or few ribotypes . AIM To compare patient and episode characteristics for CDI due to different ribotypes . METHODS The ribotyping results from 3333 toxin-producing isolates collected from 110 Belgian hospitals between October 2010 and December 2015 were matched to clinical data from the national CDI surveillance data base . Data for ribotypes with at least 100 occurrences were compared . In addition , the national reference laboratory quantitatively measured the level of toxin production in five r and omly chosen cultured isolates for each of the most common ribotypes . FINDINGS Ribotypes with more than 100 occurrences were R014 , R020 , R002 , R078 , R027 , R005 and R106 ( Brazier classification ) . The median age for all patients was 79 years [ patients with R027 , 83 years ( P<0.001 ) ; patients with R106 , 73 years ( P<0.001 ) ] . In total , 10 % of episodes were recurrences ; values were higher for R027 ( 22 % ) and R106 ( 18 % ) . CDI due to R078 was not significantly more likely to be community associated than healthcare associated ( 28 % vs 24 % ; P=0.1 ) . Complications occurred in 7 % of all episodes , and 12 % for those with R027 and R078 . However , after adjusting for age , onset outside the hospital and recurrence , R027 was no longer associated with complications [ odds ratio ( OR ) 1.3 , 95 % confidence interval ( CI ) 0.7 - 2.4 ] , unlike R078 ( OR 1.7 , 95 % CI 1.0 - 2.6 ; P=0.04 ) . A positive stool toxin test and greater levels of toxin production in the cultured isolates were more likely for R078 and R027 . CONCLUSION Out of the seven most common ribotypes in hospital patients , R078 and R027 were associated with higher rates of complications . Infections with R027 and R106 were more likely to be recurrent . The presence of toxin in stools was most likely with R078 , R027 and R106 , with highest levels of toxin production in vitro for R078 and R027 . R060 produced the lowest levels of toxin in vitro BACKGROUND Most Clostridium difficile infection ( CDI ) surveillance programs neither specify the diagnostic method to be used nor stratify rates accordingly . We assessed the difference in  healthcare-associated CDI ( HA-CDI ) incidence and complication rates obtained by 2 vali date d diagnostic methods . METHODS This was a prospect i ve cohort study of patients for whom a C. difficile test was ordered between 1 August 2010 and 31 July 2011 . All specimens were tested in parallel by a commercial polymerase chain reaction ( PCR ) assay targeting toxin B gene tcdB , and a 3-step algorithm detecting glutamate dehydrogenase and toxins A and B by enzyme immunoassay and cell culture cytotoxicity assay ( EIA/CCA ) .  CDI incidence rate ratios were calculated using univariate Poisson regression . RESULTS A total of 1321 stool sample s were tested during a period totaling 95 750 patient-days . Eighty-five HA-CDI cases were detected by PCR and 56 cases by EIA/CCA ( P = .01 ) . The overall incidence rate was 8.9 per 10 000 patient-days ( 95 % confidence interval [ CI ] , 7.1 - 10.9 ) by PCR and 5.8 per 10 000 patient-days ( 95 % CI , 4.4 - 7.4 ) by EIA/CCA ( P = .01 ) . The incidence rate ratio comparing PCR and EIA/CCA was 1.52 ( 95 % CI , 1.08 - 2.13 ; P = .015 ) . Overall complication rate was 27 % ( 23/85 ) when CDI was diagnosed by PCR and 39 % ( 22/56 ) by EIA/CCA ( P = .16 ) . Cases detected by PCR only were less likely to develop a complication of CDI compared with cases detected by both PCR and EIA/CCA ( 3 % vs 39 % , respectively ; P < .001 ) . CONCLUSIONS Performing PCR instead of EIA/CCA is associated with a > 50 % increase in the CDI incidence rate . St and ardization of diagnostic methods may be indicated to improve interhospital comparison 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 aim ed 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 prospect i ve 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 result ing 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 Abstract Background : In 2003 , hospitals in Quebec , Canada experienced an increase of NAP1/027 Clostridium difficile infections following antibiotic administration ( CDIAA ) . At Pierre-Le Gardeur Hospital ( PLGH ) , the incidence increased from 10 to over 25 cases per 1000 patient admissions . Methods : We report a quasi-experimental , prospect i ve cohort study evaluating the effect on CDIAA of a probiotic added to existing C. difficile infection ( CDI ) st and ard preventative measures ( SPM ) in 31,832 hospitalized patients receiving antibiotics .  Phase I ( 1580 ) measured the impact of SPM alone . In Phase II , 50 to 60 × 109 cfu daily dose of oral Lactobacillus acidophilus CL1285 and L. casei LBC80R probiotic formula ( Bio-K+ ) was administered to all patients receiving antibiotics . Phase III included the same intervention after a move to a new hospital facility . Phases II and III included 4968 patients . During Phase IV , 25,284 patients were su bmi tted to the same regimen but outcome data were compared to those of similar hospitals in Quebec . Results : At the end of Phase III , CDIAA had decreased from more than 18 cases per 1000 patient admissions in Phase I to less than 5 cases . Reductions of CDI cases ( 73 % ) ( p < 0.001 ) and severe CDI cases ( 76.4 % ) ( p < 0.001 ) were observed . CDI recurrence rate was reduced by 39 % ( p < 0.001 ) . During the following 6 years , the CDI rate averaged 2.71 cases per 10,000 patient-days at PLGH compared to 8.50 cases per 10,000 patient-days in equivalent hospitals located in Quebec . Study limitation : This study is not a r and omized clinical trial ; it is an open prospect i ve study and should be treated as such . Also , following Phase II , PLGH moved into a new facility and this could have contributed to lower CDI . Conclusions : Specific probiotic product added to SPM and antibiotic stewardship activities result ed in a further reduction in CDI rates and was shown to be safe Background Clostridium difficile infection ( CDI ) is one of the most dreaded causes of hospital-acquired diarrhea . Main objective was to investigate whether confocal laser endomicroscopy ( CLE ) has the capability for in vivo diagnosis of C. difficile associated histological changes . Second objective was to prove the presence of intramucosal bacteria using CLE . Methods 80 patients were prospect ively included , 10 patients were diagnosed with CDI based on toxigenic culture . To vali date the presence of intramucosal bacteria ex vivo , CLE was performed in pure C. difficile culture ; additionally fluorescence in situ hybridization ( FISH ) was performed . Finally , CLE with fluorescence labelled oligonucleotide probe specific for C. difficile was performed ex vivo in order to prove the presence of bacteria . Results CLE identified CDI-associated histological changes in vivo ( sensitivity and accuracy of 88.9 % and 96.3 % ) . In addition , intramucosal bacteria were visualized . The presence of these bacteria could be proven by CLE with labeled , specific molecular C. difficile probe and FISH-technique . Based on comparison between CLE and FISH analyses , sensitivity and specificity for the presence of intramucosal bacteria were 100 % . Conclusion CLE has the potential for in vivo diagnosis of CDI associated colitis . In addition , CLE allowed the detection of intramucosal bacteria in vivo
Older age , use of antibiotics after diagnosis , use of proton pump inhibitors , and strain type were the most frequent risk factors for recurrence .
Older age , leucocytosis , renal failure and co-morbidities were frequent risk factors for complicated CDI .
When considered alone , mortality was associated with age , co-morbidities , hypo-albuminemia , leucocytosis , acute renal failure , and infection with ribotype 027 .
BACKGROUND Clostridium difficile infection ( CDI ) can lead to complications , recurrence , and death .
Numerous studies have assessed risk factors for these unfavourable outcomes , but systematic review s or meta-analyses published so far were limited in scope or in quality .