title: Clinical and laboratory evaluation of a real-time PCR for Clostridium difficile toxin A and B genes Reducing the risk of severe complications among patients with Clostridium difficile infection. A simulation study of the number of events per variable in logistic regression analysis. Treatment with monoclonal antibodies against Clostridium difficile toxins. Factors associated with prolonged symptoms and severe disease due to Clostridium difficile. Fidaxomicin versus vancomycin for Clostridium difficile infection. A common polymorphism in the interleukin-8 gene promoter is associated with an increased risk for recurrent Clostridium difficile infection. Impact of the type of diagnostic assay on Clostridium difficile infection and complication rates in a mandatory reporting program. Hospital-acquired Clostridium difficile infection: determinants for severe disease Mortality in patients with Clostridium difficile infection correlates with host pro-inflammatory and humoral immune responses. A prospective study of risk factors and historical trends in metronidazole failure for Clostridium difficile infection. Effect of age on treatment outcomes in Clostridium difficile infection. Proton Pump Inhibitor Use and Recurrent Clostridium difficile-associated Disease: A Case-control Analysis Matched by Propensity Score Recurrent Clostridium difficile diarrhea: characteristics of and risk factors for patients enrolled in a prospective, randomized, double-blinded trial. Clostridium difficile infection in the "oldest" old: clinical outcomes in patients aged 80 and older. Lack of association of outcomes with treatment duration and microbiologic susceptibility data in Clostridium difficile infections in a non-NAP1/BI/027 setting Recurrent Clostridium difficile disease: epidemiology and clinical characteristics. Vitamin D status and severity of Clostridium difficile infections: a prospective cohort study in hospitalized adults. Lymphopenia as a novel marker of Clostridium difficile infection recurrence. Mortality of patients with antibiotic-associated diarrhoea: the impact of Clostridium difficile. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea
abstract: Many laboratories use enzyme immunoassays ( EIAs ) for the diagnosis of Clostridium difficile infection ( CDI ) . More recently , polymerase chain reaction (PCR)-based diagnosis has been described as a sensitive test . Real-time PCR for the detection of C. difficile toxin A and B genes was evaluated . A prospect i ve evaluation was performed on stool sample s from 150 hospitalized adult patients and 141 healthy volunteers .  PCR was compared to toxigenic culture ( TC ) , direct cytotoxicity test ( CTT ) , ImmunoCard ® Toxin A and B ( Meridian Bioscience ) , and enzyme-linked immunosorbent assay ( ELISA ) ( Vidas ) . The results were correlated with clinical data using a st and ardized question naire . The diagnostic yield of the PCR was further evaluated after implementation . Using toxigenic culture as the gold st and ard , the sensitivity and specificity of PCR were 100 and 99.2 % , respectively . Patients were categorized as follows : TC/PCR-positive ( n = 17 ) and negative TC ( n = 133 ) . The differences in these groups were more frequent use of antibiotics and leukocytosis ( p < 0.05 ) . The diagnostic yield of PCR  was evaluated during a period of 6 months and showed an increase of positive patients by 50 % . PCR for the detection of toxigenic C. difficile has a high sensitivity and can rule out CDI , but can not differentiate CDI from asymptomatic carriage . Clinicians should be aware of this in order to prevent inappropriate treatment and delay of other diagnostics BACKGROUND The incidence and severity of Clostridium difficile infections are increasing , and there is a need to optimize the prevention of complicated disease . OBJECTIVE To identify modifiable processes of care associated with an altered risk of C difficile complications . METHODS A retrospective cohort study ( with prospect i ve case ascertainment ) of all C difficile infections during 2007⁄2008 at a tertiary care hospital was conducted . RESULTS Severe complications were frequent ( occurring in 97 of 365 [ 27 % ] C difficile episodes ) , with rapid onset ( median three days postdiagnosis ) . On multivariable analysis , nonmodifiable predictors of complications included repeat infection ( OR 2.67 ) , confusion ( OR 2.01 ) , hypotension ( OR 0.97 per increased mmHg ) and elevated white blood cell count ( OR 1.04 per 109 cells⁄L ) . Protection from complications was associated with initial use of vancomycin ( OR 0.24 ) ; harm was associated with ongoing use of exacerbating antibiotics ( OR 3.02 ) . CONCLUSION C difficile infections often occur early in the disease course and are associated with high complication rates . Clinical factors that predicted a higher risk of complications included confusion , hypotension and leukocytosis . The most effective ways to improve outcomes for patients with C difficile colitis are consideration of vancomycin as first-line treatment for moderate to severe cases , and the avoidance of unnecessary antibiotics We performed a Monte Carlo study to evaluate the effect of the number of events per variable ( EPV ) analyzed in logistic regression analysis . The simulations were based on data from a cardiac trial of 673 patients in which 252 deaths occurred and seven variables were cogent predictors of mortality ; the number of events per predictive variable was ( 252/7 =) 36 for the full sample . For the simulations , at values of EPV = 2 , 5 , 10 , 15 , 20 , and 25 , we r and omly generated 500 sample s of the 673 patients , chosen with replacement , according to a logistic model derived from the full sample . Simulation results for the regression coefficients for each variable in each group of 500 sample s were compared for bias , precision , and significance testing against the results of the model fitted to the original sample . For EPV values of 10 or greater , no major problems occurred . For EPV values less than 10 , however , the regression coefficients were biased in both positive and negative directions ; the large sample variance estimates from the logistic model both overestimated and underestimated the sample variance of the regression coefficients ; the 90 % confidence limits about the estimated values did not have proper coverage ; the Wald statistic was conservative under the null hypothesis ; and paradoxical associations ( significance in the wrong direction ) were increased . Although other factors ( such as the total number of events , or sample size ) may influence the validity of the logistic model , our findings indicate that low EPV can lead to major problems BACKGROUND New therapies are needed to manage the increasing incidence , severity , and high rate of recurrence of Clostridium difficile infection . METHODS We performed a r and omized , double-blind , placebo-controlled study of two neutralizing , fully human monoclonal antibodies against C. difficile toxins A ( CDA1 ) and B ( CDB1 ) . The antibodies were administered together as a single infusion , each at a dose of 10 mg per kilogram of body weight , in patients with symptomatic C. difficile infection who were receiving either metronidazole or vancomycin .  The primary outcome was laboratory-documented recurrence of infection during the 84 days after the administration of monoclonal antibodies or placebo . RESULTS Among the 200 patients who were enrolled ( 101 in the antibody group and 99 in the placebo group ) , the rate of recurrence of C. difficile infection was lower among patients treated with monoclonal antibodies ( 7 % vs. 25 % ; 95 % confidence interval , 7 to 29 ; P<0.001 ) . The recurrence rates among patients with the epidemic BI/NAP1/027 strain were 8 % for the antibody group and 32 % for the placebo group ( P=0.06 ) ; among patients with more than one previous episode of C. difficile infection , recurrence rates were 7 % and 38 % , respectively ( P=0.006 ) . The mean duration of the initial hospitalization for in patients did not differ significantly between the antibody and placebo groups ( 9.5 and 9.4 days , respectively ) . At least one serious adverse event was reported by 18 patients in the antibody group and by 28 patients in the placebo group ( P=0.09 ) . CONCLUSIONS The addition of monoclonal antibodies against C. difficile toxins to antibiotic agents significantly reduced the recurrence of C. difficile infection . ( Clinical Trials.gov number , NCT00350298 . OBJECTIVE toxigenic Clostridium difficile is responsible for a spectrum of disease severity ranging from mild diarrhoea to fulminant colitis . This study attempts to determine the proportion of patients in each category of severity and evaluate the risk factors for a more prolonged and complicated course . DESIGN prospect i ve cohort study . SETTING university teaching hospital . SUBJECTS all patients with symptomatic C. difficile infection during 4 months of an outbreak ( January-April 1995 ) ; n=73 ; median age 74 years ( range 17 - 91 ) . MEASUREMENTS incidence of C. difficile-associated disease ( CDAD ) ; severity of disease ; percentage of patients in each category of severity ; risk factors for severe disease/prolonged symptoms ( univariate and multivariable analyses ) . RESULTS the incidence of CDAD was 0.93 % . Of the cases identified , 18 ( 24.7 % ) had mild , self-limiting disease ; 26 ( 35.6 % ) had moderately severe disease ; 23 ( 31.5 % ) had prolonged symptoms and six ( 8.2 % ) had a complicated course . Although CDAD was more common in older patients ( P < 0.001 ) , increasing age was not a risk factor for severity . Significant risk factors for severe CDAD included low Barthel and abbreviated mental test scores ( P < 0.01 , P < 0.001 respectively ) and recent endoscopy ( P=0.03 ) . Logistic regression analysis revealed the following independent predictors of severe CDAD : endoscopy [ odds ratios ( OR ) 4.0 , P=0.03 ] and cognitive impairment ( OR 11.0 , P < 0.01 ) . A trend towards significance was noted for nasogastric tube insertion ( OR 3.1 , P=0.08 ) . Complications of infection included dehydration , malnutrition and faecal incontinence ( which was statistically significantly associated with more severe disease ; P < 0.01 ) . CONCLUSION risk factors for severity of CDAD include functional disability , cognitive impairment , and recent endoscopy . Anticipation of severe CDAD may limit morbidity and mortality BACKGROUND Clostridium difficile infection is a serious diarrheal illness associated with substantial morbidity and mortality . Patients generally have a response to oral vancomycin or metronidazole ; however , the rate of recurrence is high . This phase 3 clinical trial compared the efficacy and safety of fidaxomicin with those of vancomycin in treating C. difficile infection . METHODS Adults with acute symptoms of C. difficile infection and a positive result on a stool toxin test were eligible for study entry . We r and omly assigned patients to receive fidaxomicin ( 200 mg twice daily ) or vancomycin ( 125 mg four times daily ) orally for 10 days . The primary end point was clinical cure ( resolution of symptoms and no need for further therapy for C. difficile infection as of the second day after the end of the course of therapy ) . The secondary end points were recurrence of C. difficile infection ( diarrhea and a positive result on a stool toxin test within 4 weeks after treatment ) and global cure ( i.e. , cure with no recurrence ) . RESULTS A total of 629 patients were enrolled , of whom 548 ( 87.1 % ) could be evaluated for the per- protocol analysis . The rates of clinical cure with fidaxomicin were noninferior to those with vancomycin in both the modified intention-to-treat analysis ( 88.2 % with fidaxomicin and 85.8 % with vancomycin ) and the per- protocol analysis ( 92.1 % and 89.8 % , respectively ) . Significantly fewer patients in the fidaxomicin group than in the vancomycin group had a recurrence of the infection , in both the modified intention-to-treat analysis ( 15.4 % vs. 25.3 % , P=0.005 ) and the per- protocol analysis ( 13.3 % vs. 24.0 % , P=0.004 ) . The lower rate of recurrence was seen in patients with non – North American Pulsed Field type 1 strains . The adverse-event profile was similar for the two therapies . CONCLUSIONS The rates of clinical cure after treatment with fidaxomicin were noninferior to those after treatment with vancomycin . Fidaxomicin was associated with a significantly lower rate of recurrence of C. difficile infection associated with non – North American Pulsed Field type 1 strains . ( Funded by Optimer Pharmaceuticals ; Clinical Trials.gov number , NCT00314951 . 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 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 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 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 BACKGROUND & AIMS Recent studies of Clostridium difficile infection ( CDI ) have indicated a dramatic increase in metronidazole failure . The aims of this study were to compare current and historical rates of metronidazole failure and to identify risk factors for metronidazole failure . METHODS Eighty-nine patients with CDI in 2004 to 2006 were followed for 60 days and were compared with a historical cohort of 63 CDI patients studied prospect ively in 1998 . Metronidazole failure was defined as persistent diarrhea after 10 days of therapy or a change of therapy to vancomycin . Stool sample s were analyzed for the presence of the North American pulsed-field gel electrophoresis type-1 ( NAP-1 ) strain . RESULTS Metronidazole failure rates were 35 % in both cohorts . There was no difference in the median time to resolution of diarrhea ( 8 vs 5 d ; P = .52 ) or the proportion with > 10 days of diarrhea ( 35 % vs 29 % ; P = .51 ) . Risk factors for metronidazole failure included recent cephalosporin use ( odds ratio [ OR ] , 32 ; 95 % confidence interval [ CI ] , 5 - 219 ) , CDI on admission ( OR , 23 ; 95 % CI , 3 - 156 ) , and transfer from another hospital ( OR , 11 ; 95 % CI , 2 - 72 ) . The frequency of NAP-1 infection in patients with and without metronidazole failure was similar ( 26 % vs 21 % ; P = .67 ) . CONCLUSIONS We found no difference in metronidazole failure rates in 1998 and 2004 to 2006 . Patients with recent cephalosporin use , CDI on admission , and transfer from another hospital were more likely to metronidazole failure . Infection with the epidemic NAP-1 strain was not associated with metronidazole failure in endemic CDI 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 Background and Aim : Clostridium difficile has been increasingly diagnosed in hospitalized patients . An association between proton pump inhibitors ( PPIs ) use and Clostridium difficile-associated disease ( CDAD ) and between recurrent CDAD has been suggested . The aim of this study is to investigate whether PPI use is associated with the development of recurrent CDAD . Methods : This was a retrospective case-control study of patients with CDAD at Yeungnam University Medical Center , seen from January 2004 to December 2008 . C. difficile infection was diagnosed by the presence of C. difficile toxin in the stool . Those with recurrent disease were matched with nonrecurrent controls using multivariate matched sampling methods that incorporated the propensity score . Results : Recurrent CDAD developed in 28 ( 14.1 % ) of the 198 patients with diarrhea and positive C. difficile stool toxin assays . Multivariate analysis of the total population of recurrent versus nonrecurrent CDAD revealed that additional use of non-C. difficile antimicrobial therapy  ( concomitant with the treatment or after or both ) , poor response to therapy with metronidazole  or vancomycin , and recent gastrointestinal surgery were risk factors for recurrent CDAD . We were able to match 21 recurrent CDAD subjects with 21 without recurrent CDAD . Among the matched patients only PPI use was associated with recurrent CDAD ( ie , 47.6 % vs. 4.8 % , P=0.004 for recurrent vs. nonrecurrent CDAD , respectively ) . Conclusions : Among the matched patient groups , only PPI therapy was associated with recurrent CDAD . Prospect i ve studies are needed to clarify whether avoidance of PPIs or specific cotherapies will reduce the incidence of recurrent C. difficile-associated diarrhea Recurrent Clostridium difficile diarrhea ( RCDD ) occurs in 20 % of patients after they have received st and ard antibiotic treatment with vancomycin or metronidazole , but the reasons for the recurrences are largely unknown . Patients receiving vancomycin or metronidazole for active C. difficile diarrhea ( CDD ) were referred to our study centers for treatment and a 2-month follow-up as part of a r and omized placebo-controlled trial . Sixty patients had RCDD ( median number of episodes , 3.0 ; range , 2 - 9 episodes ) and 64 were having their first episode of CDD . Patients with RCDD had more-severe abdominal pain and were more likely to have fever but initially responded well to antibiotic therapy . Data on sequential episodes showed no progression in disease severity . Five factors were associated with a higher risk of RCDD : the number of previous CDD episodes , onset of the initial disease in the spring , exposure to additional antibiotics for treatment of other infections , infection with immunoblot type 1 or 2 strains of C. difficile , and female gender . These factors may help to identify patients who are more likely to develop RCDD  and require careful medical supervision 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 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 OBJECTIVE To describe the epidemiology , diagnosis , risk factors , patient impact , and treatment strategies for recurrent Clostridium difficile-associated disease ( CDAD ) . DESIGN Data were collected as part of a blinded , placebo-controlled clinical trial testing a new combination treatment for recurrent CDAD . Retrospective data regarding prior CDAD episodes were collected from interviews and medical-chart review . Prospect i ve data on the current CDAD episode , risk factors , and recurrence rates were collected during a 2-month follow-up . SETTING S National referral study . PARTICIPANTS Patients with recurrent CDAD . INTERVENTIONS Treatment with a 10-day course of low-dose ( 500 mg/d ) or high-dose ( 2 g/d ) vancomycin or metronidazole ( 1 g/d ) . RESULTS Recurrent CDAD was found to have a lengthy course involving multiple episodes of diarrhea , abdominal cramping , nausea , and fever . CDAD may recur over several years despite frequent treatment with antibiotics . Recurrence rates were similar regardless of the choice or dose of antibiotic . Recurrent CDAD is not a trivial disease : patients may have multiple episodes ( as many as 14 ) , may require hospitalization , and the mean lifetime cost of direct medical care was $ 10,970 per patient . Fortunately , the disease does not become progressively more severe as the number of episodes increase . Two risk factors predictive for recurrent CDAD were found : increasing age and a decreased quality -of-life score at enrollment . CONCLUSIONS Recurrent CDAD is a persistent disease that may result in prolonged hospital stays , additional medical costs , and rare serious complications BACKGROUND Clostridium difficile is the most common cause of nosocomial diarrhea , affecting up to 10 % of hospitalized patients . Preliminary studies suggest an association between vitamin D status and C difficile infections ( CDIs ) . Our goal was to investigate whether serum 25-hydroxyvitamin D ( 25(OH)D ) levels are associated with CDI severity . METHODS We prospect ively enrolled patients diagnosed with CDI and divided them into 2 severity groups : group A ( positive toxin A/B enzyme immunoassay only ) and group B ( positive toxin A/B enzyme immunoassay with abdominal computed tomography scan findings consistent with colitis ) .  Serum 25(OH)D levels ( 25(OH)D3 , 25(OH)D2 , and total 25(OH)D ) were measured on all patients after diagnosis of CDI . We performed multivariable logistic regression analyses to investigate the association between 25(OH)D levels and CDI severity , while adjusting for age , Deyo-Charlson Comorbidity Index , recent hospitalization , and vitamin D supplementation . RESULTS One hundred patients were enrolled between July 2011 and February 2013 . The mean ( st and ard deviation ) cohort age and Deyo-Charlson Comorbidity Index were 62 ( 19 ) years and 4 ( 3 ) , respectively ; 54 % of patients were male . Mean serum total 25(OH)D level was 22 ( 10 ) ng/mL. Mean 25(OH)D3 level was significantly higher in group A ( n = 71 ) than in group B ( n = 29 ) : 21 ( 1 ) vs 15 ( 2 ) ng/mL , respectively ( P = .005 ) . There was no observed difference in mean 25(OH)D2 levels and total 25(OH)D levels between the 2 groups . Multivariable logistic regression analysis demonstrated an association between 25(OH)D3 levels and CDI severity ( adjusted odds ratio , 0.92 ; 95 % confidence interval , 0.87 - 0.98 ) . CONCLUSIONS We found a significant inverse association between 25(OH)D3 levels and CDI severity . Further studies are needed to determine whether vitamin D supplementation can improve outcomes in patients with CDI 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 Previous studies have shown conflicting results concerning mortality related to Clostridium difficile infection . The objective of this study was to determine the impact of C. difficile infection on short- and long-term mortality in hospitalised patients with antibiotic-associated diarrhoea . We therefore undertook a prospect i ve case-control study of 217 hospitalised patients who received antibiotics , developed diarrhoea and underwent stool enzyme immunoassay for C. difficile TOX A/B.  The Kaplan-Meier and the log-rank test were used to determine univariate survival analysis and a Cox regression model for multivariate analysis of 28 day and long-term mortality . Fifty-two ( 24 % ) of the 217 patients who met the study criteria were positive for C. difficile TOX A/B. The crude 28 day and long-term mortality rates of the entire cohort were 12.4 % and 56 % , respectively . On Cox regression analysis , hypoalbuminaemia , impaired functional capacity and elevated serum urea levels were found to be the only independent and statistically significant variables associated with long-term mortality . C. difficile toxin positivity per se was not associated with increased short- or long-term mortality rates . In conclusion , hypoalbuminaemia , renal failure , and impaired function capacity predict mortality due to antibiotic-associated diarrhoea , but C. difficile involvement by itself does not further increase the risk of death in these patients BACKGROUND We have reported that symptom-free carriers of Clostridium difficile have a systemic anamnestic immune response to toxin A. The aim of this study was to determine whether an acquired immune response to toxin A , during an episode of C. difficile diarrhoea , influences risk of recurrence . METHODS We prospect ively studied 63 patients with nosocomial C. difficile diarrhoea . Serial serum IgA , IgG , and IgM concentrations against C. difficile toxin A , toxin B , or non-toxin antigens were measured by ELISA . Individuals were followed for 60 days . FINDINGS 19 patients  died ( 30 % ) . Of the 44 who survived , 22 had recurrent C. difficile diarrhoea . Patients with a single episode of C. difficile diarrhoea ( n=22 ) had higher concentrations of serum IgM against toxin A on day 3 of their first episode of diarrhoea than those with recurrent diarrhoea ( n=22 , p=0.004 ) . On day 12 , serum IgG values against toxin A were higher in patients who had a single episode of diarrhoea ( n=7 ) than in those who subsequently had recurrent diarrhoea ( n=9 , p=0.009 ) . The odds ratio for recurrence associated with a low concentration of serum IgG against toxin A , measured 12 days after onset of C. difficile diarrhoea , was 48.0 ( 95 % CI 3.5 - 663 ) . INTERPRETATION A serum antibody response to toxin A , during an initial episode of C. difficile diarrhoea , is associated with protection against recurrence
target: 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: 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 .