Clostridium difficile infection(CDI)is a major global public health concern,accounting for 15%-25%of antibiotic-associated diarrhea,50%-75%of antibiotic-associated colitis,and nearly all cases of pseudomembranous coli...Clostridium difficile infection(CDI)is a major global public health concern,accounting for 15%-25%of antibiotic-associated diarrhea,50%-75%of antibiotic-associated colitis,and nearly all cases of pseudomembranous colitis.Over the past decade,CDI outbreaks have become increasingly prevalent in North America and Europe,with rising incidence and mortality rates.In 2019,the Centers for Disease Control and Prevention(CDC)in the United States classified CDI as a“critical”public health threat in their report on antibiotic resistance threats[1].CDI incidence varies widely across countries,healthcare settings,and age groups,with cumulative incidence rates ranging from 1.12 to 631.80 per 100,000 people annually[2].As the epidemiology of CDI continues to evolve and our understanding of the disease advances,reassessing its burden remains essential.The Global Burden of Disease,Injury,and Risk Factors Study(GBD 2021)database offers new insights into this issue.展开更多
BACKGROUND Clostridium difficile infection(CDI)is common in patients with inflammatory bowel disease(IBD).AIM To assess the association of CDI with clinical outcomes of IBD.METHODS PubMed,EMBASE,Web of Science,and the...BACKGROUND Clostridium difficile infection(CDI)is common in patients with inflammatory bowel disease(IBD).AIM To assess the association of CDI with clinical outcomes of IBD.METHODS PubMed,EMBASE,Web of Science,and the Cochrane Library databases were searched from inception to March 2024.Eligible articles included observational studies that reported on outcomes such as mortality,colectomy,hospitalization,intensive care unit(ICU)admission,complication rates,and length of hospital stay in IBD patients with and without CDI.Data were extracted,and a randomeffects model was used to calculate pooled odds ratios(ORs)and mean differences(MDs).RESULTS As shown in the data from 21 studies with 1249158 participants,CDI significantly increased the risk of mortality in IBD patients[pooled OR=4.569,95%confidence intervals(95%CI):2.584 to 8.079].Although the pooled OR for colectomy was 1.409(95%CI:0.922 to 2.155),it was not statistically significant.Similarly,CDI did not impact hospitalization(pooled OR=1.056,95%CI:0.512 to 2.179)and ICU admission outcomes(pooled OR=1.970,95%CI:0.420 to 9.246)of patients with IBD.The rate of complications was comparable in the two groups(pooled OR=0.658,95%CI:0.378 to 1.147).However,CDI was associated with a significantly more extended hospital stay(pooled MD=0.349 days,95%CI:0.002 to 0.696).CONCLUSION CDI is linked to increased mortality and prolonged hospitalization in IBD patients.These results emphasize the need for early detection and appropriate management.Implementing routine CDI screening during IBD flare-ups and stringent infection control measures could mitigate severe complications and reduce the healthcare burden.展开更多
In recent years,nosocomial infections caused by Clostridium difficile(C.difficile)have risen,becoming a leading cause of hospital-acquired diarrhea.The global prevalence of C.difficile infection(CDI)varies across regi...In recent years,nosocomial infections caused by Clostridium difficile(C.difficile)have risen,becoming a leading cause of hospital-acquired diarrhea.The global prevalence of C.difficile infection(CDI)varies across regions and populations.The diagnosis relies primarily on laboratory testing,including toxin,glutamate dehy-drogenase,and nucleic acid amplification tests.Treatment strategies for CDI in-clude antimicrobial therapy(e.g.,metronidazole,vancomycin,and fidamycin),fecal transplantation,and immunotherapy(e.g.,belotozumab),depending on the patient’s specificity and severity.This paper reviews recent research on CDI’s epidemiological characteristics,risk factors,diagnosis,treatment,and prevention,aiming to support hospitals and public health initiatives in implementing effective detection,prevention,and treatment strategies.展开更多
BACKGROUND Clostridium difficile(C.difficile)infection(CDI)is a rare clinical disease caused by changes in the intestinal microenvironment,which has a variety of causes and a poor prognosis,and for which there is no s...BACKGROUND Clostridium difficile(C.difficile)infection(CDI)is a rare clinical disease caused by changes in the intestinal microenvironment,which has a variety of causes and a poor prognosis,and for which there is no standardized clinical treatment.CASE SUMMARY A patient experienced recurrent difficulty in bowel movements over the past decade.Recently,symptoms worsened within the last ten days,leading to a clinic visit due to constipation.The patient was subsequently referred to our depart-ment.Preoperatively,the patient was diagnosed with obstructed colon accom-panied by gallstones.Empirical antibiotics were administered both before and after surgery to prevent infection.On the fourth day post-surgery,symptoms of CDI emerged.Stool cultures confirmed the presence of C.difficile DNA.Treatment involved a combination of vancomycin and linezolid,resulting in the patient's successful recovery upon discharge.However,the patient failed to adhere to the prescribed medication after discharge and was discovered deceased during a follow-up two months later.CONCLUSION CDI is the leading cause of nosocomial post-operative care,with limited clinical cases and poor patient prognosis,and comprehensive clinical treatment guidelines are still lacking.This infection can be triggered by a variety of factors,including intestinal hypoxia,inappropriate antibiotic use,and bile acid circulation disorders.In patients with chronic bowel disease and related etiologies,prompt preoperative attention to possible CDI and preoperative bowel preparation is critical.Adequate and prolonged medication should be maintained in the treatment of CDI to prevent recurrence of the disease.展开更多
Susceptibility to pathogens in the elderly is heightened with age,largely because of immunosenescence.As an immune regulatory organ,bone marrow creates immune cells that move to other organs and tis-sues through the b...Susceptibility to pathogens in the elderly is heightened with age,largely because of immunosenescence.As an immune regulatory organ,bone marrow creates immune cells that move to other organs and tis-sues through the blood.Despite the significance of this process of this organ,there is limited research on changes in immune cell generation in the bone marrow and their effects on immunosenescence.In this study,the compositions of immune cells in bone marrow from young(three months)and old(24+months)mice were compared by means of mass cytometry,with further validation obtained through the reanalysis of single-cell RNA sequencing data and cell sorting via flow cytometry.The effects of differential immune cells on immunosenescence in old mice were evaluated using the Clostridium difficile(C.difficile)infection model.Our results showed that aged mice presented with a reduction in bone tra-beculae structure,which was accompanied by a notable increase in polymorphonuclear(PMN)-myeloid-derived suppressor cell(MDSC)abundance.Through bulk-seq and reverse transcription quantitative polymerase chain reaction(RT-qPCR)analysis,we identified differential genes associated with the immune response—specifically,the Th17 cell differentiation pathway.Furthermore,the increase in exported PMN-MDSCs to the large intestine resulted in increased gut permeability and inflammatory damage to the colon following C.difficile infection.After clearing the PMN-MDSCs in old mice using the anti-Gr-1 antibody,the symptoms induced by C.difficile were significantly relieved,as evidenced by an inhibited IL-17 pathway in the colon and reduced gut permeability.In conclusion,aging increases the number of PMN-MDSCs in both the generated bone marrow and the outputted intestine,which con-tributes to susceptibility to C.difficile infection.This study provides a novel target for anti-aging therapy for immunosenescence,which is beneficial for improving immune function in elders.展开更多
Clostridium difficile infection(CDI)has been increasing due to the effect of recurrent hospitalizations.The use of antibiotics has been shown to alter the gut microbiome and lead to CDIs.The treatment is limited to th...Clostridium difficile infection(CDI)has been increasing due to the effect of recurrent hospitalizations.The use of antibiotics has been shown to alter the gut microbiome and lead to CDIs.The treatment is limited to three major antibiotics;however,the incidence of recurrent CDIs has been increasing and drug resistance is a major concern.This aspect is a growing concern in modern medicine especially in the elderly population,critical care patients,and immunocompromised individuals who are at high risk of developing CDIs.Clostridium difficile can lead to various complications including septic shock and fulminant colitis that could prove to be lethal in these patients.Newer modalities of treatment have been developed including bezlotoxumab,a monoclonal antibody and fecal microbiota transplant.There have been studies showing asymptomatic carriers and drug resistance posing a major threat to the healthcare system.Newer treatment options are being studied to treat and prevent CDIs.This review will provide an insight into the current treatment modalities,prevention and newer modalities of treatment and challenges faced in the treatment of CDIs.展开更多
Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,leading to fibrosis,cirrhosis and hepatocellular carcinoma and also associated with increased cardiovascular disease mortality.The pathog...Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,leading to fibrosis,cirrhosis and hepatocellular carcinoma and also associated with increased cardiovascular disease mortality.The pathogenesis of NAFLD is not fully understood,although NAFLD is thought to be a hepatic form of metabolic syndrome.There is an increasing understanding of the role of microbiota disturbances in NAFLD pathogenesis,and as with many other conditions affecting the microbiota,NAFLD may be a novel risk factor for Clostridioides difficile(C.difficile)colonization(CDC)and C.difficile infection(CDI).CDI is an emerging nosocomial disease,and community-acquired cases of infection are growing,probably due to an increase in CDC rates.The association of NAFLD with CDI has been shown in only 4 studies to date,three of which included less than 1000 patients,although the frequency of NAFLD in these studies was observed in almost 20%of the total patient cohort.These data revealed that NAFLD is a risk factor for CDI development and,moreover,is a risk factor for intestinal complications of CDI.More studies are needed to investigate this association and move forward CDC and CDI screening efforts for this group of patients.展开更多
To compare the efficacy and safety of fidaxomicin and vancomycin for the treatment of patients with Clostridium difficile infection （CD1）, randomized controlled trials （RCTs） of fidaxomicin versus vancomycin for t...To compare the efficacy and safety of fidaxomicin and vancomycin for the treatment of patients with Clostridium difficile infection （CD1）, randomized controlled trials （RCTs） of fidaxomicin versus vancomycin for the treatment of CDI published in Pubmed, Embase, Web of Science and the Cochrane library were searched. Two reviewers independently extracted the data. The primary outcome was the rates of clinical cure. The secondary endpoints were the rates of CDI recurrence in the 4 weeks period after the end of therapy and rates of global cure, adverse events. Meta-analysis was performed using the Mantle-Haenszel fixed effect method （FEM）. Odds ratios （ORs） with 95% confidence intervals （95% CIs） were reported. The results indicated that two large randomized controlled trials were included in the meta-analysis. Clinical cure with fidaxomicin was similar to with vancomycin both in the modified intention to treat （OR = 1.17, 95% CI 0.82-1.66, P = 0.40） and in the per-protocol population （OR = 1.24, 95% CI 0.80-1.92, P = 0.34）. There were no significant differences in the rates of clinical cure between fidaxomicin and vancomycin in the subgroups analyzed by age, patients＇ status, and previous CDI, infection with B 1 strain, severity baseline, and exposure to concomitant antibiotics. Recurrence of CDI was significantly less common among fidaxomicin-treated patients compared with vancomycin-treated patients both in the modified intention-to-treat population （OR = 0.47, 95% CI 0.34-0.65, P〈0.00001） and in the per-protocol population （OR = 0.45, 95% CI 0.31-0.62, P〈0.0001）. Treatment with fidaxomicin compared with vancomycin was associated with significantly higher rates of global cure both in the modifed intention-to-treat population （OR = 1.75, 95% CI 1.35-2.27, P〈0.0001） and in the per-protocol population （OR = 1.86, 95% CI 1.40-2.47, P〈0.0001）. Our recta-analysis suggests that fidaxomicin is not superior to vancomycin in rates of clinical cure, while fidaxomicin significantly decreases the rates of CDI recurrence and significantly improves the rates of global cure compared with vancomycin. Thus, fidaxomicin is a promising candidate for treatment of the CDI, especially in decreasing the rates of CDI recurrence and improving the rates of global cure.展开更多
Clostridium difficile infections(CDI)are a leading cause of antibiotic-associated and nosocomial diarrhea.Despite effective antibiotic treatments,recurrent infections are common.With the recent emergence of hypervirul...Clostridium difficile infections(CDI)are a leading cause of antibiotic-associated and nosocomial diarrhea.Despite effective antibiotic treatments,recurrent infections are common.With the recent emergence of hypervirulent isolates of C.difficile,CDI is a growing epidemic with higher rates of recurrence,increasing severity and mortality.Fecal microbiota transplantation(FMT)is an alternative treatment for recurrent CDI.A better understanding of intestinal microbiota and its role in CDI has opened the door to this promising therapeutic approach.FMT is thought to resolve dysbiosis by restoring gut microbiota diversity thereby breaking the cycle of recurrent CDI.Since the first reported use of FMT for recurrent CDI in 1958,systematic reviews of case series and case report have shown its effectiveness with high resolution rates compared to standard antibiotic treatment.This article focuses on current guidelines for CDI treatment,the role of intestinal microbiota in CDI recurrence and current evidence about FMT efficacy,adverse effects and acceptability.展开更多
Clostridioides difficile(C.difficile)is the most common pathogen causing health care-associated infections.C.difficile TcdA and TcdB have been shown to activate enteric neurons;however,what population of these cells i...Clostridioides difficile(C.difficile)is the most common pathogen causing health care-associated infections.C.difficile TcdA and TcdB have been shown to activate enteric neurons;however,what population of these cells is more profoundly influenced and the mechanism underlying these effects remain unknown.AIM To characterize a specific population of TcdA-affected myenteric neurons and investigate the role of the P2X7 receptor in TcdA-induced ileal inflammation,cell death,and the changes in the enteric nervous system in mice.METHODS Swiss mice were used to model TcdA-induced ileitis in ileal loops exposed to TcdA(50μg/Loop)for 4 h.To investigate the role of the P2X7 receptor,Brilliant Blue G(50 mg/kg,i.p.),which is a nonspecific P2X7 receptor antagonist,or A438079(0.7μg/mouse,i.p.),which is a competitive P2X7 receptor antagonist,were injected one hour prior to TcdA challenge.Ileal samples were collected to analyze the expression of the P2X7 receptor(by quantitative real-time polymerase chain reaction and immunohistochemistry),the population of myenteric enteric neurons(immunofluorescence),histological damage,intestinal inflammation,cell death(terminal deoxynucleotidyltransferasemediated dUTP-biotin nick end labeling),neuronal loss,and S100B synthesis(immunohistochemistry).RESULTS TcdA upregulated(P<0.05)the expression of the P2X7 receptor gene in the ileal tissues,increasing the level of this receptor in myenteric neurons compared to that in control mice.Comparison with the control mice indicated that TcdA promoted(P<0.05)the loss of myenteric calretinin+(Calr)and choline acetyltransferase+neurons and increased the number of nitrergic+and Calr+neurons expressing the P2X7 receptor.Blockade of the P2X7 receptor decreased TcdAinduced intestinal damage,cytokine release[interleukin(IL)-1β,IL-6,IL-8,and tumor necrosis factor-α],cell death,enteric neuron loss,and S100B synthesis in the mouse ileum.CONCLUSION Our findings demonstrated that TcdA induced the upregulation of the P2X7 receptor,which promoted enteric neuron loss,S100B synthesis,tissue damage,inflammation,and cell death in the mouse ileum.These findings contribute to the future directions in understanding the mechanism involved in intestinal dysfunction reported in patients after C.difficile infection.展开更多
BACKGROUND The Centers for Disease Control and Prevention estimate that Clostridioides difficile(C.difficile)causes half a million infections(CDI)annually and is a major cause of total infectious disease death in the ...BACKGROUND The Centers for Disease Control and Prevention estimate that Clostridioides difficile(C.difficile)causes half a million infections(CDI)annually and is a major cause of total infectious disease death in the United States,causing inflammation of the colon and potentially deadly diarrhea.We recently reported the isolation of ADS024,a Bacillus velezensis(B.velezensis)strain,which demonstrated direct in vitro bactericidal activity against C.difficile,with minimal collateral impact on other members of the gut microbiota.In this study,we hypothesized that in vitro activities of ADS024 will translate in vivo to protect against CDI challenge in mouse models.AIM To investigate the in vivo efficacy of B.velezensis ADS024 in protecting against CDI challenge in mouse models.METHODS To mimic disruption of the gut microbiota,the mice were exposed to vancomycin prior to dosing with ADS024.For the mouse single-dose study,the recovery of ADS024 was assessed via microbiological analysis of intestinal and fecal samples at 4 h,8 h,and 24 h after a single oral dose of 5×108 colony-forming units(CFU)/mouse of freshly grown ADS024.The single-dose study in miniature swine included groups that had been pre-dosed with vancomycin and that had been exposed to a dose range of ADS024,and a group that was not pre-dosed with vancomycin and received a single dose of ADS024.The ADS024 colonies[assessed by quantitative polymerase chain reaction(qPCR)using ADS024-specific primers]were counted on agar plates.For the 28-d miniature swine study,qPCR was used to measure ADS024 levels from fecal samples after oral administration of ADS024 capsules containing 5×109 CFU for 28 consecutive days,followed by MiSeq compositional sequencing and bioinformatic analyses to measure the impact of ADS024 on microbiota.Two studies were performed to determine the efficacy of ADS024 in a mouse model of CDI:Study 1 to determine the effects of fresh ADS024 culture and ADS024 spore preparations on the clinical manifestations of CDI in mice,and Study 2 to compare the efficacy of single daily doses vs dosing 3 times per day with fresh ADS024.C.difficile challenge was performed 24 h after the start of ADS024 exposure.To model the human distal colon,an anerobic fecal fermentation system was used.MiSeq compositional sequencing and bioinformatic analyses were performed to measure microbiota diversity changes following ADS024 treatment.To assess the potential of ADS024 to be a source of antibiotic resistance,its susceptibility to 18 different antibiotics was tested.RESULTS In a mouse model of CDI challenge,single daily doses of ADS024 were as efficacious as multiple daily doses in protecting against subsequent challenge by C.difficile pathogen-induced disease.ADS024 showed no evidence of colonization based on the observation that the ADS024 colonies were not recovered 24 h after single doses in mice or 72 h after single doses in miniature swine.In a 28-d repeat-dose study in miniature swine,ADS024 was not detected in fecal samples using plating and qPCR methods.Phylogenetic analysis performed in the human distal colon model showed that ADS024 had a selective impact on the healthy human colonic microbiota,similarly to the in vivo studies performed in miniature swine.Safety assessments indicated that ADS024 was susceptible to all the antibiotics tested,while in silico testing revealed a low potential for off-target activity or virulence and antibioticresistance mechanisms.CONCLUSION Our findings,demonstrating in vivo efficacy of ADS024 in protecting against CDI challenge in mouse models,support the use of ADS024 in preventing recurrent CDI following standard antibiotic treatment.展开更多
Antibiotic-associated diarrhea(AAD) and Clostridum difficile infections(CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments d...Antibiotic-associated diarrhea(AAD) and Clostridum difficile infections(CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. A systematic review of the literature using databases Pub Med(June 3, 1978-2015) was conducted to compare AAD and CDI in pediatric and adult populations and determine significant differences and similarities that might impact clinical decisions. In general, pediatric AAD and CDI have a more rapid onset of symptoms, a shorter duration of disease and fewer CDI complications(required surgeries and extended hospitalizations) than in adults. Children experience more community-associated CDI and are associated with smaller outbreaks than adult cases of CDI. The ribotype NAP1/027/BI is more common in adults than children. Children and adults share some similar risk factors, but adults have more complex risk factor profiles associated with more co-morbidities, types of disruptive factors and a wider range of exposures to C. difficile in the healthcare environment. The treatment of pediatric and adult AAD is similar(discontinuing or switching the inciting antibiotic), but other treatment strategies for AAD have not been established. Pediatric CDI responds better to metronidazole, while adult CDI responds better to vancomycin. Recurrent CDI is not commonly reported for children. Prevention for both pediatric and adult AAD and CDI relies upon integrated infection control programs, antibiotic stewardship and may include the use of adjunctive probiotics. Clinical presentation of pediatric AAD and CDI are different than adult AAD and CDI symptoms. These differences should be taken into account when rating severity of disease and prescribing antibiotics.展开更多
Clostridium difficile(C.difficile)infection(CDI)is the leading identifiable cause of antibiotic-associated diarrhea.While there is an alarming trend of increasing incidence and severity of CDI in the United States and...Clostridium difficile(C.difficile)infection(CDI)is the leading identifiable cause of antibiotic-associated diarrhea.While there is an alarming trend of increasing incidence and severity of CDI in the United States and Europe,superimposed CDI in patients with inflammatory bowel disease(IBD)has drawn considerable attention in the gastrointestinal community.The majority of IBD patients appear to contract CDI as outpatients.C.difficile affects disease course of IBD in several ways,including triggering disease flares,sustaining activity,and in some cases,acting as an"innocent"bystander.Despite its wide spectrum of presentations,CDI has been reported to be associated with a longer duration of hospitalization and a higher mortality in IBD patients.IBD patients with restorative proctocolectomy or with diverting ileostomy are not immune to CDI of the small bowel or ileal pouch.Whether immunomodulator or corticosteroid therapy for IBD should be continued in patients with superimposed CDI is controversial.It appears that more adverse outcomes was observed among patients treated by a combination of immunomodulators and antibiotics than those treated by antibiotics alone.The use of biologic agents does not appear to increase the risk of acquisition of CDI.For CDI in the setting of underlying IBD,vancomycin appears to be more efficacious than metronidazole.Randomized controlled trials are required to clearly define the appropriate management for CDI in patients with IBD.展开更多
Clostridium difficile(C.difficile)is the leading cause of antibiotic associated colitis and nosocomial diarrhea.Patients with inflammatory bowel disease(IBD)are at increased risk of developing C.difficile infection(CD...Clostridium difficile(C.difficile)is the leading cause of antibiotic associated colitis and nosocomial diarrhea.Patients with inflammatory bowel disease(IBD)are at increased risk of developing C.difficile infection(CDI),have worse outcomes of CDI-including higher rates of colectomy and death,and experience higher rates of recurrence.However,it is still not clear whether C.difficile is a cause of IBD or a consequence of the inflammatory state in the intestinal environment.The burden of CDI has increased dramatically over the past decade,with severe outbreaks described in many countries,which have been attributed to a new and more virulent strain.A parallel rise in the incidence of CDI has been noted in patients with IBD.IBD patients with CDI tend be younger,have less prior antibiotic exposure,and most cases of CDI in these patients represent outpatient acquired infections.The clinical presentation of CDI in these patients can be unique-including diversion colitis,enteritis and pouchitis,and typical findings on colonoscopy are often absent.Due to the high prevalence of CDI in patients hospitalized with an IBD exacerbation,and the prognostic implications of CDI in these patients,it is recommended to test all IBD patients hospitalized with a disease flare for C.difficile.Treatment includes general measures such as supportive care and infection control measures.Antibiotic therapy with either oral metronidazole,vancomycin,or the novel antibiotic-fidaxomicin,should be initiated as soon as possible.Fecal macrobiota transplantation constitutes another optional treatment for severe/recurrent CDI.The aim of this paper is to review recent data on CDI in IBD:role in pathogenesis,diagnostic methods,optional treatments,and outcomes of these patients.展开更多
To address the management of Clostridium difficile (C. difficile) infection (CDI) in the setting of suspected inflammatory bowel disease (IBD)-flare. METHODSA systematic search of the Ovid MEDLINE and EMBASE databases...To address the management of Clostridium difficile (C. difficile) infection (CDI) in the setting of suspected inflammatory bowel disease (IBD)-flare. METHODSA systematic search of the Ovid MEDLINE and EMBASE databases by independent reviewers identified 70 articles including a total of 932141 IBD patients or IBD-related hospitalizations. RESULTSIn those with IBD, CDI is associated with increased morbidity, including subsequent escalation in IBD medical therapy, urgent colectomy and increased hospitalization, as well as excess mortality. Vancomycin-containing regimens are effective first-line therapies for CDI in IBD inpatients. No prospective data exists with regards to the safety or efficacy of initiating or maintaining corticosteroid, immunomodulator, or biologic therapy to treat IBD in the setting of CDI. Corticosteroid use is a risk factor for the development of CDI, while immunomodulators and biologics are not. CONCLUSIONStrong recommendations regarding when to initiate IBD specific therapy in those with CDI are precluded by a lack of evidence. However, based on expert opinion and observational data, initiation or resumption of immunosuppressive therapy after 48-72 h of targeted antibiotic treatment for CDI may be considered.展开更多
AIM To perform a systematic review and meta-analysis on proton pump inhibitors(PPIs) therapy and the risk of Clostridium difficile infection(CDI). METHODS We conducted a systematic search of MEDLINE/Pub Med and seven ...AIM To perform a systematic review and meta-analysis on proton pump inhibitors(PPIs) therapy and the risk of Clostridium difficile infection(CDI). METHODS We conducted a systematic search of MEDLINE/Pub Med and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios(ORs) estimates with 95% confidence intervals(CIs) were calculated using the random effect. Heterogeneity was assessed by I^2 test and Cochran's Q statistic.Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale(NOS). RESULTS Fifty-six studies(40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI(pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control(OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort(OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted(OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted(OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter(OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter(OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years(OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years(OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses(test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies(I^2 = 85.4%, P < 0.001) as well as evidence of publication bias(funnel plot asymmetry test, P = 0.002). CONCLUSION This meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal.展开更多
AIM:To investigate if antibiotics administered within 8 h of endoscopy reduce mortality or increase the incidence of Clostridium difficile infection(CDI).METHODS:A 2-year retrospective analysis of all patients who pre...AIM:To investigate if antibiotics administered within 8 h of endoscopy reduce mortality or increase the incidence of Clostridium difficile infection(CDI).METHODS:A 2-year retrospective analysis of all patients who presented with first variceal hemorrhage was undertaken.The primary outcome measure was 28-d mortality.Secondary outcome measures were 28-d rebleeding rates and 28-d incidence of CDI.All patients were admitted to a tertiary liver unit with a consultantled,24-h endoscopy service.Patients received standard care including terlipressin therapy.Data collection included:primary and secondary outcome measures,timing of first administration of intravenous antibiotics,eti-ology of liver disease,demographics,endoscopy details and complications.A prospective study was undertaken to determine the incidence of CDI in the study population and general medical inpatients admitted for antibiotic therapy of at least 5 d duration.Statistical analysis was undertaken using univariate,non-parametric tests and multivariate logistic regression analysis.RESULTS:There were 70 first presentations of variceal hemorrhage during the study period.Seventy percent of cases were male and 65.7% were due to chronic alcoholic liver disease.In total,64/70(91.4%) patients received antibiotics as prophylaxis during their admission.Specifically,53/70(75.7%) received antibiotics either before endoscopy or within 8 h of endoscopy [peri-endoscopy(8 h) group],whereas 17/70(24.3%) received antibiotics at > 8 h after endoscopy or not at all(non peri-endoscopy group).Overall mortality and rebleeding rates were 13/70(18.6%) and 14/70(20%),respectively.The periendoscopy(8 h) group was significantly less likely to die compared with the non peri-endoscopy group [13.2% vs 35.3%,P = 0.04,odds ratio(OR) = 0.28(0.078-0.997)] and showed a trend towards reduced rebleeding [17.0% vs 29.4%,P = 0.27,OR = 0.49(0.14-1.74)].On univariate analysis,the non peri-endoscopy group [P = 0.02,OR = 3.58(1.00-12.81)],higher model for end-stage liver disease(MELD) score(P = 0.02),presence of hepatorenal syndrome [P < 0.01,OR = 11.25(2.24-56.42)] and suffering a clinical episode of sepsis [P = 0.03,OR = 4.03(1.11-14.58)] were significant predictors of death at 28 d.On multivariate logistic regression analysis,lower MELD score [P = 0.01,OR = 1.16(1.04-1.28)] and periendoscopy(8 h) group [P = 0.01,OR = 0.15(0.03-0.68)] were independent predictors of survival at 28 d.The CDI incidence(5.7%) was comparable to that in the general medical population(5%).CONCLUSION:Antibiotics administered up to 8 h following endoscopy were associated with improved survival at 28 d.CDI incidence was comparable to that in other patient groups.展开更多
Clostridium difficile （C.difficile） infection has become one of the major hospital-associated infections in Western countries in the last two decades.However,there is limited information on the status of C.difficile...Clostridium difficile （C.difficile） infection has become one of the major hospital-associated infections in Western countries in the last two decades.However,there is limited information on the status of C.difficile infection in Chinese healthcare settings.Given the large and increasing elderly population and the well-recognized problem of over-prescribing of broad spectrum antibiotics in China,it is critical to understand the epidemiology and potential risk factors that may contribute to C.difficile infection in China.A literature review of available published studies,including those in Chinese language-based journals,was conducted.A review of the currently available literature suggested the presence of C.difficile infections in China,but also suggested that these infections were not particularly endemic.This finding should lead to better designed and greatly expanded studies to provide a more reliable epidemiologically-based conclusion on the actual status of C.difficile infection in China,including the identification of any associated risk factors.Such information is ultimately valuable to develop appropriate strategies to prevent C.difficile infection and the vast negative impact of such infections in China and other developing countries.展开更多
AIM:To investigate the risk factors for Clostridiumdifficile-associated diarrhea(CDAD)recurrence,and its relationship with proton pump inhibitors(PPIs). METHODS:Retrospective data of 125 consecutive hospitalized patie...AIM:To investigate the risk factors for Clostridiumdifficile-associated diarrhea(CDAD)recurrence,and its relationship with proton pump inhibitors(PPIs). METHODS:Retrospective data of 125 consecutive hospitalized patients diagnosed with CDAD between January 2006 and December 2007 were collected by medical chart review.Collected data included patient characteristics at baseline,underlying medical disease, antibiotic history before receiving a diagnosis of CDAD, duration of hospital stay,severity of CDAD,concurrenttreatment with PPIs,laboratory parameters,response to CDAD therapy,and recurrence of disease within 90 d of successful treatment.Various clinical and laboratory parameters were compared in patients in whom CDAD did or did not recur. RESULTS:Of the 125 patients(mean age,67.6± 13.9 years)that developed CDAD,98(78.4%)did not experience recurrence(non-recurrent group)and 27 (21.6%)experienced one or more recurrences(recurrent group).Prior to the development of CDAD,96% of the 125 patients were prescribed antibiotics,and 56(44.8%)of the patients received PPIs.Age older than 65 years(P=0.021),feeding via nasogastric tube(NGT)(P=0.045),low serum albumin level(P =0.025),and concurrent use of PPIs(P=0.014) were found to be risk factors for CDAD recurrence by univariate analysis.However,sex,length of hospital stay,duration and type of antibiotics used,severity of disease,leukocyte count and C-reactive protein(CRP) were not associated with risk of CDAD recurrence.On multivariate analysis,the important risk factors were advanced age(>65 years,adjusted OR:1.32,95% CI:1.12-3.87,P=0.031),low serum albumin level(< 2.5 g/dL,adjusted OR:1.85,95%CI:1.35-4.91,P= 0.028),and concurrent use of PPIs(adjusted OR:3.48, 95%CI:1.64-7.69,P=0.016). CONCLUSION:Advanced age,serum albumin level< 2.5 g/dL,and concomitant use of PPIs were found to be significant risk factors for CDAD recurrence.展开更多
基金supported by the Beijing Natural Science Foundation(No.L202008)the Chinese Center for Disease Control and Prevention Foundation(No.201833).
文摘Clostridium difficile infection(CDI)is a major global public health concern,accounting for 15%-25%of antibiotic-associated diarrhea,50%-75%of antibiotic-associated colitis,and nearly all cases of pseudomembranous colitis.Over the past decade,CDI outbreaks have become increasingly prevalent in North America and Europe,with rising incidence and mortality rates.In 2019,the Centers for Disease Control and Prevention(CDC)in the United States classified CDI as a“critical”public health threat in their report on antibiotic resistance threats[1].CDI incidence varies widely across countries,healthcare settings,and age groups,with cumulative incidence rates ranging from 1.12 to 631.80 per 100,000 people annually[2].As the epidemiology of CDI continues to evolve and our understanding of the disease advances,reassessing its burden remains essential.The Global Burden of Disease,Injury,and Risk Factors Study(GBD 2021)database offers new insights into this issue.
文摘BACKGROUND Clostridium difficile infection(CDI)is common in patients with inflammatory bowel disease(IBD).AIM To assess the association of CDI with clinical outcomes of IBD.METHODS PubMed,EMBASE,Web of Science,and the Cochrane Library databases were searched from inception to March 2024.Eligible articles included observational studies that reported on outcomes such as mortality,colectomy,hospitalization,intensive care unit(ICU)admission,complication rates,and length of hospital stay in IBD patients with and without CDI.Data were extracted,and a randomeffects model was used to calculate pooled odds ratios(ORs)and mean differences(MDs).RESULTS As shown in the data from 21 studies with 1249158 participants,CDI significantly increased the risk of mortality in IBD patients[pooled OR=4.569,95%confidence intervals(95%CI):2.584 to 8.079].Although the pooled OR for colectomy was 1.409(95%CI:0.922 to 2.155),it was not statistically significant.Similarly,CDI did not impact hospitalization(pooled OR=1.056,95%CI:0.512 to 2.179)and ICU admission outcomes(pooled OR=1.970,95%CI:0.420 to 9.246)of patients with IBD.The rate of complications was comparable in the two groups(pooled OR=0.658,95%CI:0.378 to 1.147).However,CDI was associated with a significantly more extended hospital stay(pooled MD=0.349 days,95%CI:0.002 to 0.696).CONCLUSION CDI is linked to increased mortality and prolonged hospitalization in IBD patients.These results emphasize the need for early detection and appropriate management.Implementing routine CDI screening during IBD flare-ups and stringent infection control measures could mitigate severe complications and reduce the healthcare burden.
文摘In recent years,nosocomial infections caused by Clostridium difficile(C.difficile)have risen,becoming a leading cause of hospital-acquired diarrhea.The global prevalence of C.difficile infection(CDI)varies across regions and populations.The diagnosis relies primarily on laboratory testing,including toxin,glutamate dehy-drogenase,and nucleic acid amplification tests.Treatment strategies for CDI in-clude antimicrobial therapy(e.g.,metronidazole,vancomycin,and fidamycin),fecal transplantation,and immunotherapy(e.g.,belotozumab),depending on the patient’s specificity and severity.This paper reviews recent research on CDI’s epidemiological characteristics,risk factors,diagnosis,treatment,and prevention,aiming to support hospitals and public health initiatives in implementing effective detection,prevention,and treatment strategies.
文摘BACKGROUND Clostridium difficile(C.difficile)infection(CDI)is a rare clinical disease caused by changes in the intestinal microenvironment,which has a variety of causes and a poor prognosis,and for which there is no standardized clinical treatment.CASE SUMMARY A patient experienced recurrent difficulty in bowel movements over the past decade.Recently,symptoms worsened within the last ten days,leading to a clinic visit due to constipation.The patient was subsequently referred to our depart-ment.Preoperatively,the patient was diagnosed with obstructed colon accom-panied by gallstones.Empirical antibiotics were administered both before and after surgery to prevent infection.On the fourth day post-surgery,symptoms of CDI emerged.Stool cultures confirmed the presence of C.difficile DNA.Treatment involved a combination of vancomycin and linezolid,resulting in the patient's successful recovery upon discharge.However,the patient failed to adhere to the prescribed medication after discharge and was discovered deceased during a follow-up two months later.CONCLUSION CDI is the leading cause of nosocomial post-operative care,with limited clinical cases and poor patient prognosis,and comprehensive clinical treatment guidelines are still lacking.This infection can be triggered by a variety of factors,including intestinal hypoxia,inappropriate antibiotic use,and bile acid circulation disorders.In patients with chronic bowel disease and related etiologies,prompt preoperative attention to possible CDI and preoperative bowel preparation is critical.Adequate and prolonged medication should be maintained in the treatment of CDI to prevent recurrence of the disease.
基金supported by the National Key Research and Development Program of China(2022YFF1100504)the 111 project from the Education Ministry of China(B18053)+2 种基金the National Natural Science Foundation of China(32101938 and 32302758)the China Postdoctoral Science Foundation(2022M723422)the Postdoctoral Fellowship Program of CPSF(GZB20230848).
文摘Susceptibility to pathogens in the elderly is heightened with age,largely because of immunosenescence.As an immune regulatory organ,bone marrow creates immune cells that move to other organs and tis-sues through the blood.Despite the significance of this process of this organ,there is limited research on changes in immune cell generation in the bone marrow and their effects on immunosenescence.In this study,the compositions of immune cells in bone marrow from young(three months)and old(24+months)mice were compared by means of mass cytometry,with further validation obtained through the reanalysis of single-cell RNA sequencing data and cell sorting via flow cytometry.The effects of differential immune cells on immunosenescence in old mice were evaluated using the Clostridium difficile(C.difficile)infection model.Our results showed that aged mice presented with a reduction in bone tra-beculae structure,which was accompanied by a notable increase in polymorphonuclear(PMN)-myeloid-derived suppressor cell(MDSC)abundance.Through bulk-seq and reverse transcription quantitative polymerase chain reaction(RT-qPCR)analysis,we identified differential genes associated with the immune response—specifically,the Th17 cell differentiation pathway.Furthermore,the increase in exported PMN-MDSCs to the large intestine resulted in increased gut permeability and inflammatory damage to the colon following C.difficile infection.After clearing the PMN-MDSCs in old mice using the anti-Gr-1 antibody,the symptoms induced by C.difficile were significantly relieved,as evidenced by an inhibited IL-17 pathway in the colon and reduced gut permeability.In conclusion,aging increases the number of PMN-MDSCs in both the generated bone marrow and the outputted intestine,which con-tributes to susceptibility to C.difficile infection.This study provides a novel target for anti-aging therapy for immunosenescence,which is beneficial for improving immune function in elders.
文摘Clostridium difficile infection(CDI)has been increasing due to the effect of recurrent hospitalizations.The use of antibiotics has been shown to alter the gut microbiome and lead to CDIs.The treatment is limited to three major antibiotics;however,the incidence of recurrent CDIs has been increasing and drug resistance is a major concern.This aspect is a growing concern in modern medicine especially in the elderly population,critical care patients,and immunocompromised individuals who are at high risk of developing CDIs.Clostridium difficile can lead to various complications including septic shock and fulminant colitis that could prove to be lethal in these patients.Newer modalities of treatment have been developed including bezlotoxumab,a monoclonal antibody and fecal microbiota transplant.There have been studies showing asymptomatic carriers and drug resistance posing a major threat to the healthcare system.Newer treatment options are being studied to treat and prevent CDIs.This review will provide an insight into the current treatment modalities,prevention and newer modalities of treatment and challenges faced in the treatment of CDIs.
文摘Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,leading to fibrosis,cirrhosis and hepatocellular carcinoma and also associated with increased cardiovascular disease mortality.The pathogenesis of NAFLD is not fully understood,although NAFLD is thought to be a hepatic form of metabolic syndrome.There is an increasing understanding of the role of microbiota disturbances in NAFLD pathogenesis,and as with many other conditions affecting the microbiota,NAFLD may be a novel risk factor for Clostridioides difficile(C.difficile)colonization(CDC)and C.difficile infection(CDI).CDI is an emerging nosocomial disease,and community-acquired cases of infection are growing,probably due to an increase in CDC rates.The association of NAFLD with CDI has been shown in only 4 studies to date,three of which included less than 1000 patients,although the frequency of NAFLD in these studies was observed in almost 20%of the total patient cohort.These data revealed that NAFLD is a risk factor for CDI development and,moreover,is a risk factor for intestinal complications of CDI.More studies are needed to investigate this association and move forward CDC and CDI screening efforts for this group of patients.
文摘To compare the efficacy and safety of fidaxomicin and vancomycin for the treatment of patients with Clostridium difficile infection （CD1）, randomized controlled trials （RCTs） of fidaxomicin versus vancomycin for the treatment of CDI published in Pubmed, Embase, Web of Science and the Cochrane library were searched. Two reviewers independently extracted the data. The primary outcome was the rates of clinical cure. The secondary endpoints were the rates of CDI recurrence in the 4 weeks period after the end of therapy and rates of global cure, adverse events. Meta-analysis was performed using the Mantle-Haenszel fixed effect method （FEM）. Odds ratios （ORs） with 95% confidence intervals （95% CIs） were reported. The results indicated that two large randomized controlled trials were included in the meta-analysis. Clinical cure with fidaxomicin was similar to with vancomycin both in the modified intention to treat （OR = 1.17, 95% CI 0.82-1.66, P = 0.40） and in the per-protocol population （OR = 1.24, 95% CI 0.80-1.92, P = 0.34）. There were no significant differences in the rates of clinical cure between fidaxomicin and vancomycin in the subgroups analyzed by age, patients＇ status, and previous CDI, infection with B 1 strain, severity baseline, and exposure to concomitant antibiotics. Recurrence of CDI was significantly less common among fidaxomicin-treated patients compared with vancomycin-treated patients both in the modified intention-to-treat population （OR = 0.47, 95% CI 0.34-0.65, P〈0.00001） and in the per-protocol population （OR = 0.45, 95% CI 0.31-0.62, P〈0.0001）. Treatment with fidaxomicin compared with vancomycin was associated with significantly higher rates of global cure both in the modifed intention-to-treat population （OR = 1.75, 95% CI 1.35-2.27, P〈0.0001） and in the per-protocol population （OR = 1.86, 95% CI 1.40-2.47, P〈0.0001）. Our recta-analysis suggests that fidaxomicin is not superior to vancomycin in rates of clinical cure, while fidaxomicin significantly decreases the rates of CDI recurrence and significantly improves the rates of global cure compared with vancomycin. Thus, fidaxomicin is a promising candidate for treatment of the CDI, especially in decreasing the rates of CDI recurrence and improving the rates of global cure.
文摘Clostridium difficile infections(CDI)are a leading cause of antibiotic-associated and nosocomial diarrhea.Despite effective antibiotic treatments,recurrent infections are common.With the recent emergence of hypervirulent isolates of C.difficile,CDI is a growing epidemic with higher rates of recurrence,increasing severity and mortality.Fecal microbiota transplantation(FMT)is an alternative treatment for recurrent CDI.A better understanding of intestinal microbiota and its role in CDI has opened the door to this promising therapeutic approach.FMT is thought to resolve dysbiosis by restoring gut microbiota diversity thereby breaking the cycle of recurrent CDI.Since the first reported use of FMT for recurrent CDI in 1958,systematic reviews of case series and case report have shown its effectiveness with high resolution rates compared to standard antibiotic treatment.This article focuses on current guidelines for CDI treatment,the role of intestinal microbiota in CDI recurrence and current evidence about FMT efficacy,adverse effects and acceptability.
基金Supported by PRONEX CNPq/FUNCAP,No.PR2-0101-00060.01.00/15Sao Paulo Research Foundation(FAPESP),No.2014/25927-2 and No.2018/07862-1.
文摘Clostridioides difficile(C.difficile)is the most common pathogen causing health care-associated infections.C.difficile TcdA and TcdB have been shown to activate enteric neurons;however,what population of these cells is more profoundly influenced and the mechanism underlying these effects remain unknown.AIM To characterize a specific population of TcdA-affected myenteric neurons and investigate the role of the P2X7 receptor in TcdA-induced ileal inflammation,cell death,and the changes in the enteric nervous system in mice.METHODS Swiss mice were used to model TcdA-induced ileitis in ileal loops exposed to TcdA(50μg/Loop)for 4 h.To investigate the role of the P2X7 receptor,Brilliant Blue G(50 mg/kg,i.p.),which is a nonspecific P2X7 receptor antagonist,or A438079(0.7μg/mouse,i.p.),which is a competitive P2X7 receptor antagonist,were injected one hour prior to TcdA challenge.Ileal samples were collected to analyze the expression of the P2X7 receptor(by quantitative real-time polymerase chain reaction and immunohistochemistry),the population of myenteric enteric neurons(immunofluorescence),histological damage,intestinal inflammation,cell death(terminal deoxynucleotidyltransferasemediated dUTP-biotin nick end labeling),neuronal loss,and S100B synthesis(immunohistochemistry).RESULTS TcdA upregulated(P<0.05)the expression of the P2X7 receptor gene in the ileal tissues,increasing the level of this receptor in myenteric neurons compared to that in control mice.Comparison with the control mice indicated that TcdA promoted(P<0.05)the loss of myenteric calretinin+(Calr)and choline acetyltransferase+neurons and increased the number of nitrergic+and Calr+neurons expressing the P2X7 receptor.Blockade of the P2X7 receptor decreased TcdAinduced intestinal damage,cytokine release[interleukin(IL)-1β,IL-6,IL-8,and tumor necrosis factor-α],cell death,enteric neuron loss,and S100B synthesis in the mouse ileum.CONCLUSION Our findings demonstrated that TcdA induced the upregulation of the P2X7 receptor,which promoted enteric neuron loss,S100B synthesis,tissue damage,inflammation,and cell death in the mouse ileum.These findings contribute to the future directions in understanding the mechanism involved in intestinal dysfunction reported in patients after C.difficile infection.
文摘BACKGROUND The Centers for Disease Control and Prevention estimate that Clostridioides difficile(C.difficile)causes half a million infections(CDI)annually and is a major cause of total infectious disease death in the United States,causing inflammation of the colon and potentially deadly diarrhea.We recently reported the isolation of ADS024,a Bacillus velezensis(B.velezensis)strain,which demonstrated direct in vitro bactericidal activity against C.difficile,with minimal collateral impact on other members of the gut microbiota.In this study,we hypothesized that in vitro activities of ADS024 will translate in vivo to protect against CDI challenge in mouse models.AIM To investigate the in vivo efficacy of B.velezensis ADS024 in protecting against CDI challenge in mouse models.METHODS To mimic disruption of the gut microbiota,the mice were exposed to vancomycin prior to dosing with ADS024.For the mouse single-dose study,the recovery of ADS024 was assessed via microbiological analysis of intestinal and fecal samples at 4 h,8 h,and 24 h after a single oral dose of 5×108 colony-forming units(CFU)/mouse of freshly grown ADS024.The single-dose study in miniature swine included groups that had been pre-dosed with vancomycin and that had been exposed to a dose range of ADS024,and a group that was not pre-dosed with vancomycin and received a single dose of ADS024.The ADS024 colonies[assessed by quantitative polymerase chain reaction(qPCR)using ADS024-specific primers]were counted on agar plates.For the 28-d miniature swine study,qPCR was used to measure ADS024 levels from fecal samples after oral administration of ADS024 capsules containing 5×109 CFU for 28 consecutive days,followed by MiSeq compositional sequencing and bioinformatic analyses to measure the impact of ADS024 on microbiota.Two studies were performed to determine the efficacy of ADS024 in a mouse model of CDI:Study 1 to determine the effects of fresh ADS024 culture and ADS024 spore preparations on the clinical manifestations of CDI in mice,and Study 2 to compare the efficacy of single daily doses vs dosing 3 times per day with fresh ADS024.C.difficile challenge was performed 24 h after the start of ADS024 exposure.To model the human distal colon,an anerobic fecal fermentation system was used.MiSeq compositional sequencing and bioinformatic analyses were performed to measure microbiota diversity changes following ADS024 treatment.To assess the potential of ADS024 to be a source of antibiotic resistance,its susceptibility to 18 different antibiotics was tested.RESULTS In a mouse model of CDI challenge,single daily doses of ADS024 were as efficacious as multiple daily doses in protecting against subsequent challenge by C.difficile pathogen-induced disease.ADS024 showed no evidence of colonization based on the observation that the ADS024 colonies were not recovered 24 h after single doses in mice or 72 h after single doses in miniature swine.In a 28-d repeat-dose study in miniature swine,ADS024 was not detected in fecal samples using plating and qPCR methods.Phylogenetic analysis performed in the human distal colon model showed that ADS024 had a selective impact on the healthy human colonic microbiota,similarly to the in vivo studies performed in miniature swine.Safety assessments indicated that ADS024 was susceptible to all the antibiotics tested,while in silico testing revealed a low potential for off-target activity or virulence and antibioticresistance mechanisms.CONCLUSION Our findings,demonstrating in vivo efficacy of ADS024 in protecting against CDI challenge in mouse models,support the use of ADS024 in preventing recurrent CDI following standard antibiotic treatment.
文摘Antibiotic-associated diarrhea(AAD) and Clostridum difficile infections(CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. A systematic review of the literature using databases Pub Med(June 3, 1978-2015) was conducted to compare AAD and CDI in pediatric and adult populations and determine significant differences and similarities that might impact clinical decisions. In general, pediatric AAD and CDI have a more rapid onset of symptoms, a shorter duration of disease and fewer CDI complications(required surgeries and extended hospitalizations) than in adults. Children experience more community-associated CDI and are associated with smaller outbreaks than adult cases of CDI. The ribotype NAP1/027/BI is more common in adults than children. Children and adults share some similar risk factors, but adults have more complex risk factor profiles associated with more co-morbidities, types of disruptive factors and a wider range of exposures to C. difficile in the healthcare environment. The treatment of pediatric and adult AAD is similar(discontinuing or switching the inciting antibiotic), but other treatment strategies for AAD have not been established. Pediatric CDI responds better to metronidazole, while adult CDI responds better to vancomycin. Recurrent CDI is not commonly reported for children. Prevention for both pediatric and adult AAD and CDI relies upon integrated infection control programs, antibiotic stewardship and may include the use of adjunctive probiotics. Clinical presentation of pediatric AAD and CDI are different than adult AAD and CDI symptoms. These differences should be taken into account when rating severity of disease and prescribing antibiotics.
文摘Clostridium difficile(C.difficile)infection(CDI)is the leading identifiable cause of antibiotic-associated diarrhea.While there is an alarming trend of increasing incidence and severity of CDI in the United States and Europe,superimposed CDI in patients with inflammatory bowel disease(IBD)has drawn considerable attention in the gastrointestinal community.The majority of IBD patients appear to contract CDI as outpatients.C.difficile affects disease course of IBD in several ways,including triggering disease flares,sustaining activity,and in some cases,acting as an"innocent"bystander.Despite its wide spectrum of presentations,CDI has been reported to be associated with a longer duration of hospitalization and a higher mortality in IBD patients.IBD patients with restorative proctocolectomy or with diverting ileostomy are not immune to CDI of the small bowel or ileal pouch.Whether immunomodulator or corticosteroid therapy for IBD should be continued in patients with superimposed CDI is controversial.It appears that more adverse outcomes was observed among patients treated by a combination of immunomodulators and antibiotics than those treated by antibiotics alone.The use of biologic agents does not appear to increase the risk of acquisition of CDI.For CDI in the setting of underlying IBD,vancomycin appears to be more efficacious than metronidazole.Randomized controlled trials are required to clearly define the appropriate management for CDI in patients with IBD.
文摘Clostridium difficile(C.difficile)is the leading cause of antibiotic associated colitis and nosocomial diarrhea.Patients with inflammatory bowel disease(IBD)are at increased risk of developing C.difficile infection(CDI),have worse outcomes of CDI-including higher rates of colectomy and death,and experience higher rates of recurrence.However,it is still not clear whether C.difficile is a cause of IBD or a consequence of the inflammatory state in the intestinal environment.The burden of CDI has increased dramatically over the past decade,with severe outbreaks described in many countries,which have been attributed to a new and more virulent strain.A parallel rise in the incidence of CDI has been noted in patients with IBD.IBD patients with CDI tend be younger,have less prior antibiotic exposure,and most cases of CDI in these patients represent outpatient acquired infections.The clinical presentation of CDI in these patients can be unique-including diversion colitis,enteritis and pouchitis,and typical findings on colonoscopy are often absent.Due to the high prevalence of CDI in patients hospitalized with an IBD exacerbation,and the prognostic implications of CDI in these patients,it is recommended to test all IBD patients hospitalized with a disease flare for C.difficile.Treatment includes general measures such as supportive care and infection control measures.Antibiotic therapy with either oral metronidazole,vancomycin,or the novel antibiotic-fidaxomicin,should be initiated as soon as possible.Fecal macrobiota transplantation constitutes another optional treatment for severe/recurrent CDI.The aim of this paper is to review recent data on CDI in IBD:role in pathogenesis,diagnostic methods,optional treatments,and outcomes of these patients.
文摘To address the management of Clostridium difficile (C. difficile) infection (CDI) in the setting of suspected inflammatory bowel disease (IBD)-flare. METHODSA systematic search of the Ovid MEDLINE and EMBASE databases by independent reviewers identified 70 articles including a total of 932141 IBD patients or IBD-related hospitalizations. RESULTSIn those with IBD, CDI is associated with increased morbidity, including subsequent escalation in IBD medical therapy, urgent colectomy and increased hospitalization, as well as excess mortality. Vancomycin-containing regimens are effective first-line therapies for CDI in IBD inpatients. No prospective data exists with regards to the safety or efficacy of initiating or maintaining corticosteroid, immunomodulator, or biologic therapy to treat IBD in the setting of CDI. Corticosteroid use is a risk factor for the development of CDI, while immunomodulators and biologics are not. CONCLUSIONStrong recommendations regarding when to initiate IBD specific therapy in those with CDI are precluded by a lack of evidence. However, based on expert opinion and observational data, initiation or resumption of immunosuppressive therapy after 48-72 h of targeted antibiotic treatment for CDI may be considered.
文摘AIM To perform a systematic review and meta-analysis on proton pump inhibitors(PPIs) therapy and the risk of Clostridium difficile infection(CDI). METHODS We conducted a systematic search of MEDLINE/Pub Med and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios(ORs) estimates with 95% confidence intervals(CIs) were calculated using the random effect. Heterogeneity was assessed by I^2 test and Cochran's Q statistic.Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale(NOS). RESULTS Fifty-six studies(40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI(pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control(OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort(OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted(OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted(OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter(OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter(OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years(OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years(OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses(test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies(I^2 = 85.4%, P < 0.001) as well as evidence of publication bias(funnel plot asymmetry test, P = 0.002). CONCLUSION This meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal.
文摘AIM:To investigate if antibiotics administered within 8 h of endoscopy reduce mortality or increase the incidence of Clostridium difficile infection(CDI).METHODS:A 2-year retrospective analysis of all patients who presented with first variceal hemorrhage was undertaken.The primary outcome measure was 28-d mortality.Secondary outcome measures were 28-d rebleeding rates and 28-d incidence of CDI.All patients were admitted to a tertiary liver unit with a consultantled,24-h endoscopy service.Patients received standard care including terlipressin therapy.Data collection included:primary and secondary outcome measures,timing of first administration of intravenous antibiotics,eti-ology of liver disease,demographics,endoscopy details and complications.A prospective study was undertaken to determine the incidence of CDI in the study population and general medical inpatients admitted for antibiotic therapy of at least 5 d duration.Statistical analysis was undertaken using univariate,non-parametric tests and multivariate logistic regression analysis.RESULTS:There were 70 first presentations of variceal hemorrhage during the study period.Seventy percent of cases were male and 65.7% were due to chronic alcoholic liver disease.In total,64/70(91.4%) patients received antibiotics as prophylaxis during their admission.Specifically,53/70(75.7%) received antibiotics either before endoscopy or within 8 h of endoscopy [peri-endoscopy(8 h) group],whereas 17/70(24.3%) received antibiotics at > 8 h after endoscopy or not at all(non peri-endoscopy group).Overall mortality and rebleeding rates were 13/70(18.6%) and 14/70(20%),respectively.The periendoscopy(8 h) group was significantly less likely to die compared with the non peri-endoscopy group [13.2% vs 35.3%,P = 0.04,odds ratio(OR) = 0.28(0.078-0.997)] and showed a trend towards reduced rebleeding [17.0% vs 29.4%,P = 0.27,OR = 0.49(0.14-1.74)].On univariate analysis,the non peri-endoscopy group [P = 0.02,OR = 3.58(1.00-12.81)],higher model for end-stage liver disease(MELD) score(P = 0.02),presence of hepatorenal syndrome [P < 0.01,OR = 11.25(2.24-56.42)] and suffering a clinical episode of sepsis [P = 0.03,OR = 4.03(1.11-14.58)] were significant predictors of death at 28 d.On multivariate logistic regression analysis,lower MELD score [P = 0.01,OR = 1.16(1.04-1.28)] and periendoscopy(8 h) group [P = 0.01,OR = 0.15(0.03-0.68)] were independent predictors of survival at 28 d.The CDI incidence(5.7%) was comparable to that in the general medical population(5%).CONCLUSION:Antibiotics administered up to 8 h following endoscopy were associated with improved survival at 28 d.CDI incidence was comparable to that in other patient groups.
基金supported by Jiangsu Province’s Key Laboratory inInfectious Diseases
文摘Clostridium difficile （C.difficile） infection has become one of the major hospital-associated infections in Western countries in the last two decades.However,there is limited information on the status of C.difficile infection in Chinese healthcare settings.Given the large and increasing elderly population and the well-recognized problem of over-prescribing of broad spectrum antibiotics in China,it is critical to understand the epidemiology and potential risk factors that may contribute to C.difficile infection in China.A literature review of available published studies,including those in Chinese language-based journals,was conducted.A review of the currently available literature suggested the presence of C.difficile infections in China,but also suggested that these infections were not particularly endemic.This finding should lead to better designed and greatly expanded studies to provide a more reliable epidemiologically-based conclusion on the actual status of C.difficile infection in China,including the identification of any associated risk factors.Such information is ultimately valuable to develop appropriate strategies to prevent C.difficile infection and the vast negative impact of such infections in China and other developing countries.
基金Supported by A Seoul National University Boramae Hospital Grant(03-2007-1)
文摘AIM:To investigate the risk factors for Clostridiumdifficile-associated diarrhea(CDAD)recurrence,and its relationship with proton pump inhibitors(PPIs). METHODS:Retrospective data of 125 consecutive hospitalized patients diagnosed with CDAD between January 2006 and December 2007 were collected by medical chart review.Collected data included patient characteristics at baseline,underlying medical disease, antibiotic history before receiving a diagnosis of CDAD, duration of hospital stay,severity of CDAD,concurrenttreatment with PPIs,laboratory parameters,response to CDAD therapy,and recurrence of disease within 90 d of successful treatment.Various clinical and laboratory parameters were compared in patients in whom CDAD did or did not recur. RESULTS:Of the 125 patients(mean age,67.6± 13.9 years)that developed CDAD,98(78.4%)did not experience recurrence(non-recurrent group)and 27 (21.6%)experienced one or more recurrences(recurrent group).Prior to the development of CDAD,96% of the 125 patients were prescribed antibiotics,and 56(44.8%)of the patients received PPIs.Age older than 65 years(P=0.021),feeding via nasogastric tube(NGT)(P=0.045),low serum albumin level(P =0.025),and concurrent use of PPIs(P=0.014) were found to be risk factors for CDAD recurrence by univariate analysis.However,sex,length of hospital stay,duration and type of antibiotics used,severity of disease,leukocyte count and C-reactive protein(CRP) were not associated with risk of CDAD recurrence.On multivariate analysis,the important risk factors were advanced age(>65 years,adjusted OR:1.32,95% CI:1.12-3.87,P=0.031),low serum albumin level(< 2.5 g/dL,adjusted OR:1.85,95%CI:1.35-4.91,P= 0.028),and concurrent use of PPIs(adjusted OR:3.48, 95%CI:1.64-7.69,P=0.016). CONCLUSION:Advanced age,serum albumin level< 2.5 g/dL,and concomitant use of PPIs were found to be significant risk factors for CDAD recurrence.
