Clostridium difficile infection after stoma reversal surgery: a systematic review and meta-analysis of the literature.

BACKGROUND: Clostridium difficile infection (CDI) has been described in the early post-operative phase after stoma reversal. This systematic review aimed to describe the incidence of CDI after stoma reversal and to identify pre-operative variables correlated with an increased risk of infection. METHODS: A systematic review of the literature was conducted according to the PRISMA guidelines in March 2024. Manuscripts were included if reported at least one patient with CDI-associated diarrhoea following stoma reversal (colostomy/ileostomy). The primary outcome of interest was the incidence of CDI; the secondary outcome was the comparison of clinical variables (age, sex, time to stoma reversal, neo-adjuvant and adjuvant therapies after index colorectal procedure) in CDI-positive versus CDI-negative patients. A meta-analysis was performed when at least three studies reported on those variables. RESULTS: Out of 43 eligible manuscripts, 1 randomized controlled trial and 10 retrospective studies were selected, including 17,857 patients (2.1% CDI). Overall, the mean age was 64.3 ± 11.6 years in the CDI group and 61.5 ± 12.6 years in the CDI-negative group (p = 0.51), with no significant difference in sex (p = 0.34). Univariable analyses documented that the mean time to stoma reversal was 53.9 ± 19.1 weeks in CDI patients and 39.8 ± 15.0 weeks in CDI-negative patients (p = 0.40) and a correlation between neo-adjuvant and adjuvant treatments with CDI (p < 0.001). A meta-analysis was performed for time to stoma reversal, age, sex, and neo-adjuvant therapies disclosing no significant differences for CDI (stoma delay, MD 11.59; 95%CI  24.32-1.13; age, MD 0.97; 95%CI 2.08-4.03; sex, OR1.11; 95%CI 0.88-1.41; neo-adjuvant, OR0.81; 95%CI 0.49-1.35). Meta-analysis including patients who underwent adjuvant therapy evidenced a higher risk of CDI (OR 2.88; 95%CI 1.01-8.17, p = 0.11). CONCLUSION: CDI occurs in approximately 2.1% of patients after stoma reversal. Although a trend of increased delay in stoma reversal and a correlation with chemotherapy were documented in CDI patients, the use of adjuvant therapy was the only possible risk factor documented on meta-analysis. PROSPERO REGISTRATION NUMBER: CRD42023484704.

Vonoprazan poses no additional risk of developing Clostridioides difficile infection compared to proton pump inhibitors.

BACKGROUND AND AIM: The use of proton pump inhibitors (PPIs) has been repeatedly reported as a trigger of Clostridioides difficile infection (CDI), a leading cause of nosocomial diarrhea. However, only a few studies have reported on the association between vonoprazan, a novel potassium-competitive acid blocker providing potent acid suppression, and CDI, with no studies having been conducted in a clinical setting. We therefore evaluated the association between various classes of acid suppressants and CDI with special attention paid to differences in the magnitudes of association between PPIs and vonoprazan. METHODS: A retrospective hospital-based cohort from a secondary-care hospital in Japan (n = 25 821) was collected, wherein eligible CDI cases were defined as hospital-onset cases (n = 91). A multivariable adjusted logistic regression analysis for the entire cohort and propensity analyses for subgroups consisting of PPI and/or vonoprazan users at various doses (n = 10 306) were performed. RESULTS: The overall CDI incidence rate was 1.42/10 000 patient-days, which was comparable with previous reports. A multivariable analysis showed that both PPIs and vonoprazan were positively associated with CDI (odds ratios [95% confidence intervals]: 3.15 [1.67-5.96] and 2.63 [1.01-6.88], respectively). In addition, matched subgroup analyses showed that PPIs and vonoprazan had equivalent magnitudes of association with CDI. CONCLUSIONS: We found that both PPIs and vonoprazan were associated with CDI, and the magnitude of the association was comparable. Because vonoprazan is widely available in Asian countries, further studies on the association of its usage with CDI are warranted.

Delivery of a therapeutic antibody to the lower gastrointestinal tract for the treatment of Clostridium difficile infection (CDI).

The colonic delivery system of toxin neutralizing antibody is a promising method for treating Clostridium difficile infection (CDI) and has some advantages over the parental administration of a neutralizing antibody. However, colonic delivery of biologics presents several challenges, including instability of biologics during encapsulation into the delivery system and harsh conditions in the upper GI tract. In this work, we described a multi-particulate delivery system encapsulating a tetra-valent antibody ABAB-IgG1 with the potential to treat CDI. This work first approved that the cecum injection of ABAB-IgG1 into the lower GI tract of mice could relieve the symptoms, enhance the clinical score, and improve the survival rate of mice during CDI. Then, the antibody was spray layered onto mannitol beads and then enteric coated with pH-sensitive polymers to achieve colon-targeting release. The in vitro release of antibody from the multi-particulate system and the pH-sensitive release of antibody was monitored. The in vivo efficacy of this system was further examined and confirmed in mice and hamsters. In summary, the findings of this study should provide practical information and potential treatment options for CDI through colonic delivery of antibody therapeutics to the lower GI tract using a multi-particulate delivery system.

Clostridium difficile Infections in an Emergency Surgical Unit from North-East Romania.

Background and Objectives: Colitis with Clostridium difficile is an important health problem that occurs with an intensity that varies between mild and severe. Surgical interventions are required only in fulminant forms. There is little evidence regarding the best surgical intervention in these cases. Materials and Methods: Patients with C. difficile infection were identified from the two surgery clinics from the 'Saint Spiridon' Emergency Hospital Iași, Romania. Data regarding the presentation, indication for surgery, antibiotic therapy, type of toxins, and post-operative outcomes were collected over a 3-year period. Results: From a total of 12,432 patients admitted for emergency or elective surgery, 140 (1.12%) were diagnosed with C. difficile infection. The mortality rate was 14% (20 cases). Non-survivors had higher rates of lower-limb amputations, bowel resections, hepatectomy, and splenectomy. Additional surgery was necessary in 2.8% of cases because of the complications of C. difficile colitis. In three cases, terminal colostomy was performed and as well as one case with subtotal colectomy with ileostomy. All patients who required the second surgery died within the 30-day mortality period. Conclusions: In our prospective study, the incidence was increased both in cases of patients with interventions on the colon and in those requiring limb amputations. Surgical interventions are rarely required in patients with C. difficile colitis.

Vedolizumab does not increase risk of clostridium difficile infection in patients with inflammatory bowel disease using vedolizumab: A retrospective cohort study.

Introduction: Several studies have shown increased incidence, recurrence, and severity of Clostridium difficile infection (CDI) over the last decade. Patients with inflammatory bowel disease (IBD) who develop CDI are more prone to morbidity and mortality than CDI in patients without IBD. This study seeks to evaluate whether IBD patients who use vedolizumab are at increased risk of CDI compared to IBD patients using other therapies. Methods: This was a retrospective cohort study, and 684 patients with confirmed IBD (228 on vedolizumab, 228 on anti-TNF, and 228 on 5- Aminosalicylates acid therapy) were enrolled from January 2009 to August 2019 at a tertiary referral IBD center at McMaster University Medical Centre (MUMC) in Hamilton, Ontario, Canada. The primary outcome was time to the development of CDI in IBD patients using different therapies. Secondary outcomes included rates of CDI and the association between baseline variables and risk of CDI. A Cox proportional hazards (PH) model was used to evaluate baseline factors and development of CDI. Result: There was no difference in time to CDI between the three treatment groups (log rank p-value 0.37). CDI occurred in 16 patients (2.3%), specifically four patients (1.75%) in the vedolizumab group, four patients (1.75%) in the anti-TNF group, and eight patients (3.5%) in the 5-ASA group. The Cox PH model found current smoking, older age, and concomitant immunomodulator use as risk factors for CDI, after adjustment for other covariates. Vedolizumab was not associated with increased risk of CDI in the model. Conclusion: Biologic therapy with vedolizumab or anti-TNF did not impact risk of CDI. Risk factors for CDI in IBD patients included smoking, older age at the onset of medication, and immunomodulator therapy. Clinicians should have high degree of suspicion for CDI in IBD patients presenting with diarrhea, particularly in those with risk factors identified in this study.

A Single-Center, Retrospective Cohort Study Evaluating the Use of Probiotics for the Prevention of Hospital-Onset Clostridioides difficile Infection in Hospitalized Patients Receiving Intravenous Antibiotics.

Background: Exposure to antimicrobials is a known risk factor for Clostridioides difficile infection (CDI). Antimicrobials cause collateral damage by disrupting the natural intestinal microbiota allowing for C. difficile to thrive and production of C. difficile toxins. Probiotics could modulate the onset and course of CDI. However, the data on probiotics for the prevention of CDI is conflicting. Objective: To evaluate the rates of hospital-onset Clostridioides difficile infection (HO-CDI) among patients who received intravenous (IV) antibiotics plus probiotics versus IV antibiotics alone. Design: Retrospective, single-center cohort study. Methods: We included adult patients that received at least 1 dose of IV antibiotics and had a hospital length of stay of at least 3 days between August 2017 and July 2020. Patients were separated into 2 cohorts, either receipt of probiotics or non-receipt of probiotics. Patients with positive C. difficile toxin test prior to antibiotic therapy, or receipt of only C. difficile active treatment were excluded. The primary outcome was incidence of HO-CDI in patients who received IV antibiotics plus probiotics compared to those that received IV antibiotics alone. Logistic regression was performed to account for confounding variables. Results: We identified 17 598 patients that received IV antibiotics alone and 2659 patients received IV antibiotics plus probiotics. HO-CDI occurred in 46 (0.26%) of those that received antibiotics alone compared to 5 (0.19%) of those that received probiotics with IV antibiotics (OR 0.72, 95% CI 0.28-1.81). ICU admission (OR 1.81, 95% CI 1.02-3.19) and history of CDI (OR 3.37, 95% CI 1.07-10.97) in the past 12 months were associated with a higher incidence of HO-CDI. Conclusion: The addition of probiotics did not reduce the incidence of HO-CDI among inpatients receiving IV antibiotics.

Time to Place Clostridium difficile Infections in Major Healthcare-associated Infections List.

How to cite this article: Sinha S, Behera S. Time to Place Clostridium difficile Infections in Major Healthcare-associated Infections List. Indian J Crit Care Med 2023;27(2):152-153.

Cost-effectiveness of Fecal Microbiota Transplantation for First Recurrent Clostridioides difficile Infection.

BACKGROUND: Both the American College of Gastroenterology and the Infectious Diseases Society of America (IDSA)/Society for Healthcare Epidemiology of America 2021 Clostridioides difficile infection (CDI) guidelines recommend fecal microbiota transplantation (FMT) for persons with multiple recurrent CDI. Emerging data suggest that FMT may have high cure rates when used for first recurrent CDI. The aim of this study was to assess the cost-effectiveness of FMT for first recurrent CDI. METHODS: We developed a Markov model to simulate a cohort of patients presenting with initial CDI infection. The model estimated the costs, effectiveness, and cost-effectiveness of different CDI treatment regimens recommended in the 2021 IDSA guidelines, with the additional option of FMT for first recurrent CDI. The model includes stratification by the severity of initial infection, estimates of cure, recurrence, and mortality. Data sources were taken from IDSA guidelines and published literature on treatment outcomes. Outcome measures were quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). RESULTS: When FMT is available for first recurrent CDI, the optimal cost-effective treatment strategy is fidaxomicin for initial nonsevere CDI, vancomycin for initial severe CDI, and FMT for first and subsequent recurrent CDI, with an ICER of $27 135/QALY. In probabilistic sensitivity analysis at a $100 000 cost-effectiveness threshold, FMT for first and subsequent CDI recurrence was cost-effective 90% of the time given parameter uncertainty. CONCLUSIONS: FMT is a cost-effective strategy for first recurrent CDI. Prospective evaluation of FMT for first recurrent CDI is warranted to determine the efficacy and risk of recurrence.

Clostridium difficile Toxin Biology.

Clostridium difficile is the cause of antibiotics-associated diarrhea and pseudomembranous colitis. The pathogen produces three protein toxins: C. difficile toxins A (TcdA) and B (TcdB), and C. difficile transferase toxin (CDT). The single-chain toxins TcdA and TcdB are the main virulence factors. They bind to cell membrane receptors and are internalized. The N-terminal glucosyltransferase and autoprotease domains of the toxins translocate from low-pH endosomes into the cytosol. After activation by inositol hexakisphosphate (InsP6), the autoprotease cleaves and releases the glucosyltransferase domain into the cytosol, where GTP-binding proteins of the Rho/Ras family are mono-O-glucosylated and, thereby, inactivated. Inactivation of Rho proteins disturbs the organization of the cytoskeleton and affects multiple Rho-dependent cellular processes, including loss of epithelial barrier functions, induction of apoptosis, and inflammation. CDT, the third C. difficile toxin, is a binary actin-ADP-ribosylating toxin that causes depolymerization of actin, thereby inducing formation of the microtubule-based protrusions. Recent progress in understanding of the toxins' actions include insights into the toxin structures, their interaction with host cells, and functional consequences of their actions.

Clostridioides difficile infection in solid organ and hematopoietic stem cell transplant recipients: A prospective multinational study.

BACKGROUND: Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality in recipients of solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT). In retrospective single center analyses, severe disease and relapse are common. We undertook an international, prospective cohort study to estimate the response to physician determined antibiotic treatment for CDI in patients with SOT and HSCT. METHODS: Adults with a first episode of CDI within the first 2 years of SOT or HSCT were enrolled. Demographics, comorbidities, and medication history were collected, and over 90 days of follow-up clinical cure, recurrences, and complications were assessed. Logistic regression was used to study associations of baseline predictors of clinical cure and recurrence. Odds ratios (ORs) and 95% confidence intervals (CIs) are cited. RESULTS: A total of 132 patients, 81 SOT and 51 HSCT (32 allogeneic), were enrolled with a median age of 56 years; 82 (62%) were males and 128 (97%) were hospitalized at enrollment. One hundred and six (80.3%) were diagnosed by DNA assay. CDI occurred at a median of 20 days post-transplant (interquartile range, IQR: 6-133). One hundred and eight patients (81.8%) were on proton pump inhibitors; 126 patients (95.5%) received antibiotics within the 6 weeks before CDI. The most common initial CDI treatments prescribed, on or shortly before enrollment, were oral vancomycin alone (50%) and metronidazole alone (36%). Eighty-three percent (95% CI: 76, 89) of patients had clinical cure; 18% (95% CI: 12, 27) of patients had recurrent CDI; global clinical cure occurred in 65.2%. Of the 11 patients who died, two (1.5% of total) were related to CDI. In multivariable logistic regression analyses, the type of initial treatment was associated with clinical cure (p = .009) and recurrence (p = .014). A history of cytomegalovirus (CMV) after transplant was associated with increased risk of recurrence (44% with versus 13% without CMV history; OR: 5.7, 95% CI: 1.5, 21.3; p = .01). CONCLUSIONS: Among adults who develop CDI after SOT or HSCT, despite their immunosuppressed state, the percentage with clinical cure was high and the percentage with recurrence was low. Clinical cure and recurrence varied by type of initial treatment, and CMV viremia/disease was associated with an increased risk of recurrence.

The global incidence of adverse events associated with fecal microbiota transplantation in children over the past 20 years: A systematic review and meta-analysis.

OBJECTIVES: To understand the global incidence of the adverse events associated with fecal microbiota transplantation (FMT) in children over the past 20 years. METHODS: We searched PubMed, Web of Science, Embase, and three Chinese databases (CNKI, Wanfang, and Chongqing Weipu) for high-quality articles written over the past 20 years and made selections based on the quality standard score. The study characteristics and incidences of adverse events were extracted from each article, meta-analysis was performed using the R.3.6.3 software, and randomized-effect or fixed-effect meta-analyses were used to determine the incidence of adverse events. Subgroup analysis was performed to determine heterogeneity. RESULTS: A total of 18 articles involving 681 children were included in the analysis. The total effective rate of FMT in children was 85.75% (95% CI: 76.23-93.15%), of which the overall efficacy of FMT for the treatment of Clostridium difficile infection was 91.22% (95% CI: 83.49-96.68%) and the overall adverse event rate was 28.86% (95% CI: 19.56-39.15%), with a mild to moderate adverse event rate of 27.72% (95% CI: 17.86-38.83%) and a severe adverse event rate of 0.90% (95% CI: 0.33-1.76%). The most common mild to moderate adverse events were as follows: bellyache, 14.02% (95% CI: 5.43-25.77%); diarrhea, 7.75% (95% CI: 2.69-15.11%); and bloating, 7.36% (95% CI: 1.79-16.28%). Other adverse events included fever, 2.34%; vomiting, 3.12%; nausea, 1.50%; hematochezia, 2.30%; anorexia, 1.94%; and fatigue, 0.03%. The only death reported was in a study from China, in which the patient died of sepsis and liver failure 4 weeks after FMT. The other serious adverse event was an immunodeficiency patient with severe hematochezia. Another study in the United States described seven serious adverse events including one death that was not considered to be related to FMT; however, they did not describe the events in detail. There was no difference in the incidence of adverse events between the upper and lower gastrointestinal tracts (OR = 0.61, 95% CI: 0.02-15.42, P = 0.76). CONCLUSION: Adverse events related to FMT in children are mostly mild to moderate, of short duration, and self-limiting. Therefore, the use of FMT in children is safe and worthy of widespread promotion.

Real-world comparison of fidaxomicin versus vancomycin or metronidazole in the treatment of Clostridium difficile infection: a systematic review and meta-analysis.

PURPOSE: There is a lack of real-world evidence of the comparative effectiveness of fidaxomicin versus vancomycin or metronidazole for treating patients with Clostridium difficile (CDI) infection. No systematic evidence comparing these treatment regimens using real-world observational studies was published up to date. The goal of this study is to compare the fidaxomicin and vancomycin/metronidazole regimens in terms of treatment outcomes in CDI patients. METHODS: Systematic and comprehensive search was carried out in the following databases and search engines: EMBASE, Cochrane, MEDLINE, ScienceDirect, and Google Scholar from 1954 until January 2022. Newcastle-Ottawa (NO) scale was used to assess the risk of bias. Meta-analysis was carried out using random effects model, and pooled odds ratios (OR) with 95% confidence interval (CI) were reported. RESULTS: A total of 10 studies satisfied the inclusion criteria, most of them were with poorer quality. The pooled OR was 0.40 (95% CI: 0.09-1.68; I2 = 82.4%) for clinical cure and 2.02 (95% CI: 0.36-11.39; I2 = 88.4%) for sustained cure. We reported pooled OR of 0.69 (95% CI: 0.40-1.20; I2 = 65.7%) for the recurrence rate, 2.81 (95% CI: 1.08-7.29; I2 = 70.6%) for the treatment failure, and 0.73 (95% CI: 0.50-1.07; I2 = 0%) for all-cause mortality between patients that received fidaxomicin and vancomycin. The pooled OR was 0.71 (95% CI: 0.05-9.47; I2 = 69.6%) in terms of recurrence between patients receiving fidaxomicin and metronidazole. CONCLUSION: Fidaxomicin and vancomycin/metronidazole regimens did not have significant difference in terms of treatment outcomes, such as clinical cure, sustained cure, recurrence, and all-cause mortality. However, there was significantly higher risk of treatment failure in CDI patients taking fidaxomicin.

Design and characterization of a novel lytic protein against Clostridium difficile.

Clostridium difficile (C. difficile) is a Gram-positive, spore-forming, toxin-producing anaerobe that can cause nosocomial antibiotic-associated intestinal disease. Autolysin is a lytic enzyme that hydrolyzes peptidoglycans of the bacterial cell wall, with a catalytic domain and cell wall-binding domains, proven to be involved in bacterial cell wall remodeling and cell division. Although autolysins in C. difficile have been reported, the autolysins have failed to yield impressive results when used as exogenous lytic agents. In this study, we expressed and characterized the binding domains (Cwp19-BD and Acd-BD) and catalytic domains (Cwp19-CD, Acd-CD, and Cwl-CD) of C. difficile autolysins, and the domains with the best binding specificity and lytic activity were selected towards C. difficile to design a novel lytic protein Cwl-CWB2. Cwl-CWB2 showed good biosafety with significantly low hemolysis and without cytotoxicity. The results of fluorescence analysis and lytic assay demonstrated that Cwl-CWB2 has higher binding specificity and stronger lytic activity with a minimum inhibitory concentration at 13.39 ± 5.80 µg/mL against living C. difficile cells, which is significantly stronger than commercial lysozyme (3333.33 ± 1443.37 µg/mL) and other reported C. difficile autolysins. Besides, Cwl-CWB2 exhibited good stability as about 75% of the lytic activity was still retained when incubated at 37 °C for 96 h, which is considered to be a potential antimicrobial agent to combat C. difficile. KEY POINTS: • Several binding domains and catalytic domains, deriving from several Clostridium difficile autolysins, were expressed, purified, and functionally characterized. • A novel C. difficile lytic protein Cwl-CWB2 was designed from C. difficile autolysins. • The binding specificity and lytic activity of Cwl-CWB2 against C. difficile showed advantages compared with other reported C. difficile autolysins. • Cwl-CWB2 exhibited significantly low hemolysis and cytotoxicity against normal-derived colon mucosa 460 cell.

Clostridioides difficile infection in a rural New Zealand secondary care centre: an incidence case-control study.

BACKGROUND: Clostridioides difficile infection (CDI) is a form of antibiotic-associated infectious diarrhoea resulting in significant morbidity and mortality. Community-acquired disease in low-risk individuals is increasingly recognised. There are limited New Zealand data published. AIM: To determine the incidence and location of onset of CDI cases in the Manawatu region, and further describe the demographics, risk factors and prevalent C. difficile ribotypes of the population. METHODS: We performed an incidence case-control study of CDI in the Manawatu region between September 2018 and September 2019. Cases were matched to controls with a negative test for C. difficile. Demographic and comorbidity data, location of onset, drug exposure, disease recurrence and 30-day mortality were collected. Ribotype analysis was performed on C. difficile isolates. RESULTS: Thirty-two specimens tested toxin positive over 12 months, yielding an incidence of 18.3 cases per 100 000 person-years. Twenty-five percent of cases had community onset disease. Cases were more likely to have had amoxicillin/clavulanate or ceftriaxone prescribed. Elevated blood white cell count and lower HbA1c were significantly associated with CDI. The dominant ribotype was 014/020. Two cases were RT 023. CONCLUSION: Our data are similar to previous national data. RT 023 has not been previously reported in New Zealand and has been associated with severe colitis. We demonstrated a significant proportion of community-acquired cases and the true incidence might be higher. Vigilance for community onset disease is required. These data may allow observation of temporal changes in incidence and infection patterns of CDI in New Zealand.

A case of vasculitis triggered by infective endocarditis in a patient undergoing maintenance hemodialysis: a case report.

BACKGROUND: Immunoglobulin A vasculitis (IgA vasculitis) is one of the most common forms of vasculitis in children. It rarely occurs in adults. It is a systemic vasculitis with IgA deposition and is characterized by the classical tetrad of purpura, arthritis/arthralgia, gastrointestinal and renal involvement. Certain types of infections, and pharmacological agents have been reported to be associated with IgA vasculitis. Here, we describe a case of IgA vasculitis triggered by infective endocarditis in a patient undergoing maintenance hemodialysis. CASE PRESENTATION: A 70-year-old man undergoing hemodialysis was admitted because of skin purpura, abdominal pain, diarrhea, and lower back pain. We suspected him as IgA vasculitis based on the clinical features and skin biopsy findings. Transesophageal echocardiography revealed infective endocarditis, which predisposed him to IgA vasculitis. He was treated with antibiotics and low-dose corticosteroids, which led to resolution of vasculitis. CONCLUSIONS: This is the first case of IgA vasculitis triggered by infective endocarditis in a patient undergoing hemodialysis. Patients undergoing hemodialysis are at a high risk of infection because of immune dysfunction and frequent venipuncture. The incidence of infective endocarditis associated with IgA vasculitis is very low, but it has been repeatedly reported. Therefore, it is necessary to consider infective endocarditis in patients with clinical features that indicate IgA vasculitis.

Risk factors for postoperative Clostridium difficile infection after radical cystectomy for bladder cancer: a NSQIP database analysis.

INTRODUCTION: Patients undergoing cystectomy for bladder cancer are at an increased risk for Clostridium difficile infection (CDI) due to prolonged antibiotics and underlying comorbidities. We aim to evaluate CDI risk factors in cystectomy patients. MATERIALS AND METHODS: Utilizing National Surgical Quality Improvement Program (NSQIP), patients undergoing cystectomy with diagnosis of bladder cancer between 2015-2017 were included. Baseline demographics including age, sex, comorbidities, and preoperative labs were collected. Univariate and multivariable logistic regression were used to evaluate risk factors for and complications of CDI during the index hospitalization. RESULTS: There were a total of 6,432 patients included in the analysis, with 6,242 (96%) and 190 (4%) in the non-CDI vs. CDI groups, respectively. Patients with a diagnosis of postoperative CDI were more likely to be female [4.09% vs. 2.71%, p = 0.001] and have lower preoperative albumin [3.78 g/dL (0.52) vs. 3.92 g/dL (0.48), p = 0.003]. Patients with a history of female sex (OR 1.46, p = 0.03), neobladder (OR 1.57, p = 0.01), and low preoperative albumin (OR 1.45, p = 0.04) were at the highest risk for development of CDI postoperatively. Patients with a diagnosis of CDI were more likely to experience readmission within 30 days (31.1% vs. 19.2%, p < 0.001). CONCLUSION: Utilizing the NSQIP database, we identified predictors for development of CDI in cystectomy patients. Female sex, continent diversion, and low preoperative albumin all significantly increased the rate of CDI. While our findings are retrospective, they are compelling enough to warrant further prospective investigation.

Alteration of gut microbial composition associated with the therapeutic efficacy of fecal microbiota transplantation in Clostridium difficile infection.

BACKGROUND/PURPOSE: Clostridium difficile infection (CDI) leads to a significant cause of hospital-acquired morbidity and mortality. Fecal microbiota transplantation (FMT) is effective to treat recurrent or refractory CDI (rCDI). However, the change of microbial composition contributed by FMT and its association with treatment outcomes is not well determined in Taiwan. We aimed to investigate the efficacy of FMT and the association with microbial alteration endemically. METHODS: Twelve patients who received FMT for rCDI in Taipei Veterans General Hospital were prospectively enrolled from April 2019 to July 2020. The clinical assessments and fecal microbial analyses in comparison with fecal materials of unrelated donors were conducted before and after FMT. RESULTS: The overall success rate of FMT for rCDI was 91.7%. A prominence of Proteobacteria, Gammaproteobacteria and Enterobacteriales were observed in the feces of patients with rCDI. Increased fecal phylogenetic diversities and a significant microbial dissimilarity were provided by successful FMT compared to patients before treatment. However, the distinctness was not obvious between patients' feces at baseline and after unsuccessful FMT. Moreover, dynamic change of fecal microbial composition after FMT was observed during follow-up but did not interrupt the treatment effects of FMT. CONCLUSION: Gut dysbiosis commonly co-exists in patients with rCDI. Restoration of gut microbial communities by FMT provides a promising strategy to treat antibiotic-failed CDI, and the extent of microbial change would be related to the treatment outcomes of FMT. Besides, the effectiveness of FMT for CDI could be maintained even the gut microbiota has diverged over time.

Gut Microbiota and Clostridium difficile: What We Know and the New Frontiers.

Our digestive system, particularly our intestines, harbors a vast amount of microorganisms, whose genetic makeup is referred to as the microbiome. Clostridium difficile is a spore-forming Gram-positive bacterium, which can cause an infection whose symptoms range from asymptomatic colonization to fearsome complications such as the onset of toxic megacolon. The relationship between gut microbiota and Clostridium difficile infection has been studied from different perspectives. One of the proposed strategies is to be able to specifically identify which types of microbiota alterations are most at risk for the onset of CDI. In this article, we understood once again how crucial the role of the human microbiota is in health and especially how crucial it becomes, in the case of its alteration, for the individual's disease. Clostridium difficile infection is an emblematic example of how a normal and physiological composition of the human microbiome can play a very important role in immune defense against such a fearsome disease.

Enhanced Clostridioides difficile Infection Prevention With a Pharmacy-Controlled Policy That Adds a 3-Strain Lactobacillus Probiotic Concomitantly to Antibiotic Therapy.

When 70% of antibiotic users took a 3-strain Lactobacillus probiotic preparation the hospital-wide rate of healthcare-associated Clostridioides difficile infection improved significantly. The incidence of C. difficile infection for those taking the probiotic along with multiple antibiotics or a single high-risk antibiotic was decreased by at least half.

Outcomes of C difficile infection in solid-organ transplant recipients: The National Inpatient Sample (NIS) 2015-2016.

BACKGROUND: Clostridioides (formerly Clostridium) difficile infection (CDI) is one of the leading causes of morbidity and mortality worldwide. Solid organ transplant (SOT) recipients are at an increased risk for CDI. A recent study showed an overall improvement in mortality amongst hospitalized individuals with CDI, but it is unclear if this benefit extends to SOT recipients. METHODS: We scrutinized the 2015 and 2016 National Inpatient Sample (NIS), the largest all-payer inpatient database in the United States for CDI data in patients with SOT. SOT was defined as any recipient who had received a heart, lung, liver, intestinal, kidney, pancreas, or combined thoracic and/or abdominal organ transplantation. Baseline characteristics, comorbidities, and concomitant diagnosis of pneumonia or urinary tract infection were adjusted for in our analysis. Primary outcomes included inpatient mortality, hospital length of stay and total hospital charges. RESULTS: A total of 105 780 hospital discharges of SOT recipients were included. The incidence of CDI was 3554 (3.36%) among SOTs. CDI was associated with a higher inpatient mortality (OR 1.85, 95% CI 1.56-2.20, P < .01), longer length of hospital stay (mean difference 5.07 days, 95% CI 4.43-5.71, P < .01) and higher total hospital charges (mean difference 43 958 US dollars, P < .01). CONCLUSION: Our study found that CDI is associated with poorer overall outcomes among hospitalized SOT recipients. However, there was a possible improving trend of the outcomes when compare to previous studies.