Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridioides difficile infection (CDI), with emerging data on intermediate and long-term safety.
A prospective ...survey-based study was conducted (September 2012–June 2018) in patients undergoing FMT for recurrent CDI. Data on demographics and comorbidities were abstracted from medical records. Patients were contacted at 1 week, 1 month, 6 months, 1 year (short-term), and ≥2 years post-FMT (long-term). Symptoms and new medical diagnoses were recorded at each time point. Data were weighted to account for survey nonresponse bias. Multivariate logistic regression models for adverse events were built using age (per 10-year increment), sex, time of survey, and comorbidities. P < .05 was considered statistically significant.
Overall, 609 patients underwent FMT; median age was 56 years (range, 18–94), 64.8% were women, 22.8% had inflammatory bowel disease (IBD). At short-term follow-up (n = 609), >60% of patients had diarrhea and 19%-33% had constipation. At 1 year, 9.5% reported additional CDI episodes. On multivariable analysis, patients with IBD, dialysis-dependent kidney disease, and multiple FMTs had higher risk of diarrhea; risk of constipation was higher in women and lower in IBD (all P < .05). For long-term follow-up (n = 447), median time of follow-up was 3.7 years (range, 2.0–6.8). Overall, 73 new diagnoses were reported: 13% gastrointestinal, 10% weight gain, 11.8% new infections (all deemed unrelated to FMT). Median time to infections was 29 months (range, 0–73) post-FMT.
FMT appears safe with low risk of transmission of infections. Several new diagnoses were reported, which should be explored in future studies.
The growing recognition of the older inflammatory bowel disease (IBD) patient is heightened by the entry of the 77.2 million baby boomers who will turn 65 beginning of 2011. It is anticipated that ...this will occur at a rate of 10,000 per day or 4 million per year for the next 19 years. The management of IBD in this population is complex because of problems with co-morbidities, polypharmacy, impaired mobility, and cognition, as well as difficult social and financial issues. This review focuses on the older IBD patient's unique concerns and provides guidance in their diagnosis and management.
The effect of rationally defined nonpathogenic, nontoxigenic, commensal strains of Clostridia on prevention of Clostridioides difficile infection (CDI) is unknown.
To determine the efficacy of VE303, ...a defined bacterial consortium of 8 strains of commensal Clostridia, in adults at high risk for CDI recurrence. The primary objective was to determine the recommended VE303 dosing for a phase 3 trial.
Phase 2, randomized, double-blind, placebo-controlled, dose-ranging study conducted from February 2019 to September 2021 at 27 sites in the US and Canada. The study included 79 participants aged 18 years or older who were diagnosed with laboratory-confirmed CDI with 1 or more prior CDI episodes in the last 6 months and those with primary CDI at high risk for recurrence (defined as aged ≥75 years or ≥65 years with ≥1 risk factors: creatinine clearance <60 mL/min/1.73 m2, proton pump inhibitor use, remote >6 months earlier CDI history).
Participants were randomly assigned to high-dose VE303 (8.0 × 109 colony-forming units CFUs) (n = 30), low-dose VE303 (1.6 × 109 CFUs) (n = 27), or placebo capsules (n = 22) orally once daily for 14 days.
The primary efficacy end point was the proportion of participants with CDI recurrence at 8 weeks using a combined clinical and laboratory definition. The primary efficacy end point was analyzed in 3 prespecified analyses, using successively broader definitions for an on-study CDI recurrence: (1) diarrhea consistent with CDI plus a toxin-positive stool sample; (2) diarrhea consistent with CDI plus a toxin-positive, polymerase chain reaction-positive, or toxigenic culture-positive stool sample; and (3) diarrhea consistent with CDI plus laboratory confirmation or (in the absence of a stool sample) treatment with a CDI-targeted antibiotic.
Baseline characteristics were similar across the high-dose VE303 (n = 29; 1 additional participant excluded from efficacy analysis), low-dose VE303 (n = 27), and placebo (n = 22) groups. The participants' median age was 63.5 years (range, 24-96); 70.5% were female; and 1.3% were Asian, 1.3% Black, 2.6% Hispanic, and 96.2% White. CDI recurrence rates through week 8 (using the efficacy analysis 3 definition) were 13.8% (4/29) for high-dose VE303, 37.0% (10/27) for low-dose VE303, and 45.5% (10/22) for placebo (P = .006, high-dose VE303 vs placebo).
Among adults with laboratory-confirmed CDI with 1 or more prior CDI episodes in the last 6 months and those with primary CDI at high risk for recurrence, high-dose VE303 prevented recurrent CDI compared with placebo. A larger, phase 3 study is needed to confirm these findings.
ClinicalTrials.gov Identifier: NCT03788434.
Summary
Background
Clostridium difficile infection (CDI) may not respond to initial therapy and frequently recurs, but predictors of response and recurrence are inconsistent. The impact of specific ...alterations in the gut microbiota determining treatment response and recurrence in patients with CDI is unknown.
Aim
To assess microbial signatures as predictors of treatment response and recurrence in CDI.
Methods
Pre‐treatment stool samples and clinical metadata including outcomes were collected prospectively from patients with their first CDI episode. Next generation 16s rRNA sequencing using MiSeq Illumina platform was performed and changes in microbial community structure were correlated with CDI outcomes.
Results
Eighty‐eight patients (median age 52.7 years, 60.2% female) were included. Treatment failure occurred in 12.5% and recurrence after response in 28.5%. Patients who responded to treatment had an increase in Ruminococcaceae, Rikenellaceae, Clostridiaceae, Bacteroides, Faecalibacterium and Rothia compared to nonresponders. A risk‐index built from this panel of microbes differentiated responders (mean 0.07 ± 0.24) from nonresponders (0.52 ± 0.42; P = 0.0002). Receiver operating characteristic (ROC) curve demonstrated that risk‐index was a strong predictor of treatment response with an area under the curve (AUC) of 0.85. Among clinical parameters tested, only proton pump inhibitor use predicted recurrent CDI (OR 3.75, 95% CI 1.27–11.1, P = 0.01). Patients with recurrent CDI had statistically significant increases in Veillonella, Enterobacteriaceae, Streptococci, Parabacteroides and Lachnospiraceae compared to patients without recurrence and a risk index was able to predict recurrence (AUC = 0.78).
Conclusion
Gut microbiota signatures predict treatment response and recurrence potentially, allowing identification of patients with Clostridium difficile infection that may benefit from early institution of alternate therapies.
Clostridium difficile infection (CDI) is a common hospital-acquired infection with increasing incidence, severity, recurrence, and associated morbidity and mortality. There are emerging data on the ...occurrence of CDI in nonhospitalized patients. However, there is a relative lack of community-based CDI studies, as most of the existing studies are hospital based, potentially influencing the results by referral or hospitalization bias by missing cases of community-acquired CDI.
To better understand the epidemiology of community-acquired C. difficile infection, a population-based study was conducted in Olmsted County, Minnesota, using the resources of the Rochester Epidemiology Project. Data regarding severity, treatment response, and outcomes were compared in community-acquired vs. hospital-acquired cohorts, and changes in these parameters, as well as in incidence, were assessed over the study period.
Community-acquired CDI cases accounted for 41% of 385 definite CDI cases. The incidence of both community-acquired and hospital-acquired CDI increased significantly over the study period. Compared with those with hospital-acquired infection, patients with community-acquired infection were younger (median age 50 years compared with 72 years), more likely to be female (76% vs. 60%), had lower comorbidity scores, and were less likely to have severe infection (20% vs. 31%) or have been exposed to antibiotics (78% vs. 94%). There were no differences in the rates of complicated or recurrent infection in patients with community-acquired compared with hospital-acquired infection.
In this population-based cohort, a significant proportion of cases of CDI occurred in the community. These patients were younger and had less severe infection than those with hospital-acquired infection. Thus, reports of CDI in hospitalized patients likely underestimate the burden of disease and overestimate severity.
Background & Aims There are several drugs that might decrease the risk of relapse of Crohn’s disease (CD) after surgery, but it is unclear whether one is superior to others. We estimated the ...comparative efficacy of different pharmacologic interventions for postoperative prophylaxis of CD, through a network meta-analysis of randomized controlled trials. Methods We conducted a systematic search of the literature through March 2014. We identified randomized controlled trials that compared the abilities of mesalamine, antibiotics, budesonide, immunomodulators, anti–tumor necrosis factor α (anti-TNF) (started within 3 months of surgery), and/or placebo or no intervention to prevent clinical and/or endoscopic relapse of CD in adults after surgical resection. We used Bayesian network meta-analysis to combine direct and indirect evidence and estimate the relative effects of treatment. Results We identified 21 trials comprising 2006 participants comparing 7 treatment strategies. In a network meta-analysis, compared with placebo, mesalamine (relative risk RR, 0.60; 95% credible interval CrI, 0.37–0.88), antibiotics (RR, 0.26; 95% CrI, 0.08–0.61), immunomodulator monotherapy (RR, 0.36; 95% CrI, 0.17–0.63), immunomodulator with antibiotics (RR, 0.11; 95% CrI, 0.02–0.51), and anti-TNF monotherapy (RR, 0.04; 95% CrI, 0.00–0.14), but not budesonide (RR, 0.93; 95% CrI, 0.40–1.84), reduced the risk of clinical relapse. Likewise, compared with placebo, antibiotics (RR, 0.41; 95% CrI, 0.15–0.92), immunomodulator monotherapy (RR, 0.33; 95% CrI, 0.13–0.68), immunomodulator with antibiotics (RR, 0.16; 95% CrI, 0.04–0.48), and anti-TNF monotherapy (RR, 0.01; 95% CrI, 0.00–0.05), but neither mesalamine (RR, 0.67; 95% CrI, 0.39–1.08) nor budesonide (RR, 0.86; 95% CrI, 0.61–1.22), reduced the risk of endoscopic relapse. Anti-TNF monotherapy was the most effective pharmacologic intervention for postoperative prophylaxis, with large effect sizes relative to all other strategies (clinical relapse: RR, 0.02–0.20; endoscopic relapse: RR, 0.005–0.04). Conclusions Based on Bayesian network meta-analysis combining direct and indirect treatment comparisons, anti-TNF monotherapy appears to be the most effective strategy for postoperative prophylaxis for CD.
Abstract Clostridium difficile was first described as a cause of diarrhea in 1978 and is now among the leading 3 hospital-acquired infections in the United States, along with methicillin-resistant ...Staphylococcus aureus and vancomycin-resistant enterococci. In the past 2 decades, there has been an increase in the incidence, severity, and recurrence rates of C difficile infection, all of which are associated with poor outcomes. In addition, several novel risk factors and newer treatment methods are emerging, including fidaxomicin therapy, treatment using monoclonal antibodies, and fecal microbiota transplantation, that have shown promise for the treatment of C difficile infection. This review focuses on the changing epidemiology, risk factors, and newer methods for treatment of C difficile infection.
Microscopic colitis is an inflammatory bowel disease divided into two subtypes: collagenous colitis and lymphocytic colitis. With an increasing incidence of microscopic colitis exceeding those of ...ulcerative and Crohn's disease among elderly people in some countries, microscopic colitis is a debilitating life experience. Therefore, physicians should be familiar with its clinical features and management strategies because the disease deserves the same attention as the classical inflammatory bowel diseases. Here, state-of-the-art knowledge of microscopic colitis is provided from a global perspective with reference to etiopathology and how to establish the diagnosis with the overall aim to create awareness and improve rational management in clinical practice. The immune system and a dysregulated immune response seem to play a key role combined with risk factors (e.g. cigarette smoking) in genetically predisposed individuals. The symptoms are characterized by recurrent or chronic nonbloody, watery diarrhea, urgency, weight loss, and a female preponderance. As biomarkers are absent, the diagnosis relies on colonoscopy with a histological assessment of biopsy specimens from all parts of the colon. Although the disease is not associated with a risk of colorectal cancer, a recent nationwide, population-based cohort study found an increased risk of lymphoma and lung cancer. Budesonide is the first-line therapy for management, whereas immunomodulatory drugs (including biologics) and drugs with antidiarrheal properties may be indicated in those failing, dependent, or intolerant to budesonide. In microscopic colitis induced by checkpoint inhibitors, a drug class used increasingly for a wide range of malignancies, a more aggressive therapeutic approach with biologics introduced early seems reasonable. However, particular attention needs to be drawn to the existence of incomplete forms of microscopic colitis with the risk of being overlooked in routine clinical settings.
Summary
The pathophysiology of microscopic colitis is unknown, although it is thought to be because of an abnormal immune reaction to luminal antigens in predisposed hosts. Specific antigens have not ...been proved, although various infectious triggers and drugs have been proposed. The responsibility of several drugs has been questioned, some with strong clinical and/or histological evidence suggesting causality. The issue of drug‐induced microscopic colitis is important because of the burden of this disease. Thus, any case that can be cured by withdrawal of a drug must be identified. In this report, we propose a scoring system for drug‐induced microscopic colitis, adapting existing criteria of drug causality, and review the literature using this framework. Based on this review, several drugs are identified with intermediate or high likelihood of inducing microscopic colitis. Finally, we suggest how to treat individual patients suspected of having drug‐induced colitis according to the level of evidence for that particular drug.
We performed an updated study to investigate the rates of urinary tract infections (UTIs) in patients with recurrent
Clostridioides difficile
infection (CDI) who received fecal microbiota ...transplantation (FMT) for CDI. We found a significant reduction in number of UTIs after FMT compared to patients who received antibiotics for CDI treatment. After FMT, we also observed a trend towards reduction of antibiotic resistance in organisms causing UTI.
PDF
