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BackgroundClostridioides difficile infection (CDI) is associated with poor outcomes in inflammatory bowel disease (IBD) patients. Data are scarce on efficacy of fecal microbiota transplant (FMT) for recurrent CDI in IBD patients.MethodsWe reviewed health records of IBD patients (18 years of age or older) with recurrent CDI who underwent FMT. Outcomes of FMT for CDI were assessed on the basis of symptoms and stool test results.ResultsWe included 145 patients (75 women [51.7%]; median age, 46 years). Median IBD duration was 8 (range, 0–47) years, 36.6% had Crohn disease, 61.4% had ulcerative colitis, and 2.1% had indeterminate colitis. Median number of prior CDI episodes was 3 (range, 3–20), and 61.4% had received vancomycin taper. Diarrhea resolved after FMT in 48 patients (33.1%) without further testing. Ninety-five patients (65.5%) underwent CDI testing owing to post-FMT recurrent diarrhea; 29 (20.0%) had positive results. After FMT, 2 patients received empiric treatment of recurrent CDI without symptom resolution, suggesting IBD was the cause of symptoms. The overall cure rate of CDI after FMT was 80.0%, without CDI recurrence at median follow-up of 9.3 (range, 0.1–51) months. Forty-three patients (29.7%) had planned IBD therapy escalation after CDI resolution; none de-escalated or discontinued IBD therapy. Overall, 7.6% had worsening IBD symptoms after FMT that were treated as new IBD flares. No clinical predictors of FMT failure were identified.ConclusionsFew patients had new IBD flare after FMT. Fecal microbiota transplantation effectively treats recurrent CDI in IBD patients but has no apparent beneficial effect on the IBD course.

The pathogenesis of Clostridioides difficile infection (CDI) has largely been attributed to the action of two major toxins – A and B. An enhanced systemic humoral immune response against these toxins has been shown to be protective against recurrent CDI. Over the years, fully human monoclonal antibodies against both of these toxins have been developed in an attempt to counter the increasing incidence of recurrent CDI. Clinical trials conducted to evaluate the efficacy of anti-toxin A monoclonal antibody, actoxumab, and anti-toxin B monoclonal antibody, bezlotoxumab, demonstrated that bezlotoxumab substantially lowered the rate of recurrent infection, while actoxumab did not. A significant therapeutic benefit was appreciated in patients with at least one high-risk factor for recurrence, including, age ⩾65 years, immunocompromised state, prior CDI and severe CDI. In light of toxins A and B being immunogenic, vaccine trials are underway with the aim to prevent primary infection.

Background Clostridioides difficile is a serious problem for the aging population. Aged mouse model of C. difficile infection (CDI) has emerged as a valuable tool to evaluate the mechanism of aging in CDI. Methods We reviewed five published studies utilizing aged mice (7–28 months) for CDI model for findings that may advance our understanding of how aging influences outcome from CDI. Results Aged mouse models of CDI uniformly demonstrated more severe disease in the old compared to young mice. Diminished neutrophil recruitment to intestinal tissue in aged mice is the most consistent finding. Differences in innate and humoral immune responses were also observed. The effects of aging on the outcome of infection were reversed by pharmacologic or microbiota-targeted interventions. Conclusion The aged mouse presents an important in vivo model to study CDI and elucidate the mechanisms underlying advanced age as an important risk factor for severe disease.

This chapter discusses the histologic features of commonly encountered infections of the gastrointestinal (GI) tract and correlates the morphologic findings with microbiological and molecular testing. It also discusses the major differential diagnoses of infectious diseases of the GI tract that are encountered in practice.

Background Clostridium difficile infection (CDI) is due to the effects of toxins, toxin A and toxin B on the host. Severe CDI is associated with systemic signs of infection. Animal models of CDI demonstrate a strong correlation between systemic toxemia and the occurrence of severe disease. However, current technologies have low sensitivity to detect C difficile toxemia in human subjects. Raman spectroscopy (RS) is an upcoming technology that is used to detect bacteria and their toxins. We speculate that RS may be a sensitive method to detect clinically relevant concentrations of C difficile toxins in serum. Materials and methods Serum samples were spiked with varying concentrations of toxin A, toxin B, and both. RS was performed on an air-dried serum drop that was placed on a mirror-polished stainless steel slide. Raman spectra were obtained, background corrected, vector normalized, and analyzed by Partial Least Square Linear Discriminant Analysis and Support Vector Machine for Classification. Model accuracy was measured by cross-validation and bootstrap methods. Results Toxin-spiked sera of various concentrations (1 ng/mL, 1 pg/mL, and 0.1 pg/mL) were distinguished from control serum 100% with cross-validation error rate ranging from 0% to 18% and bootstrap error rate ranging from 0% to 12% for various concentrations. The sensitivity ranged from 87% to 100% and specificity ranged from 77% to 100% for various concentrations of toxin-spiked serum. Conclusions We conclude that RS may be a sensitive method to detect clinically relevant concentrations of C difficile toxins in serum and thus to help diagnose severe CDI in patients in real-time at the point of care.

Aim: to evaluate antagonistic properties of Lactobacilli against clinically relevant Clostridium (Clostridioides) difficile strains. Materials and methods: we assessed antagonistic properties of 21 Lactobacilli strains isolated from the patients’colon biotope against 31 clinically relevant C. difficile strains isolated from faeces of the patients with C. difficile-associated diarrhea by means of a double-step culturing in the combined cultivation system. Results: Lactobacilli strains isolated from the patients’colon biotope had selective antagonistic properties against C. difficile. Lactobacilli strains had different spectrum and intensity of antagonistic activity that showed no correlation neither with species, nor with natural population size. We isolated Lactobacilli strains with high antagonistic activity (L. paracasei 101, L. gasseri 341/2, L. paracasei 340/1). We isolated bacteriocins from Lactobacilli cultures. The influence of bacteriocins on C. difficile strains correlated with antagonistic activity of Lactobacilli; bacteriocins suppressed C. difficile growth in dose-dependent manner. Conclusion: evaluation of Lactobacilli antagonistic activity is a prospective approach to struggle against nosocomial infection caused by resistant strains, particularly using Lactobacilli autostrains for suppression of toxigenic C. difficile strains growth.

Clostridium difficile infection is caused by the proliferation of a gram-positive anaerobic bacteria after medical or surgical intervention and can result in toxic complications, emergent surgery, and death.This analysis evaluates the incidence of C difficile infection in elective restoration of intestinal continuity compared with elective colon resection.This was a retrospective database review of the 2015 American College of Surgeons National Surgical Quality Improvement Project and targeted colectomy database.The intervention cohort was defined as the primary Current Procedural Terminology codes for ileostomy/colostomy reversal (44227, 44620, 44625, and 44626) and International Classification of Diseases codes for ileostomy/colostomy status (VV44.2, VV44.3, VV55.2, VV55.3, Z93.2, Z93.3, Z43.3, and Z43.2).A total of 2235 patients underwent elective stoma reversal compared with 10403 patients who underwent elective colon resection.Multivariate regression modeling of the impact of stoma reversal on postoperative C difficile infection risk was used as the study intervention.The incidence of C difficile infection in the 30 days after surgery was measured.The incidence of C difficile infection in the 30-day postoperative period was significantly higher (3.04% vs 1.25%; p0.001) in patients undergoing stoma reversal. After controlling for differences in cohorts, regression analysis suggested that stoma reversal (OR = 2.701 (95% CI, 1.966-3.711); p0.001), smoking (OR = 1.520 (95% CI, 1.063-2.174); p = 0.022), steroids (OR = 1.677 (95% CI, 1.005-2.779); p = 0.048), and disseminated cancer (OR = 2.312 (95% CI, 1.437-3.719); p = 0.001) were associated with C difficile infection incidence in the 30-day postoperative period.The study was limited because it was a retrospective database review with observational bias.Patients who undergo elective stoma reversal have a higher incidence of postoperative C difficile infection compared with patients who undergo an elective colectomy. Given the impact of postoperative C difficile infection, a heightened sense of suspicion should be given to symptomatic patients after stoma reversal. See at Video Abstract at http://links.lww.com/DCR/A553.

We retrospectively studied vancomycin taper and pulse treatment on 100 consecutive, evaluable patients with recurrent Clostridium difficile infection. Following taper to once-daily vancomycin dosing, 22 of 36 patients (61%) who received every-other-day dosing (QOD) and 50 of 64 (81%) who received QOD followed by every-third-day dosing were cured (P = .03).

There has been an explosion of interest in studying the indigenous microbiota, which plays an important role in human health and disease. Traditionally, the study of microbes in relationship to human health involved consideration of individual microbial species that caused classical infectious diseases. With the interest in the human microbiome, an appreciation of the influence that complex communities of microbes can have on their environment has developed. When considering either individual pathogenic microbes or a symbiotic microbial community, researchers have employed a variety of model systems with which they can study the host-microbe interaction. With the use of studies of infections with the toxin-producing bacterium Clostridium difficile as a model for both a pathogen and beneficial bacterial communities as an example, this review will summarize and compare various model systems that can be used to gain insight into the host-microbe interaction.

Clostridioides difficile is the leading cause of diarrhea in hospitalized U.S. patients and results in over 400,000 cases of C. difficile infection per year. C. difficile infections have mortality rates of 6 to 30% and significantly increase health care costs, because of increased length of stay and increased frequency of readmissions due to recurrences. Efforts to reduce the spread of C. difficile in hospitals have led to the development of rapid sensitive diagnostic methods., Clostridioides difficile is the leading cause of diarrhea in hospitalized U.S. patients and results in over 400,000 cases of C. difficile infection per year. C. difficile infections have mortality rates of 6 to 30% and significantly increase health care costs, because of increased length of stay and increased frequency of readmissions due to recurrences. Efforts to reduce the spread of C. difficile in hospitals have led to the development of rapid sensitive diagnostic methods. A multicenter study was performed to establish the performance characteristics of the Revogene C. difficile test (Meridian Bioscience, Cincinnati, OH, USA) for use in detection of the toxin B (tcdB) gene from toxigenic C. difficile. The Revogene instrument is a new molecular platform that uses real-time PCR to detect nucleic acids in up to 8 specimens at a time. A total of 2,461 specimens from symptomatic patients that had been submitted for C. difficile testing were enrolled at 7 sites throughout the United States and Canada for evaluation of the assay. Each stool specimen was tested for the presence of the tcdB gene using the Revogene C. difficile test, and results were compared with those of the reference method, a combination of direct and enriched culture methods. Overall, the Revogene C. difficile test demonstrated a sensitivity of 85.0% (95% confidence interval, 80% to 88%) and a specificity of 97.2% (95% confidence interval, 96% to 98%). The Revogene C. difficile test, using clinical stool specimens for detection of tcdB in C. difficile, demonstrated acceptable sensitivity and specificity, with a short turnaround time.

Clostridioides difficile infections are a significant threat to our healthcare system, and rapid and accurate diagnostics are crucial to implement the necessary infection prevention and control measurements. Nucleic acid amplification tests are such reliable diagnostic tools for the detection of toxigenic Clostridioides difficile strains directly from stool specimens. In this multicenter evaluation, we determined the performance of the revogene C. difficile assay. The analysis was conducted on prospective stool specimens collected from six different sites in Europe. The performance of the revogene C. difficile assay was compared to the different routine diagnostic methods and, for a subset of the specimens, against toxigenic culture. In total, 2621 valid stool specimens were tested, and the revogene C. difficile assay displayed a sensitivity/specificity of 97.1% [93.3–99.0] and 98.9% [98.5–99.3] for identification of Clostridioides difficile infection. Discrepancy analysis using additional methods improved this performance to 98.8% [95.8–99.9] and 99.6% [99.2–99.8], respectively. In comparison to toxigenic culture, the revogene C. difficile assay displayed a sensitivity/specificity of 93.0% [86.1–97.1] and 99.5% [98.7–99.9], respectively. These results indicate that the revogene C. difficile assay is a robust and reliable aid in the diagnosis of Clostridioides difficile infections.

Background Clostridioides difficile infection and colonization are common in pediatric Crohn’s disease (CD). Our aims were to test the relationship between C. difficile positivity and bowel resection surgery and to characterize microbial shifts associated with C. difficile carriage and surgery. Methods A retrospective single-center study of 75 pediatric CD patients tested for association between C. difficile carriage and bowel resection surgery. A prospective single-center study of 70 CD patients utilized C. difficile testing and shotgun metagenomic sequencing of fecal samples to define microbiota variation stratified by C. difficile carriage or history of surgery. Results The rate of bowel resection surgery increased from 21% in those without C. difficile to 67% in those with (P = 0.003). From a Kaplan-Meier survival model, the hazard ratio for time to first surgery was 4.4 (95% CI, 1.2–16.2; P = 0.00) in patients with positive C. difficile testing in the first year after diagnosis. Multivariable logistic regression analysis confirmed this association (odds ratio 16.2; 95% CI, 2.2–120; P = 0.006). Larger differences in microbial abundance and metabolic pathways were observed in patients with prior surgery than in those with C. difficile carriage. Depletion of Alistipes and Ruminococcus species and reduction in methionine biosynthesis were noted in patients with both C. difficile carriage and past surgery. Conclusions A positive C. difficile test during the first year after diagnosis is associated with decreased time to first bowel resection surgery in pediatric Crohn’s disease. Depletion of beneficial commensals and methionine biosynthesis in patients with C. difficile carriage may contribute to increased risk for surgery.

Clostridium difficile (CD) diagnosis is very varied and under discussion. Different research groups disagree on the clinical significance of patients with negative direct toxin and positive polymerase chain reaction (PCR) or even more with direct toxin and glutamate dehydrogenase (GDH) both negatives, but CD detected by toxigenic culture (TC). The objective was to analyze the characteristics of patients with 3 different diagnostic criteria. We compared these 3 groups of patients: group 1: (GDH+/direct toxin+/PCR+), group 2: (GDH+/direct toxin-/PCR+) and group 3: (GDH-/direct toxin-/PCR not done/TC+). The proportion of patients with CD infection (CDI) (not colonization) for groups 1 to 3 was, respectively, 90.3%, 95.4%, and 59.1%. No differences between severity (40.8%, 38.5%, 27.3%), recurrence (20.3%, 24.1%, 7.6%), or related mortality (12.5%, 5.2%, 0%) were found within the 3 groups of patients. Laboratory clinical results should not be used as the only tool to differentiate CDI versus colonization or severity. We recommend that PCR or a second-look TC be performed on all patients.

Necrotizing pancreatitis (NP) patients commonly require antibiotic treatment during the several month-long disease course. We hypothesized that Clostridium difficile infection (CDI) is common in NP and significantly impacts outcomes.Retrospective review of 704 NP patients treated at a single-institution (2005-2018).10% (67/704) of patients developed CDI a mean 78 days after NP onset. Patients developing CDI experienced increased total hospital days (CDI, 104; No CDI, 42; P 0.001), readmission rates (CDI, 85%; No CDI, 64%; P = 0.006), and duration of NP (CDI, 248 days; No CDI, 183; P = 0.001). Risk factors for CDI included antibiotic use (OR, 96.2; 95% CI, 5.9-1556.2; P = 0.001) and any organ failure (OR, 2.0; 95% CI, 1.2-3.3, P = 0.008). Mortality was not affected by CDI (CDI, 10%; No CDI, 9%; P = 0.7).Clostridium difficile infection is common in necrotizing pancreatitis and negatively impacts morbidity and disease recovery.

This research compares the performance and diagnostic accuracy of three molecular tests for the detection of Clostridium difficile in stool samples, with the Xpert® C. difficile assay. Fifty-nine positive and twenty-five stool negative samples were analyzed by the BDmax™ Cdiff, the Simplexa C. difficile Direct, and the GenomEra™ C. difficile, and compared with the Xpert® C. difficile routinely used in our laboratory. The highest sensitivity was 94.9% for the BDmax™ Cdiff, followed by GenomEra™ C. difficile with 93.2%, and Simplexa™ C. difficile Direct with 89.8%. The specificities of all assays were 100%. GenomEra™ C. difficile had the highest retesting rate (12%). Simplexa™ C. difficile Direct benefits from both short hands-on time and total-turnaround time and 0% retesting. The differences in performance and accuracy between these three molecular assays are insignificant and all may be used as part of the routine algorithm for detection of C. difficile.

Rifaximin is an antimicrobial which is used for prophylaxis of hepatic encephalopathy in patients with cirrhosis and has known anti-Clostridioides difficile activity. The aim of this study is to assess whether the rate of C. difficile infection (CDI) is decreased in patients with cirrhosis on chronic rifaximin compared with those who are not. We retrospectively identified consecutive patients admitted to Montefiore Medical Center from 2010 to 2014 with cirrhosis and diarrhea who were tested for CDI. Demographics, comorbidities, medication exposure, baseline laboratory data, and outcomes were recorded. Patients with cirrhosis and diarrhea on chronic rifaximin were compared with those not on rifaximin. The chronic rifaximin group was then isolated, and those with and without CDI were compared. Of 701 patients with cirrhosis and diarrhea, 149 were on chronic rifaximin and 552 were not. 12.8% of patients on chronic rifaximin had CDI compared with 29.7% of those not on rifaximin (P

Background Gastrointestinal symptoms are common in patients with COVID-19, but prevalence of co-infection with enteric pathogens is unknown. Aims This study assessed the prevalence of enteric infections among hospitalized patients with COVID-19. Methods We evaluated 4973 hospitalized patients ≥ 18 years of age tested for COVID-19 from March 11 through April 28, 2020, at two academic hospitals. The primary exposure was a positive COVID-19 test. The primary outcome was detection of a gastrointestinal pathogen by PCR stool testing. Results Among 4973 hospitalized individuals, 311 were tested for gastrointestinal infections (204 COVID-19 positive, 107 COVID-19 negative). Patients with COVID-19 were less likely to test positive compared to patients without COVID-19 (10% vs 22%, p

Clostridium difficile infection has been associated with negative outcomes in the general population and in pregnant patients. Fecal microbiota transplant has become the standard for treatment of recurrent as well as refractory C difficile infection.We present a case of a 28-year-old pregnant woman who presented with recurrent C difficile infection despite treatment with vancomycin and fidaxomicin and underwent a successful fecal microbiota transplant through colonoscopy at 18 weeks of gestation. She no longer required antibiotics for the remainder of her pregnancy to treat C difficile and had a term vaginal delivery at 39 weeks of gestation.Our pregnant patient tolerated and responded to a fecal microbiota transplant for treatment of recurrent C difficile infection. Future large-scale studies are needed to determine the efficacy, safety, and long-term effects of manipulating the microbiome in pregnant patients and the neonates.