Khanna, Sahil

Abstract Background Fecal microbiota transplantation (FMT) cures ~90% of patients with recurrent Clostridioides difficile infection (rCDI). Ongoing or repeated exposure to risk factors, especially antibiotics (a modifiable risk factor but often necessary), may lead to future CDI. However, it is not known if FMT provides durable protection against future CDI despite subsequent antibiotic exposure. We studied the long-term durability of FMT against antibiotic exposure post-FMT. Methods A retrospective cohort study of patients undergoing FMT via colonoscopy for rCDI from Sep 2012 - Jun 2018 was performed. Patients were followed up for 1 year after FMT; data regarding future CDI episodes (watery diarrhea with positive stool test after interim symptom resolution), healthcare exposure, systemic non-CDI antibiotics and acid blocker therapy were collected. Primary outcome was ‘durability’ of response to FMT (defined as no CDI within 1 year post-FMT). Descriptive statistics, Chi square test, Wilcoxon test and multivariate logistic regression were used as appropriate. Results The study included 460 patients; median age 57 years (range 18–94 years), 65.2% (300) female. Overall 31.6% (144) received antibiotics; median number of courses of antibiotics, 2 (range 1–7). Of those who received antibiotics, the incidence of future CDI was 24.3% (n = 34), compared with 9% (n = 28) of those who did not receive antibiotics (P < .001). Median time to first CDI episode post-FMT was 103 (range 5–338) days. Incremental antibiotic courses did not lead to increased risk of future CDI (comparing 1, 2 or ≥3 courses, p = .68). In patients with antibiotic exposure, age and risk factors were similar in patients with and without future CDI (Table 1). Amongst those without antibiotic exposure, inflammatory bowel disease (IBD) predicted future CDI (p = .02). After controlling for risk factors and comorbidities, antibiotic use (p = .004) and IBD (p = .02) independently increased risk of future CDI. Conclusion The majority of patients with rCDI have a durable response to FMT despite ongoing risk factors. These data suggest that three-fourth of patients who receive antibiotics after FMT do not develop future CDI. IBD and antibiotic exposure independently increase the risk of future CDI. Disclosures All authors: No reported disclosures.

Abstract Introduction: C. difficile infection (CDI) is a common nosocomial infection. Immune suppression is thought to be a major risk factor for CDI. Hematopoietic stem cell transplant (HSCT) recipients represent a major subgroup of immunologically vulnerable patients. It is unclear if these patients have novel risk factors for CDI development. We, therefore, performed a systematic review and meta-analysis to evaluate the predictors of CDI in HSCT recipients. Methods: A systematic search of Medline, Embase, and Web of Science was performed from January 2000 up to June 2018. All studies that assessed risk factors associated with CDI development in HSCT recipients were eligible for inclusion. Data on clinical characteristics and risk factors associated with CDI development were collected. Study quality was assessed using the Newcastle-Ottawa scale. Meta-analyses were performed using random effects models and pooled odds ratios with 95% confidence interval (CI) for risk factors reported in ≥ 2 studies were calculated. Results: Overall, 17 studies, including 6328 HSCT patients were included. Of those 874 patients developed CDI. The rate of CDI development in these patients was 13.81% with a follow up ranging from 1- 36 months. A total of 34 different risk factors were studied, of which 20 were identified in ≥ 2 studies. Our analysis showed that cephalosporin use (Odds ratio [OR] 2.21, 95% confidence interval [CI] 1.26-3.87), cord blood transplant (OR 1.36, 95% CI 1.01-1.83), graft versus host disease (GVHD) (OR 1.63, 95% CI 1.07-2.48) & prior hospitalization within 90 days of HSCT (OR 1.85, 95% CI 1.21-2.83) were associated with statistically significant increased risk of CDI in HSCT patients (Figure 1). On the other hand, many characteristics of HSCT patients including age, diabetes, lung disease, fluoroquinolones, proton pump inhibitors, rituximab, mucositis, myeloablative therapy, melphalan use before BMT, total body irradiation, growth factor use during admission, neutropenia, autologous vs allogenic transplant and use of matched related donor were not associated with increased risk of CDI. Conclusion: HSCT recipients are at an increased risk of CDI compared to general population. In addition to the common risk factors like cephalosporin use and prior hospitalization, these patients have novel characteristics including presence of GVHD and cord blood transplant that puts them at a higher risk of CDI. HSCT patients with these risk factors may warrant a closer surveillance for early detection and treatment of CDI. Table 1. Table 1. Disclosures No relevant conflicts of interest to declare.

INTRODUCTION: Currently, surgery is the primary treatment option for refractory, severe-complicated Clostridioides difficile infection (CDI) in the inpatient setting. There are limited series reporting the efficacy of Fecal Microbiota Transplantation (FMT) to treat such cases as an alternative to surgery or in patients who are not surgical candidates. We aimed to assess the response rate and prognosis of these patients after inpatient FMT. METHODS: We conducted a retrospective chart review of patients with CDI (watery diarrhea with positive stool assay) admitted in the ICU, and who received FMT from January 2013 to July 2016. Potential cases were identified by diagnosis codes and eligibility was confirmed through manual chart review. Severe-complicated CDI was defined as CDI with any of the following: ICU admission, hypotension, shock, sepsis, megacolon, colectomy or death due to CDI. CDI was termed refractory in the absence of clinical response to antibiotics after 5 days. Recurrence was defined as typical CDI symptoms and positive stool assay within 56 days of treatment with interim symptom resolution. The primary outcome was resolution of CDI (clinical cure with no recurrence). Secondary outcomes included risk of recurrent CDI and mortality. Microsoft Excel was used for descriptive statistical analysis. RESULTS: Of 273 patients screened, 6 cases met inclusion criteria. Five patients received FMT via colonoscopy, one via retention enema. The mean age at time of FMT was 72 (range, 54-88) years, 4 (66%) patients were female. All had severe-complicated CDI, 3 had concomitant diverticulosis and none had inflammatory bowel disease (IBD). The median follow-up after FMT was 8.5 (range, 1-18) months. Three patients received non-CDI antibiotics within 6 months post-FMT, 3 received acid suppression therapy (Table 1). FMT was performed after a median of 3 (range, 1-5) episodes of CDI with a median of 4.5 previous courses of antibiotics (range 2-6 courses) (Table 1). Four of the six patients (66%) had resolution of CDI, 2 patients had recurrence. One patient died due to sepsis secondary to CDI; 3 died due to unrelated causes. CONCLUSION: In this small retrospective study, inpatient FMT was effective for treating refractory severe-complicated CDI. There was one CDI-related mortality by the end of follow up. FMT may be an alternative therapy in patients with severe-complicated CDI.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at significantly increased risk for Clostridium difficile infection (CDI). CDI in IBD is associated with increased in-hospital mortality, IBD treatment failure, re-hospitalization and high CDI recurrence rates. The existing literature on predictors of these adverse outcomes is limited. We evaluated four potentially modifiable novel risk factors (BMI, statin use, opioid use, and antidepressant use) on the risk and outcomes of CDI in patients with IBD. METHODS: CDI disease severity and other clinical outcomes, including colon surgery, CDI recurrence, CDI-related hospitalization, IBD exacerbations, and mortality were abstracted using the electronic medical record. Additionally, variables including BMI, statin use, opioid use, and antidepressant use at the time of CDI were abstracted from records for patients with IBD and CDI from 2008 and 2013. Statistical analysis comprised of descriptive statistics and univariate and multivariate logistic regression analyses. RESULTS: There were 137 patients with IBD and CDI included in this study: 70 with ulcerative colitis (51%), 63 with Crohn's disease (46%), and 4 with indeterminate colitis (3%). The median age was 46 years, and 55% were female. On multivariate analysis controlling for age, 43% of patients in the overweight BMI category had severe or severe complicated CDI, compared to 22% of patients in the underweight/normal BMI (OR, 2.85, P = 0.02) and 19% in the obese category (OR, 3.95, P = 0.04). Statin use was associated with severe or severe complicated CDI when controlling for age and BMI (OR, 5.66, P = 0.01). On multivariate analysis controlling for age and CDI severity, there was no association between statin use and post-CDI IBD exacerbations. Opioid and antidepressant use were not associated with CDI disease severity or IBD exacerbations. BMI category, statin use, opioid use, and antidepressant use were not associated with colon surgery, CDI recurrence, CDI-related hospitalizations, or mortality at 1 year. CONCLUSION: An overweight BMI and statin use were associated with severe or severe complicated CDI. There was no association between statin use and IBD exacerbations following CDI. Opioid and antidepressant use were not associated with disease severity or frequency of IBD exacerbations following CDI. Further studies are needed to better understand how these results could impact management of patients with IBD to improve clinical outcomes and potentially reduce the risk of CDI.

INTRODUCTION: Graft versus Host disease (GVHD) is a major cause of mortality and morbidity in allogenic hematopoietic stem cell transplant recipients (HSCT). Gut microbiome dysbiosis secondary to conditioning regimens (which include antibiotics) in HSCT, appears to play a significant role in gut GVHD development through its interaction with the immune system. Fecal Microbiota Transplantation (FMT) has been explored for the treatment of gut GVHD owing to its ability to restore the gut microbiome. We performed a systemic review and meta-analysis to review the efficacy and safety of FMT for gut GVHD. METHODS: A systematic search of Medline, Embase, and Web of Science was performed from January 2000 through May 2019. Articles included for meta-analysis were observational studies which included patients with steroid-dependent or resistant gut GVHD after HSCT who underwent one or more FMTs. The main outcomes were pooled proportions of patients achieving response defined as a decrease in gastrointestinal symptoms including stool volume and frequency or reduction of steroid or immunosuppressant dose. Partial response was defined as a decrease of gastrointestinal symptoms followed by recurrence of symptoms. RESULTS: Five studies (4 prospective single arm pilot studies and 1 retrospective case series) including 37 patients were included with follow up ranging from 1–13 months. Three studies used naso-duodenal route, one used oral capsules and one used colonoscopy for FMT. Median number of FMTs per study was 2 (range, 1–6). Unrelated donors were used in 4 studies. A total of 23/37 patients achieved complete response with a pooled proportion of 61.0% (95% confidence interval [CI] 46–76.0), with no heterogeneity (I 2 = 0%). Partial response was seen in 3 patients. Hence, the overall response rate was 74.0% (95% CI 49–93, I 2 53%). FMT was generally well tolerated. No treatment-related mortality was reported by any study. Serious adverse events were reported in 3 patients (hypoxia in one patient and bacteremia in two patients) but were not directly attributed to FMT. CONCLUSION: FMT is a promising modality for management of gut GVHD and appears to be safe as a salvage therapy based on the current limited data. Ongoing placebo-controlled prospective clinical trials will help to further establish its safety and efficacy.

INTRODUCTION: Microscopic colitis (MC) is a common cause of chronic watery diarrhea. Cross-sectional studies have suggested that patients with MC have a lower incidence of colon polyps compared to those without MC. However, existing literature is limited by a lack of longitudinal follow-up and the use of average-risk patients, rather than those with chronic diarrhea as controls. We aimed to further explore the association between MC and colon adenomas. METHODS: This retrospective cohort study included patients that underwent colonoscopy at Mayo Clinic (Rochester, MN) or Columbia University Medical Center (New York, NY) between 7/1/2006 and 12/31/2016. Consecutive cases with MC were identified using pathology databases at each center. Controls had chronic diarrhea, underwent colonoscopy, and did not have MC on biopsy. Cases and controls were matched 1:2 by age (±3 years), sex, and date of index colonoscopy (±6 months). Data was collected on demographics, tobacco and alcohol use, personal and family history of colon neoplasia, and presence of adenomas at the index or follow-up colonoscopies. RESULTS: The study included 376 patients with MC and 752 non-MC patients with chronic diarrhea. The median (range) age of patients was 64 (21, 88) years and 72% were female. Duration of follow-up was not significantly different between the 2 groups (total person years: cases 577, controls 972; P = 0.99) and 51 subjects had a new adenoma on follow-up. There were no significant differences in age, sex, alcohol use, family history of colon neoplasia, and personal history of inflammatory bowel disease between cases and controls. Patients with MC were more likely to be current tobacco users (10% vs. 6%, P = 0.02) and less likely to have a history of prior colon neoplasia (9% vs. 17%, P < 0.001). Patients with MC were significantly less likely to have colon adenomas at the time of their index colonoscopy (5% vs. 12%; odds ratio 0.36; 95% CI 0.21, 0.60; P < 0.001) after adjusting for tobacco use and history of prior lesions. However, when followed over time, there was no significant association between MC and risk of colon adenomas (Figure 1, P = 0.45) after adjusting for tobacco use, history of prior lesions, and presence of adenoma at index colonoscopy. CONCLUSION: Patients with MC are less likely to have colon adenomas at their index colonoscopy compared to those with chronic diarrhea without MC. However, when followed longitudinally, there appears to be no significant association between MC and risk of colon adenomas.

Introduction: Clostridioides difficile infection (CDI) is associated with substantial emergency department (ED) and inpatient burden. To date, few studies have evaluated the ED burden of CDI. Using the Nationwide Emergency Department Sample, we evaluated trends in ED use, ED and inpatient charges, admission and mortality rates, length of stay, and independent risk factors for hospital admission and mortality after an ED visit. Methods: Using Nationwide Emergency Department Sample for 2006 through 2014, we identified all patients with the primary diagnosis of CDI (using diagnostic codes). We determined the trends in ED visits and used survey logistic regression analysis to identify factors associated with hospital admission. Results: Overall, 909,236 ED visits for CDI resulted in 817,935 admissions (90%) to the hospital. The number of visits increased from 76,709 in 2006 to 106,869 in 2014, and the admission rate decreased from 92.4% to 84.4%. ED charges adjusted for inflation went up from US$1433.0 to 2900, a significant rise even accounting for inflation. The overall length of hospital stay decreased from 7 to 5.8 days. Independent predictors of admission after ED visits included smoking, use of alcohol, and presence of multiple comorbidities. Independent risk factors for mortality in admitted patients include increasing age and presence of comorbidities. Conclusions: Although ED use for CDI increased, rates of hospital admission decreased over 9 years. Identification of predictors of admission and in-hospital mortality will help guide policies and interventions to reduce the burden on health care resources.

e18244 Background: Clostridioides difficile infection (CDI) has higher incidence in cancer patients. To characterize the extent of CDI burden among hematologic cancer patients, we used the National Hospital Discharge Survey (NHDS) to report the incidence and outcomes of CDI. Methods: NHDS data from 2001-2010 were analyzed using diagnosis codes to identify patients with hematologic cancers and CDI. Demographics and discharge information were compared amongst hematologic cancer patients with and without CDI. Logistic regression models were runto estimate the impact of CDI on hematologic cancer patient outcomes, using STATA 12.0. Results: During the years 2001-2010, about 3.7 million patients (weighted data) were discharged with hematologic cancer. Among them, the incidence of CDI was 2.3%. Hematologic cancer patients with CDI were younger (mean age 66 vs 68 years), more likely to be men (66% vs 64.5%), to be of white race (68.1% vs 67.7%) and to have emergent admissions (73% vs 69%), all p values < 0.001. CDI incidence in these patients showed a steeper increase than non-cancer patients, with highest incidence in 2008-2009. Hematologic cancer patients with CDI had a longer mean Length of stay (16.9 vs 7.1 days; adjusted odds ratio (aOR) 9.5, 95% CI 9.4-9.6), all cause hospital mortality (11.3% vs 6.3%; aOR 1.92, 95% CI 1.88-1.97) and discharge to a care facility (28.4% vs 18.8%; aOR 2.06, 95% CI 2.02-2.10) compared to non-CDI cancer patients. Conclusions: CDI incidence is higher in patients with hematologic malignancy. They also have worse outcomes including overall mortality, longer hospitalizations and discharge to healthcare facility. These patients warrant closer screening and prompt treatment of CDI as they are at greater risk of unfavorable outcomes. [Table: see text]

Clostridioides difficile infection (CDI) is a common cause of diarrhea in both inpatient and outpatient settings. The last few years have seen major changes in the treatment spectrum of CDI, most notably, recommendations against using metronidazole for initial CDI, the addition of fidaxomicin and bezlotoxumab, and emergence of microbial replacement therapies. Several other therapies are undergoing clinical trials. This narrative review focuses on the treatment of CDI with a summary of literature on the newer modalities and the treatment guidelines issued by Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases.