Management Of Clostridioides Difficile Infection Research Articles

Microbiota restoration for recurrent Clostridioides difficile: Getting one step closer every day!

Clostridioides difficile infection (CDI) is an urgent health threat being the most common healthcare-associated infection, and its management is a clinical conundrum. Over 450000 infections are seen in the United States with similar incidence seen in the rest of the developed world. The majority of infections seen are mild-moderate with fulminant disease and mortality being rare complications seen in the elderly and in those with comorbidities. The most common complication of CDI is recurrent infection with rates as high as 60% after three or more infections. A dilemma in the management of primary and recurrent CDI is testing due to the high sensitivity of the nucleic acid amplification tests such as the polymerase chain reaction, which leads to clinical false positives if patients are not chosen carefully (with symptoms) before testing. A newer testing regimen involving a 2-step strategy is emerging using glutamate dehydrogenase as a screening strategy followed by enzyme immunoassay for the C.difficile toxin. Microbiota restoration therapies are the cornerstone of management of recurrent CDI to prevent future recurrences. The most common modality of microbiota restoration is faecal microbiota transplantation, which has been tainted with heterogeneity and adverse events such as serious infectious transmission. The success rates for recurrence prevention from microbiota restoration therapies are over 90% compared with less than 50% of recurrence prevention with courses of antibiotics. This has led to development and emergence of standardized microbiota restoration therapies in capsule and enema forms. Capsule-based therapies include CP101 (positive phase II results), RBX7455 (positive phase I results), SER-109 (positive phase III results) and VE303 (ongoing phase II trial). Enema-based therapy includes RBX2660 (positive phase III data). This review summarizes the principles of management and diagnosis of CDI and focuses on emerging and existing data on faecal microbiota transplantation and standardized microbiota restoration therapies.

Diagnosis and management of Clostridioides difficile infection in patients with inflammatory bowel disease.

Clostridioides difficile infection (CDI) may complicate the course of ulcerative colitis and Crohn's disease. The clinical presentation of CDI in this population is often atypical, and patients may experience exacerbations of their underlying inflammatory bowel disease (IBD) secondary to C. difficile. In this review, we aim to review the risk factors, diagnosis, and management of CDI in the context of IBD. Patients with colonic involvement of their IBD are at higher risk for CDI and colonization may be more common than in the general population. Therefore, CDI is confirmed using a two-step approach to stool testing. Oral vancomycin or fidaxomicin are the preferred agents for nonfulminant disease, and oral metronidazole is no longer recommended as first-line therapy. For all patients with CDI recurrence, fecal microbiota transplant (FMT) should be considered, as this has been shown to be safe and effective. Among those who have worsening of their underlying IBD, retrospective research suggest that outcomes are improved for those who undergo escalation of immunosuppression with appropriate antimicrobial treatment of C. difficile, however prospective data are needed. CDI may complicate the course of IBD, however the presentation may not be typical. Therefore, all patients with worsening gastrointestinal symptoms should be evaluated for both CDI and IBD exacerbation. Providers should consider FMT for all patients with recurrent CDI as well as escalation of immunosuppression for patients who fail to improve with appropriate antimicrobial therapy.

Long-Term Bacterial and Fungal Dynamics following Oral Lyophilized Fecal Microbiota Transplantation in Clostridioides difficile Infection.

Oral lyophilized fecal microbiota transplantation (FMT) is effective in recurrent Clostridioides difficile infection (CDI); however, limited data exist on its efficacy in primary CDI and long-term microbial engraftment. Patients with primary or recurrent CDI were prospectively enrolled to receive oral FMT. Changes in the bacterial and fungal communities were characterized prior to and up to 6 months following treatment. A total of 37 patients with CDI (15 primary, 22 recurrent) were treated with 6 capsules each containing 0.35-g lyophilized stool extract. A total of 33 patients (89%) had sustained CDI cure, of whom 3 required a second course. There were no safety signals identified. FMT significantly increased bacterial diversity and shifted composition toward donor profiles in responders but not in nonresponders, with robust donor contribution observed to 6 months following FMT (P < 0.001). Responders showed consistent decreases in Enterobacteriaceae and increases in Faecalibacterium sp. to levels seen in donors. Mycobiome profiling revealed an association with FMT failure and increases in one Penicillium taxon, as well as coexclusion relationships between Candida sp. and bacterial taxa enriched in both donors and responders. Primary CDI was associated with more robust changes in the bacterial community than those with recurrent disease. Oral FMT leads to durable microbial engraftment in patients with primary and recurrent CDI, with several microbial taxa being associated with therapy outcome. Novel coexclusion relationships between bacterial and fungal species support the clinical relevance of transkingdom dynamics.IMPORTANCE Clostridioides difficile infection (CDI) is a substantial health concern worldwide, complicated by patterns of increasing antibiotic resistance that may impact primary treatment. Orally administered fecal microbiota transplantation (FMT) is efficacious in the management of recurrent CDI, with specific bacterial species known to influence clinical outcomes. To date, little is known about the efficacy of FMT in primary CDI and the impact of the mycobiome on therapeutic outcomes. We performed matched bacterial and fungal sequencing on longitudinal samples from a cohort of patients treated with oral FMT for primary and recurrent CDI. We validated many bacterial signatures following oral therapy, confirmed engraftment of donor microbiome out to 6 months following therapy, and demonstrated coexclusion relationships between Candida albicans and two bacterial species in the gut microbiota, which has potential significance beyond CDI, including in the control of gut colonization by this fungal species.

Establishment of a French surveillance system of Clostridiodes difficile infection: Comparison of patient’s characteristics with other national and European data

IntroductionThe magnitude and scope of Clostridioides difficile infection (CDI) has changed with an increase in incidence and severity. The epidemiology of CDI is not well known in France due to difficulties to conduct large continuous surveillance. The objectives were to compare the characteristics of patients with CDI collected through repeated point prevalence survey via DIFTEC™, a free electronic tool, with those from previous French or European studies. MethodsDIFTEC™ was developed to evaluate epidemiological burden, diagnostic strategies and management of CDI in France. National and European guidelines were used for definitions.A literature review of studies conducted in Western Europe on CDI and published between January 2008 and May 2018 was done to compare their data with those included in the DIFTEC™ database. ResultsFrom January 2016, to December 2017, 455 CDI episodes from 22 French hospitals were included. Most of CDI cases were health-care associated (HCA) (78%).The comparison between included patients and French literature data showed that the rates of previous antibiotics exposure, crude mortality and recurrence were not statistically different. However HCA-CDI was significantly more frequent in the DIFTEC™ study.Gender distribution, recurrence and crude mortality rates were not statistically different compared to European data. HCA-CDI was more frequent in the DIFTEC™ study whereas previous treatment with proton pump inhibitors and antibiotics were significantly higher in European studies. DiscussionThese results illustrated the added value of a new tool for increasing the reliable knowledge of CDI in France based on epidemiological surveillance implemented in health-care settings.

Usefulness of a newly developed high-speed polymerase chain reaction analysis system for the diagnosis of Clostridioides difficile infection

IntroductionThe incidence of Clostridioides difficile infection (CDI) has been continuously increasing and thereby became an important issue worldwide. Appropriate diagnosis, management, and infection control are required for patients with CDI. Enzyme immunoassay (EIA) is a widely used standard diagnostic tool for C. difficile-specific glutamate dehydrogenase (GDH) and C. difficile toxins (toxins A and B). However, the sensitivity of EIA in detecting C. difficile toxins has been reported to be relatively low, resulting in CDI underdiagnosis. Therefore, nucleic acid amplification tests (NAAT) are recently developed for higher sensitivity/specificity test. MethodsIn this study, a total of 279 stool samples submitted for CDI diagnosis were examined using an independently developed new high-speed polymerase chain reaction (PCR) device (PathOC RightGene, Metaboscreen). In parallel, results were compared with those of definitive diagnosis and conventional diagnostic methods (EIA, real-time PCR) to assess the inspection accuracy. ResultsPathOC RightGene showed high sensitivity (96.7%) and specificity (96.7%). Regarding the measurement time, C. difficile-specific and C. difficile toxin genes were simultaneously detected in approximately 25 min for one sample (including the preprocessing and measurement time). ConclusionPathOC RightGene has been found to show both excellent sensitivity and rapidity and thus can be used for the reliable and early diagnosis, which are needed for the appropriate management of CDI.

Management and characteristics of patients suffering from Clostridiodes difficile infection in primary care

Background Clostridioides difficile infection (CDI) is rising and increases patient healthcare costs due to extended hospitalisation, tests and medications. Management of CDI in French primary care is poorly reported. Objectives To characterise patients suffering from CDI, managed in primary care and describe their clinical outcomes. Methods Retrospective observational study based on survey data among 500 randomly selected General Practitioners (GPs) surveyed in France from September 2018 to April 2019. GPs were asked to complete a multiple-choice questionnaire for each reported patient presenting a CDI. Responses were analysed according to clinical characteristics. Treatment strategies were compared according to the outcome: recovery or recurrent infection. Results Participation rate was 8.6% (n = 43/500) with two incomplete questionnaires. Data from 41 patients with an actual diagnosis of CDI were analysed. Recovery was observed in 61% of patients with a confirmed diagnosis of CDI. In the recovery group, this was exclusively a primary episode, most patients (72%) had no comorbidities, were significantly younger (p = 0.02) than the ones who relapsed and 92% were successfully treated with oral metronidazole. Duration of diarrhoea after antimicrobial treatment initiation was significantly shorter in the recovery group (≤ 48 h) (p = 0.03). Cooperation with hospital specialists was reported in 28% of the recovery group versus 87.5% of the recurrent group (p = 0.0003). Overall, GPs managed successfully 82.9% of cases without need of hospital admission. Conclusion GPs provide relevant ambulatory care for mild primary episodes of CDI using oral metronidazole. Persistent diarrhoea despite an appropriate anti-Clostridiodes regimen should be interpreted as an early predictor of relapse.

The interplay of Clostridioides difficile infection and inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic disease of the intestinal tract that commonly presents with diarrhea. Clostridioides difficile infection (CDI) is one of the most common complications associated with IBD that lead to flare-ups of underlying IBD. The pathophysiology of CDI includes perturbations of the gut microbiota, which makes IBD a risk factor due to the gut microbial alterations that occur in IBD, predisposing patients CDI even in the absence of antibiotics. Superimposed CDI not only worsens IBD symptoms but also leads to adverse outcomes, including treatment failure and an increased risk of hospitalization, surgery, and mortality. Due to the overlapping symptoms and concerns with false-positive molecular tests for CDI, diagnosing CDI in patients with IBD remains a clinical challenge. It is crucial to have a high index of suspicion for CDI in patients who seem to be experiencing an exacerbation of IBD symptoms. Vancomycin and fidaxomicin are the first-line treatments for the management of CDI in IBD. Microbiota restoration therapies effectively prevent recurrent CDI in IBD patients. Immunosuppression for IBD in IBD patients with CDI should be managed individually, based on a thorough clinical assessment and after weighing the pros and cons of escalation of therapy. This review summarizes the epidemiology, pathophysiology, the diagnosis of CDI in IBD, and outlines the principles of management of both CDI and IBD in IBD patients with CDI.

A preliminary study of bowel rest strategy in the management of Clostridioides difficile infection

Clostridioides difficile infection (CDI) is an important nosocomial infection and is the leading cause of infectious diarrhea in hospitalized patients. We aimed to assess the effect of bowel rest on the management of CDI. A single-center retrospective cohort study was conducted. The primary outcome was the composite of the all-cause mortality and CDI recurrence within 30 days. The main secondary outcome was switching from metronidazole to vancomycin. Of the 91 patients with CDI enrolled as the full cohort, 63 patients (69%) and 28 patients (31%) constituted the control group and the bowel rest group, respectively. After one-to-one propensity score matching, a total of 46 patients were included as the matched cohort. In the full cohort, the composite outcome occurred in 19.0% and 14.3% of the patients in the control and the bowel rest group, respectively (p = 0.768). In the matched cohort, it was 17.4% in each group. Although there was no statistically significant difference, the trend of switching was lower in the bowel rest group. The bowel rest may not affect the all-cause mortality and CDI recurrence within 30 days. However, in those prescribed bowel rest, switching from metronidazole to vancomycin may reduce.

Clostridioides difficile infection in a long-term convalescence hospital: A real tale of pitfalls and outdated therapy.

ABSTRACTObjectiveThe aim of the study was to know the characteristics and risk factors of Clostridioides difficile infection (CDI) in a long-term hospital is key to improve its management.Material and methodsRetrospective study with 37 patients, along 43 months. We describe demographic variables, clinical data, time to diagnosis, treatment, and evolution.ResultsAnalysis of 46 episodes (37 patients, mean age=82.2 years). 77.8% were absolutely dependent, 41.7% had chronic kidney disease, 64.9% had received antibiotics in the previous three months, 40.5% received antibiotics at diagnosis. It was the first episode in 78.4%, and first recurrence in 21.6%. Therapy was started in the first 24 hours after diagnosis in 89.2%, mostly metronidazole. 83.3% recovered, 3 patients died from CDI, diagnosis was registered in the discharge report in 91.1%.ConclusionsPrevious antibiotic therapy, high grade of dependency and renal failure were the main risk factors. There is room for improvement in CDI management at our hospital.

Critical Care Management of the Patient with Clostridioides difficile.

To review published clinical evidence on management of Clostridioides difficile infection in critically ill patients. We obtained relevant studies from a PubMed literature review and bibliographies of reviewed articles. We selected English-language studies addressing aspects of C. difficile infection relevant to critical care clinicians including epidemiology, risk factors, diagnosis, treatment, and prevention, with a focus on high-quality clinical evidence. We reviewed potentially relevant studies and abstracted information on study design, methods, patient selection, and results of relevant studies. This is a synthetic (i.e., not systematic) review. C. difficile infection is the most common healthcare-associated infection in the United States. Antibiotics are the most significant C. difficile infection risk factor, and among antibiotics, cephalosporins, clindamycin, carbapenems, fluoroquinolones, and piperacillin-tazobactam confer the highest risk. Age, diabetes mellitus, inflammatory bowel disease, and end-stage renal disease are risk factors for C. difficile infection development and mortality. C. difficile infection diagnosis is based on testing appropriately selected patients with diarrhea or on clinical suspicion for patients with ileus. Patients with fulminant disease (C. difficile infection with hypotension, shock, ileus, or megacolon) should be treated with oral vancomycin and IV metronidazole, as well as rectal vancomycin in case of ileus. Patients who do not respond to initial therapy should be considered for fecal microbiota transplant or surgery. Proper infection prevention practices decrease C. difficile infection risk. Strong clinical evidence supports limiting antibiotics when possible to decrease C. difficile infection risk. For patients with fulminant C. difficile infection, oral vancomycin reduces mortality, and adjunctive therapies (including IV metronidazole) and interventions (including fecal microbiota transplant) may benefit select patients. Several important questions remain regarding fulminant C. difficile infection management, including which patients benefit from fecal microbiota transplant or surgery.

S1279 Web-Based Comparison of Traditional Didactics and Flipped Classroom on the Management of Clostridioides difficile Infection Among Internal Medicine Interns

INTRODUCTION: Interns in internal medicine are expected to manage a wide array of diseases; one being Clostridioides difficile infection (CDI). Considerable knowledge gaps in internal medicine exist in first year residents and thus we sought to focus intern education on the prevention, containment, and treatment of CDI. Furthermore, delivering education has faced a major challenge given the COVID-19 pandemic, forcing teaching to online platforms. Resident education often follows a passive teacher-centered model. In contrast, flipped classroom is an instructional model focused on student engagement while promoting active learning. The goals of this study were to determine CDI knowledge-gaps of interns at a large, tertiary care academic medical center and compare the effectiveness of traditional didactics (TD) vs. flipped classroom (FC) on an online platform. METHODS: A CDI curriculum was created using ACG and IDSA 2017 guidelines covering four major areas: epidemiology, diagnostics, medical management, and advanced management (Figure 1). Nineteen interns were enrolled: ten receiving the TD lecture and nine receiving the FC method (Figure 2) via an online conferencing site. TD learners individually completed an electronic 10-question pre-intervention survey to assess prior CDI knowledge. FC learners were provided with a pre-intervention lecture over video and answered the survey while collaborating in small groups on video chat rooms. All interns were surveyed again four-week post intervention. The primary outcome was the pre-post intervention increase in standardized CDI test scores. Secondary outcomes included quantification of CDI knowledge gaps of interns in internal medicine. RESULTS: Eighteen interns completed the study and were included in the analysis. Pre-intervention test results included epidemiology (25%), medical management (40%), diagnosis (53%), and advanced management (65%) for an overall average of 46% (Figure 3). There was no improvement in subtopic scores or overall score in the TD group. The FC group demonstrated an improvement in performance over three major subtopics with a pre-to-post increase in total score of 37% (P < 0.001). CONCLUSION: Interns in internal medicine have considerable knowledge gaps pertaining to CDI. Our FC strategy provided superior results than TD in terms of pre-to-post intervention survey scores. FC can be successfully executed using an online platform, thereby facilitating continued effective teaching for residents especially in times of social distancing.Figure 1.: Breakdown of the Clostridioides difficile curriculum used for both TD and FC groups.Figure 2.: TD learners (n = 10) were given a pre-test prior to in-class learning with slide presentation. FC learners (n = 9) were sent a video lecture prior to in-class team-based learning (TBL). All learners were asked to repeat the survey after four weeks.Figure 3.: A direct comparison of topic specific pre-test results with TD and FC post-intervention test results. Pre-test results were taken from TD learners only as they were individually completed prior to any intervention.

S0262 The Predictors of of Toxic Megacolon in Patients With Clostridioides difficile Infection

INTRODUCTION: Clostridioides difficile is anaerobic, gram-positive bacillus that can cause considerable morbidity and mortality. Toxic megacolon (TMC) is one of the most serious complications associated with Clostridioides difficile infection (CDI) which can lead to increased morbidity and mortality. Therefore, we conducted this study to assess the predictors for TMC in patients CDI using very large inpatient database. METHODS: We queried data from the National Inpatient Sample (NIS) database between 2002 and 2014. We identified all adult patients (≥ 18 year old ) who were diagnosed with CDI using the International Classification of Diseases ICD-9 codes. We divided the patients into two groups: patients with TMC (study group) and patients without TMC (control group). We assessed the predictors of TMC using multivariable logistic regression. RESULTS: We identified total of 802,293 patients between 2002 and 2014 who had CDI. Patients with TMC were older (71 vs 69), less likely to be female (58.5% vs 53.9%) and more likely to be Caucasian (80.7% vs 75.8%). In addition, patients in the study group were more likely to be obese (7.7% vs 6.7%, P < 0.001). Using multivariable analysis and after adjusting for potential cofounding factors including age, gender, obesity and Elixhauser comorbidities, Patients with coagulopathy were 50 % more likely to have TMC [Odds Ratio (OR): 1.5, 95% confidence interval (CI): 1.21–1.86, P < 0.001]. Additionally, TMC patients were more likely to have paraplegia [OR: 1.61, 95% CI: 1.25–2.07, P < 0.05], peripheral vascular disease (PVD) [OR: 1.37, 95% CI: 1.1–1.6], electrolytes abnormalities [OR: 1.8, 95% CI: 1.55–2.11] and malnutrition [OR: 2.29, 95% CI: 1.97–2.66], P < 0.05 for all. CONCLUSION: To our knowledge, this is the largest study that evaluated the risk of TMC in patients with CDI. We found that patients with TMC are older. In addition, patients with PVD, paraplegia, electrolyte abnormalities, coagulopathy and malnutrition are at higher risk for TMC. Early recognition of TMC during CDI and appropriate management are essential to improve outcomes in this population.

Management of Clostridioides difficile infection in patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a common diarrheal illness with gastrointestinal and extraintestinal manifestations and complications. The most common infectious complication associated with IBD is Clostridioides difficile infection (CDI). Active IBD predisposes to CDI due to alterations in the gut microbiome. C. difficile is a toxin producing bacterium leading to worsening of underlying IBD, increasing the risk of IBD treatment failure and an increased risk of hospitalization and surgery. Since the symptoms of CDI overlap with those of an IBD flare; it is prudent to recognize that the diagnosis of CDI is challenging and diagnostic tests (nucleic-acid and toxin-based assays) should be interpreted in context of symptoms and test performance. First line treatments for management of CDI in IBD include vancomycin or fidaxomicin. Recurrence prevention strategies should be implemented to mitigate recurrent CDI risk. One needs to monitor IBD disease progression and manage immunosuppression. The risk of recurrent CDI after a primary infection is higher in IBD compared to non-IBD patients. Microbiota restoration therapies are effective to prevent recurrent CDI in IBD patients. This review summarizes the epidemiology, pathophysiology, diagnostic testing, outcomes and management of both CDI and IBD, in CDI complicating IBD.

Follow your Gut: Microbiome-Based Approaches in the Developmental Pipeline for the Prevention and Adjunctive Treatment of Clostridioides difficile Infection (CDI)

Antibiotic use is the most important modifiable risk factor for the development of Clostridioides difficile infection (CDI). In addition, up to a quarter of patients treated with standard-of-care antibiotics experience disease recurrence. Until 2016, when bezlotoxumab was approved by the U.S. Food and Drug Administration (FDA), antibiotics were the only medication class approved for use in CDI. A growing knowledge of the roles that the gut microbiome and immune system play in CDI progression and recovery demands new approaches to treatment. As a result, there are many agents, including adjunctive biotherapeutics, nontoxigenic C. difficile competitors, enzymes, and antibiotic binders, used to prevent and treat CDI in the developmental pipeline. The purpose of this focused review is to summarize these unique therapies in all stages of development. Here, we discuss 13 agents in development, including four that have completed phase II trials, four in phase II trials, three in phase I trials, and two still undergoing preclinical trials. A number of new approaches including adjunctive biotherapeutics (n = 7), nontoxigenic C. difficile competitors (n = 1), enzymes used to prevent gut dysbiosis (n = 4), and antibiotic binders (n = 1) are discussed here. The CDI therapeutic pipeline contains a variety of unique microbiome-based approaches targeting both prevention and adjunctive treatment of CDI. The future of CDI management promises a variety of innovative approaches to better manage this disease state.

Effect of a prospective audit with intervention and feedback on Clostridioides difficile infection management.

Background Clostridioides difficile infections are associated with morbidity and mortality in several countries. Their increasing incidence and frequent recurrence make them an urgent public health threat. The lack of adherence to international treatment guidelines for Clostridioides difficile infections is a proven mortality risk factor. Objective To evaluate long-term prescribers' adherence to recommendations on the management of Clostridioides difficile infections and its impact on clinical outcomes after an educational and Clostridioides difficile-prospective audit with intervention and feedback period. Setting All patients admitted to a 1500-bed university hospital with positive Clostridioides difficile tests identified were included. Methods Data were collected retrospectively over a baseline period (May-November 2014) and prospectively over a Clostridioides difficile-prospective audit with intervention and feedback period (November 2015-May 2016) and an observation period (November 2017-September 2018). All Clostridioides difficile cases were reviewed by a Clostridioides difficile-prospective audit with intervention and feedback team composed of pharmacists, an infectious diseases specialist and a microbiologist to obtain a complete overview of patient records in each area of expertise. Main outcome measures Percentage of conformity to the protocol, percentage of recovery at 10days and percentage of relapse, as well as Clostridioides difficile incidence and percentage of Fidaxomicin use. Results A total of 183 patients were included over the three periods. A significant improvement in conformity to the local protocol was observed between the intervention period (23.9%) and the observation period (67.3%) (P < 10-3). Fidaxomicin prescriptions increased significantly (P = 0.006). Clinical outcomes improved significantly with an increase in the percentage of recovery at 10days (P = 0.001) and a decrease in the percentage of relapse (P = 0.016). The Clostridioides difficile incidence rate improved significantly to 1.3 per 10,000 patient-days during the observation period. Conclusion This study shows the lasting effect of an educational and Clostridioides difficile-prospective audit with intervention and feedback period on prescribers' adherence to recommendations and a significant impact on clinical outcomes.

Predictors of Clostridioides difficile Infection-Related Complications and Treatment Patterns among Nucleic Acid Amplification Test-Positive/Toxin Enzyme Immunoassay-Negative Patients.

The addition of toxin enzyme immunoassay (EIA) to nucleic acid amplification tests, including PCR, creates challenges in the diagnosis and management of Clostridioides difficile infection (CDI). There are limited data in large cohorts, with discordant results, that is, PCR-positive/EIA-negative (PCR+/EIA-) results. We conducted a retrospective cohort study on all PCR+/EIA- adult inpatients and assessed CDI-related complications and clinical failure. We identified 240 individuals. Twenty-three (9.6%) patients experienced a CDI-related complication, including 2 cases of megacolon, 1 colectomy, and 22 intensive care unit (ICU) admissions. In multivariable logistic regression analyses, baseline severe disease by Infectious Diseases Society of America (IDSA) criteria (odds ratio [OR], 5.84; 95% confidence interval [CI], 1.88 to 18.1; P = 0.002), baseline fulminant colitis (OR, 84.7; 95% CI, 14.3 to 500; P < 0.001), fever of >38.5°C (OR, 4.61; 95% CI, 1.42 to 15.0; P = 0.011), and proton pump inhibitor (PPI) use (OR, 3.50; 95% CI, 1.19 to 10.3; P = 0.023) were associated with increased odds of CDI-related complications. For 67 PCR+/EIA- patients who did not receive complete treatment, clinical failure was observed in 10 (15%) patients. A comparison of PCR+/EIA- patients who received complete treatment to all 112 PCR+/EIA+ patients showed no differences in CDI-related complications (11% and 13% for PCR+/EIA- and PCR+/EIA+ patients, respectively), 60-day all-cause mortality (17% and 18% for PCR+/EIA- and PCR+/EIA+ patients, respectively), or recurrent CDI (7% and 9% for PCR+/EIA- and PCR+/EIA+ patients, respectively). Predictors of CDI-attributable complications among PCR+/EIA- patients include baseline severe disease by IDSA criteria, baseline fulminant colitis, and fever of >38.5°C. Identifying the subgroup of PCR+/EIA- patients who could have true disease, and therefore allowing them to be targeted for treatment, is critical.

Evaluating Adherence to Guideline-Directed C Difficile Infection Management Pre- and Postimplementation of an Electronic Order Set

Background: After publication of the Clostridioides difficile infection (CDI) guidelines by the Infectious Disease Society of America (IDSA) in early 2018, we identified that many prescribers at our institution continued to practice using the older guidelines. Objective: This study aimed to determine whether the implementation of an electronic order set for CDI would increase prescriber compliance to current IDSA recommendations for CDI management. Methods: This was a single-center, prospective cohort study of adult inpatients with a confirmed CDI. The study was conducted between March 1, 2018, and April 1, 2019. Patients were stratified into a preintervention and postintervention group before and after order set implementation. The primary outcome was a composite of appropriate CDI therapy selection and discontinuation of nonessential antimicrobials and acid-suppressive agents. The secondary outcome evaluated appropriate CDI therapy medications prescribed at hospital discharge. Results: Of the 149 patients included in this study, 96 were included in a preintervention group and 53 included in a postintervention group. The primary outcome was met in 45% of patients in the preintervention group and 66% of patients in the postintervention group (P = .01). The secondary outcome occurred in 86% of patients in the preintervention group and 100% of patients in the postintervention group (P = .02). Conclusion: Implementation of a CDI electronic order set and alert bundle was associated with enhanced prescriber adherence to guideline-directed therapy. Our results suggest that order sets not only improve inpatient compliance to guidelines but may also improve medication-related adherence to guideline recommendations upon discharge.

Efficacy of Fecal Microbiota Transplant in Hematological Cancers Patients with Recurrent Clostridioides Difficile Infection: A Systemic Review and Meta-Analysis

Introduction: Fecal microbiota transplant (FMT) has been shown to be an effective treatment for recurrent Clostridioides difficile infection (CDI). Immunosuppression is one of the risk factors for CDI. However, most of the trials evaluating efficacy of FMT have excluded immunocompromised patients. Patients with hematological cancers represent a major class of immunocompromised patients. Hence, we performed a meta-analysis to evaluate the efficacy of FMT in patients with hematological cancer for the treatment of recurrent CDI. Methods: A systematic search of Medline, Embase, and Web of Science was performed from January 2000 up to December 2018. Articles included for meta-analysis were case series and case reports that assessed efficacy of FMT in hematological cancer patients were included. Study quality was assessed using the Newcastle-Ottawa scale. The main outcomes were pooled proportions of patients achieving cure after first FMT. The cure rate was defined as resolution of diarrhea without any recurrence. Results: 10 studies (5 case series and 5 case reports) were included in the analysis, making up 29 patients who underwent 38 total FMT procedures. The follow up period ranged from 1- 14 months. Of the included patients, 17 had leukemia, 10 had lymphoma and 2 patients had multiple myeloma and myelodysplastic syndrome each. 7 of these patients had undergone hematopoietic stem cell transplant. The pooled cure rate was 82% [confidence interval (CI) 67-94%] after 1 FMT with no heterogeneity (I2=0%). Minor publication bias was seen on visual inspection of funnel plot. FMT was generally well tolerated by these patients. No serious side effects were reported in any study. One of the studies reported death due to cardiac arrest 5 days after FMT which was thought to be unrelated to the procedure. Mild side effects including mild abdominal pain, transient diarrhea, fecal urgency, constipation and nausea were reported in 5 patients. Conclusion: Based on limited observational data, FMT seems to be an effective and safe modality for management of recurrent CDI in patients with hematological cancers. However, further prospective clinical trials are needed to establish its safety as a first line therapy for recurrent CDI in this population. Figure Disclosures Jamshed: Takeda Pharmaceutical: Honoraria. Khanna:Rebiotix, Inc: Research Funding; Probio Tech, LLC: Consultancy; Facile Therapeutics: Consultancy; Shire, Plc: Consultancy.

The engulfasome in C. difficile: Variations on protein machineries

Clostridioides difficile infection (CDI) continues to be a substantial healthcare burden, and the changing disease profile raises new challenges in CDI management, both in clinical settings and in the community. CDI is transmitted by spores, which are formed by a subset of the cell population where an asymmetric septum is formed. A full copy of the chromosome is transported into the smaller compartment which is then engulfed by the mother cell. After engulfment, multiple metabolic and morphological changes occur, eventually resulting in the release of the mature spore. Whilst studies in the model organism Bacillus subtilis have demonstrated the importance of the DMP and Q:AH machineries in engulfment, it is becoming clear that there are fundamental differences in the way the two organisms organise these machineries. As spores are the infectious agent in CDI, it is crucial to understand how these dormant cells are formed, and how sporulation can be prevented or disrupted with the view of reducing CDI. Here, we review the current literature on the DMP and Q:AH machineries in C. difficile, and how they compare and contrast to those of B. subtilis.

Mo1967 – Disparities in Management of Clostridioides Difficile Infection Between Teaching and Non-Teaching Hospitals

Mo1967 – Disparities in Management of Clostridioides Difficile Infection Between Teaching and Non-Teaching Hospitals