Diagnosis Of CDI Research Articles

Clinical case of complicated and recurrent course of Cl. difficile-associated colitis in a child under 1 year of age

Currently, antibiotic-associated diarrhea caused by Clostridioides difficile (Cl. difficile) is one of the problems of the health care system in many countries of the world and the main causative agent of healthcare-associated infections. The article describes a clinical case from our own practice of the occurrence of Cl. difficile associated diarrhea (CDI) in a child in the first year of life. In the described clinical case, the child developed the first episode of CDI against the background of antibiotic therapy, which, due to the inadequate duration of treatment, led to a relapse of the disease and the development of complications in the form of sepsis. Thus, with clinical case, we want to draw the attention of practitioners to the problem of CDI in young children. Currently, despite significant changes in the diagnosis of CDI, the diagnosis of CDI in young children is challenging, requiring the development of accurate diagnostic criteria for diagnosis and the definition of additional diagnostic markers to distinguish healthy carriage from disease.

Outcomes and risk factors for mortality in clostridioides difficile infection in patients with NAFLD and NASH

Introduction and ObjectivesNon-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH) and, ultimately, cirrhosis. Clostridioides difficile is the most common nosocomial cause of diarrhea and is associated with worse clinical outcomes in other liver diseases, including cirrhosis, but has not been extensively evaluated in concomitant NAFLD/NASH. Materials and MethodsWe conducted a retrospective cohort study using the National Inpatient Sample database from 2015 to 2017. Patients with a diagnosis of CDI, NAFLD, and NASH were identified using International Classification of Diseases (Tenth Revision) codes. The outcomes of our study include length of stay, hospitalization cost, mortality, and predictors of mortality. ResultsThe CDI and NASH cohort had a higher degree of comorbidity burden and prevalence of peptic ulcer disease, congestive heart failure, diabetes mellitus, and cirrhosis. Patients with NASH and CDI had a significantly higher mortality rate compared to the CDI only cohort (mortality, 7.11 % vs. 6.36 %; P = 0.042). Patients with CDI and NASH were at increased risk for liver-related complications, acute kidney injury, and septic shock (P < 0.001) compared to patients with CDI only. Older age, intestinal complications, pneumonia, sepsis and septic shock, and liver failure conferred an increased risk of mortality among the CDI and NASH cohort. ConclusionsPatients with NASH had a higher rate of liver-related complications, progression to septic shock, and mortality rate following CDI infection compared to the CDI only cohort.

157. Implementation of multidisciplinary diagnostic stewardship for Clostridioides difficile infection during the COVID-19 pandemic at a small Japanese hospital

Abstract Background Clostridioides difficile infection (CDI) is a common, healthcare-associated infection. However, its incidence has reportedly declined in the United States owing to the COVID-19 pandemic. On the other hand in Japan, testing for CDI has been infrequent, suggesting that this disease may be underdiagnosed. The present study examined the implementation of multifaceted, diagnostic stewardship for CDI in a small Japanese hospital during the pandemic. Methods The following interventions were introduced at Tama-Nambu Chiiki Hospital, a small community hospital in Tokyo: 1) criteria for CDI testing were added to the hospital's guidelines; 2) clinical pharmacists and nurses assessed the need for CDI testing in patients with nosocomial diarrhea and made recommendations for CDI testing to physicians; 3) a tutorial on CDI testing was given to physicians, nurses, and pharmacists; 4) data on the density of CDI testing and the CDI incidence in the hospital were provided to healthcare workers every three months. The outcomes were CDI testing frequency and the CDI incidence per 10,000 patient days. Segmented regression in interrupted time-series analysis (ITSA) was performed before the pandemic (2018/04-2020/03), after the pandemic (2020/04-2022/03), and after the intervention (2022/04-2023/03). Results The frequency of CDI testing tended to increase before the pandemic (+0.16/10,000 PD, P=0.28) but decreased significantly after the pandemic (-0.79/10,000 PD, P=0.02), then increased significantly immediately after the intervention (+29.6/10,000 PD, P&amp;lt; 0.01). Similarly, the incidence of CDI increased significantly before the pandemic (+0.23/10,000PD, P=0.02) but decreased significantly after the pandemic (-0.45/10,000PD, P=0.01). Implementation of the intervention resulted in an immediate, significant increase in the CDI incidence (+6.8/10,000PD, P&amp;lt; 0.01). Conclusion Multifaceted, diagnostic stewardship involving multiple specialists was effective in improving CDI testing, suggesting that appropriate testing can contribute to the accurate diagnosis of CDI. Disclosures All Authors: No reported disclosures

136. Impact of a Tele-Stewardship and Tele-Infection Prevention Program on Hospital-Onset Clostridioides Difficile Rates in a Community Three-Hospital Health System

Abstract Background Clostridioides difficile infection (CDI) is a common hospital-acquired infection (HAI) that can be difficult to diagnose accurately given the numerous test modalities with differing performance characteristics. Inaccurate diagnosis of CDI can negatively affect patient care decisions as well as reimbursement rates. Community and rural hospitals (CARH) may lack specialized personnel or knowledge to implement diagnostic best practices, but telehealth solutions like tele-infection prevention (TIP) and tele-antimicrobial stewardship (TASP) can provide specialist support for CARHs to optimize diagnostic pathways, improve accuracy, and reduce unnecessary treatment. Methods In June 2021 under the guidance of TIP and TASP recommendations, C. difficile testing was transitioned from a 1-step nucleic acid amplification test (NAAT)-only algorithm to a 2-step algorithm that included NAAT and toxin enzyme immunoassay (EIA) testing. A 6-month pre- and post-implementation assessment was conducted to assess the impacts of this change in hospital-onset CDI (HO-CDI) case rate. Additionally, total C. difficile (community- and hospital-onset CDI) rates per 1000 patient days (PD) and consumption of CDI therapeutics were assessed. For statistical analysis, Wilcoxon ranked-sum test to assess changes in CDI rates. Estimated annualized cost-savings for therapeutics were calculated based on institutional purchasing costs. Results Following implementation, a 35.9% reduction in HO-CDI was observed (pre 0.96 cases/1000PD vs. 0.61 cases/1000PD; p = 0.054). A 10.2% reduction was observed in total CDI (pre 3.66 cases/1000PD vs. 3.28 cases/1000PD; p = 0.37). Additionally, a 30.6% reduction was observed in consumption of CDI therapeutics (20.1 doses/1000PD vs. 14.0 doses/1000PD) resulting in an annualized cost-savings of approximately $9200. Conclusion Our TIP and TASP advised a community three-hospital health system on optimal diagnostics resulting in a change in their algorithm. Following this, considerable reductions were observed in HO-CDI, total CDI, consumption of CDI therapeutics, and the associated costs of care. Disclosures Erin K. McCreary, PharmD, Abbvie: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Honoraria|La Jolla (Entasis): Advisor/Consultant|LabSimply: Advisor/Consultant|Merck: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Honoraria

OR20-06 Diagnosing Central Diabetes Insipidus Using Copeptin Upon Hypertonic Saline Versus Arginine Stimulation

Abstract Disclosure: J. Refardt: None. C. Atila: None. I.O. Chifu: None. E. Ferrante: None. Z. Erlic: None. J.B. Drummond: None. B. Mantovani: None. R. Drexhage: None. C.O. Sailer: None. A. Widmer: None. S. Felder: None. A.S. Powlson: None. N. Hutter: None. D. Vogt: None. M. Gurnell: None. B. Rocha: None. J. Hofland: None. F. Beuschlein: None. M. Fassnacht: None. B.F. Winzeler: None. M. Christ-Crain: None. Background: The main challenge in the diagnosis of central diabetes insipidus (cDI) is its distinction against primary polydipsia (PP). Hypertonic saline stimulated copeptin has a high diagnostic accuracy of 97%, but comprises discomfort for patients and requires close sodium monitoring. Arginine stimulated copeptin showed similar diagnostic accuracy of 93% with better tolerability, but a head-to-head comparison is lacking. We hypothesized that arginine stimulated copeptin is non-inferior (non-inferiority margin 10%) to hypertonic saline stimulated copeptin for the diagnosis of cDI. Methods: In this prospective randomized multicentre study conducted between 2018-2022 in seven tertiary medical centres, consecutive patients with cDI and PP underwent diagnostic evaluation with hypertonic saline and arginine stimulation. Serum copeptin levels were measured at sodium-level of &amp;gt;149 mmol/L after hypertonic saline and 60 minutes after arginine infusion, respectively. The final diagnosis was made after treatment response assessment at three-month follow-up blinded to copeptin levels. The main outcome measure was the overall diagnostic accuracy using the pre-defined copeptin cut-off of 4.9 pmol/L for hypertonic saline and 3.8 pmol/L for arginine stimulation. Results: 158 patients underwent both tests, of which 69 (44%) were diagnosed with cDI and 89 (56%) with PP. Forty-one (59%) patients had a complete and 28 (41%) patients had partial cDI. The diagnostic accuracy [95% CI] to differentiate patients with cDI from patients with PP was 95.6% [91.1,97.8] for hypertonic saline stimulated copeptin compared to 74.4% [67.0, 80.6] for arginine stimulated copeptin. Accordingly, arginine stimulation was inferior to hypertonic saline stimulation (estimated difference [95% CI] -21.2% [-28.7, -14.3]). Side effects were less frequent and less severe under arginine stimulation, resulting in a clear 72% of patients preferring the arginine stimulation over hypertonic saline stimulation. In addition, arginine stimulated copeptin of 3.0 pmol/L diagnosed cDI with a specificity of 90.9% (sensitivity of 59.5%), while a cut-off of 5.2 pmol/L diagnosed PP with a specificity of 91.4% (sensitivity of 56.4%). Conclusion: In the diagnostic evaluation of cDI, copeptin upon hypertonic saline stimulation was superior to arginine stimulation. Arginine stimulation can be used as a first well-tolerated test diagnosing &amp;gt;50% of patients with high accuracy, but hypertonic saline stimulation remains the test with the highest diagnostic accuracy. Presentation: Saturday, June 17, 2023

A233 OUTCOMES OF CLOSTRIDIOIDES DIFFICILE INFECTION IN SURGICAL PATIENTS: RESULTS FROM NATIONAL INPATIENT SAMPLE 2016-2019

Abstract Background Clostridioides difficile infection (CDI) is the most common nosocomial infection and is associated with significant morbidity and mortality. Purpose We aimed to identify the burden of CDI in patients undergoing common gastrointestinal (GI) surgical procedures in a national inpatient cohort, as GI surgeries have been thought to be a risk factor for CDI. Method We used the National Inpatient Sample (NIS) database from Unites States for the years 2016-2019 for this study. We included adult patients (age ≥ 18), who underwent common GI surgeries (identified using ICD-10 procedure codes), and among them identified patients with diagnosis of CDI. Outcomes assessed included risk of CDI among different surgeries, inpatient mortality, length of stay (LOS) and cost of hospitalization using regression analyses Result(s) From 2016 to 2019, an estimated total of 4,438,778 patients were hospitalized and underwent any of the studied GI surgeries. CDI was reported in 32,180 admissions (0.72%). Median age for CDI was higher than non-CDI patients (66 vs 56, p&amp;lt;0.001). Incidence of CDI was 2.5 times higher in patients admitted emergently compared to elective admissions (1.00% vs 0.40%, p&amp;lt;0.0001). Among all surgeries, the incidence of CDI was the highest for small bowel resection at 2.1% followed by partial esophagectomy at 1.6% and partial colectomy at 1.4%. Logistic regression analysis showed the patients undergoing esophagectomy had the highest risk with adjusted Odds Ratio (aOR) of 2.48, (95% CI 2.01 – 3.07, p&amp;lt;0.0001), followed by pancreatectomy with aOR 2.03 (95% CI 1.91 – 2.16, p&amp;lt;0.0001). Overall, surgical patients with CDI had a significantly higher in-patient mortality compared to non-CDI patients (8.2% vs 1.4%, p&amp;lt;0.0001). Logistic regression analysis showed an increased risk of inpatient mortality with CDI, with aOR 1.36, 95% CI 1.30 – 1.42, p&amp;lt;0.0001. Median LOS for surgical patients with CDI was higher than non-CDI patients (14 days vs 3 days, p&amp;lt;0.0001). The linear regression analysis for length of stay showed that among patients undergoing surgical procedures, CDI was associated with an increased LOS with beta of 8.39 days ± SE 0.04 (95% CI 8.31 – 8.46, p&amp;lt;0.0001). The mean cost of hospitalization for surgical patients with CDI was higher than non-CDI patients ($90,590 vs $31,702, p&amp;lt;0.0001) after adjusting for inflation over the four-year period. The linear regression analysis showed that CDI was associated with an increased cost of hospitalization with a beta of $25,343 ± SE 166 (95% CI 25,017 – 25,670, p&amp;lt;0.0001). Conclusion(s) CDI among GI surgeries leads to increase in inpatient mortality, length of stay and cost of hospitalization. Although the rate of CDI is showing a downwards trend, its impact on these outcome measures makes it an important complication to prevent and promptly treat in these surgical patients. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Diagnosis and Management of New-Onset Central Diabetes Insipidus in Critically Ill Children Varies between Pediatric Critical Care Medicine and Pediatric Endocrinology Clinicians

AbstractThe diagnosis and management of central diabetes insipidus in critically ill children is not standardized. Our objective was to characterize differences between Pediatric Critical Care Medicine (PCCM) and Pediatric Endocrinology (PE) clinicians in the diagnosis and management of new-onset CDI in the pediatric intensive care unit. We also sought to characterize knowledge gaps among general pediatrics (GP) residents. This is a scenario-based survey to assess patterns of diagnosis and management of new-onset CDI that was distributed to PCCM, PE, and GP clinicians who work in a quaternary care urban children's hospital. Of 275 PCCM, PE, and GP clinicians surveyed, 158 (57%) responded. More PCCM than PE clinicians relied on serum sodium levels (96 vs. 75%, p &lt;0.01) and more PE than PCCM clinicians relied on serum osmolality (91 vs. 40%, p &lt; .001) for diagnosis. Fewer PCCM than PE clinicians favored restricting IV fluids to two-thirds maintenance rate (4 vs. 37%, p &lt;0.001). More PCCM than PE clinicians favored a starting dose of 0.5 milli-units/kg/h for IV vasopressin infusion (76 vs. 53%, p = 0.048). More PCCM clinicians than PE clinicians favored titrating the IV vasopressin infusion every 20 minutes (24 vs. 2%, p = 0.02), whereas more PE clinicians than PCCM clinicians favored titration every 60 minutes (38 vs. 14%, p = 0.03). GP residents earlier in training had greater self-reported gaps in knowledge. We observed substantial variability in the diagnosis and management of new-onset CDI in critically ill children among PCCM, PE, and GP clinicians. There is a need for greater standardization in care of these patients.

Novel immunoassay for diagnosis of ongoing Clostridioides difficile infections using serum and medium enriched for newly synthesized antibodies (MENSA)

BackgroundClostridioides difficile infections (CDI) have been a challenging and increasingly serious concern in recent years. While early and accurate diagnosis is crucial, available assays have frustrating limitations. ObjectiveDevelop a simple, blood-based immunoassay to accurately diagnose patients suffering from active CDI. Materials and methodsUninfected controls (N = 95) and CDI patients (N = 167) were recruited from Atlanta area hospitals. Blood samples were collected from patients within twelve days of a positive CDI test and processed to yield serum and PBMCs cultured to yield medium enriched for newly synthesized antibodies (MENSA). Multiplex immunoassays measured Ig responses to ten recombinant C. difficile antigens. ResultsSixty-six percent of CDI patients produced measurable responses to C. difficile antigens in their serum or MENSA within twelve days of a positive CDI test. Fifty-two of the 167 CDI patients (31%) were detectable in both serum and MENSA, but 32/167 (19%) were detectable only in MENSA, and 27/167 (16%) were detectable only in serum. DiscussionWe describe the results of a multiplex immunoassay for the diagnosis of ongoing CDI in hospitalized patients. Our assay resolved patients into four categories: MENSA-positive only, serum-positive only, MENSA- and serum-positive, and MENSA- and serum-negative. The 30% of patients who were MENSA-positive only may be accounted for by nascent antibody secretion prior to seroconversion. Conversely, the serum-positive only subset may have been more advanced in their disease course. Immunocompromise and misdiagnosis may have contributed to the 34% of CDI patients who were not identified using MENSA or serum immunoassays. ImportanceWhile there was considerable overlap between patients identified through MENSA and serum, each method detected a distinctive patient group. The combined use of both MENSA and serum to detect CDI patients resulted in the greatest identification of CDI patients. Together, longitudinal analysis of MENSA and serum will provide a more accurate evaluation of successful host humoral immune responses in CDI patients.

Incidence of CDI and Association with Antibiotics in a Cohort of Patients with Newly Diagnosed Acute Myeloid Leukemia Receiving Induction Chemotherapy

Background:Because bacterial infections are a common complication during neutropenia and a major cause for morbidity and mortality, patients with Acute Myeloid Leukaemia (AML) often receive prolonged courses of broad-spectrum antibiotics during induction chemotherapy. This extended exposure to antibiotics deeply disrupts the gut microbiota and may result in its colonization by resistant, opportunistic and potentially pathogenic microbes.Clostridioides difficile (C.difficile)is one such bacteria often found in patients whose microbiota has been strongly disrupted. Aim:The purpose of this study was to measure the incidence ofC. difficileinfection (CDI) in newly diagnosed AML patients who received induction chemotherapy and to evaluate the association between CDI and the use of antibiotics. Methods:We retrospectively studied the medical history of patients treated from 01/2016 to 12/2018 at the Department of Internal Medicine I of the University Hospital Cologne. The observational period was defined as 100 successive days after onset of induction chemotherapy or from onset of induction chemotherapy until microbiological confirmed CDI, or until death, whichever event occurred first. The diagnosis of CDI was confirmed by microbiological findings indicating the presence of toxin-producingC. difficilein stool isolates of symptomatic patients. The associations between therapeutic and prophylactic antibiotics and CDI were determined by use of a multivariable backward-stepwise binary logistic regression model. Findings:133 patients were included in the study. 30 patients developed CDI during the study period. 5 patients had two episodes or more. The incidence rate for CDI per 10,000 patient days in the observational period was 29.9. The incidence rates of CDI for the period after onset of induction chemotherapy reached 10.5% (n=14) at 8 weeks and 18.8% (n=25) at 120 days. In the analysis, we could not identify a specific antibiotic as risk factor for CDI but the result may be biased by the different mean observational periods for the group with and without CDI (the observational period for the group with CDI ends at the day of CDI). Conclusions:CDI is a frequent comorbidity affecting patients with newly diagnosed AML and receiving induction chemotherapy and deserves the attention of the medical teams in charge of the patients for adequate prevention and treatment approaches. Disclosures Bauquet: Da Volterra:Current Employment.Buffet:Da Volterra:Current Employment;Alfa Collaborative Group:Current Employment.Vehreschild:Berlin Chemie:Consultancy, Honoraria;Organobalance:Research Funding, Speakers Bureau;Pfizer:Research Funding, Speakers Bureau;Da Volterra:Research Funding;Seres Therapeutics:Research Funding;Astellas Pharma:Consultancy, Honoraria, Research Funding, Speakers Bureau;3M:Research Funding;Gilead:Research Funding, Speakers Bureau;MSD/Merck:Consultancy, Honoraria, Research Funding, Speakers Bureau;Basilea:Speakers Bureau.Vehreschild:Rigshospitalet Copenhagen:Research Funding;Academy for Infectious Medicine:Honoraria;University Manchester:Honoraria;German Society for Infectious Diseases (DGI):Honoraria;Ärztekammer Nordrhein:Honoraria;University Hospital Aachen:Honoraria;Back Bay Strategies:Honoraria;German Society for Internal Medicine (DGIM):Honoraria;Merck / MSD:Research Funding;Gilead:Research Funding;Pfizer:Research Funding;Astellas Pharma:Research Funding;Basilea:Research Funding;German Centre for Infection Research (DZIF):Research Funding;), German Federal Ministry of Education and Research (BMBF):Research Funding;(PJ-T: DLR):Research Funding;University of Bristol:Research Funding;Merck/MSD:Honoraria;Gilead:Honoraria;Pfizer:Honoraria;Astellas Pharma:Honoraria;Basilea:Honoraria;German Centre for Infection Research (DZIF):Honoraria;University Hospital Freiburg/ Congress and Communication:Honoraria.

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.

Cardiac implantable electronic device infection: Does the device need to be extracted?

BackgroundCardiac implantable electronic devices (CIED) have become a common treatment modality in clinical practice. The increase in utilization of these devices has been associated with an increase in infection rates. Published guidelines define when a device is deemed infected (CDI); recommendations for the work‐up of CDI and criteria for extraction. Few data exist as to adherence to these guidelines.ObjectiveWe wanted to o evaluate whether devices diagnosed as CDI fit guidelines, whether clinicians followed work‐up recommendation of CDI, and whether CIED was extracted according to the guidelines criteria in our hospital.MethodsA retrospective review was performed in our hospital between 2008 and 2017. Adult patients (pts) 18 years and older who had their device extracted (DE) with a diagnosis of CDI were included. A total of 95 pts were identified.ResultsWe included 95 pts who were diagnosed as having CDI and who had their DE. Work‐up of patients with a diagnosis of CDI was inconsistently followed. Blood cultures, Echocardiogram, lead cultures (LC), and device pocket cultures (PC) were done in 100%, 90.5%, 75.6%, and 49.3%, respectively. Thirty out of 90 pts. (33%) did not meet guidelines criteria for extraction.ConclusionsIn our institution, a one third of the pts diagnosed with CDI who had DE had no indication for DE per guidelines recommendations. Clinicians did not follow recommendations for work‐up of CDI consistently. Low adherence was seen in obtaining LC and PC. CIED extraction guidelines should be followed to prevent unnecessary complications and cost.

A162 THE UTILITY OF FECAL CALPROTECTIN IN PREDICTING SEVERITY OF CLOSTRIDIUM DIFFICILE INFECTION: A SYSTEMATIC REVIEW

Abstract Background Clostridium difficile is an anaerobic, spore-forming, gram-positive bacillus, and a leading cause of infectious diarrhea in hospitalized patients. It is associated with high mortality and morbidity, and places an enormous burden on the healthcare system. Symptoms and severity of CDI vary widely, from illness that resolves with antibiotics, to toxic megacolon, colectomy, and death. The ability to risk-stratify patients to predict severe versus non-severe outcomes at baseline would be clinically useful. The role of fecal calprotectin in predicting severity of CDI has not been well established. Aims To perform a systematic review of the literature on the ability of fecal calprotectin to predict disease severity in patients with CDI. Methods PubMed, OVID (EMBASE/MedLine) and Cochrane Library databases were searched up until October 2, 2019. Publications of pediatric populations, Inflammatory Bowel diseases, and those only published as abstracts were excluded. Results 130 non-duplicate citations were screened; after title/abstract screening, and full-text review, 7 articles were included for analysis. Articles were from 2014 onwards, and varied from 29 to 232 patients/samples analyzed; 832 patients in total were analyzed. Three studies were conducted in the USA, two in Europe, one in Israel and in South Korea. Four studies were prospective, and the remaining three were retrospective cohort studies. There was significant heterogeneity between studies with respect to population size, age (when reported), fecal calprotectin assay and cutoff used, method of diagnosis of CDI, and criteria for defining disease severity. There was wide variation in median fecal calprotectin levels between studies. Four studies demonstrated a statistically significant difference of fecal calprotectin according to disease severity, and three did not, of which two of these demonstrated an overall predictive trend with fecal calprotectin. Conclusions It is unclear whether fecal calprotectin is predictive of severity of CDI in adult patients without IBD. In the existing literature, there seems to be a statistically significant association or trend towards association in most studies, but due to heterogeneity of methods, assays, cutoffs and populations, the data within these studies cannot be pooled in meta-analysis. Further high-powered, well-designed studies are required to clarify this important clinical question. Funding Agencies None

Clostridium Difficile Infection in Hematopoietic Stem Cell Transplant Patients: A National Study

Introduction Clostridium difficile infection (CDI) is the leading cause of infectious diarrhea among hospitalized patients. Patients undergoing hematopoietic stem-cell transplant (HSCT), either autologous stem cell transplant (Auto-SCT) or allogeneic stem cell transplant (Allo-SCT), are at high risk for CDI. We aim to describe the incidence and epidemiological trends for CDI in Auto-SCT and Allo-SCT in the United States, using the National Inpatient Sample (NIS) database provided by Healthcare Cost and Utilization Project (HCUP). Methods A descriptive, retrospective study was conducted on the National Inpatient Sample (NIS) Database for the years 2005-2014. Admissions with diagnosis of CDI were selected based on International Classification of Diseases-Ninth Revision (ICD-9), Clinical Modification diagnoses codes (00845). ICD-9 procedure codes were used to identify HSCT hospitalizations (autologous: 4101, 4104, 4107, and 4109; allogeneic: 4102, 4103, 4105, 4106, and 4108). Complex survey design, weights and clustering were accounted for during analysis. Results The mean age of patients undergoing HSCT was 45.69 + 20.35 years and 41.13% were female. There were total of 89,374 Auto-SCT patients and 66,044 Allo-SCT patients hospitalized between 2005-2014. Auto-SCTs constituted 55.5% of all the HSCTs. The incidence of Auto-SCT related hospitalizations increased from 205 per million admissions (pma) in 2005 to 291 pma in 2014 with an annual percentage change (APC) of 5.8, p&lt;0.001. During the same period the incidence of Allo-SCT related hospitalizations increased from 151 pma to 224 pma with and APC of 6.3, p&lt;0.001. Overall 6.67% of patients with Auto-SCT and 9.96% of Allo-SCT were diagnosed with CDI. There were statistically higher CDI rates in Allo-SCT when compared to Auto-SCT (p&lt;0.001). The incidence of CDI in Auto-SCT patients showed a non-significant decrease from 2005-2009 and a significant increase from 2009-2014 (APC 7, p&lt;0.001). The incidence of CDI in Allo-SCT patients increased significantly from 2005 to 2014 with an APC of 5.9, p&lt;0.001. Conclusion The number of individuals being hospitalized for HSCTs in the United States is increasing and this increase is seen for both Auto-SCT and Allo-SCT procedures. One in fifteen patients undergoing Auto-SCT and one in ten patients undergoing Allo-SCT were diagnosed with CDI during hospitalization. There were significantly more CDIs in patients with Allo-SCT when compared to Auto-SCTs. The incidence of CDI in patients undergoing both Autologous and Allogeneic HSCT increased from 2005-2014 in the United States. Disclosures No relevant conflicts of interest to declare.

2356. Increased Clinical Specificity with Ultrasensitive Detection of Clostridioides difficile Toxins: Reduction of Overdiagnosis Compared with Nucleic Acid Amplification Tests

Background Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections, resulting in significant morbidity, mortality, and economic burden. Diagnosis of CDI relies on the assessment of clinical presentation and laboratory tests. We have evaluated the clinical performance of ultrasensitive Single Molecule Counting technology for detection of C. difficile toxins A and B.MethodsStool specimens from 298 patients with suspected CDI were tested with nucleic acid amplification test (NAAT; BD MAX™ Cdiff assay or Xpert® C. difficile assay) and Singulex Clarity® C. difficile toxins A/B assay. Specimens with discordant results were tested with cell cytotoxicity neutralization assay (CCNA), and results were correlated with disease severity and outcome.ResultsThere were 64 NAAT-positive and 234 NAAT-negative samples. Of the 32 NAAT+/Clarity− and 4 NAAT-/Clarity+ samples, there were 26 CCNA− and 4 CCNA- samples, respectively. CDI relapse or overall death was more common in NAAT+/toxin+ patients than in NAAT+/toxin− and NAAT−/toxin− patients, and NAAT+/toxin+ patients were 3.7 times more likely to experience relapse or death (Figure 1). The clinical specificity of Clarity and NAAT was 97.4% and 89.0%, respectively, and overdiagnosis was over three times more common in NAAT+/toxin− than in NAAT+/toxin+ patients (Figure 2). Negative percent agreement between NAAT and Clarity was 98.3%, and positive percent agreement increased from 50.0% to effective 84.2% and 94.1% after CCNA testing and clinical assessment.ConclusionThe Clarity assay was superior to NAATs in diagnosis of CDI, by reducing overdiagnosis and thereby increasing clinical specificity, and presence of toxins was associated with disease severity and outcome. Disclosures All authors: No reported disclosures.

2360. Impact of a Two-Step Antimicrobial Stewardship Intervention on C. difficile Infection Diagnosis at an Urban Veteran’s Affairs Medical Center

Background C. difficile infection (CDI) is a common healthcare-associated infection and quality measure for hospitals. Diagnosis of CDI is challenging as testing modalities, i.e., nucleic acid amplification test (NAAT), are highly sensitive but cannot differentiate between colonization and infection. Therefore, judicious use of testing is critical to avoid unnecessary diagnosis and treatments.MethodsThis single-center, retrospective chart review evaluated the impact of a two-step diagnostic stewardship intervention on C. difficile diagnosis and use of oral vancomycin in the inpatient setting. For the first step of the intervention, providers were educated on appropriate diagnosis and treatment, and given access to an optional electronic CDI clinical decision support system (CDSS). For the second step of the intervention, the CDI NAAT stand-alone testing option was removed from the lab ordering menu and providers were required to use the CDSS to order testing. Clinical data including bed-days of care (BDOC), total number tests ordered, number of positive tests and use of oral vancomycin was collected for the pre-intervention period (1/1/16 – 3/31/17), post intervention period 1 (April 1, 2017–October 31/18) and post-intervention period 2 (November 1, 2018–March 31, 2019).ResultsCompared with the pre-intervention group, there were no significant differences in the number of total CDI NAATs ordered, positive CDI NAATs or vancomycin DOT/10,000 BDOC in post-intervention group 1. There was a reduction in the number of total CDI NAATs ordered (341 vs. 42 [87.7%]) and the number of positive CDI NAATs (56 vs. 7 [87.5%]) in post-intervention group 2, respectively. When this data were normalized based on bed days of care (BDOC), there were still significant reductions in NAATs ordered and number of positive CDI NAATs (64 vs. 27 [57.8%]; 11 vs. 5, respectively, [54.5%]) and with vancomycin oral DOT/10,000 BDOC (72 vs. 7 [90.3%]) (Table 1).ConclusionProvider education and an optional CDSS did not significantly impact CDI NAAT ordering or use of oral vancomycin for CDI. However, implementation of a mandatory CDSS for CDI testing was shown to significantly decrease the number of tests ordered, the number of positive tests, and the use of oral vancomycin. Disclosures All authors: No reported disclosures.

2357. Toxin Detection Using Single Molecule Counting Technology: The Best of Both Worlds?

BackgroundAccurate diagnosis of CDI remains challenging as there is no standalone laboratory test with adequate clinical sensitivity and specificity. Thus, many clinical laboratories currently employ a multistep algorithm incorporating a sensitive screening test followed by a specific toxin test. An automated ultrasensitive toxin immunoassay (Singulex Clarity® C. difficile toxins A/B assay) has demonstrated excellent performance compared with cell cytotoxicity neutralization assay (CCNA). In this study, the Clarity assay was evaluated relative to glutamate dehydrogenase (GDH), toxin EIA, toxin B gene PCR, multistep algorithms, and C. difficile culture with ribotyping.MethodsResidual clinical stool samples (n = 293) were collected from patients with suspected CDI. The samples were tested on-site with GDH (C. DIFF CHEK™-60), PCR (EntericBio realtime® C. difficile assay), a membrane-type toxin EIA (Tox A/B Quik Chek®), and culture and ribotyping. In total, 188 samples were tested with GDH and 239 samples were tested by PCR. All PCR-positive samples (n = 148) and prospectively tested GDH samples (n = 97) were tested with the toxin EIA. Culture and ribotyping information were available for 205 samples.ResultsThree of the samples tested gave no result using the Clarity assay and were excluded from the analysis. The Singulex Clarity C. difficile toxins A/B assay had high positive percent agreement (PPA) and low negative percent agreement (NPA) compared with toxin EIA and multistep algorithms ending with toxin EIA. The Clarity assay had high NPA and low PPA compared with PCR, GDH, and the multistep algorithm ending with PCR (figure). Less than 70% of the detected C. difficile PCR positive samples had toxins present. There was no difference in toxin concentration between the ribotypes.ConclusionThe Clarity assay had strong PPA compared with toxin EIA and strong NPA compared with PCR. The low NPA and PPA compared with toxin EIA and PCR, respectively, may reflect the poor sensitivity of current toxin EIAs and low specificity of PCR. The Clarity assay detected 30 different ribotype strains, and less than 70% of samples (by PCR) or strains (by ribotyping) had toxins present. The Clarity assay may be considered for use as a standalone test for CDI diagnosis. Disclosures All authors: No reported disclosures.

2829 Patients Eligible for Trials of Microbiota-Based Therapeutics Do Not Represent the Population With Recurrent Clostridioides difficile Infection

INTRODUCTION: Industry-funded trials of microbiota-based therapeutics for treatment of Clostridioides difficile are ongoing, however due to strict enrollment criteria, not all patients are eligible. Furthermore, given the widespread availability of fecal microbiota transplantation (FMT) and overwhelming evidence supporting its efficacy, patients may refuse enrollment in trials with a placebo-arm. METHODS: This is a retrospective study performed at four tertiary referral centers for FMT. The electronic medical record at each was reviewed to capture patients referred for recurrent CDI over a 6- month time period. FMT eligibility was determined based on current CDI treatment guidelines.3 Inclusion and exclusion criteria for a clinical trial of an oral microbiota-based therapeutic were applied to determine eligibility, based on current enrolling trials at these centers. RESULTS: Of 199 patients referred for a diagnosis of recurrent CDI, 130 (65%) were deemed to be eligible for FMT based on the number and severity of episodes. Of the patients in whom FMT was determined to be an appropriate option, 94 (72%) met inclusion criteria for an RCT of a microbiota-based therapeutic drug, however 62 (66%) of those meeting inclusion criteria had one or more exclusion criteria (Table 1) precluding participation and 16 (17%) were eligible but refused to enroll. Only 16 (12%) of FMT-eligible patients were enrolled in the drug trial. Conventional FMT using stool-bank donor material was performed in 96 patients (74%) of those deemed eligible to undergo the procedure (Figure 1). Most patients (79%) met a single exclusion criterion, 14.5% met two criteria and 6.5% met three criteria. The most common reason for study exclusion was immunocompromise (17; 27%). Other common exclusions were inflammatory bowel disease (13; 21%), having already received more than 21 days of vancomycin (11; 18%) and diarrhea-predominant irritable bowel syndrome (10; 16%). CONCLUSION: Less than half of patients deemed eligible for FMT based on clinical history of recurrent CDI met eligibility criteria for a clinical trial of an encapsulated microbiota product. A smaller but relevant proportion of eligible patients refused to participate. Restrictions on stool banks would have detrimental effects on patient access to FMT. Furthermore, these results demonstrate that a relevant number of patients affected by recurrent CDI are currently being excluded from industry-funded trials.

Thickening of the pituitary stalk in children and adolescents with central diabetes insipidus: Causes and consequences

BackgroundCentral diabetes insipidus (CDI) is a rare disorder in children. The aetiology of CDI in childhood is heterogeneous. The aim of this study is to illustrate the importance of a careful clinical and neuro-radiological follow-up of the pituitary and hypothalamus region in order to identify the aetiology and the development of associated hormonal deficiencies. MethodsClinical and auxological variables of 15 children diagnosed with CDI were retrospectively analysed in a paediatric hospital. Evaluations of adenohypophyseal function and cranial MRI were performed periodically. ResultsThe mean age at diagnosis of CDI was 9.6 years (range: 1.32–15.9). The aetiological diagnosis could be established initially in 9 of the 15 patients, as 7 with a germinoma and 2 with a histiocytosis. After a mean follow-up of 5.5 years (range: 1.6–11.8), the number of idiopathic cases was reduced by half. At the end of the follow-up, the aetiological diagnoses were: 9 germinoma (60%), 3 histiocytosis (20%), and 3 idiopathic CDI (20%). There is a statistically significant association between stalk thickening and tumour aetiology. At least one adenohypophyseal hormonal deficiency was found in 67% of cases, with the majority developing in the first two years of follow-up. Growth hormone deficiency (60%) was the most prevalent. ConclusionThe follow-up of CDI should include hormone evaluation with special attention, due to its frequency, to GH deficiency. In addition, a biannual MRI in an idiopathic CDI should be performed, at least during the first 2–3 years after diagnosis, as 50% of them were diagnosed with a germinoma or histiocytosis during this period.

Epidemiology of Clostridium difficile infection in hospitalized adults and the first isolation of C. difficile PCR ribotype 027 in central China

BackgroundClostridium difficile infection (CDI) is an emerging healthcare problem in the world. The purpose of this study was to perform a systematic epidemiological research of CDI in Tongji hospital, the central of China.MethodsStool samples from hospitalized adults suspected of CDI were enrolled. The diagnosis of CDI were based on the combination of clinical symptoms and laboratory results. Clinical features of CDI and non-CDI patients were compared by appropriate statistical tests to determine the risk factors of CDI. Multilocus sequence typing (MLST) was employed for molecular epidemiological analysis. Susceptibility testing and relevant antimicrobial agent resistance genes were performed as well.ResultsFrom June 2016 to September 2017, 839 hospitalized adults were enrolled. Among them, 107 (12.8%, 107/839) patients were C. difficile culture positive, and 73 (8.7%, 73/839) were infected with toxigenic C. difficile (TCD), with tcdA + tcdB+ strains accounting for 90.4% (66/73) and tcdA-tcdB+ for 9.6% (7/73). Meanwhile, two TCD strains were binary toxin positive and one of them was finally identified as CD027. Severe symptoms were observed in these two cases. Multivariate analysis indicated antibiotic exposure (p = 0.001, OR = 5.035) and kidney disease (p = 0.015, OR = 8.329) significantly increased the risk of CDI. Phylogenetic tree analysis demonstrated 21 different STs, including one new ST (ST467); and the most dominant type was ST54 (35.6%, 26/73). Multidrug-resistant (MDR) TCD were 53.4% (39/73); resistance to ciprofloxacin, erythromycin, and clindamycin were > 50%. Other antibiotics showed relative efficiency and all strains were susceptible to metronidazole and vancomycin. All moxifloxacin-resistant isolates carried a mutation in GyrA (Thr82 → Ile), with one both having mutation in GyrB (Ser366 → Ala).ConclusionsKnowledge of epidemiological information for CDI is limited in China. Our finding indicated tcdA + tcdB+ C. difficile strains were the dominant for CDI in our hospital. Significant risk factors for CDI in our setting appeared to be antibiotic exposure and kidney disease. Metronidazole and vancomycin were still effective for CDI. Although no outbreak was observed, the first isolation of CD027 in center China implied the potential spread of this hypervirulent clone. Further studies are needed to enhance our understanding of the epidemiology of CDI in China.

494. Use of a Clinical Prediction Tool to Predict Clostridium difficile Infection

Background Clostridium difficile is a pathogen that may be a component of normal microbiota. In 2011, there were an estimated 453,000 cases of CDI in the United States and 29,300 deaths. Diagnosis of CDI is of often accomplished through nucleic acid amplification testing (NAAT) for C. difficile toxin genes, which carries a risk of false-positive results. In 1996, Katz et al. created a screen for CDI that was positive if the patient had significant diarrhea and either abdominal pain or prior antibiotic usage. Today, we believe that this tool is worth revisiting with increased incidence of CDI and improved testing methods. Our aim is to determine the current usefulness of the Katz et al. 1996 clinical decision tool for CDI.MethodsWe conducted a retrospective cross-sectional chart review at a Midwestern teaching hospital. All patients tested for CDI between June 1, 2016 and May 31, 2017 were initially eligible. Participants were excluded from data collection on the basis of missing information, a previous positive CDI test in the last 8 weeks or age <18 years. Charts were reviewed for age, sex, diarrhea, abdominal pain, antibiotic use, prior positive testing for CDI, and length of hospitalization. Data were analyzed using SAS Software.ResultsOf the initial 432 charts analyzed, 202 (46.8%) had no documented amount of diarrhea and 16 more were missing other data points, leaving 214 of 432 (49.5%) charts that included all data to be used for analysis. Of these 18 of 214 (8.4%) were positive results. The Katz screen was positive in 85 of 214 (40.2%) cases. The sensitivity, specificity, positive predictive value, and negative predictive value, respectively, were 61, 62, 13, and 95.ConclusionKatz et al. found a sensitivity, specificity, positive predictive value and negative predictive value of 80, 45, 18 and 94, respectively. The differences between these values and our own may be due to changes in the testing methodology and prevalence of CDI compared with a 1992 study population. The negative predictive value remains a strength. If this screening tool had been applied to our population, there may have been 128 (59.8%) fewer tests, but seven (38.9%) missed positive results.Disclosures All authors: No reported disclosures.