bluuebunny/crossref_metadata_2025_split huggingface dataset:
748. The Changing Epidemiology of Clostridioides difficile Infection and the NAP1/027 Strain in Two Quebec Hospitals
Authors: Couture Sandrine , Frenette Charles , Alfaro Rowin , Schweitzer Lorne , Schiller Ian , Doherty Nancy , Nanda Rahul , Longtin Yves , Thirion Daniel , Loo Vivian 
Published: December 2021

Abstract

Background
In 2003, many hospitals in Québec, Canada experienced an increase in the incidence of healthcare-associated C. difficile infection (HA-CDI) associated with increased morbidity and mortality. This increase was associated with the dissemination of the NAP1/027 strain. The objective of this study was to describe the epidemiology of HA-CDI in two tertiary care hospitals based in Montréal from 2003 to 2019.

Methods
Surveillance for HA-CDI was performed using standard definitions from 2003 to 2019 at the Montreal General Hospital (MGH) and Royal Victoria Hospital (RVH), in Montréal, Québec. C. difficile was isolated from stool specimens using standard methods. Pulsed field gel electrophoresis and ribotyping were performed to determine genotype. Antibiotic utilization and infection control interventions implemented over the same time period were reviewed.

Results
A total of 4314 cases of CDAD were identified during the study period: 2295 at the RVH and 2019 at the MGH. The incidence decreased from 29.5 to 5.9 cases per 10,000 patient-days between 2003 and 2019 at the RVH and from 23.8 to 3.9 cases per 10,000 patient-days at the MGH. Of the 124 isolates available for genotyping in 2003, 112 were NAP1 (90.3%) compared to 5 out of 53 (9.4%) in 2019. Fluoroquinolone utilization decreased from 230 to 139 DDDs per 1,000 patient-days between 2003 and 2019, whereas total antibiotic utilization increased from 1296 to 1550 DDDs per 1,000 patient-days. Infection Control interventions included empirically placing patients with diarrhea on precautions, intensified cleaning measures, formal antibiotic stewardship, introduction of a real-time PCR C. difficile test in June 2010, and a move to a facility with only single rooms at the RVH in April 2015.
Incidence of HA-CDI at the RVH and MGH and antibiotic utilization between 2003 and 2019

Conclusion
An important change in HA-CDI epidemiology was observed in two Canadian tertiary care hospitals based in Montréal between 2003 and 2019. There was a significant decrease in incidence of HA-CDI and a genotype shift from a predominance of NAP1 strains to non-NAP1 strains. Utilization of fluoroquinolones, to which the NAP1 strain is resistant, concurrently decreased. Infection control interventions targeting isolation, diagnosis, disinfection, and antibiotic stewardship have contributed to the major observed reduction in HA-CDI incidence.

Disclosures
All Authors: No reported disclosures
751. Impact of Changing from a Three-step to Two-step Testing Algorithm for the Diagnosis of Clostridioides difficile
Authors: Lapin Jonathan , Athans Vasilios , Binkley Shawn , Lee Tiffany , Patel Sonal , Richard-Greenblatt Melissa , Glaser Laurel , Hamilton Keith W , Saw Stephen 
Published: December 2021

Abstract

Background
The optimal method for laboratory diagnosis of Clostridioides difficile infection (CDI) remains undefined and national guidelines do not make a recommendation for a preferred diagnostic algorithm. Aiming to improve infection control measures, the Hospital of the University of Pennsylvania changed its testing process for the diagnosis of CDI from a 3-step to a 2-step algorithm (Figure 1) in September 2018. Starting an algorithm with nucleic acid amplification testing (NAAT) has been hypothesized to lead to potential diagnostic uncertainty if the result is positive by NAAT alone, as this test cannot distinguish between active infection and colonization.
Three-Step and Two-Step Diagnostic Testing Algorithms

Methods
This retrospective, single-center, quasi-experimental study included patients ≥ 18 years of age that tested positive for C. difficile between May 1st, 2018 and January 31st, 2019. The study period encompassed 4 months prior to the algorithm change, a 1-month washout immediately following the change, and the subsequent 4 months. The primary outcome was proportion of patients who tested positive for C. difficile and received targeted treatment for CDI. Secondary outcomes included total number of patients who tested positive for C. difficile and received targeted treatment for CDI, duration of treatment for CDI, and hospital length of stay.

Results
Sixty-nine patients in the pre-group (3-step) and 75 patients in the post-group (2-step) tested positive for C. difficile. A higher proportion of patients in the post-group tested positive by NAAT alone (59.4% vs. 73.3%). CDI severity and prior history of CDI were similar between groups. The primary outcome occurred in 89.9% of patients in the pre-group and 83.8% in the post-group (p=0.213). Sixty-two patients in each group received targeted treatment for CDI (p=0.213), median treatment duration was 15 (IQR 11.25-25.75) and 14 (IQR 11-25) days (p=0.505), and median hospital length of stay was 9 (IQR 3-15) and 6 (IQR 3-20) days (p=0.690) in the pre-group and post-group, respectively.

Conclusion
Although there was a higher percentage of patients in the post-group that tested positive for C. difficile by NAAT alone, there was no difference in the proportion or total number of patients who received targeted CDI treatment between time periods.

Disclosures
All Authors: No reported disclosures
754. A Two-step Testing Algorithm for Hospital-onset Clostridioides difficile Infection (CDI) Reduces Prescribing of C. difficile (CD) Therapy but Its Ability to Guide Treatment Decisions Remains Unclear
Authors: Dolan Mackenzie , Cox Heather , Warren Cirle A , Sifri Costi , Poulter Melinda , Donohue Lindsay E , Mathers Amy J 
Published: December 2021

Abstract

Background
Determining true CDI versus CD colonization through CD testing is a continuing challenge. A previously introduced decision support tool at UVA Health significantly reduced inappropriate testing without adverse outcomes. More recently, our methodology changed from nucleic acid amplification test (NAAT) alone to an initial NAAT followed by ELISA for toxin to improve specificity. The purpose of this analysis was to assess provider interpretation of test results, using targeted CD therapy as a surrogate.

Methods
This single-center, retrospective study evaluated all patients with a positive NAAT (Cepheid Xpert® C. difficile) on day 4 or later of hospitalization following 2-step algorithm implementation from Feb 2020 through Feb 2021. Toxin negative (TOX-) test results (C. DIFF QUIK CHEK COMPLETE®) were accompanied by a comment that discordance may represent colonization or CDI and to consider ID consult. The proportion of toxin positive (TOX+) versus TOX- patients receiving ≥ 1 dose of CD therapy served as the primary outcome with partial courses considered &lt; 10 days. Clinical outcomes were also compared.

Results
Ninety patients with NAAT+ results were included, of whom 58 (64%) were TOX-. Thirty-two (100%) TOX+ (median days of therapy [IQR] = 14 [11-17]) versus 51 (88%) TOX- patients (median days of therapy [IQR] = 11 [7-14]) received CD therapy (p=0.04). Treatment decisions were guided by ID physicians for 32 (63%) TOX- patients; ID recommendations to discontinue CD therapy were followed in 2 out of 9 (22%) cases. TOX- patients received partial therapy due to patient death (n=5), presumptive colonization (n=3), and provider error (n=1). Of TOX- patients receiving partial or no treatment, there were no CDI-related adverse outcomes during the admission. CDI-related colectomy occurred in 2 (6%) and 1 (2%) TOX+ and TOX- patients, respectively. Five in-hospital deaths with CDI as a contributing factor occurred in the TOX+ group.

Conclusion
Adoption of a 2-step NAAT plus toxin testing algorithm for hospital-onset CDI reduced the frequency with which TOX- patients received CD therapy but the vast majority were still treated. Most providers considered a positive NAAT indicative of CDI, regardless of TOX status.

Disclosures
All Authors: No reported disclosures
755. Clostridioides difficile Testing and the Use of Laxatives in Immunocompromised Adults
Authors: Al-Bahou Amanda , Quilitz Rod , Pasikhova Yanina , Greene John 
Published: December 2021

Abstract

Background
Clostridioides difficile infection (CDI) rates have plateaued at historical highs in the United States since 2010 and remains a major health problem. While optimal CDI testing remains unclear, current literature recommends testing patients whose symptoms are not clinically attributable to underlying conditions, e.g., laxatives. At Moffitt Cancer Center, a soft-stop alert was implemented to alert the provider if the patient received a laxative within the previous 48 hours of CDI testing. We aim to evaluate the incidence of CDI rates with prior laxative use in immunocompromised patients, as well as, the impact of the soft-stop alert in reducing CDI testing.

Methods
Retrospective, single-center, review of adult patients who were tested for CDI after the implementation of the soft-stop alert from October 1, 2020 to December 21, 2020. These patients were compared to a historical cohort of patients who were tested for CDI prior to the alert implementation from October 1, 2019 to December 31, 2019. The primary outcome was the percent of patients that received a laxative within 48 hours of CDI testing pre-alert compared to post-alert. Secondary outcomes included the percent of colonization versus active infection in this immunocompromised population, number and type of laxatives administered prior to testing, and the frequency of alert and reduction of CDI tests ordered. A cost-benefit analysis was also performed.

Results
In the historical cohort (n=480), 14.8% received a laxative within 48 hours of CDI testing (Figure 1). Within patients who received a laxative in this group, 4.2% had a definitive active infection. After the alert was implemented, a total of 630 CDI tests were ordered from October 1, 2020 to December 31, 2020, and the alert was fired for 123 (19.5%) tests ordered (Figure 2). Of the tests where the alert was fired, the CDI test was removed for 42.3% and continued for 57.7% of orders resulting in savings of &3,263. In this cohort, 5.6% of patients had a definitive active CDI infection who received a laxative and testing was continued (Figure 3).

Figure 2: CDI Test and Laxative Administration Alert

Figure 3: Post-Alert Laxatives Administered and CDI Test Result

Conclusion
The soft-stop alert implemented reduced CDI testing in patients who received a laxative in the last 48 hours correlating with a financial benefit, improvement in guideline adherence, and reduction in laboratory labor.

Disclosures
All Authors: No reported disclosures
756. Clostridioides difficile Burden of Disease: A Prospective Population-Based Surveillance Study of Hospitalized Adults in Louisville, Kentucky
Authors: Furmanek Stephen , Carrico Ruth , Angulo Fredrick J , Zamparo Joann , Gonzalez Elisa , Ford Kimbal D , Ramirez Julio 
Published: December 2021

Abstract

Background
Clostridioides difficile (C. difficile) is an important cause of morbidity and mortality. C. difficile infection (CDI) may be frequently under-diagnosed because laboratory confirmation requires collection of a stool specimen from a patient with diarrhea and appropriate laboratory testing.

Methods
A prospective population-based CDI surveillance study was launched in 8 adult hospitals in Louisville, Kentucky on September 16, 2019. Surveillance officers in each hospital identified all cases of new-onset diarrhea (≥3 loose stools in the past but not preceding 24 hours) in Louisville residents ≥50 years of age. After informed consent, stool samples were collected and tested at the University of Louisville reference laboratory for 1) glutamate dehydrogenase (GDH) and 2) Clostridioides difficile toxins A and B using C. DIFF QUIK CHEK COMPLETE®, Techlab. We defined CDI as GDH positive and toxin positive. The study was paused on April 3, 2020, due to COVID-19 restrictions.

Results
There were 85,719 eligible patient-days during the study period. A total of 1541 patients had new-onset diarrhea corresponding to 1.8 cases of new-onset diarrhea per 100 eligible patient-days. We enrolled 84% (1291/1541) of patients with new-onset diarrhea and tested stool samples for C. difficile from 82% (1055/1291) for a testing density of 123 per 10,000 patient-days. Of the 1055 tested stool specimens, 73 (7%) were GDH positive and toxin positive (Figure 1) yielding a hospital-based CDI incidence of 8.5 CDI cases per 10,000 patient-days.
Figure 1. Patient Ascertainment Flow Chart

Conclusion
New-onset diarrhea was common among hospitalized adults ≥50 years of age. CDI was frequently identified through stool specimens collected from eligible inpatients with new-onset diarrhea. Further analysis of these data and additional laboratory testing will contribute to a better understanding of the frequency of CDI underdiagnosis and the burden of CDI in the United States.

Disclosures
Ruth Carrico, PhD, DNP, APR, CIC, Pfizer (Consultant, Research Grant or Support, Speaker's Bureau)Sanofi Pasteur (Consultant, Grant/Research Support, Speaker's Bureau) Fredrick J. Angulo, DVM, PhD, Pfizer, Inc. (Employee) Joann Zamparo, MPH, Pfizer, Inc. (Employee) Elisa Gonzalez, MS, Pfizer, Inc. (Employee) Kimbal D. Ford, PharmD, Pfizer, Inc. (Employee) Julio Ramirez, M.D., FACP, Pfizer, Inc. (Scientific Research Study Investigator, Research Grant or Support, Speaker's Bureau)
757. Evaluating Use of the New ICD-10 Codes for Clostridioides difficile Infection in the Premier U.S. Hospital Discharge Database
Authors: Deshpande Abhishek , Chen Yiyun , Boye-Codjoe Eugenia , Obi Engels N 
Published: December 2021

Abstract

Background
The single ICD-10 code for Clostridioides difficile infection (CDI) A04.7 was replaced in Oct 2017 with two codes delineating “recurrent CDI” (rCDI, A04.71) and “nonrecurrent CDI” (nrCDI, A04.72). This study aims to evaluate and validate use of the new ICD-10 codes for CDI among inpatient encounters at hospitals contributing to the Premier Healthcare Database (PHD).

Methods
This retrospective study included inpatient encounters with a CDI-related ICD code between Oct 2016-May 2019 in the PHD. Trends in CDI-related ICD coding were examined pre- and post- the Oct 2017 code update. Post Oct 2017, CDI-related inpatient encounters were characterized by clinical, facility, and provider variables, and whether coding was concordant or discordant to the 2017 IDSA guidelines ‘within 60-days (2 months) from index CDI episode’ time window for capturing rCDI. Multivariable regression examined variables associated with concordant coding.

Results
There was widespread adoption of the new CDI codes across hospitals in the PHD in Oct 2017. Post-Oct 2017, a total of 21,446 CDI-related encounters met sample selection criteria. About 67% of rCDI encounters and 25% of nrCDI encounters were coded concordantly. In the overall sample, the rCDI vs. nrCDI-coded encounters (p&lt; 0.05) had higher proportions with emergency room admission, admitted by a gastroenterologist or infectious disease specialist, and receiving fidaxomicin, bezlotoxumab or FMT. Trends in inpatient characteristics for rCDI vs. nrCDI-coded encounters did not differ by coding concordance status. In regression analyses, encounters coded concordantly were significantly more likely to be for rCDI (OR 5.67), a non-elective admission (OR 1.17-1.42), or prescribed fidaxomicin (OR 1.11), or FMT (OR 1.29).
Encounter Frequency

Frequency Table

Resource and Cost Table

Conclusion
There was no delay in transition to the new CDI-related ICD codes across hospitals in the PHD. Important for disease management, drug treatment trends for encounters coded as rCDI vs. nrCDI were consistent with guideline-recommendations for CDI. Coding concordance status based on the IDSA 60-day time window for identifying rCDI did not affect direction of observed trends in descriptive analyses, suggesting that other validation methods maybe needed.
Regression Table

Disclosures
Abhishek Deshpande, MD, PhD, Merck & Co., Inc (Consultant, Shareholder)The Clorox Company (Grant/Research Support) Yiyun Chen, PhD, Merck & Co., Inc (Employee) Eugenia Boye-Codjoe, MPH, Merck & Co., Inc (Employee) Engels N. Obi, PhD, Merck & Co. (Employee, Shareholder)
759. Impact of Clostridium difficile (CD) Nucleic Acid Amplification Test (NAAT) Approval on Hospital-Onset C. difficile Infection (HO-CDI): A Diagnostic Stewardship Intervention
Authors: Touzard-Romo Francine , Jackson Gail , Andrea Sarah , Valerie Whitehead , Chargualaf Tiffany , Lonks John 
Published: December 2021

Abstract

Background
NAAT is highly sensitive in detecting toxigenic CD but if used inappropriately can lead to overdiagnosis and financial penalties. Despite diligent infection control (IC) measures, HO-CDI rates at our hospital remained above target benchmarks. We implemented mandatory CD testing approval to decrease HO-CDI rates.

Methods
On 7/1/2019, we implemented CD testing approval for stool samples collected after admission day 3 in our 129-bed community hospital. An algorithm instructed providers about approval granted by IC 7 days-a-week. The micro-lab would not process samples unless pre-approved. We prospectively collected data on demographics, ICU, laxative, antibiotic use, CDI signs/symptoms, prior CDI and outcomes (length of stay, in-hospital death) and estimated unadjusted relative risk ratios comparing those whose test was approved vs not approved. We also performed an interrupted time series analysis to assess the trend change of CD testing and HO-CDI per 1000 patient days (x 1000-PD) in the 18 months following the intervention (7/2019 - 12/2020) compared to the pre-intervention period (01/2018 - 6/2019). Lastly, using the National Healthcare Safety Network criteria, we calculated pre and post-intervention Standard Infection Ratios (SIR).

Results
A total of 72 samples required CD testing authorization; 65 (90%) were approved. Baseline demographics, in-hospital death and length of stay were similar in both groups, but approved patients were 4 times as likely to have ≥ 3 loose stools in 24h compared to not approved. The number of CD tests was 13 at baseline with a decrease of 6 tests in the 1st month of intervention (95% CI: -10.0, - 1.35), followed by an insignificant decline in the monthly trend (-0.14; 95%CI: -0.49, 0.20). There were 22 HO-CDI pre-intervention and 10 post-intervention. Pre-intervention, incidence of HO-CDI was 0.51 cases x 1000-PD and increased every month by 0.11 (95% CI: 0.07,0.16). In July 2019, there was a significant decline of 1.16 case x 1000-PD (95% CI: -1.99, -0.33), followed by monthly decline (-0.16; 95% CI: -0.23, -0.09). Our calculated SIR after the intervention decreased to 0.77 from 1.03.

Trends of CD testing and HO-CDI in the pre-intervention and post-intervention period

Conclusion
CD testing approval is a successful strategy to optimize testing and lower HO-CDI rates, without resulting in worst outcomes even when CD test was not approved.

Disclosures
All Authors: No reported disclosures
760. Incidence, Predictors and 30-Day Outcomes of Clostridoides difficile Infection in Patients Undergoing Cystectomy: A Nationwide Analysis Using the ACS-NSQIP Database
Authors: Mansoor Armaghan-e-Rehman , Hadi Yousaf B , Salkini Mohamad , Sarwari Arif R 
Published: December 2021

Abstract

Background
Clostridoides difficile infection is the second most common healthcare acquired infection (HAI) and the most common gastrointestinal HAI, with an estimated 365,200 cases reported by the CDC in 2017. CDI continues to remain a major cause of inpatient admission and utilization of healthcare resources. The exact incidence of peri-procedural CDI with cystectomy is unknown, and reported incidence of CDI in literature vary widely

Methods
We conducted an analysis of patients undergoing cystectomy between 2015 and 2017 using the ACS National Surgical Quality Improvement Program (NSQIP) to study the incidence, risk factors and 30-day post-surgical outcomes associated with CDI following cystectomy. Developed by the American College of Surgery, this is a nationally validated, risk-adjusted, outcomes-based program designed to determine and improve the quality of surgical and post-surgical care.

Results
The incidence of CDI following cystectomy was 3.6% in our patient cohort. 18.8% of patients developed CDI following hospital discharge. Non-elective surgeries, and complete cystectomy procedures had higher rate of CDI. 48.4% of patients with CDI had a preceding post-operative infection. Post-operative organ space infections (OR 1.95), post-operative renal failure (OR 2.38), post-operative sepsis (OR 2.49) and septic shock (OR 2.33) were independently associated with development of CDI, (all p values &lt; 0.05). Patients who developed post-operative CDI during hospitalization had lengthier hospital admissions than those who did not develop a CDI (OR 2.29) and had a higher risk of DVT formation (2.48), and were also more likely to have unplanned readmissions (OR 7.8)

Conclusion
This is the first nationwide study looking at inpatient and 30-day post-operative CDI after cystectomy in the US. A sizable number of patients experience CDIs after cystectomy procedures, and CDI development is associated with an increase in length of stay and unplanned readmissions. This study lends further evidence to the need for continued interventions and initiatives to reduce this burden of post-operative CDI.

Disclosures
All Authors: No reported disclosures
761. Host Intestinal Defenses Against Clostridioides difficile Infection in Chemotherapy Patients
Authors: Weinstein Claire , Wilkinson Racheal , Apewokin Senu 
Published: December 2021

Abstract

Background
Clostridioides difficile infection (CDI) is a common complication in patients undergoing cancer treatment with cytotoxic chemotherapy. Exposure to antibiotics or chemotherapy disrupts the microbiome by killing protective intestinal flora which consequently promotes C. difficile spore germination and disease. The host defense against CDI includes colonization resistance conferred by the healthy microbiome and innate defenses provided by intestinal epithelial cells. One protective factor secreted by Paneth cells of the intestinal epithelium is lysozyme, an enzyme that degrades the cell walls of Gram-positive bacteria such as C. difficile. We hypothesized that chemotherapy-induced mucosal barrier injury and the resultant death of Paneth cells leads to decreased production of lysozyme. We thus sought to examine changes in lysozyme concentration in stools of chemotherapy patients.

Methods
We collected stool samples from six patients undergoing cancer treatment at four different time points. The first stool sample corresponded to the day prior to the start of chemotherapy (day zero). We then performed ELISA assays to determine the lysozyme concentration for each stool sample.

Results
On day zero, the lysozyme levels (n=6) averaged 268.1 ± 131.7 ng/mL. Over the course of chemotherapy, the lysozyme levels decreased 78.70 ± 24.19% from the starting value. The lowest values were observed around days 5 through 11 for most patients, coinciding with when they were most neutropenic around day 11. One of the patients developed CDI on day 5 and experienced more fluctuating lysozyme levels thereafter. On the day that the patient developed CDI, lysozyme was measured as 6.63 ng/mL. Throughout treatment, 3/6 patients showed recovery of lysozyme production with white blood cell recovery.

Conclusion
Our data indicate that chemotherapy causes decreased concentrations of lysozyme in stool. Low lysozyme levels could in part account for the increased susceptibility to CDI during chemotherapy. Future experiments will include bioinformatics analyses to determine how the microbiome changes in response to chemotherapy. Together, these experiments will inform our approach to determining patient susceptibility to chemotherapy-associated CDI.

Disclosures
All Authors: No reported disclosures