bluuebunny/crossref_metadata_2025 huggingface dataset:
742. Evaluation of Chagas Disease Diagnostic Testing Practices in Four Hospital Systems in California and Texas
Authors: Kelly Emily A , Echeverri Alegre Jose I , Promer Katherine , Hayon Jesica , Iordanov Roumen , Zhang Jerry J , Fang Zian , Huang Cindy , Bittencourt Cassiana , Reed Sharon L , Andrade Rosa , Bern Caryn , Clark Eva , Whitman Jeffrey
Published: December 2021

Background

Chagas disease (CD) is a neglected parasitic disease that affects >6 million people in the Americas, including >200,000 people in the United States (US). Medical provider knowledge of CD is key to decreasing morbidity and transmission; however, few studies have assessed diagnostic practices in US health systems serving at-risk patients. Our study aimed to describe existing provider approaches to diagnosing CD in California and Texas.

Methods

Site-based research teams at four hospital systems (the University of California [UC] San Francisco [UCSF], San Diego [UCSD], Irvine [UCI], and the Harris Health System [HHS] in Houston, TX) retrospectively identified patients ≥18 years old tested for CD between 2016-2019 and systematically extracted electronic medical record data using complementary electronic data entry forms. Specifically, eligible patients were identified using laboratory orders at UCSF and UCI, while the remaining sites employed SlicerDicer (Epic Systems). This study was approved by institutional review boards at each site.

Results

We identified 333 patients tested for CD, including 109 from UCSF, 88 from UCSD, 25 from UCI, and 111 from HHS. These patients had 125, 99, 31, and 181 tests sent to commercial laboratories, respectively. Test reactivity varied by system with the greatest percent reactivity among tests ordered at UCI (23%) followed by UCSD (16%), HHS (15%), and UCSF (10%). Among patients who screened positive for CD by commercial assays, confirmatory testing through the Centers for Disease Control and Prevention was sought for 100% at UCI; 59% at HHS, 55% at UCSF, and 40% at UCSD. The medical specialty that most often ordered CD testing was Cardiology at all UC sites (UCSF, 50%; UCSF, 55%; UCI, 35%) and Internal Medicine at HHS (46%; Cardiology ordered 13%). Only one recorded CD test was ordered by an Obstetrics/Gynecology service at any site.

Conclusion

These early results report positivity rates between our healthcare systems and demonstrate inconsistency in attaining recommended confirmatory testing, as well as a paucity of CD testing ordered through Obstetrics/Gynecology despite risk of congenital transmission. These findings suggest areas of opportunity to improve provider awareness and lay a foundation for standardizing CD diagnostic practices in the US.

Disclosures

Caryn Bern, MD, MPH, UpToDate (Wolters Kluwer) (Other Financial or Material Support, Author Royalties)
744. Incidence and Duration of Diagnostic Delays Associated with Dengue Fever
Authors: Miller Aaron C , arakkal alan , koeneman scott , Polgreen Philip M , streit judy A
Published: December 2021

Background

Dengue fever is a prominent emerging arboviral infection in the tropics and subtropics, and an important cause of systemic febrile illness among some international travelers. Signs and symptoms are similar to more common infectious illnesses in temperate climates, and dengue may not be promptly considered when patients seek evaluation.

Methods

We conducted a retrospective cohort study of patients diagnosed with dengue fever using the IBM MarketScan Research database from 2001-2017. We identified cases of dengue fever where patients were enrolled ≥ 1 year prior to the index diagnosis. All healthcare visits in the year prior to the index diagnosis were collected and we identified visits with signs/symptoms compatible with dengue or a diagnosis made of an illness with similar symptoms (e.g., influenza) before the index dengue diagnosis. We used a time-series change-point analysis to identify the time before diagnosis in which symptoms of dengue became more prominent. We conducted a bootstrap-based simulation analysis to estimate the duration and frequency of missed diagnostic opportunities.

Results

We identified 4,449 cases of dengue fever that met eligibility criteria. We found that 2,791 (62.7%) had ≥ 1 healthcare visit(s) prior to diagnosis with characteristic symptoms of dengue recorded. Our simulations analysis supports that 32.9% (95% CI: 31.1-35.0) experienced 1 or more missed opportunities for diagnosis. Among these patients, the average duration of diagnostic delay was 8.26 (CI: 6.32-11.38) days and ~21% of patients had a diagnostic delay of 2 or more weeks. Patients with a delayed diagnosis averaged 2.2 (CI 2.11-2.29) healthcare visits which represented missed opportunities. Missed opportunities were more likely during weekend, ED or outpatient visits.

Conclusion

Dengue fever is not considered in the majority of patients at the time of the initial symptomatic evaluation in the U.S., indicating delays in diagnosis are common. Enhanced education of providers about dengue fever could lead to more prompt diagnosis that should help optimize patient management.

Disclosures

All Authors: No reported disclosures
745. Evaluation of a Pharmacist-driven Risk Factor Tool for the Prevention of Hospital-onset Clostridium difficile Infection in a Community Hospital
Authors: Weiss Jennifer , Patel Gargi , Cavanaugh Joseph
Published: December 2021

Background

Clostridium difficile infection (CDI) is the most frequently reported nosocomial infection and is the major cause of healthcare and antibiotic associated diarrhea. Guideline recommended preventative strategies include antibiotic stewardship, hand hygiene, barrier precautions, and disinfection of environmental spaces to reduce the risk of hospital onset CDI (HO-CDI); however, there is no standardized scoring method to tactically detect high-risk patients in order to prevent HO-CDI. The objective of this study was to implement a risk stratification procedure for a pharmacist to prospectively identify high-risk patients and make early interventions to prevent the incidence of HO-CDI.

Methods

In this single center, ambidirectional cohort study, patients who acquired HO-CDI from January 2019 to June 2020 were identified and evaluated to determine which modifiable risk factors were most prominent. A pharmacist prospectively screened patients who were admitted from October 2020 to February 2021 using a web-based screening tool to detect high-risk patients based on the previously identified risk factors. An interdisciplinary approach was used to make early interventions for high-risk patients such as discontinuation or de-escalation of antibiotics, discontinuation of gastric acid suppression, and early CDI testing before 72 hours of admission. The primary outcome was incidence of HO-CDI per 10,000 patient days and secondary outcomes were length of hospital stay and duration of non-CDI antibiotic therapy. Appropriate statistical tests were used to measure significance.

Results

The primary outcome of HO-CDI cases per 10,000 patient days occurred at a median rate of 3.95 (IQR 3.38 – 6.30) in the retrospective cohort versus 2.15 (IQR 1.68 – 3.04) in the prospective cohort [p < 0.0125]. There were no significant differences in length of non-CDI antibiotic therapy or length of hospital stay.

Baseline Characteristics

Primary Outcome

Secondary Outcomes

Conclusion

In patients at high-risk of developing HO-CDI, pharmacist intervention resulted in a reduced rate of HO-CDI cases per 10,000 patient days.

Disclosures

All Authors: No reported disclosures
746. Clinical and Microbiological Characteristics of Clostridioides difficile Infection After a Change in Diagnostic Testing Algorithm
Authors: Crone Andrew S , Skinner Andrew M , Cheknis Adam , Johnson Stuart , Pacheco Susan M
Published: December 2021

Background

There is a lack of consensus on the most appropriate testing for C. difficile infection (CDI). The objective of this study was to determine the clinical and microbiological characteristics of CDI following a switch from stool PCR testing only to PCR reflexed to toxin testing.

Figure 1. PCR Cycle Threshold Values

Methods

We reviewed the characteristics and outcomes of 50 consecutive patients who tested positive for CD by PCR (Xpert CD, Cepheid) between October 2019 and January 2020 at the Hines VA Hospital. Cases were defined by results of reflex toxin testing (Cdiff quick check complete, Alere/TechLab) after a positive PCR result. Baseline characteristics, symptoms, initial laboratory data, and treatments were compared as well as patient outcomes, including hospital readmission due to CDI at 30 days, and recurrent CDI (rCDI) at 30 and 90 days. The cycle threshold for the stool PCR result was recorded. Stools were cultured anaerobically for CD, and restriction endonuclease analysis (REA) strain typing was performed on the recovered CD isolates.

Results

Toxin testing was positive in 19/50 (38%) cases. Compared to stool toxin-negative cases, toxin-positive cases were older (95% vs. 71% were age ≥ 65, p = 0.06), more likely to have a history of CDI (37% vs. 23%, p = 0.34), and have ≥ 1 CDI episodes within 6 months (37% vs. 19%, p = 0.26). Treatment for CDI was more common in patients who had a positive toxin text. (95% vs 61%, p= 0.009). Among the 38 patients that received treatment, 33 received vancomycin (87%) and 8 patients (21%) had rCDI at 30 days. Of the 8 patients with rCDI, 2 were re-admitted to the hospital for CDI. The average PCR cycle threshold was lower in the toxin-positive stools compared to toxin-negative stools (24.46 and 29.96, p< 0.001; Fig. 1) The endemic REA group Y was the most common CD strain recovered (30%) and the previously epidemic and virulent REA group BI strain was recovered in 11% of the cases.

Conclusion

CDI cases diagnosed by positive stool PCR and positive toxin tests had more typical risk factors for CDI, a lower PCR cycle threshold and were more likely to have been treated for CDI. Outcomes were similar in this setting where infection with the virulent BI strain was uncommon.

Disclosures

Stuart Johnson, MD, Acurx Pharmaceuticals (Advisor or Review Panel member)Bio-K+ (Advisor or Review Panel member)Ferring Pharmaceutical (Advisor or Review Panel member)
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

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

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

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 < 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

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

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

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< 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

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

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 < 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

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
762. Real-World Utilization of C. difficile Drug Treatments and Associated Clinical Outcomes in a US Hospital System
Authors: McDaniel Lauren , Everson Nathan , White Melissa , Obi Engels N , Chen Yiyun , Kohinke Rose , Lockhart Ellen Rachel
Published: December 2021

Background

IDSA recommends use of fidaxomicin or oral vancomycin for treatment of initial episode or first recurrence of Clostridioides difficile infection (CDI). This study aimed to evaluate impact of a clinical decision support order set driving appropriate use of fidaxomicin on utilization of CDI drug treatments and associated clinical outcomes.

Methods

This was a retrospective, quasi-experimental study evaluating CDI therapies pre- (8/2016-11/2017) and post- (5/2018-1/2020) CDI order set implementation at a level-one trauma center located in Virginia. Admitted adult patients were included if CDI testing was positive for a 1st or 2nd episode and received active CDI treatment. Exclusions included fulminant CDI and CDI diagnosis by PCR with < 3 bowel movements or laxative use within 24 hours. The primary outcome was CDI recurrence within 30 days of completing therapy in patients who achieved clinical cure. Secondary outcomes were evaluated at 30 and 90 days and included sustained response and CDI-related readmissions.

Results

After screening, 186 patients in the pre-group and 187 in the post-group were included. Median age was 68 [59-77], most patients had an initial CDI episode (88.2%) and were diagnosed with severe CDI (50.7%). Baseline characteristics were similar between each group on Charlson comorbidity index, ICU admission, CDI risk factors, and concomitant antibiotic use. Primary treatment options in the pre-group were most commonly metronidazole 47.9% and oral vancomycin 50.5%, and in the post-group were fidaxomicin 56.7% and oral vancomycin 41.7% (Figure 1). CDI recurrence rates at 30 days post-index medication (17.2% vs. 6.3%, p=0.004) were lower in the post-group (Table 1). Clinical cure (84.4% vs. 94.1%, p=0.002) and sustained response at 90 days (55.9% vs. 73.3%, p< 0.001) were higher in the post-group. CDI recurrence rates at 90 days and CDI-related readmissions at 30 and 90 days were also lower in the post group.

Figure 1. CDI Treatment Utilization

Table 1. Clinical Outcomes

Conclusion

Implementation of the CDI order set increased fidaxomicin use and was associated with a decrease in CDI recurrences and CDI-related readmissions and increase in clinical cure and sustained response. Findings suggest increased first-line use of fidaxomicin results in better clinical outcomes.

Disclosures

Lauren McDaniel, Pharm.D., BCIDP, Merck Sharp & Dohme Corp (Grant/Research Support) Nathan Everson, Pharm.D., BCIDP, AAHIVE, Merck & Co. (Grant/Research Support) Melissa White, PharmD, Merck Sharpe & Co (Grant/Research Support) Engels N. Obi, PhD, Merck & Co. (Employee, Shareholder) Yiyun Chen, PhD, Merck & Co., Inc (Employee) Rose Kohinke, PharmD, Merck Sharpe & Co (Research Grant or Support)
763. Impact of Two-Step Testing Algorithm on Hospital-onset Clostridioides difficile Infections and Oral Vancomycin Prescription Practices at an Academic Medical Center
Authors: Wingler Mary Joyce , Cretella David A , Parham Jason , Navalkele Bhagyashri
Published: December 2021

Background

Clostridioides difficile infection (CDI) is one of the leading causes of hospital –onset (HO) infections. Clinically distinguishing true CDI versus colonization with C.difficile is challenging. We implemented a two-step testing algorithm to discriminate true CDI from colonization then evaluated the effect on rate of HO CDI and oral vancomycin.

Methods

In May 2020, a two-step testing algorithm was implemented utilizing C. difficile PCR and enzyme immunoassay (EIA) glutamate dehydrogenase (Figure 1). Rates of HO CDI and use of oral vancomycin was compared in the three quarters preceding and after this intervention (July 2019-March 2020 and July 2020-March 2021, respectively). HO CDI was defined based on National Healthcare Safety Network (NHSN) Laboratory Identified (LabID) event as last positive C.difficile test result performed on a specimen collected >3 calendar days after admission to the facility. HO CDI rates were assessed based on Standardized Infection Ratio (SIR) data and antimicrobial use was reported in days of therapy (DoT) per 1000 patient days.

Figure 1. Two-Step Testing Algorithm for Diagnosing Clostridioides difficile infection

Results

During the pre-intervention period 30 HO CDI cases were reported compared to 9 cases in the post-intervention period (p=0.02) (Figure 2). There was a non-statistically significant reduction in CDI SIR in post-intervention period (0.133 vs. 0.305, p=0.11). Oral vancomycin use was similar in the pre- and post-intervention periods (3.89 vs. 3.84, p=0.96). Fidaxomicin use was rare (< 0.2 DoT/1000 pt days). Of 26 HO C.difficile colonized patients in post-intervention period, 14 (54%) patients received oral vancomycin treatment. Infectious diseases was consulted on 7/14 and recommended discontinuation of treatment in 3 while treatment was continued for other patients based on clinical status and immunocompromising conditions.

Figure 2. Comparison of pre- and post-intervention trend in Hospital-onset CDI rate

Conclusion

We successfully reduced our HO CDI infections and SIR below national average after implementation of two-step testing algorithm for CDI. There was no impact on the rate of oral vancomycin use. We observed at 54% rate of treatment for patients categorized as likely colonization. Provider education and stewardship interventions are necessary to reduce inappropriate use of oral vancomycin in colonized patients.

Disclosures

All Authors: No reported disclosures
764. Will the Addition of Probiotics to Patients Receiving Intravenous Antimicrobial Therapy Reduce the Incidence of Healthcare Facility-Onset Clostridium difficile Infection?
Authors: Shah Punit , Kay Jessica , Akogun Adanma , Wise Silvia , Aly Sarfraz , Daoura Nicolas
Published: December 2021

Background

Exposure to antimicrobials is a known risk factor for Clostridium difficile infection (CDI). Antimicrobials cause collateral damage by disrupting the natural intestinal microbiota allowing for C.difficile to thrive and production of C.difficile toxins. Probiotics could modulate the onset and course of CDI. However, the data on probiotics for the prevention of CDI is conflicting.

Methods

We conducted an IRB approved retrospective cohort study at a 340-bed community hospital. All hospitalized patients from August 1, 2017 through July 31, 2020 were evaluated for enrollment. Patients were included if they received at least one dose of intravenous (IV) antibiotic and had a length of stay of at least 3 days. Patients were excluded if they were younger than 18 years, or if they had a positive C.difficile polymerase chain reaction test before antibiotics were started. The primary outcome was the incidence of healthcare facility-onset Clostridium difficile infection (HO-CDI). Descriptive statistics were used to analyze demographics data, and the primary outcome of HO-CDI was analyzed using Fisher’s exact test and multiple logistic regression.

Results

A total of 20,257 patients received IV antibiotics during the study time frame. Of these, 2,659 patients received probiotics. Primary outcome of HO-CDI occurred in 46 patients in the IV antibiotics alone cohort (0.26%) and 5 patients in the probiotics plus IV antibiotics cohort (0.19%). The difference in HO-CDI between these two groups was not statistically significant, p=0.677. A multiple logistic regression was performed to see the impact of proton pump inhibitor use, age, ICU admission, Charlson Comorbidity Index, probiotic use and CDI in the past 12 months on the primary outcome. C.difficile infection in prior 12 months [OR 3.37, 95%CI 1.04-10.97] and ICU admission [OR 1.81, 95%CI 1.02-3.19] were associated with higher CDI. The addition of probiotics to patients on IV antibiotics did not exhibit a protective effect [OR 0.72, 95% CI 0.28-1.81].

Conclusion

The addition of probiotics to standard of care was not beneficial in the prevention of HO-CDI. We endorse robust antibiotic stewardship practices as part of the standard of care bundle that institutions should employ to decrease the incidence of HO-CDI.

Disclosures

All Authors: No reported disclosures
765. The Burden of Illness Associated with Recurrent Clostridioides difficile Infection: A Claims-based Analysis
Authors: Black Rachel M , Stanford Richard , Gratie Dan
Published: December 2021

Background

Clostridioides difficile infection (CDI) is a significant public health concern and the leading cause of infection related healthcare utilizations in adults in the United States. A considerable proportion of CDI patients suffer recurrent episodes of CDI (rCDI). The objective of this study was to describe the impact of CDI on healthcare resource utilization (HCRU) and patient burden.

Methods

A retrospective analysis of patients with a CDI diagnosis claim was conducted using the HealthVerity database. Continuous enrollment with medical and pharmacy benefits was required for 12 months before and after the first occurrence of CDI diagnosis (index date). Patients were stratified by total number of CDI episodes. rCDI episodes were defined as episodes that occurred within 12 weeks of the previous episode. Baseline demographics, treatment by episode, and HCRU data were captured.

Results

5,964 patients with a CDI episode were identified. The average age was 56.6 years with 30.2% of the population being ≥ 65 years old. 65.7% of patients were female and 61.2% had a claim for ≥ 1 antibiotic in the 90 days leading up to the index date. Vancomycin was the predominant treatment used across all episodes (54-67%). Use of fecal microbiota transplant (FMT) increased with number of CDI episodes (12.6% for the 3rd episode; 20.7% for 5th episode). Fidaxomicin was used for initial CDI treatment in 7.5% of cases. Prior to the initial CDI episode, 24% of patients had ≥ 1 emergency department (ED) visit, 64% had an outpatient office visit and 49% had an inpatient admission due to any cause. In the post-index period, 73% of patients experienced ≥ 1 ED visits, 95% had an outpatient office visit and 72% were admitted to the hospital for any cause. As the number of CDI episodes increased, the number of ED visits, inpatient admissions and ICU admissions trended upwards.

Conclusion

Results from this observational analysis suggest that the presence of CDI seems to lead to a considerable increase in HCRU after the initial episode. Despite variation in treatment patterns by episode, some HCRU seems to increase with additional episodes.

Disclosures

Rachel M. Black, PharmD, Seres Therapeutics (Consultant) Richard Stanford, PharmD, MS, AbbVie (Consultant)Sanofi-Genzyme (Consultant)Seres Therapeutics (Consultant) Dan Gratie, PharmD, MS, Seres Therapeutics (Consultant)
769. Risk Factors of Central Line-associated Bloodstream Infection in an Academic Medical Center
Authors: Conrad Zane , Kang Minji , Thomas Elizabeth , Arocha Doramarie , Trivedi Julie B
Published: December 2021

Background

Central line-associated bloodstream infections (CLABSI) are one of the leading healthcare-acquired infections (HAI) with significant morbidity and mortality. We aimed to identify risk factors of CLABSI at an academic medical center to determine high-risk populations and target interventions.

Methods

This is an observational retrospective cohort study at William P. Clements Jr. University Hospital from January 1, 2017 to December 31, 2020. Retrospective chart review was conducted to identify demographics and co-morbidities of hospitalized patients diagnosed with CLABSI as defined by National Healthcare Safety Network (NHSN). Infections due to mucosal barrier injuries were excluded. Means were compared using independent-samples T-test and proportions were compared using chi-square.

Results

Ninety-three CLABSI events were identified with an increase in the standardized infection ratio from 0.38 in 2017 to 0.74 in 2020 (Figure 1). Bacterial organisms were identified in 71 (76%) cases while fungal organisms were identified in 22 (24%) (Table 2). There was no significant difference in the timing of CLABSI after line insertion (p=0.09) or organism identified (p=0.61) in PICC lines (n=33, 34%) vs all other central lines (n=60, 67%). When comparing immunocompromised patients with CLABSI (n=47, 51%) vs non-immunocompromised (n=46, 50%), there was a significant difference in the indication for line (chemotherapy), but no difference was seen in the number of line days prior to event (p=0.57), line type (p=0.17), or organism identified (p=0.94). Of all CLABSI, 46% (n=43) were in the intensive care unit (ICU) with significantly more Candida species (p=0.018) identified compared to non-ICU patients with CLABSI (n= 50, 54%).

Figure 1. CLABSI Rate and SIR from 2017 to 2020 by Quarter

Conclusion

Candida species were more likely to be found in ICU patients with CLABSI as compared to non-ICU counterparts with further investigation in the ICU population revealing lack of flushing after administration of total parenteral nutrition. Otherwise, this observational cohort of CLABSI events did not identify any difference in immunosuppression status or line type. Given this information, infection prevention efforts will continue to be directed towards proper central line maintenance and removal when no longer indicated.

Disclosures

All Authors: No reported disclosures