bluuebunny/crossref_metadata_2025_split huggingface dataset:
659. Geographical Clustering of the Likelihood of Treatment in Histologically Diagnosed Helicobacter pylori in the BOSTON-HP Cohort
Authors: Noriega Marco , Lee Christina , Feuerstein Joseph , Bonilla Silvana , Flier Sarah , Villafuerte-Gálvez Javier 
Published: November 2023

Abstract

Background
The BIDMC Optimization & Standardization for Treatment Outcomes in New England for Helicobacter Pylori (BOSTON-HP) study included 1002 patients with confirmed Helicobacter pylori (HP) via gastric histopathology from 2016-2022 to evaluate the effects of a Multidisciplinary Division Wide Program. Our previous data showed that demographic factors, such as race/ethnicity and preferred language, are associated with treatment, test-of-cure, and eradication outcomes. We hypothesize that given an unlikely even geographic distribution of demographic factors, HP outcomes may cluster geographically.

Methods
The BOSTON-HP cohort patient addresses were transformed to georeferenced coordinates which were mapped using QGIS (3.30 's-Hertogenbosch) onto OpenStreetMap. We calculated the maximum Euclidean distance matrix to assign heatmap weights for each outcome, and calculated global spatial autocorrelation to evaluate the extent of spatial clustering.

Results
Eight hundred and sixty-eight patients (86.6%) received treatment with confirmed eradication in 416 (47.9%) of them. A statistically significant positive spatial autocorrelation of clusters (Moran’s I = 0.080, p =0.003, z=2.787) was observed for the likelihood of treatment. Layering transportation and healthcare units revealed key clustering patterns (see Figures 1. & 2.). Clusters in the vicinity of Longwood Medical Area (LMA), and South Cove Medical Center (SCMC) were more likely to receive treatment, while those in the Brighton collegiate area (BCA) and along the Red Line Axis in Roxbury-Dorchester (RLRD) were less likely to receive treatment. Test-of-cure and eradication success were not statistically significant for clustering (Moran’s I = 0.007, p =0.388, z=0.284) (Moran’s I = 0.006, p =0.441, z=0.149), respectively.Figure 1. BOSTON-HP Treatment Cohort.Figure 2. Untreated in the BOSTON-HP Cohort.

Conclusion
A moderate and significant spatial correlation existed between the likelihood of HP treatment and the geographic location of the patient’s residence. Identification of groups for targeted quality improvement interventions (RLRD) and models of success within the system (SCMC) can help improve treatment outcomes and reduce geographic disparities.

Disclosures
Javier Villafuerte-Gálvez, MD, Milky Way Biosciences: Partial Research Support.
670. Clinical Characteristics and Outcomes in Patients with Healthcare Facility-Onset Clostridiodes difficile Infections
Authors: Joshi Seema , Alvi Rija B R , Shanahan Clare , Ruby Abigail , Chami Eman , Suleyman Geehan 
Published: November 2023

Abstract

Background
Healthcare facility-onset (HCFO) Clostridiodes difficile infection (CDI) is the most common hospital-acquired infection. Although risk factors associated with CDI have been described, characterization and outcome of HFCO-CDI are limited.

Methods
This was a retrospective observational study comparing disease severity among adult patients with HCFO-CDI from January 1, 2020, to December 31, 2022, at an 877-bed tertiary care hospital in Detroit. Patients were identified using National Healthcare Safety Network (NHSN) definition. CDI was classified as nonsevere, severe, or fulminant. Severe disease was defined as having white blood cell (WBC) count ≥ 15,000 cells/mm3 or acute kidney injury (AKI) defined as increase in creatinine of ≥ 0.3mg/dL within 48 hours of diagnosis. Fulminant disease included patients with ileus or toxic megacolon, or need for colectomy, intensive care unit or vasopressors. Risk factors, treatment and outcomes were evaluated.

Results
98 patients were diagnosed with HFCO CDI during the study period (Table 1); 37 (38%) were non-severe, 47 (38%) severe and 14 (24%) fulminant. Median age was 66 years, 50% were female and 45% white. Almost half were immune suppressed; 5% had prior CDI. Most patients (88%) were exposed to antibiotics (abx) prior to CDI with no difference between the groups (p=0.427); 61% received cephalosporins. Cirrhosis was more common among patients with fulminant disease (p=0.048) and receipt of chemotherapy was associated with severe and/or fulminant disease cases (p=0.049). AKI (p&lt; 0.001), fever (p=0.030), and WBC &gt;25,000 or &lt; 2,000 cells/mm3 (p&lt; 0.001) were more prevalent among patients with fulminant CDI; combination or alternative therapy was more common among fulminant cases (p&lt; 0.001). Most were eligible, but only 6% received bezlotoxumab (BZX). Although outcomes were not significantly different between the groups, length of stay was longer and refractory disease and recurrence were more common in severe/fulminant CDI.

Conclusion
In our HCFO-CDI cohort, most patients were exposed to abx, and cirrhosis and chemotherapy were associated with more severe CDI. Efforts should focus on appropriate abx utilization and increasing use of BZX to reduce burden of CDI and risk of recurrence and readmission.

Disclosures
All Authors: No reported disclosures
675. The Fidaxomicin Cascade: Analysis of Success Rates and Barriers of Fidaxomicin Discharge Prescriptions for Inpatients Diagnosed with Clostridiodes Difficile
Authors: Cook Ellen , Mehta Jigar , Blecher Alexis L , Lee Matthew S 
Published: November 2023

Abstract

Background
Current IDSA guidelines prefer Fidaxomicin for initial and first recurrent Clostridiodes difficile (C. difficile) infection. A barrier to increasing Fidaxomicin usage has been the medication’s potential high co-pay. The objective of this study was to evaluate the discharge success rate and financial/co-pay barriers for inpatients initiated on Fidaxomicin at our institution.

Methods
Our cohort consisted of inpatients that received Fidaxomicin for the treatment of C. difficile during 2022. For inpatient discharges, a transitions of care (TOC) pharmacy evaluation is available for high co-pay medications. Charts were retrospectively reviewed for demographic, clinical, insurance, and pharmacy data.  The primary outcome was the proportion of patients successfully discharged on Fidaxomicin. Secondary outcomes included proportion of patients with co-pays &gt;$50 and direct out-of-pocket patient cost after TOC pharmacy intervention.

Results
29 patients were initiated on Fidaxomicin for CDI treatment in 2022. The majority of patients had Medicare (62%), a prior history of CDI (75%), were immunocompromised (55%), and met non-severe IDSA criteria (62%) (Table 1). 7% (2/29) switched to oral vancomycin early due to ID consult or stewardship recommendations and 28% (8/29) completed the course prior to discharge (Figure). All the remaining patients (19/19) discharged to extended care or home were able to be discharged on Fidaxomicin.
74% (14/19) of patients discharged on Fidaxomicin had TOC pharmacy evaluations with co-pay data available (Figure). 50% of these patients (7/14) had high co-pays (Figure) with a mean co-pay of $470.25 (range $65-1384.95) (Table 2). The majority (5/7) of the “high co-pay” group had Medicare; three Medicare patients had out-of-pocket cost reduced after TOC pharmacy intervention (Table 2). Post-TOC intervention, the mean patient out-of-pocket cost was $181.20 (range $0-566.44).Table 1:Patient Demographic and Clinical DataTable 2:“High Co-Pay” Patient Group (defined as Co-Pay &gt; $50)Figure:Fidaxomicin Prescribing Cascade

Conclusion
All inpatients continued on Fidaxomicin for the treatment of C. difficile were able to be “successfully” discharged with the medication. However, the co-pay remains potentially high for certain individuals, particularly those with Medicare and prolonged tapers. TOC pharmacy evaluations, if available, are critical for financial assistance prior to discharge.

Disclosures
All Authors: No reported disclosures
679. Retrospective Analysis of Vancomycin and Fidaxomicin for the Treatment of Recurrent Clostridioides difficile Infection
Authors: Fabian Amy , Frantz Tyler , Patel Rachana , Kier Karen 
Published: November 2023

Abstract

Background
It is estimated that one out of every six patients with a Clostridioides difficile infection (CDI) will develop a recurrence. Guidelines recommend treatment with fidaxomicin rather than vancomycin standard course or tapered and pulsed regimens for the treatment of recurrent CDI (rCDI). The objective of this study is to evaluate clinical outcomes for three different pharmacological approaches for the treatment of rCDI.

Methods
This is a multi-centered, retrospective cohort of patients who have had more than one episode of CDI who received either fidaxomicin, conventional vancomycin dosing, or vancomycin tapered and pulsed. Inclusion criteria are adult patients who have received at least one dose of oral vancomycin or fidaxomicin and had a positive stool assay for CDI from October 1st, 2021 to September 30th, 2022. Patients who presented with an initial CDI, were pregnant, experienced in-hospital death prior to completion of antibiotic, were less than 18 years old, and elected palliative or hospice care were excluded. The primary outcome is the proportion of patients who develop rCDI at eight weeks. Secondary outcomes include time to recurrence, proportion of patients prescribed guideline-preferred therapy, and the proportion of patients with rCDI or mortality at three months and six months from starting therapy for rCDI. Primary and secondary outcomes will be analyzed using ANOVA testing, and a multi-variable regression analysis was performed to identify significant risk factors for rCDI.

Results
Among 71 patients, no difference was detected between fidaxomicin (n=11, 16%), vancomycin conventional dosing (n=48, 68%), and vancomycin tapered and pulsed (n=12, 17%) in the proportion of patients with rCDI at eight weeks (p = 0.335). A subgroup analysis of patients with infectious diseases (ID) consults (n=34, 47%) was performed, and they were more likely to be prescribed fidaxomicin (n=11, 32%; p = ≤ 0.001) and less likely to have rCDI (n=12, 17%; p = 0.008).

Conclusion
Compliance with guideline preferred therapy for rCDI in the community hospital setting is low among non-ID providers. Further research should be conducted to determine the impact that an ID consult can have on clinical outcomes in patients with rCDI.

Disclosures
All Authors: No reported disclosures
680. Comparison of Extended Duration Vancomycin Regimens for Clostridioides difficile Infection in Patients on Prolonged Antibiotic Courses
Authors: Garzia Christopher , Loo Angela , Kubin Christine J 
Published: November 2023

Abstract

Background
Antibiotic exposure is a primary risk factor for Clostridioides difficile infection (CDI) and recurrence. We compared CDI recurrence in patients who received extended oral vancomycin (poV) after diagnosis of CDI, at a dose of q12-24h compared to q6h, while on concomitant systemic antibiotic therapy.

Methods
Retrospective study of adult patients admitted 2/2020-9/2022 to NewYork-Presbyterian Hospital, diagnosed with CDI, and received at least 14 days poV including initial CDI therapy, and at least 2 days of extension with concomitant systemic antibiotics with no interruptions. Patients were grouped based on vancomycin extended dosing to either q6h or q12-24h. Patients were excluded if CDI regimen included vancomycin pulse/taper or fidaxomicin, &gt;1 day interruption between final day of CDI treatment and extended dosing, and incomplete resolution of CDI at day 14. The primary outcome of recurrent CDI at 90 days was compared between the two groups via chi-squared test. Predictors of CDI recurrence were assessed using a logistic regression model.

Results
110 patients were included:77 received q6h and 33 received q12-24h extended poV. Median age was 63 years (IQR 55,74), 51% were hospital onset-CDI, and the median total duration of poV was 25 days (IQR 19,38 days). The only significant differences between q6h and q12-24h groups were total days of vancomycin (22 vs. 37 days; p&lt; 0.001) and patients with previous CDI episodes (7% vs 24%; p=0.02). Recurrence at 90 days was similar between q6h and q12-24h groups (13.2% and 6.3% respectively; p=0.505). On multivariable analysis, while controlling for severe and fulminant CDI and patients with inflammatory bowel disease, poV regimen of q12h-24h did not impact recurrence (OR 0.428, 95% CI 0.08-2.21).

Conclusion
No significant differences were seen in CDI recurrence between extended poV q6h compared to q12-24h. For patients who require extended poV dosing beyond an initial treatment course, q12h-24h dosing may be an option with improved patient convenience and reduced drug cost. The long-term impact of this reduced dosing frequency remains to be determined.

Disclosures
All Authors: No reported disclosures
683. Understanding Clostridioides difficile toxinB gene conservation through surveillance of public data
Authors: Mulholland Kelly , Godfrey Victoria , Stanley Ann Marie , Brady Tyler , Sellman Bret R , Tkaczyk Christine , Gopalakrishnan Vancheswaran 
Published: November 2023

Abstract

Background
Clostridioides difficile infection (CDI) is the leading cause of antibiotic and healthcare-associated infective diarrhea. It is linked to 365,000 infections and causes approximately 20,000 deaths annually in the US. CDI is mediated by the action of toxin B (TcdB) in humans. Monoclonal antibodies (mAbs) that neutralize TcdB function have shown protection against CDI in preclinical models and more recently in the clinic. Several regions on the TcdB gene have been targeted by therapeutic mAbs including the glucosyltransferase (GTD) and the C-terminal combined repetitive oligopeptides (CROPS) domains. We have developed AZD5148, an anti-TcdB mAb targeting a region within the GTD. To understand its strain coverage, we examined sequence variations of GTD including the AZD5148 epitope in contemporary C. difficile strains utilizing a public data repository.

Methods
8,085 assembled C. difficile genomes collected between 2015-2022 were obtained from Enterobase. These were annotated with Prokka to identify the TcdB gene coding sequence, and subsequently aligned to the R20291 strain reference. Phylogeny was determined with ParSnp and visualized using iTol. From the aligned sequences, variants were identified using an in-house tool (RADAR).

Results
A majority of the C. difficile genomes deposited were from North America, specifically the United States. Ribotype (RT) information was available for 9.6% of the genomes with RT-078 being the most common. Phylogenetic analysis did not reveal any patterns by geography or collection year, though clades tended to be associated with ribotypes. Degree of conservation was calculated at each TcdB genomic residue and was evaluated both regionally and temporally. We found GTD to be highly conserved in US isolates as well as globally. Additionally, among contact residues for AZD5148, any variations observed were single, and were seen for positions 323 (Y-H), 329 (G-E), 349 (V-A), and 350 (L-I).

Conclusion
These findings have important implications for drug development including for AZD5148. Specifically, our findings reveal that the GTD domain of the TcdB gene has lower variance globally over the last 7 years making it a promising target for a C. difficile TcdB neutralizing mAb.

Disclosures
Kelly Mulholland, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Victoria Godfrey, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Ann Marie Stanley, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Tyler Brady, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Bret R. Sellman, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Christine Tkaczyk, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Vancheswaran Gopalakrishnan, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds
690. Analysis of high-risk antibiotics for Clostridioides difficile infections in Korean hospitals: A nationwide multi-center study
Authors: Kim Bongyoung , Myung Rangmi , Kim Jieun , Kim Uh Jin , Kim Yeon-Sook , Kim Eu Suk , Kim Tark , Park Dae Won , Lee Mi Suk , Lee Sun Hee , Lee Chang-Seop , Chang Hyun-Ha , Lee Myoung-jae , Pai Hyunjoo 
Published: November 2023

Abstract

Background
Clostridioides difficile infection (CDI) is a representative healthcare-associated infection, and the incidence rate continues to increase in Korea. The purpose of this study is to identify antibiotics that are highly related to CDI incidence in Korean hospitals.

Methods
From January-December 2019, all antibiotic prescription records, CDI test results, and a daily number of hospitalized patients were retrospectively collected from 10 university-affiliated hospitals in Korea. To exclude duplication, CDI tests that were conducted within 10 days after conducting previous CDI tests were excluded. When a positive result was detected from C. difficile toxin assay or PCR tests, we considered it as CDI. Antibiotics were defined as drugs corresponding to J01 in the WHO ATC classification, excluding anti-tuberculosis drugs, anti-parasitic drugs, antiviral drugs, and local antibiotics. The antibiotic usage was calculated as Days of Therapy (DOT). The CDI incidence rate and antibiotic usage were collected on a weekly basis and then corrected to 1,000 patient days. The correlation between CDI incidence rate and antibiotic usage was analyzed using the cross-correlation function test.

Results
CDI incidence and total antibiotic usage in each hospital ranged from 0.49-1.58/1,000 patient-days and 588.7-1000.4 DOT/1,000 patient-days, respectively. Cross-correlation function test shows that antibiotics that are highly related to CDI incidence were 2nd generation cephalosporin that was prescribed 6 weeks prior to CDI event (coefficient 0.320, P = 0.021), 4th generation cephalosporin that was prescribed 1 week prior to CDI event (coefficient 0.307, P = 0.027), and beta-lactam/beta-lactamase inhibitors (with anti-pseudomonal effects) that was prescribed 1 week prior to CDI event (coefficient 0.272, P = 0.050), lincosamide that was prescribed 2 weeks prior to CDI event (coefficient 0.278, P = 0.045), and oxazolidinone that was prescribed 8 weeks prior to CDI event (coefficient 0.362, P = 0.008).
Cross-correlation coefficients between Clostridioides difficile infection incidence and antibiotic usage

Conclusion
Antibiotics highly associated with CDI incidence in Korean hospitals were second-generation cephalosporin, fourth-generation cephalosporin, beta-lactam/beta-lactamase inhibitors (with anti-pseudomonal effects), lincosamide, and oxazolidinone.

Disclosures
All Authors: No reported disclosures
692. The Role of Fidaxomicin for the Treatment of Clostridioides Difficile Infection in the Pediatric Population in the United States
Authors: Lee Yuman , Bradley Nicole , Smith Sarah , Rakhimova Shakhzoda 
Published: November 2023

Abstract

Background
In 2020, the FDA approved fidaxomicin (FDX) for the treatment of Clostridioides difficile infection (CDI) in children 6 months and older. The latest IDSA/SHEA guidelines recommend FDX use for adults only. A survey presented at IDWeek 2022 showed that only 35% of institutions used FDX as first line in adults despite its inclusion in the guidelines. The purpose of this study is to assess the use of FDX in US pediatric patients and identify barriers to use.

Methods
An anonymous, voluntary electronic survey was distributed to the American Society of Health-System Pharmacists and the Pediatric Pharmacy Association in January 2023. Baseline demographics, current practices, knowledge, comfort, and barriers to FDX use in pediatrics were collected. Fisher’s Exact Test was used to compare categorical variables.

Results
32 pharmacists responded to the survey. Majority were from children’s hospitals within an adult hospital (62.5%), stand-alone children's hospitals (18.8%), and adult hospitals with pediatric beds (15.6%). 37.5% (12/32) reported having institutional pediatric CDI guidelines. Of which, 75% (9/12) included FDX for the treatment of previous failure 77.8% (7/9), recurrent CDI 44.4% (4/9), and fulminant CDI 22.2% (2/9). In institutions without pediatric CDI guidelines (62.5%, 20/32), FDX was used for the treatment of previous failure 65% (13/20), recurrent CDI 5% (1/20), and fulminant CDI 5% (1/20). FDX use was significantly higher in institutions with CDI guidelines for recurrent CDI compared to those without guidelines (p&lt; 0.05).
96.9% (31/32) of respondents reported at least one barrier to FDX use. Top 3 barriers were cost (71%, 22/31), inability of patients to afford upon discharge (64.5%, 20/31), and lack of provider familiarity (41.9%, 13/31). 53.1% (17/32) respondents were comfortable using FDX in pediatrics, 87.5% (28/32) were aware of its FDA approval in children, and 90.6% (29/32) were aware it was not in the IDSA guidelines.

Conclusion
Most respondents did not have institutional pediatric CDI guidelines. FDX use was most common in treatment failure. Most respondents reported at least one barrier to FDX use despite its FDA approval. Majority were comfortable using FDX in pediatrics. This study is limited by its small sample size as expected due to the studied population.

Disclosures
All Authors: No reported disclosures
695. Incidence and Risk Factors for Clostridioides difficile Infections in Non-COVID and COVID-19 Patients
Authors: Mathew Therese , Punnoose Rhema Maria 
Published: November 2023

Abstract

Background
Infections with Clostridioides difficile (CDIs) are a leading cause of healthcare-associated infections (HAIs) and impact public health globally. The aim of this study was to assess the incidence and the risk factors for healthcare-associated Clostridioides difficile infection (HA-CDI) in patients with COVID-19 and without this infection.

Methods
A single-center, prospective observational study was conducted at a tertiary care hospital in India, from January 2021 to December 2022. The entire hospital was a COVID-dedicated hospital for 12 months during the study period. The incidence density rates and risk factors for HA-CDI in patients with and without COVID-19 are presented.

Results
The incidence rates of HA-CDIs were three times higher in patients with COVID-19. The HA-CDI–COVID-patients were younger (69.9 ± 12.6 vs. 72.5 ± 11.6; p = 0.017), admitted from another hospital (20.5% vs. 2.9; p &lt; 0.001), had antimicrobial therapy before CDI (99.1% vs. 91.3%, p &lt; 0.001), received two or more antibiotics (p = 0.030) during a longer period (p = 0.035), received proton pump inhibitors (95.9% vs. 50.0%, p &lt; 0.001) during a longer period (p = 0.012) and steroids (32.8% vs. 20.4%, p &lt; 0.001). During the last month before their current hospitalization, a higher percentage of patients without COVID-19 disease were hospitalized in our hospital (p &lt; 0.001). Independent predictors for HA-CDIs in patients with COVID-19 were admission from another hospital (p = 0.003), the length of antibiotic administration (0.020), and the use of steroids in therapy (p &lt; 0.001). The HA-CDI predictors in the non-COVID patients were older age (p = 0.017), advanced-stage renal failure (p = 0.005), chemotherapy (p = 0.003), and a low albumin level (0.005).

Conclusion
Higher incidence rates of HAI-CDIs in COVID-19 patients did not occur due to reduced infection control precautions and hygiene measures but due to antibiotic therapy and therapy with other drugs used during the pandemic.

Disclosures
All Authors: No reported disclosures