bluuebunny/crossref_metadata_2025_split huggingface dataset:
384. Assessing the Multistep Approach for Clostridioides difficile Infection Diagnosis
Authors: Mendo-Lopez Rafael , Pacheco Lauren , Villafuerte-Galvez Javier A 
Published: December 2022

Abstract

Background
Clostridioides difficile infection (CDI) is a spore-forming anaerobic Gram-positive bacillus and the leading cause of nosocomial infectious diarrhea. 2017 IDSA/SHEA C. difficile guidelines recommend a multistep algorithm approach for CDI diagnosis. This algorithm entails stool testing via enzyme-linked immunosorbent assay (EIA) for glutamate dehydrogenase (GDH) and C. difficile toxins A/B (Tox). Discordant samples are arbitrated by nucleic acid amplification test (NAAT) for tcdB gene. GDH EIA has sensitivities &gt;90%, while Tox EIA has sensitivities ranging from 50-90%. We aimed to evaluate the diagnostic performance of GDH and Tox EIA using the multistep algorithm as the gold standard.

Methods
We performed a secondary analysis of an inpatient dataset collected in a tertiary community health system in the Southern US, including 9-months of the incident population from 2019 to 2020. All adults ≥ 18-years old from Princeton Baptist Medical Center (Birmingham, AL) tested for C. difficile were included. Alere TechLab C. difficile Quik Chek Complete® was used to determine GDH and Tox EIA, and Alethia C. difficile DNA Amplification Assay®, a NAAT, for discordant samples. CDI case was defined as positivity for Tox and GDH, or positivity of either Tox or GDH in addition to positive NAAT. Retesting within the same admission was allowed.

Results
Overall, 288 tests were performed. Concordant positivity for GDH & Tox was found in 29 (10.1%) tests; concordant negativity in 226 (78.5%). Discordant positivity for GDH or Tox was observed in 33 (11.5%) tests; all were tested with NAAT. Only 1 of 33 (3.03%) discordant tests was GDH negative & Tox positive, which had a positive NAAT. The remaining 32 (96.97%) discordant tests were GDH positive and Tox negative, of which 18 (56.3%) were positive for NAAT (Table 1). Performance characteristics for the above tests were calculated (Table 2). Table 1:Clostridioides difficile infection case distributions per GDH and ToxinTable 2:Test performance characteristics

Conclusion
Taking the multistep algorithm as a gold standard, the performance characteristics of GDH and Tox are concordant to previous descriptions in the literature, with GDH being highly sensitive and Tox being highly specific. A diagnostic algorithm lacking GDH and NAAT would miss over one-third of CDI cases. A diagnostic algorithm lacking Tox and NAAT could potentially overdiagnose about one-fifth of tested patients.

Disclosures
All Authors: No reported disclosures.
386. Clostridioides difficile PCR Cycle Threshold to Determine Toxin Positivity Status
Authors: Crone Andrew S , Skinner Andrew M , Wright Lorinda M , Cheknis Adam K , Johnson Stuart , Pacheco Susan M 
Published: December 2022

Abstract

Background
Many clinical laboratories rely on polymerase chain reaction (PCR) as the sole test for diagnosis of C. difficile infection (CDI). The objective of this study was to determine if the C. difficile (CD) PCR cycle threshold could be used to predict a positive CD toxin test.

Methods
We reviewed the characteristics and outcomes of 149 consecutive patients who tested positive for by PCR (Xpert CD, Cepheid) between October 2019 and December 2021 at one VA Hospital where reflex toxin testing (Cdiff quick check complete, Alere/TechLab) was performed after a positive PCR result. Baseline characteristics, symptoms, initial laboratory data, and treatments were compared as well as clinical outcomes. Determination of CDI or CD colonization was made for each patient after review of symptoms: including chronicity of symptoms, laboratory values, stool frequency, use of laxatives, and response to treatment. The cycle threshold for the CD-PCR results were recorded and positive stools were cultured for CD.

Results
Toxin testing was positive in 38% (57/149) of cases. The mean PCR cycle threshold value for all specimens tested was 27.89 (95% CI [27.14, 28.66]). Toxin-positive stools had lower mean PCR cycle thresholds when compared to toxin-negative stools (24.56 and 29.97, respectively p &lt; 0.0001). Among the 149 cases reviewed, 109 were determined to be CDI (73%), 36 were colonized (24%), and 4 cases were undetermined. Among those with toxin-positive stools, 96% (54/56) patients were determined to have CDI. 98% (56/57) of all toxin-positive stools had a cycle threshold of ≤ 32.2 compared to 63% (58/92) of toxin-negative stools, resulting in a negative predictive value of 97.2% (p &lt; 0.0001). The mean cycle threshold was lower in patients who were determined to have a CDI when compared to colonized patients (27.02 vs 30.44, p = 0.0001). [Figure] Of the patients that had CDI, 83% (91/109) had a cycle threshold of ≤ 32.2 and 58% (21/36) of colonized patients had a cycle threshold of ≤ 32.2.

Conclusion
Conclusions: In a setting where a CD toxin assay is not readily available, a CD stool PCR cycle threshold could be used to predict toxin status. In our study, a cycle threshold of ≤ 32.2 predicted both toxin-positivity and CDI.

Disclosures
Stuart Johnson, M.D., Ferring Pharmaceuticals: Membership on Ferring Publication Steering Committee|Ferring Pharmaceuticals: Employee|Summit Plc: Advisor/Consultant.
395. Impact of Racial Disparities on Clostridioides difficile Infection (CDI) Outcomes at a Southern California Academic Teaching Hospital
Authors: Zhou Anna Y , Lee Jina M , Ortiz-Gratacos Natalie M , Student Pharmacy , Isso Almas Al , Tan Karen K , Abdul-Mutakabbir Jacinda C 
Published: December 2022

Abstract

Background
Infectious diseases are the second leading contributor to racial disparities in healthcare. Clostridioides difficile infection (CDI) is a common community/hospital acquired infection that can cause life-threatening colitis. Despite the influence that socioeconomic factors, insurance status, and access to care can have on CDI outcomes, there is a dearth of literature that evaluates the impact of racial differences. The objective of this study was to identify racial disparities in CDI and describe clinical outcomes among hospitalized adults.

Methods
This is an IRB approved, retrospective study of adult patients (≥ 18 years) hospitalized with initial episodes of CDI between January 2020 to June 2021. Initial CDI episodes were identified by the ICD-10 code A04.72. Medical records were reviewed for demographics, comorbid conditions, insurance, total length of stay (LOS), and need for intensive care unit (ICU) admission. Patients were dichotomized by race/ethnicity into either the racially and ethnically minoritized (REM) group or the non-Hispanic White (n-REM) group. P value of ≤ 0.05 was defined as significant.

Results
In total 220 patients (61.8% REM, 136/220; 38.2% n-REM, 84/220) with an initial CDI episode were included. Majority of the REM patients were Hispanic (38.2%) followed by Black (13.6%), and Asian (5%). Compared to the n-REM group, the REM patients were younger (60 vs 69 years, p =0.016) and were more likely to have underlying comorbidities (diabetes mellitus 33% vs 9.5%; p &lt; 0.001 and chronic kidney disease 48.5% vs 21.3%; p &lt; 0.001). The REM patients were more likely to present with fulminant CDI (21.3% vs 11.9%; p =0.1). The REM patients were also more likely to be admitted to the ICU during their stay (41.9% vs 26.2%; p =0.021) and have a longer hospital length of stay (LOS) (12 vs 7 days; p =0.02). Lastly, the REM patients were more likely to be under-insured with 91 patients (66.9%) having Medi-Cal insurance compared to 34 patients (40.5%) in the n-REM group (p &lt; 0.001).

Conclusion
Despite being younger, REM patients were more likely to require an ICU admission, have underlying comorbidities, have a longer LOS, and be under-insured. There is a need for further studies to understand disparities between REM and n-REM patients regarding CDI.

Disclosures
All Authors: No reported disclosures.
397. Oral Vancomycin Versus Fidaxomicin for Clostridiodes difficile: A Comparative Retrospective Evaluation across a Large, Multi-center Healthcare System
Authors: Roemer Kaleb , Burgess Hayley , Sands Kenneth E , Hodgin Ryan 
Published: December 2022

Abstract

Background
The Infectious Diseases Society of America and Society for Healthcare Epidemiology of America recently published the 2021 Focused Clinical Practice Guideline Update on Management of Clostridioides difficile in Adults that recommends fidaxomicin as a preferred treatment for initial and recurrent C. difficile infection (CDI) over oral vancomycin. The aim of this study was to evaluate clinical outcomes of adult inpatients with CDI diagnosis treated with fidaxomicin versus oral or rectal vancomycin.

Methods
The patient population included adult inpatients 18 years or older admitted to a hospital within the healthcare system with CDI International Classification of Diseases, Tenth Revision (ICD-10) codes from January 1, 2017 to October 31, 2021. Data was obtained for inpatients with a discharge diagnosis of CDI and receiving fidaxomicin, oral or rectal vancomycin, or no receipt of either antibiotic. Readmission was defined as readmittance to the healthcare system within 8 weeks and a CDI diagnosis. Recurrence risk factors were defined as age 65 years or older, immunocompromised based on ICD-10 codes, and severe CDI defined as white blood cell count &gt; 15 cells/mm3 PLUS serum creatinine &gt; 1.5 mg/dL.

Results
More than 45,000 inpatients with a CDI diagnosis were evaluated. Administration rates of vancomycin, fidaxomicin, or no receipt of either was 76%, 6% and 18%, respectively. Median length of stay for vancomycin compared to fidaxomicin was 7 versus 9 days, respectively. Readmission rate was lower for total inpatients receiving vancomycin (14.6%) compared to fidaxomicin (18.5%), showing statistical significance (p &lt; 0.0000005). Subgroup analyses were performed to evaluate inpatients with risk factors for CDI recurrence. Vancomycin had a lower readmission rate for all recurrence risk factor groups. Additionally, oral vancomycin had lower readmission rates for patients with more than one risk factor (13.4% vs. 16.1%).

Conclusion
The results of this study demonstrated that fidaxomicin did not result in a shorter length of stay or lower readmission rate compared to oral/rectal vancomycin. This study supports the continued use of oral/rectal vancomycin for CDI without preference for fidaxomicin.

Disclosures
All Authors: No reported disclosures.
399. Reducing Hospital-Onset C. diff with a Provider-Driven Emergency Department Ordering Algorithm
Authors: Holdsworth Jill , Milloy Aaron , Kaylor Jordan , Richardson Rita , Meloy Patrick 
Published: December 2022

Abstract

Background
Clostridoides difficile (C. diff) can cause diarrhea and inflammation of the colon. It is one of the most common causes of heathcare-associated infections (HAIs), estimated to cause almost half a million illnesses and thousands of deaths in the United States each year. Studies have estimated that this HAI costs up to $4.8 billion each year in excess healthcare costs for acute care facilities. Early identification, treatment and initiation of isolation precautions is crucial to patient care and transmission reduction, making the Emergency Department ideal partners in efforts to reduce C. diff infections.

Methods
A C. diff testing algorithm was introduced specific to the Emergency Department in March, 2021, promoting earlier testing and isolation of patients suspected of having C. diff. Emergency medicine clinicians were awarded the "Golden Spore" Award weekly when appropriately initiating the C. diff testing and isolation, provided the patients met criteria, or were clinically suspected of having a C. diff infection.
C. diff ordering algorithm
Ordering algorithms were printed and placed in the clinician's work area to facilitate increased ordering of isolation and testing of potentially infected patients.
GoldenSporeAward
The Golden Spore is awarded weekly to emergency clinicians who successfully identify and isolate C. diff patients prior to admission.

Results
As a result of the COVID-19 pandemic, there were varying degrees of challenges for implementation of the program. Emergency clinicians sent 199 C. diff tests pre-intervention (3/15/20-3/14/21) and 234 tests post-intervention (3/15/21-3/14/22). Pre-intervention, 44 patients were found to be C. diff positive prior to admission, compared to 62 post-intervention. Clinicians enjoyed the "golden spore" award and were excited to participate.

Conclusion
The program is ongoing, though the initial results are encouraging. There was an immediate increase in the testing and subsequent isolation of patients while in the ED. Infection prevention and emergency medicine clinicians worked together to boost their numbers, and the "golden spore" continues to be awarded in weekly newsletters. Clinicians indicated they enjoyed the engagement, and found that the small change in a routine process improved their baseline awareness of potential C. diff patients, leading to an increase in the number of tests and subsequent discovery of C. diff positive patients. C. diff champions were also named and the algorithm will be shared with additional emergency departments within our system to continue to improve detection and prevention of hospital associated infections.

Disclosures
All Authors: No reported disclosures.
401. Rigor and Reproducibility of Clostridioides difficile susceptibility testing
Authors: Lancaster Chris , Eubank Taryn A , Gonzales-Luna Anne J , Dureja Chetna , Hurdle Julian , Garey Kevin W 
Published: December 2022

Abstract

Background
The growth and susceptibility testing of anaerobic bacteria presents many unique challenges. The Clinical Laboratory Standards Institute (CLSI) recommends performing minimum inhibitory concentration (MIC) testing for C. difficile through agar dilution (AD) assay, which carries logistical and time burdens compared to broth microdilution (BMD) methods. In this project we aim to assess the intra-and inter-laboratory reproducibility of MIC testing for C. difficile.

Methods
A total of 30 C. difficile isolates underwent MIC testing using AD and BMD techniques. To test intra-lab reproducibility, proficiency testing to develop a reproducible MIC testing process using 18 isolates was implemented across two multi-disciplinary labs, which was then validated in a prospective cohort of 116 isolates. MICs obtained by each method and lab were compared and essential agreement (EA) and major and minor error rates were calculated. To combat the labor and time-intensive demands of AD testing, automation with Integra Assist Plus was tested. Times for plate set up using a technician versus the Integra Assist Plus were measured twice and the average times were compared.

Results
AD and BMD yielded discordant resistant/susceptible results in 16.7% (5/30) of isolates tested. During proficiency testing, intra-lab comparison of AD MICs yielded 88.9% (16/18) EA and no disagreements occurred with more than 1 dilution difference. EA improved in the larger cohort to 93.9% (109/116), of which minor and major disagreements occurred in 17% (21/116) and 25% (29/116), respectively. A total of 10’4” minutes were saved using automation (12’44” mean) versus a technician (24’40” mean).

Conclusion
Here we present the process undertaken to ensure the rigor and reproducibility of C. difficile susceptibility testing. We developed a procedure that yields accurate results from two different labs, minimizes cost, and lowers the overall time required. Our future research will include validation with a larger sample and more academic partners.

Disclosures
Kevin W. Garey, PharmD, MS, Acurx: Grant/Research Support|cidara: Advisor/Consultant|cidara: Grant/Research Support|Paratek: Grant/Research Support|Seres Health: Grant/Research Support|Summit: Grant/Research Support.
410. Characteristics of Patients with Extended-Spectrum Beta-Lactamase (ESBL) Producing Enterobacterales, Tennessee, 2019-2020
Authors: Hitchingham Erin , Muleta Daniel , Villegas Raquel , Gambrell Ashley , Bailey Cherlly , Wilson Christopher , Mounsey Jackie 
Published: December 2022

Abstract

Background
Currently, data on the incidence of Enterobacterales bacteria that produce extended-spectrum beta-lactamases (ESBL) within community settings is lacking. We set out to describe patient characteristics for healthcare-associated (HA) and community-associated (CA) ESBL-producing Enterobacterales in Tennessee.

Methods
ESBL cases were defined as isolation of Escherichia coli, Klebsiella pneumoniae, or Klebsiella oxytoca, resistant to cefotaxime, ceftriaxone, or ceftazidime, non-resistant to all tested carbapenems, from a normally sterile body site, or urine, within Maury, Lewis, Marshall, or Wayne Counties, with a specimen collection date from July 1st, 2019, to the end of 2020. Patient data was collected by reviewing patients’ medical records. HA cases were defined as those with previous healthcare exposures, of any kind, in the year preceding specimen collection. All analysis was performed using SAS 9.4.

Results
566 cases were included in this study. Demographically, 459 (81.1%) cases identified as white with an equal number (81.1%) of patients being female. The average age was 66.2 years. 560 (98.94%) specimens were collected from urine, 468 (85.1%) patients had a urinary tract infection (UTI), and 174 (37.2%) of those patients had a record of recurrent UTIs. 243 (49.6%) cases were identified as CA. 138 (24.4%) cases were identified as being hospitalized within 29 days of their specimen collection and 247 (50.4%) cases were determined to be HA. 142 (25.1%) patients were treated with antibiotic in the month before specimen collection. Cephalosporins (31.7%), fluroquinolones (29.6%), doxycycline (7.7%), and sulfonamides (7.7%) were the most common antibiotics used to treat the patients. Among patients prescribed these antibiotics (N=109), 19 (17.4%) patients had specimens resistant. Figure 1:Characteristics of patients with extended-spectrum beta-lactamases (ESBL) producing Enterobacterales isolated from 2019-2020Figure 2:Characteristics of patients with extended-spectrum beta-lactamases (ESBL) producing Enterobacterales isolated from 2019-2020, continued

Conclusion
Most cases were described in white women with UTIs, often recurrent, coming from private residences. With approximately 50% of cases described as CA, targeted intervention outside of healthcare facilities is necessary to reduce spread of ESBL infections. As 17.4% of cases were treated with antibiotics that the organism was resistant, there is an opportunity to improve judicial use of antibiotics based on susceptibility data.

Disclosures
All Authors: No reported disclosures.
412. Clinical and demographic features associated with beta-lactamase producing Enterobacterales in an academic medical center in Loma Linda, CA
Authors: Liu Eugene W , Pappas James 
Published: December 2022

Abstract

Background
Emergence of antibiotic resistant bacteria is a threat to public health. The aim of this study is to identify clinical and demographic features associated with beta-lactamase producing Enterobacterales, specifically extended spectrum beta-lactamase producing (ESBL) and carbapenem-resistant Enterobacterales (CRE), in patients at Loma Linda University Health, an academic medical center in Loma Linda, California.

Methods
This retrospective case control study compared patients with/without beta-lactamase producing Enterobacterales. Cases and controls were identified from microbiology records with Enterobacterales isolated between January 1, 2020, and December 31, 2021. Case subjects were individuals with ≥1 CRE isolate (confirmed by nuclear amplification testing, NAT) and control subjects were those with ≥1 isolate that were all non-CRE. We identified isolates of interest, defined as the first CRE isolate in cases and the first non-CRE isolate for controls. For each isolate of interest and corresponding specimen collection date, we extracted electronic medical record data including inpatient antibiotics received in the preceding 6 months, specimen type, patient sex and age. We performed similar analysis with ESBL-producing Enterobacterales confirmed by NAT.

Results
On multiple logistic regression, age (OR, 1.02; 95%CI, 1.01-1.04), isolation of klebsiella (10.75; 4.59-25.21), providentia (20.86; 2.47-176.17), and serratia (8.01; 1.59-40.40), receipt of non-carbapenem beta-lactams (1.06; 1.03-1.10), carbapenems (1.19; 1.12-1.27), doxycycline (1.26; 1.04-1.52), and tetracycline (1.89; 1.08-3.29), were independently associated with increased odds of CRE infection. Similarly, gender (2.59; 2.07-3.24), age (1.01; 1.01-1.02), isolation of proteus (1.47; 1.01-2.13), receipt of non-carbapenem beta-lactams (1.08; 1.06-1.11), carbapenems (1.33; 1.23-1.44), and vancomycin (1.07; 1.03-1.12) were associated with increased odds of infection with ESBL-producing Enterobacterales.

Conclusion
Age and receipt of beta-lactams (including carbapenems) were associated with odds of infection with both CRE and ESBL-producing Enterobacterales in an academic medical center in Southern California, highlighting the importance of antibiotic stewardship.

Disclosures
All Authors: No reported disclosures.
418. Fosfomycin Dosing Regimens for The Treatment of Carbapenem-Resistant Enterobacteriaceae Infections in Patients Receiving Continuous Renal Replacement Therapy: a Monte Carlo Simulation
Authors: Kanchanasurakit Sukrit , Srisawat Chansinee , McPherson Charles E , Saelim Weerayuth , Siriplabpla Wuttikorn , Suthumpoung Pornsinee , Santimaleeworagun Wichai 
Published: December 2022

Abstract

Background
To predict the appropriate dosing of intravenous fosfomycin for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infection in continuous renal replacement therapy (CRRT) patients.

Methods
Minimum inhibitory concentration (MIC) values of all isolates were determined by E-test method. Population pharmacokinetic parameters were obtained from a previously published study. The percentages of a 24-hour period in which the drug concentration exceeded the MIC (%T &gt;MIC) were defined to be 70% T &gt;MIC and 100% T &gt;MIC, respectively. In addition, the 24-hour area under the unbound concentration-time curve over the MIC (AUC0-24/MIC) of 45 mg·h/L was used as a target value. All dosing regimens were estimated for the probability of target attainment (PTA) using a Monte Carlo simulation.

Results
For the effluent rate of 20 mL/kg/h, the PTA for reaching 70% T &gt;MIC, 100% T &gt;MIC, and AUC0-24/MIC of 45 mg·h/L was achieved in pathogens with a MIC of 24 mg/L, 12 mg/L, and 24 mg/L in all regimens, respectively. Meanwhile for the effluent rate of 25 mL/kg/h, the PTA for reaching 70% T &gt;MIC, 100% T &gt;MIC, and AUC0-24/MIC of 45 mg·h/L was achieved in organisms with a MIC of 16 mg/L, 12 mg/L and 24 mg/L in all regimens, respectively.

Conclusion
The appropriate fosfomycin dosing regimens for CRE infections in critically ill patients receiving CRRT were suggested based on pharmacokinetic/pharmacodynamic targets, MIC values, and effluent rates. Clinical validation is warranted.

Disclosures
All Authors: No reported disclosures.