bluuebunny/crossref_metadata_2025_split huggingface dataset:
2167. Mutational Signature Analysis to Predict Drug-resistant Pseudomonas aeruginosa
Authors: Hall Kalen M , Williams Leonard G , Bojanowski Christine M , Pursell Zachary F , Morici Lisa 
Published: November 2023

Abstract

Background
Pseudomonas aeruginosa (Pa) is one of the predominant bacteria that contributes to chronic respiratory infection, patient morbidity, and mortality in cystic fibrosis (CF) patients. Up to 60% of Pa clinical isolates are hypermutators, caused by deficiency in the DNA mismatch repair (MMR) system, and are associated with increased multidrug resistance and treatment failure. In vitro studies demonstrate a causative relationship between hypermutation and multidrug resistance, yet hypermutators are not currently tested for in the clinical setting as no diagnostic method is currently available. Mutational signatures have been computationally extracted and characterized in human tumors, but to our knowledge this analysis has never been performed in prokaryotes.

Methods
Here, we evolved MMR-deficient and -proficient Pa in vitro under nine different antibiotic treatments. We sequenced these evolved lineages to test the hypothesis that mutational signature analysis can predict MMR-status and drug resistance. We identified mutation spectra from de novo mutations in the evolved lineages after ten passages and then compared these spectra to known human tumor MMR-deficient mutational signatures. We then sequenced 14 isolates from seven CF patients and performed mutational signature analyses to assess for the presence of MMR-deficient signatures.

Results
We observed a strong signature in all evolved MMR-deficient Pa strains of C &gt;T transitions in a NCC and NCG contexts with some 5’ preference to C and G, along with T &gt;C transitions in CTN and GTN contexts. Although many antibiotics are known mutagens, we did not observe treatment-dependent changes in mutational spectra.Mutation spectra consistent with MMR-deficiency were found in four isolates, each of which were also functionally validated as hypermutant via rifampicin reversion assay.

Conclusion
These studies suggest that mutational signature analysis may be a valuable tool to identify hypermutator strains of Pa, which could inform treatment regimens and improve management of chronic Pa infections.

Disclosures
Kalen M. Hall, B.S., B.A., Informuta: 1|Informuta: Ownership Interest|Informuta: Stocks/Bonds Leonard G. Williams, B.S., Informuta: 1|Informuta: Ownership Interest|Informuta: Stocks/Bonds
2942. Successful Screening, Linkage to Care, and Treatment of Hepatitis C in a Tiny Shelter Encampment on Veterans Affairs Grounds
Authors: Lautredou Cassandra C , Lynch Kimberly A , Stricker Katherine , Capone-Newton Peter , McCoy Matthew , Kawamoto Jenna , Patel Arpan , Seckington Michele , Bhattacharya Debika 
Published: November 2023

Abstract

Background
Persons experiencing homelessness have a high prevalence of hepatitis C virus (HCV) infection and multiple barriers to diagnosis and treatment. We implemented and evaluated a universal HCV screening and HCV care coordination and treatment program for Veterans living at a tiny shelter encampment on the West Los Angeles Veterans Affairs campus.
Hepatitis C Cascade of Care
All patients who completed treatment and obtained end of treatment lab work achieved SVR12, excluding Veterans who were lost to follow up (LTFU) and/or non-adherent (NA) (n=5), on treatment (n=4), or SVR12 pending (n=5).

Methods
We implemented a low-barrier to entry HCV treatment program for Veterans experiencing homelessness (VEH) that spanned April 2020-Dec 2021 (pre-intervention) and Jan 2022-April 2023 (post-intervention). The intervention involved a novel e-consult direct-to-treatment program facilitated by pharmacists and referral to ID/GI clinics (if ineligible for e-consult) and extensive engagement by encampment providers, including provision of direct-acting antivirals (DAAs) in weekly installments. Prior to the intervention, management was achieved solely through ID/GI clinic referrals. We evaluated HCV prevalence, along with linkage to care, treatment initiation, and sustained virologic response (SVR) of this novel program pre-and post-intervention. Data, including demographics, medical history healthcare visits, and other laboratory values were abstracted from the electronic medical record. Descriptive statistics were used to characterize prevalence of HCV and other covariates.

Results
Of the 704 Veterans who sheltered at the encampment at some point from April 2020-April 2023, 587 underwent HCV antibody screening (83%). Of those, 20% (120/587) were HCV Ab positive and 44% (53/120) had HCV viremia. Median age of those who were viremic was 64 years, 100% were male, 32% (17/53) were Black, 9% (5/53) Hispanic, and 58% (31/53) White. Pre- and post-intervention, 25 and 28 Veterans with HCV viremia were identified, 11 and 21 Veterans were linked to care (44% and 75%), 4 and 20 initiated DAAs (36% and 95%), and 1 and 6 achieved SVR (25% and 30%). Nine patients are currently on treatment (n=4) or pending SVR12 (n=5).

Conclusion
After an intervention involving e-consult and encampment provider engagement in VEH, 75% of Veterans with HCV viremia were linked to care, compared to 44% of Veterans prior to the intervention. Our program demonstrates the feasibility of encampment-based HCV screening, linkage to care and treatment.

Disclosures
Debika Bhattacharya, MD, MSc, Gilead Sciences: Grant/Research Support
2188. Evaluation of biocide susceptibilities of clinical isolates of Acinetobacter baumannii
Authors: Varghese Martin M , Cadnum Jennifer , Chatterjee Piyali , Jinadatha Chetan , Donskey Curtis 
Published: November 2023

Abstract

Background
Carbapenem-resistant Acinetobacter baumannii (CRAB) is an urgent antimicrobial resistant threat due to its resistance to many antibiotics. There is a concern that some antibiotic-resistant strains of A. baumannii might also express resistance to biocides, including disinfectants and antiseptics. However, relatively little information is available on the susceptibility of A. baumannii to disinfectants.

Methods
Thirty well-characterized clinical A. baumannii isolates were studied, including 24 (%) CRAB isolates and 11 (37%) with qacE1 and amvA efflux pump genes. The efficacy of sodium hypochlorite (1:10 dilution of household bleach) and virex-II 256 (quaternary ammonium disinfectant) was evaluated using a standard disk-based quantitative carrier test method (ASTM E2197-11) in the presence of 5% fetal calf serum. The disinfectants were tested at in-use concentrations with the manufacturer-recommended exposure times. Minimum inhibitory concentrations (MICs) to virex-II 256, povidone-iodine, chlorhexidine, and were determined using a broth microdilution method. Serial passage of A. baumannii in subinhibitory concentrations of virex-II 256 were performed to assess the potential for emergence of resistance.

Results
All 30 A. baumanii isolates were reduced to undetectable levels (&gt;5.4 log10 reduction) by both disinfectants. MICs for povidone-iodine, chlorhexidine, and virex-II 256 were 2343.75 to 9375 µg/ml, 0.62 to 12.5 µg/ml, 1.06 to 2.03µg/ml, respectively. With serial passage in subinhibitory concentrations of virex-II 256, the MICs of virex-II 256 increased 4-fold from 2.03 to 8 µg/ml, and some strains developed increases in chlorhexidine MICS from 12.5 to 50 µg/ml.

Conclusion
Sodium hypochlorite and a quaternary ammonium disinfectant were effective at in-use concentrations against A. baumannii, including CRAB strains and isolates with efflux pumps. Exposure to subinhibitory concentrations of quaternary ammonium compounds may result in increases in MICs in these disinfectants and other biocides.

Disclosures
All Authors: No reported disclosures
2190. Lack of Knowledge of Antibiotic Risks Among an Outpatient Population is Associated with Intention to Use Non-Prescription Antibiotics
Authors: Amenta Eva , Trautner Barbara , Olmeda Kiara , Salinas Juanita , Arya Monisha , Laytner Lindsey , Paasche-Orlow Michael , Grigoryan Larissa 
Published: November 2023

Abstract

Background
Antibiotic use without a prescription (non-prescription use) leads to risks for patients and the public, including adverse drug reactions,
Clostridoides difficile
infections, microbiome disruption, and the development of antimicrobial resistance. We hypothesized that patients’ lack of knowledge of risks associated with antibiotic use would be associated with non-prescription use.

Methods
We surveyed patients in public clinics and private emergency department waiting rooms in Houston from January 2020 through June 2021. Respondents’ knowledge about risks associated with antibiotic use was assessed with an open-ended question, “Do you know about any risks associated with antibiotic use?” Intended use was defined as endorsing an intention to use antibiotics without a prescription. The effects of age, gender, race/ethnicity, education, and knowledge of the risks associated with antibiotics on intended use were investigated using logistic regression.

Results
We surveyed 564 individuals (median age of 51), with 72% identifying as female, 46.6% as Hispanic and 33% as Black or African American (Table 1). When asked about knowledge of antibiotic risks, 354 (63%) respondents were able to report at least one risk associated with antibiotics. Risks were categorized into themes that included side effects of antibiotics (270/564, 48%), antibiotic resistance (19%), disruption of the microbiome (5%), drug-drug interactions (4%), fear of taking medication (4%), and other (0.05%) (Table 2). Lack of knowledge of antibiotic risks OR 1.48 (95% CI 1.04-2.10) and younger age (age 18-64 years) OR 2.24 (1.29-3.89) were independently associated with intention to use non-prescription antibiotics (Table 3).

Conclusion
Over one-third of respondents reported no knowledge of antibiotic-associated risks. Only 19% of respondents were aware of the concept of antimicrobial resistance. Lack of knowledge was associated with the intention to use non-prescription antibiotics, suggesting that further patient education about potential downsides of taking antibiotics is essential to reducing non-prescription antibiotic use.

Disclosures
Barbara Trautner, MD, PhD, Genentech: Grant/Research Support|Peptilogics: Grant/Research Support
2191. An Assessment of Penicillin Allergy Documentation among Patients undergoing Elective Surgeries and Ambulatory Procedures
Authors: Banach David , Zavez Katherine , Schramm Carol , Zolla Meagan , Baron Kate , Carter Eileen J 
Published: November 2023

Abstract

Background
A documented allergy to a penicillin class antibiotic can have a significant impact on perioperative antibiotic prescribing and is associated with an increased risk of post-operative adverse events. Comprehensive penicillin allergy histories enable risk stratification to influence future antibiotic prescribing. We evaluated the documentation of penicillin allergies among patients undergoing elective surgeries and ambulatory procedures to identify opportunities to improve allergy assessments and documentation in these settings.

Methods
This was a retrospective chart review of unique records of patients who underwent elective surgeries and ambulatory procedures at UConn Health from December 2, 2022 – January 24, 2023, and had a documented allergy to a penicillin class antibiotic at the time of the surgery or procedure. Information on the documented details of the allergy, including type and timing of the reaction and who documented the allergy was recorded and analyzed.

Results
Among 233 unique records reviewed, most penicillin allergies were initially documented by a medical assistant (n=135, 58%), and not subsequently updated after initial documentation (n=211, 91%). Symptoms of allergy were documented for 177 (76%) of records, with the most common symptoms being hives/rash (n=106, 46%), gastrointestinal symptoms (n=27, 12%) and anaphylaxis (n=26, 11%). Symptoms of allergy were unknown or missing for 56 (24%) of records. In 5 (3%) of records, clinicians documented when the patient’s reaction occurred (childhood) and in 2 (1%) of records, clinicians indicated the patient tolerates cephalexin or amoxicillin.

Conclusion
Among patients undergoing elective surgeries and ambulatory procedures, we found medical assistants documented most penicillin allergy records. Penicillin allergy records were rarely updated and contained scant information for risk stratification. Efforts are needed to improve the documentation of penicillin allergies in outpatient pre-operative and pre-procedural settings.

Disclosures
All Authors: No reported disclosures
2197. Impact of an INtake FOrm for Restricted Medications to (INFORM) better antibiotic use within a long-term acute care hospital system
Authors: Hobbs Athena L V , VanCura Jennifer , Hobbs Diana A , Shea Katherine M 
Published: November 2023

Abstract

Background
Long-term Acute Care Hospitals (LTACHs) are uniquely positioned to treat patients with a high severity of illness for a long period of time. Despite this, there are substantial barriers to providing antimicrobial stewardship in this setting including limited resources and lack of patient data from transferring facilities.

Methods
This multi-center retrospective, quasi-experimental study evaluated the use of broad-spectrum antibiotics (BSAbx) over 3 timeframes in 43 LTACHs and rehabs within the Post Acute Medical System. Despite implementation of a restriction policy in June 2018, use remained high for ceftolozane/tazobactam (C/T), ceftazidime/avibactam (CZA), and meropenem/vaborbactam (MEV). In July 2020, the system antimicrobial stewardship committee created an INtake FOrm for Restricted Medications (INFORM) that required submission of pertinent clinical information for each patient receiving one of the target antibiotics as well as systematic review by an ID pharmacist. An electronic version of the INFORM was implemented in April 2022. Study timeframes included baseline (BL: July 2019-June 2020), phase 1 (P1: July 2020-March 2022), and phase 2 (P2: April 2022-March 2023). The primary objective was to determine if there was a difference in the combined use of C/T, CZA, and MEV measured as cost/acute patient day (APD) across the three timeframes. Secondary analyses included post-hoc analyses between these groups, and an evaluation of C/T, CZA, MEV with the addition of imipenem/cilastatin/relebactam (I/C/R).

Results
There was a significant reduction in antimicrobial use across intervention periods (mean cost/APD BL=2.5, P1=1.3, P2=0.8, p=0.045 using ANOVA, Figure 1). Sub-hoc analyses showed a significant difference for BL:P1 (p=0.02) and BL:P2 (p&lt; 0.01), but not for P1:P2 (p=0.6). Even when adding I/C/R to control for any shifts in utilization to this agent after it was approved by the FDA, there was a statistically significant reduction across the intervention periods (p&lt; 0.01 using ANOVA, Figure 2).
Figure 2: Cost/Acute Patient Day for C/T, CZA, MEV vs. I/C/R over time
C/T = ceftolozane/tazobactam, CZA = ceftazidime/avibactam, MEV = meropenem/vaborbactam, I/C/R = imipenem/cilastatin/relebactam

Conclusion
Completion of both the paper and electronic INFORM reduced C/T, CZA, and MEV use from baseline, showing that the systematic collection and review of patient data by an ID pharmacist reduced use of these BSAbx in a system of LTACHs and rehabs.

Disclosures
All Authors: No reported disclosures
2199. Antibiotic tracking and reporting in skilled nursing facilities: a failure to communicate
Authors: Jolles Sally , Heller Dee , Taylor Lindsay , Dowdell Ashlie , Crnich Christopher J , Ford Jay 
Published: November 2023

Abstract

Background
Antibiotic overuse and misuse are common in skilled nursing facilities (SNFs) and are drivers of adverse drug events, antibiotic resistance and Clostridioides difficile infections. CMS requires SNFs to implement antibiotic stewardship programs (ASPs) that include a system for tracking and reporting antibiotic use (AU) and antibiotic-related outcome (ARO) measures. However, there is limited understanding of the maturity of these systems in SNFs.

Methods
We conducted a descriptive study of AU/ARO tracking and reporting practices in 10 Wisconsin SNFs recruited in the fall of 2022. Key informants in study SNFs were asked to provide de-identified examples of line lists and facility antibiotic reports that included AU/ARO information. Checklists were developed to identify the types and characteristics of the different AU/ARO variables and measures. Document analyses were conducted on the retrieved source documents utilizing these checklists.

Results
36 source documents were analyzed including 24 line lists and 12 AU reports (Figure 1). Of the 20 qualifying line lists, 40% were in a format that permitted direct data manipulation (e.g., Excel spreadsheet). 70% of SNFs employed multiple line lists. 30% of SNFs were unable to provide an aggregate AU report. Although a majority of SNF line lists captured information on antibiotic indication, duration of therapy and ordering prescriber, these variables were frequently omitted from facility AU reports (Figure 2). Information on appropriateness of antibiotic prescriptions and origin of the antibiotic order (e.g., ED) were captured less frequently on SNF line lists and, by extension, facility AU reports (Figure 2).
A comparison of facility Line Lists versus Reports

Conclusion
SNF staff devote considerable resources to identifying and characterizing antibiotic events. However, this information is not stored in a format that allows data to be reviewed and analyzed easily. Additionally, a significant minority of SNFs do not routinely generate AU/ARO reports and those that do, often omit important information about prescribing practices that could inform facility quality improvement efforts. These findings suggest there is substantial opportunity to improve SNF AU/ARO tracking and reporting practices.

Disclosures
Lindsay Taylor, MD, MS, Merck: Grant/Research Support
2208. Ten years of the Irish National Outpatient Parenteral Antimicrobial Therapy (OPAT) Registry Data
Authors: Reidy Paul , Muldoon Eavan 
Published: November 2023

Abstract

Background
The Irish Outpatient Parenteral Antimicrobial Therapy (OPAT) programme, a national centrally administered outpatient antibiotic provision service was established in 2013 within the public hospital system and is operated by the Health Service Executive (HSE). Ireland is relatively unique in having a nationally coordinated OPAT programme with complete summary data since its establishment.
Here we describe the programme usage over ten years and show the data can be used to identify important trends in national antimicrobial usage, including stewardship issues, with relevant lessons for other OPAT centres.

Methods
Using data extracted from the national electronic portal we describe summary statistics from January 2013 to December 2022 (10 years).

Results
Over the ten-year period 17,559 OPAT episodes were facilitated across 42 healthcare institutions. These episodes represented 14,955 unique care episodes with the remainder being extensions or changes to active episodes.
12388 episodes were home OPAT delivered by a healthcare worker versus 5170 self OPAT where patients were taught to self-administer the antimicrobials.
The median OPAT duration of therapy was 14 days with an average of 19.9 days.
The median age of a referred patient was 59 years with an average age of 56 years.
The top five diagnoses of osteomyelitis, abscesses, cellulitis, bacteraemia, and pyelonephritis accounted for 53% of all referrals.
81.5% of patients were prescribed a single antimicrobial, 17.9% two agents and 0.6% three.
Four antibiotics – ceftriaxone, daptomycin, cefazolin and flucloxacillin continuous infusion account of 59% of the 44 different antimicrobials prescribed via the programme.
Five of the 42 healthcare institutions accounted for 57.25% of all OPAT prescriptions. The number of beds in a hospital was not the strongest predictor of OPAT usage.
The total number of bed days saved in the 10-year period was 292,860.

Conclusion
Within a health system operating on 11,171 beds available per day, for a population of just over 5 million people, with an average daily running cost of €878 per acute bed, the National OPAT programme has already contributed to significant bed day and consequent financial savings.
Starting an infectious diseases clinical service significantly increases OPAT utilisation rates.
ID Specialist appointed to centre for first time in 2021

Disclosures
All Authors: No reported disclosures
2209. Reducing Inappropriate Antibiotic Prescribing for the Treatment of Urinary Tract Infections (UTI) in Urgent Care Clinics
Authors: Vu Christine A , Salazar Veronica , Patel Fenil , Abbo Lilian M , Rosa Rossana 
Published: November 2023

Abstract

Background
In 2020, The Joint Commission released new standards to promote expansion of antimicrobial stewardship into the ambulatory care setting. Urinary tract infections (UTIs) are one of the most common bacterial infections encountered in the outpatient setting and therefore an opportunistic area for intervention. The aim of our study was to evaluate current outpatient prescribing patterns for the treatment of UTIs and develop a methodology to improve antibiotic prescribing.

Methods
A single-center, retrospective study was conducted across 5 Jackson Health-University of Miami Urgent Care Clinics (UCC) in Miami, Florida. We utilized ICD-10 diagnosis codes to identify adults diagnosed with UTIs between January 1, 2021 and October 31, 2022. We identified the top five prescribers and audited 10% of their prescriptions. The data was analyzed and as our intervention, we shared results with UCC leadership and disseminated provider-specific report cards to highlight inappropriate prescribing practices. After this, we allowed 3 months for change to occur and set a goal of reducing the percentage of inappropriate UTI durations by 50%.

Results
For baseline data, 123 charts were reviewed. We identified 95 patients with cystitis (77.3%), 26 pyelonephritis (21.1%), and 2 asymptomatic bacteriuria (1.6%). Inappropriate prescribing ranged from 17.6% to 80.6% between the UCC prescribers (Figure 1). Various types of prescribing opportunities were identified, with the most common being prolonged length of therapy (Figure 2).
For post-intervention, 114 charts were reviewed. We identified 90 patients with cystitis (78.9%), 22 pyelonephritis (19.3%), and 2 asymptomatic bacteriuria (1.8%). Inappropriate durations of UTI treatment were reduced by 25% (Figure 3), with the greatest improvement seen in nitrofurantoin prescribing (Figure 4).
Figure 1
Figure 2
Figure 3

Conclusion
Retrospective audit and feedback using provider-specific report cards was an effective antimicrobial stewardship strategy for the ambulatory care setting. Our intervention led to reduced durations of UTI treatment for nitrofurantoin but not necessarily with fluoroquinolones, trimethoprim/sulfamethoxazole, or beta-lactams. Next steps will include providing more education to further promote appropriate use of all classes of antibiotics.
Figure 4

Disclosures
Lilian M. Abbo, MD, MBA, Ferring: Advisor/Consultant|Pfizer: Advisor/Consultant|Regeneron: Grant/Research Support|Shionogi: Advisor/Consultant