bluuebunny/crossref_metadata_2025_split huggingface dataset:
2187. Earliest Description of Mobile Genetic Elements (MGEs) Involved in Establishing blaNDM Persistence Following its Spread From Acinetobacter spp. to Enterobacterales
Authors: Touati Dalila , Grenier Frédéric , Lévesque Simon , Rodrigue Sebastien , Haraoui Louis-Patrick 
Published: November 2023

Abstract

Background
bla NDM is the most prevalent carbapenemase worldwide. It originated in Acinetobacter spp. and spread to Enterobacterales on MGEs despite bottlenecks in MGE transfers between, and persistence within, these phylogenetically distinct bacteria. To elucidate how this transfer and successful expansion were achieved, we investigated MGEs among the earliest NDM-positive Gram-negative bacteria (GNB), isolated in India in 2007.

Methods
Thirteen polymerase chain reaction-confirmed NDM-positive GNB underwent whole-genome sequencing (Illumina NovaSeq and Oxford Nanopore Technologies MinION) and computational analyses: assembly (Unicycler and Trycycler), annotation (RAST), identification (Kraken2), plasmid incompatibility (PlasmidFinder).

Results
Single copies of blaNDM-1 were found in 12 Enterobacterales (6 K. pneumoniae; 3 E. coli; 2 E. cloacae; 1 E. hormaechei) and 1 A. baumannii (Ab), located on plasmids in 11/13 strains: 6 IncC, 3 IncFII, 2 IncFIB (Figure 1). Partial or complete ISAba125 was found upstream of all blaNDM, with a second complete downstream copy forming Tn125 only in Ab. blaNDM's genetic environment was highly diverse including the earliest evidence of its association with MGEs that participated in its global dissemination: insertion sequence common region 1 (ISCR1, n=5) and Tn3000 (n=4). IS3000, present in 2 copies bracketing Tn3000, was also found in single copies in 4 strains at varying distances upstream of blaNDM. In 3/4 of these, ISCR1 was downstream of blaNDM. These hybrid constructs may represent precursors leading to the formation of these MGEs, or degenerate structures.
Figure 1: Genetic environment surrounding blaNDM in 13 Gram-negative bacteria isolated in India in 2007.
Acibau: Acinetobacter baumannii; Entclo: Enterobacter cloacae; Enthor: Enterobacter hormaechei; Esccol: Escherichia coli; Klepne: Klebsiella pneumoniae.

Conclusion
We present evidence of early, rapid and diverse adaptation of blaNDM’s genetic environment following its transfer from Acinetobacter spp. to Enterobacterales. We identify for the first time potentially intermediate genetic structures in the transition between the ancestral Tn125 structure from Acinetobacter spp., and both ISCR1 and Tn3000, which overtook Tn125 as the predominant MGEs among NDM-positive Enterobacterales. Additional sequencing of early NDM-positive isolates could shed more light on the genetic events leading to the formation of MGEs associated with blaNDM, furthering our understanding of the emergence of MGEs carrying antibiotic-resistance genes.

Disclosures
All Authors: No reported disclosures
2943. Hazardous Alcohol Use and Direct-acting Antiviral Therapy Initiation Among People Who Inject Drugs with Current Hepatitis C Infection
Authors: Karimi-Sari Hamidreza , Falade-Nwulia Oluwaseun , Zook Katie , Page Kathleen R , Lucas Gregory 
Published: November 2023

Abstract

Background
People who inject drugs (PWID) have a high prevalence of hepatitis C virus (HCV) infection. However, HCV treatment rates among PWID remain low. Previous data suggest that hazardous alcohol use is negatively associated with direct-acting antiviral (DAA) therapy initiation in the general population. We aimed to evaluate the effect of hazardous alcohol use on DAA therapy initiation among PWID.

Methods
PWID were recruited through street outreach in Baltimore, Maryland 2018–2019. Participants completed a study survey and HCV testing (antibody reflex to RNA) at study visits. DAA initiation (self-report) was assessed at study follow-up in 6-month increments. Hazardous alcohol use was defined as Alcohol Use Disorders Identification Test-C (AUDIT-C) ≥4 for men or ≥3 for women. Frequency of injection drug use was categorized as ≤3 vs. &gt;3 times/day. Longitudinal data were analyzed using descriptive statistics and multivariable logistic regression analyses with generalized estimating equations (GEE).

Results
Among 720 PWID, 291 (40.4%) had current HCV infection evidenced by detectable HCV-RNA. Among 134 people with HCV viremia and awareness of their HCV infection, the mean age (± standard deviation) was 48.7 ± 10.3 years, 53% were males, 64.9% were African-American, 59.7% had hazardous alcohol use and 60.4% reported &gt;3 injections per day. DAA therapy was initiated in 16 (11.9%) PWID within 6 months (Table 1). In univariate analysis, DAA treatment was not associated with hazardous alcohol use (OR=1.84, 95%CI=.67–5.06) or injection frequency (OR=.54, 95%CI=.21–1.40) but was associated with Black race (OR=4.48, 95%CI=1.27–15.73) and age ≥50 years old (OR=7.17, 95%CI=2.04–25.26). In multivariate analysis, hazardous alcohol use (aOR=1.20, 95%CI=0.41–3.48), injection frequency (aOR=.84, 95%CI=.32–2.24), and Black race (aOR=1.88, 95%CI=.64–5.55) were not associated with DAA treatment initiation. Older age ≥50 vs. &lt; 50 years was positively associated with HCV treatment initiation (aOR=4.79, 95%CI=1.61–14.22).

Conclusion
Among our sample of PWID with HCV infection, oral DAA treatment was not associated with self-reported hazardous alcohol use. The overall very low rates of HCV treatment are concerning and need to be addressed by effective interventions, especially for younger PWID.

Disclosures
Oluwaseun Falade-Nwulia, MBBS ,MPH, Abbvie Inc: Grant/Research Support|Gilead Sciences: Advisor/Consultant
2198. Assessing Strengths and Opportunities of Antibiotic Stewardship Programs in Philadelphia Skilled Nursing Facilities
Authors: Menanno Mariah , Gould Jane , Peritz Tiina , Welsh Elizabeth , Heisey Deborah , Jacob Jerry 
Published: November 2023

Abstract

Background
Skilled nursing facilities (SNFs) have significant opportunity to improve antibiotic use and reduce multidrug-resistant organism transmission. In the summer of 2022, the Southeast Pennsylvania Long-Term Care Resiliency, Infrastructure Supports, and Empowerment (LTC-RISE) team and the Philadelphia Department of Public Health (PDPH) distributed a survey to all Philadelphia SNFs to understand strengths and opportunities for improvement of antibiotic stewardship programs (ASPs).

Methods
A REDCap survey was distributed via phone or video call to 47 SNFs addressing all elements in the CDC's Checklist for Core Elements of Antibiotic Stewardship in Nursing Homes. SNFs self-reported survey responses. Survey results were used to provide individualized feedback highlighting SNF performance against peers, and to implement broad-based interventions to strengthen ASPs.

Results
Thirty-eight SNFs (81%) responded to the survey. All 7 ASP core elements were reported present by 55% of respondents. Only one SNF did not have any core elements present. The elements most commonly reported present and absent were tracking measures of antibiotic use (97%), and monitoring outcomes of antibiotic use (79%), respectively. The ASP lead(s) most commonly identified was the Infection Preventionist (66%), Director/Assistant Director of Nursing (55%), or Medical Director (37%). Infection-specific interventions and resident educational materials were provided in only 42% and 34% of SNFs, respectively. Customized ASP reports were sent to all participating SNFs, with feedback obtained at 3 months after distribution. Survey results were used to create an educational webinar and UTI-focused resource package.

Conclusion
A majority of Philadelphia SNFs reported having ASPs with all CDC core elements in place, and almost all facilities tracked at least one measure of antibiotic use. Opportunities for improvement included tracking outcomes of antibiotic use, providing infection-specific interventions, and providing educational materials to residents. Insights provided from the survey helped to guide individualized and broad-based ASP interventions across facilities.

Disclosures
All Authors: No reported disclosures
2206. Using Day-Level Registry Data on Patients in OPAT to Assess Heterogeneous Patterns of Time-Varying Antimicrobial Exposure and Unplanned Stopping across Multiple Infection Diagnoses, 2015-2022
Authors: Ponder Madison , Boerneke Renae , Schranz Asher J , Swartwood Michael , Farel Claire E , Kinlaw Alan C 
Published: November 2023

Abstract

Background
Patients receiving outpatient parenteral antimicrobial therapy (OPAT) are often medically complex and require carefully tailored treatments to address severe and often concomitant infections.

Methods
We conducted a cohort study of patients enrolled in the University of North Carolina Medical Center OPAT program between March 2015 and December 2022 (2358 OPAT courses among 2072 unique patients). Patients were followed from OPAT regimen initiation (day 0) until observed treatment stop date, based on a grace period of 5 days to confirm discontinuation. Using hierarchical and mutually exclusive categorization schema, we classified patients into 1 of 10 infection diagnosis groups (Figure 1A), and classified all observed antibiotic cocktails (64 distinct antimicrobial medications comprising 520 distinct cocktails) into 18 treatments (Figure 1B). For each patient, we assessed their planned OPAT duration to classify their observed discontinuation as “planned,” “unanticipated early stop,” or “unanticipated prolonged treatment.” Stratified by infection diagnosis and treatment classifications, we used stacked bar charts to describe treatment heterogeneity, and Aalen-Johansen-based cumulative incidence curves to estimate occurrence of each type of discontinuation amid competing events.

Results
The cohort was 59.7% male with median age 56 years (IQR 45-66); the most common infection diagnosis was osteomyelitis +/- diabetic foot infection (28.1%, Figure 1A). Medication exposures were heterogeneous within and across infection diagnoses (Figure 1A and 1B). Median planned OPAT duration was 36 days (middle 90% 15-44). Overall cumulative incidence of unanticipated early discontinuation was 11.9%; overall incidence of unanticipated prolonged treatment was 22.9% (Figure 2).

Conclusion
Day-level data on medication use in this registry provided evidence of heterogeneity in medication exposure and unplanned discontinuation from OPAT, within and across infection diagnoses. These data highlight the need for multi-layered ascertainment of medication exposure, microorganisms, and infection diagnosis in this medically complex patient population to inform surveillance for adverse effects and comparative effectiveness research for post-discharge antibiotic treatment.

Disclosures
Asher J. Schranz, MD, MPH, WoltersKluwer: Honoraria Alan C. Kinlaw, PhD, MSPH, Genentech: Grant/Research Support
2207. Impact of an Intervention Bundle on Azithromycin Use and 5-Day Durations of Therapy for Ambulatory Pediatric Community Acquired Pneumonia
Authors: Weber Matthew J , MacBrayne Christine , Birkholz Meghan C , Poole Nicole M 
Published: November 2023

Abstract

Background
Amoxicillin for a 5-day duration is the first-line recommended treatment for pediatric uncomplicated community acquired pneumonia (CAP). This project sought to identify the impact of a bundled intervention on first-line treatment for pediatric CAP in ambulatory settings.

Methods
The bundled intervention included (1) an electronic medical record (EMR) order set that preselected a 5-day duration of therapy for patients prescribed an antibiotic for CAP (8/2020) and (2) revision of an existing clinical pathway for CAP (4/2021) that removed amoxicillin-clavulanate and azithromycin as recommended antibiotics.
A retrospective review was conducted between July 2018 and July 2022. Patients ages 60 days to 18 years with an in-person or remote ambulatory encounter and validated ICD10 diagnosis code of pneumonia were included. Hospitalized patients and those with complex chronic conditions were excluded. Data was extracted from EPIC EMR.
Primary outcomes were rates of amoxicillin and azithromycin use (encounters receiving the antibiotic of interest out of all encounters receiving an antibiotic) and 5-day duration prescriptions (encounters receiving a 5-day prescription [excluding azithromycin] out of all encounters receiving an antibiotic). Receipt of an antibiotic by demographic categories were compared by chi-squared test. Statistical process control charts with upper and lower control limits and identified “special cause” variation were used to analyze outcomes.

Results
A total 18,839 pneumonia encounters were included with 3,723 (19.7%) prescribed at least one antibiotic. After pathway implementation, the amoxicillin prescribing rate rose from 72 to 80% (p &lt; 0.01) and the azithromycin prescribing rate decreased from 13% to 4% (p = 0.01) (Graphs 1,2). Special cause variation was identified in 5-day prescriptions, which increased from 15% to 58% post-intervention (p &lt; 0.01) (Graph 3).

Conclusion
Implementation of a revised clinical pathway substantially increased the rate of 5-day prescriptions for uncomplicated CAP. An EMR order set did not change durations of therapy, likely impacted by the COVID pandemic. Amoxicillin prescribing increased and azithromycin prescribing was negligible after the pathway implementation.

Disclosures
All Authors: No reported disclosures
2944. Comparative Effectiveness and Safety of 5-7 days versus 10 days of Antibiotics for Acute Bacterial Sinusitis in Children
Authors: Savage Timothy J , Kronman Matthew , Kattinakere Sreedhara Sushama , Huybrechts Krista F 
Published: November 2023

Abstract

Background
Acute bacterial sinusitis accounts for 5 million pediatric antibiotic prescriptions in the United States each year, with 65% amoxicillin or amoxicillin-clavulanate. More than 90% of pediatric patients are prescribed 10+ days of antibiotics. No study has compared shorter to longer treatment. This study compares 5-7 days versus 10 days of treatment in children and adolescents.

Methods
This cohort study included patients &lt; 18 years with an outpatient encounter for acute sinusitis and a same-day dispensation of either a 5–7 day supply or a 10 day supply of amoxicillin or amoxicillin-clavulanate between January 1, 2017 and December 31, 2020 in the MarketScan Commercial Claims and Encounters database. Treatment failure, defined as a new antibiotic dispensation, an ED or inpatient encounter for acute sinusitis, or an inpatient complication of acute sinusitis, was assessed in the first 5, 10, and 30 days after cohort entry. Adverse and control outcomes were captured. We used Cox proportional hazards regression with propensity score (PS) overlap weights for confounding control.

Results
The initial cohort included 254,629 patients, among which 19,627 patients were prescribed a 5-7-day treatment (exposure) and 235,002 patients were prescribed a 10-day treatment (referent). After PS overlap weighting, groups were balanced on all measured covariates (Table 1). The rate of 30-day treatment failure was 167.77 per 1,000 person-years (95% CI, 155.94, 180.49) among patients dispensed 5-7 days of treatment and 150.19 per 1,000 person-years (95% CI, 145.54, 154.99) among patients dispensed 10 days of treatment (hazard ratio 1.12 [95% CI, 1.03,1.21]) (Table 2). Adverse events were rare, and there was no difference between groups in a negative control outcome (Table 3).Table 1:Patient and treatment characteristicsTable 2:Treatment FailureTable 3:Adverse and control outcomes

Conclusion
The absolute risk of treatment failure was very low. Children and adolescents dispensed 5-7 days of antibiotic treatment had a slightly higher rate of treatment failure compared to 10 days of antibiotic treatment. Adverse effects were rare, with a potentially lower rate of yeast infections following shorter treatment. The marginal benefit and increased risk of side effects with longer treatment indicates that shorter treatment of acute bacterial sinusitis, 5-7 days, may be a reasonable initial approach in some populations.

Disclosures
Timothy J. Savage, MD, MPH, MSc, UCB: Contract to Brigham and Women's Hospital Krista F. Huybrechts, PhD, MS, Takeda: Grant/Research Support|UCB: Grant/Research Support
2211. Nursing Home Infection Preventionists are Leading Antimicrobial Stewardship Programs – Should They Be? A Statewide Survey of Stewardship Leadership Roles in Nursing Homes
Authors: Zering Jessica , Kamenar Katarina , D’Angeli Marisa A , Delmer Samantha 
Published: November 2023

Abstract

Background
The Centers for Disease Control’s Core Elements (CEs) of Antibiotic Stewardship for Nursing Homes is the best-practice guideline for developing a nursing home (NH) antibiotic stewardship program (ASP). The CEs recommend that NHs select a medical director, director of nursing, and/or consultant pharmacist to lead the ASP. The Centers for Medicare and Medicaid Services’ State Operations Manual currently suggests an ASP leader and defines pharmacist involvement in ASPs as the performance of a medication regimen review at least once monthly. A survey was conducted of NHs in Washington State to assess implementation of ASP leadership best practices.

Methods
Infection Preventionists (IP) in licensed NHs in Washington State were contacted via email and asked to complete an online REDCap survey on their ASP. Non-responder facilities were contacted via phone and asked that the employee most knowledgeable about their ASP complete the survey. Responses were collected between February 15th, 2022, to May 2, 2023.

Results
A total of 101 Washington NHs out of 198 contacted (51%) responded to the survey. Approximately 90% of respondents reported that IPs led or co-led their antibiotic stewardship program (Figure 1). In comparison, directors of nursing were identified as leaders or co-leaders by 50% of respondents, medical directors by 37%, and consultant pharmacists by 34%. Subgroup analyses by number of facility licensed beds, corporate association, and hospital affiliation demonstrated that IPs were the staff primarily responsible for antibiotic stewardship efforts in NHs across Washington State (Figure 2). Common barriers reported to identifying an ASP lead were competing demands, lack of prioritization by leadership, staffing shortages and lack of expertise.

Conclusion
There is a discrepancy between NH ASP best practice recommendations and on-the-ground implementation. NH administrators can ensure alignment with best practices by putting dedicated time and responsibilities for stewardship into the job descriptions of medical directors and directors of nursing. Regulators can promote pharmacy leadership of NH ASPs by requiring greater clinical expertise and involvement of pharmacists beyond once-monthly medication regimen reviews.

Disclosures
All Authors: No reported disclosures
2216. Orthopedic Provider Adherence to American Academy of Orthopedic Surgeons (AAOS) Guidelines for Dental Prophylaxis in Total Joint Replacement
Authors: Escaler Patricia , Myers Thomas , Quartuccio Katelyn , Munsiff Sonal , Ted Louie 
Published: November 2023

Abstract

Background
Antibiotic prophylaxis before dental procedures (DP) in patients with prosthetic joints has not been shown to decrease the risk of prosthetic joint infections (PJI). Current American Academy of Orthopedic Surgeons (AAOS) guidelines do not recommend DP in low-risk patients, and no longer mention clindamycin for penicillin allergic patients. The CDC recently prioritized antimicrobial stewardship (AS) for dental procedures. Orthopedic provider compliance with AAOS guidelines is unknown.

Methods
This was a single-center, retrospective study of patients who underwent primary hip or knee replacement (TJR) from January to October 2019, and received DP prescribed by an orthopedic provider from the time of TJR through August 2021. DP was determined by chart review. Appropriateness was assessed according to 2016 AAOS guidelines. Further data was recorded, including demographics, pertinent orthopedic history, risk factors for PJI, and possible adverse effects from DP.

Results
Of 1800 patients that were evaluated, 250 patients (13.9% of TJR) were given 258 prescriptions for DP. 64.8% were prescribed by advanced practice providers. Of the patients who received DP, 66.8% were female, and 22.5% were obese. There were slightly more hip replacements than knee replacements. 2.7% of patients were immunocompromised per AAOS definitions. Of the 33 diabetic patients, 87.9% were well-controlled, and thus considered low- risk. 240/258 prescriptions for DP (93%) were inappropriate, with the great majority of those in low-risk patients. Five patients inappropriately received clindamycin. Two patients received the incorrect dosage of antibiotic. Within 6 months of DP, C. difficile was diagnosed in 0.4% of patients, and resistant organisms from any source were cultured in 0.4% of patients. One patient developed PJI within one year of TJR, despite receiving DP.

Conclusion
Though only a minority of patients undergoing TJR received DP, most were low-risk patients and thus considered inappropriate per 2016 AAOS guidelines. Further study is warranted, including analysis of dentists and other providers’ prescribing of DP, use of targeted educational materials, and utility of electronic health record order sets.

Disclosures
All Authors: No reported disclosures
2217. Evaluation of Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Swab Screening in Patients with Cancer at a Large Comprehensive Cancer Center
Authors: Herrington Mark , Vuong Nancy N , Feng Chun , Hwang Hyunsoo 
Published: November 2023

Abstract

Background
Methicillin-resistant Staphylococcus aureus (MRSA) nasal screening has a high negative predictive value (NPV) in immunocompetent patients with infections and is widely utilized as a tool for antibiotic discontinuation. The data applying nasal swab screening in patients with cancer is limited, particularly for those that are immunocompromised and in the setting of neutropenic fever. The aim of this study is to determine the predictive values of MRSA swabs screenings in patients living with cancer.

Methods
This is a retrospective cohort observational study of adult patients admitted to The University of Texas MD Anderson Cancer Center between January 2019 through October 2022. Data from patients with documented MRSA nasal swab screenings and clinical cultures taken within 7 days was collected. The first documented MRSA swab screening and culture results from unique patients were included for analysis to calculate sensitivity, specificity, positive predictive value, and NPV.

Results
A total of 6,475 patients with MRSA swab screenings had 13,129 clinical cultures taken from different anatomical sites. Of the patients included, 57% had a solid tumor and 37% had a hematological malignancy, with 82% of patients receiving an anti-MRSA antibiotic agent within 90 days of the MRSA nasal swab. There were 167 documented positive MRSA cultures, most commonly from a wound (41.3%) or respiratory source (24%). Overall sensitivity and specificity for all culture sites were 50.9% and 98.4%, respectively, with an overall NPV of 99.4%. The NPV was 99.8% for bloodstream infections, 98.5% for respiratory infections, 92.6% for wound infections, and greater than 99% for other culture sites.

Conclusion
The specificity and negative predictive value of MRSA swab screenings in patients with cancer was high overall and consistent with the literature in immunocompetent patients. These results can help guide in the discontinuation of empiric antibiotics in patients living with cancer.

Disclosures
All Authors: No reported disclosures