bluuebunny/crossref_metadata_2025_split huggingface dataset:
978. Association of oral anticoagulation therapy with dabigatran and the incidence rate of Staphylococcus aureus bacteremia among patients with atrial fibrillation
Authors: Hasegawa Shinya , Ohl Michael , Vaughan-Sarrazin Mary , Perencevich Eli N , Goto Michihiko 
Published: November 2023

Abstract

Background
Dabigatran, a univalent direct thrombin inhibitor, is used as a direct oral anticoagulant (DOAC) for patients with high-risk conditions for thrombosis, such as atrial fibrillation (AF). In-vitro and animal model studies suggest dabigatran (but not other DOACs) might also reduce the virulence of Staphylococcus aureus by inhibiting staphylothrombin, and a recent study from Denmark reported lower incidence of S aureus bacteremia (SAB) among people on dabigatran compared to other DOACs (Butt et al. CID 2021). However, clinical data for this phenomenon in other populations are still sparse. We aimed to evaluate the incidence rate of SAB among patients in the United States Veterans Health Administration (VHA) treated with dabigatran compared with those treated with other DOACs or warfarin.

Methods
This retrospective cohort study examined medication and microbiology data for all patients with AF who started new oral anticoagulation therapies in VHA in 2011-18 and followed for the duration of the first anticoagulation therapy. We calculated crude incidence rates of SAB as the number of events per 10,000 person-years, stratified by the type of oral anticoagulation therapy.

Results
Among 45,023 patients starting anticoagulation for AF during the study period, the total person-years of exposure were 5,384 for dabigatran (5,052 unique patients), 12,613 for non-dabigatran DOACs (15,449 unique patients), and 38,964 for warfarin (31,415 unique patients). There were 11 SAB events among patients on dabigatran, 52 among patients on non-dabigatran DOACs, and 194 among patients on warfarin. The crude incidence rates of SAB in each group were 20.43 (95% confidence interval [CI], 8.37-32.49), 41.23 (95%CI, 30.04-52.41), and 49.79 (95%CI, 42.80-56.78) events per 10,000 person-years, respectively (dabigatran vs non-dabigatran DOACs: p=0.043, dabigatran vs warfarin: p=0.004).

Conclusion
The crude incidence rate of SAB among Veterans with AF who were on dabigatran was lower than those on other DOACs or warfarin. This supports the prior Danish study reporting lower SAB incidence among patients on dabigatran. Further studies are needed to assess this potential association while accounting for other patient-level factors and longer follow-up durations.

Disclosures
Michihiko Goto, MD MSCI, Merck & Co.: Grant/Research Support
979. A Cluster-randomized Controlled Trial of Enhanced Carbapenem-resistant Enterobacteriaceae Prevention Program at General Medicine Wards, Siriraj Hospital
Authors: Taweesuk Apiradee , Rachakhom Siriporn , Wangchinda Walaiporn , Thamlikitkul Visanu , Assanasen Susan , Rattanaumpawan Pinyo 
Published: November 2023

Abstract

Background
Carbapenem-resistant Enterobacteriaceae (CRE) colonization is an important risk factor for CRE infection. Most of Infection prevention control (IC) strategies to reduce CRE colonization were recommended to implement in a private room setting. Data on effectiveness of IC program in general medicine wards is limited.

Methods
During February-October 2021, a cluster-randomized controlled trial was conducted among high risk for CRE-adult patients at six general medical wards, Siriraj Hospital. Six wards were randomized to receive either the standard IC care (sIC) or the enhanced CRE prevention program (eIC) plus sIC. The active CRE surveillance of stool or rectal swab specimen was performed in both groups within the first 72 hours of enrollment and then every 7 days. The eIC included a monthly healthcare education and feedback session, a real-time alert of CRE-acquisition from the active surveillance, and the CRE contact precaution visual reminder. The sIC included the cohorting and contact precaution of a CRE-acquisitioned patient, and a real-time alert of CRE-acquisition from the clinical specimen.

Results
There were 174 patients (with 1684 patient-days) in the intervention group and 189 patients (with 1517 patient-days) in the control group. Baseline characteristics were comparable between two groups. The cumulative incidence of CRE-acquisition was slightly lower in the intervention group (36.8% (64/174) vs. 46.6% (88/189);p=0.059). The incidence rate of CRE-acquisition was significantly lower in the intervention group (0.038 vs. 0.058;p=0.007). The median [range] of CRE-acquisition free time (6 days [1-73] vs. 5 days [1-81];p=0.84) were comparable. K. pneumoniae was the most common CRE pathogen isolated from the surveillance and clinical specimens. No difference in all-cause mortality and length of stay between the two groups was observed.

Conclusion
The incidence of CRE acquisition at our institute was remarkably high. The eIC could reduce the incidence of CRE-acquisition and lengthen the CRE-acquisition free time. Future study should be done to explore the benefit on morbidity and mortality outcomes.

Disclosures
All Authors: No reported disclosures
984. Detection of Mycobacterial Species from Specimens Submitted for Metagenomic Analysis
Authors: John Joseph F , Schmidt Michael G , Jarvis Courtney L , Diaz Niccole , Martin Rick 
Published: November 2023

Abstract

Background
A national U.S. epidemic of non-tuberculous mycobacterial (NTM) infections is occurring at rates unseen over earlier decades, resulting in substantial numbers of pathogenic sequelae. Culture of mycobacteria is laborious, often requiring weeks for cultivation and speciation. Next generation sequencing (NGS) to detect NTM from clinical specimens has advantages over culture methods. From January 2018 to June 2022 we queried a large national NGS database to detect NTM rates and species.

Methods
DNA was isolated from 431,716 patient specimens collected from a variety of body sites: sputum, urine, sinus, wound or an unspecified swabs. Employing an Illumina’s 16S and ITS targeted-gene, deep sequencing approach, bacterial and/or fungal species resident in the specimen were determined. The identity and relative abundance of mycobacterial DNA recovered for each specimen were reported by species as the primary outcomes.

Results
Of the 431,716 specimens analyzed in this 4.5 year retrospective study, 0.001% (468) contained mycobacterial DNA. Forty different species of mycobacteria were detected with the most common frequency including: M abscessus, 40%; M mucogenicum, 13%; M. tuberculosis, 8.5% and M immunogenum 4.6%. M. avian and M. intracellulare were each detected in only 4% of the positive NTM specimens. 15% were other NTM species and 15% were not speciated NTM. Between 2018-2022 of the 468 NTM, the annual number of M. abscessus was 38, 53, 41 and 41, respectively. The concentration or relative abundance of mycobacterial DNA within each specimen varied from 4 to 100% of the total bacterial DNA recovered.

Conclusion
Over 4.5 years , NGS performed at a national molecular diagnostic laboratory detected 40 NTM species with a predominant fraction as M. abscessus (40%), supporting the clinical concern for an epidemic increase in M. abscessus infections during the last half decade. These data support the view that NGS metagenomics can uncover NTM epidemiological trends and implicate NTM infections.

Disclosures
Joseph F. John, Jr., MD, FACP, FIDSA, MicroGenDx: Advisor/Consultant Michael G. Schmidt, PhD, MicroGenDx: Advisor/Consultant Courtney L. Jarvis, PhD, MicroGenDX: Employee Niccole Diaz, BS, MicroGenDX: Advisor/Consultant Rick Martin, BS, MicroGenDX: Ownership Interest
1016. A Qualitative Study of Patient Perspectives on the Use of Antibiotics Without a Prescription
Authors: Laytner Lindsey , Chen Patricia , Nash Susan G , Salinas Juanita , Olmeda Kiara , Zoorob Roger , Paasche-Orlow Michael , Trautner Barbara , Grigoryan Larissa 
Published: November 2023

Abstract

Background
Using antibiotics without medical guidance (nonprescription use) can be unsafe and increase antimicrobial resistance rates. Few studies have qualitatively examined patient perspectives of nonprescription use in the US. To understand the reasons and motivations underlying patients’ nonprescription use, we explored the perceptions and experiences of sociodemographically diverse patients served by two US healthcare systems.

Methods
We conducted semi-structured interviews with outpatients who had endorsed nonprescription use on a previous survey in public and private healthcare systems in Texas. Interviews were conducted remotely in English or Spanish from May 2020 through October 2021. We used inductive coding and the Kilbourne framework for health disparities research to guide our thematic analysis.

Results
Overall, 86 participants completed interviews. Over 70% of participants were female, Hispanic or African American, educated (high school or above), and attended publicly-funded clinics (Table 1). In-depth interviews revealed seven themes (reasons/motives) driving nonprescription use (Figure 1). Participants reported using nonprescription antibiotics to relieve respiratory symptoms or pain, bypass healthcare-access barriers, and for convenience. Participants stated that they “know their bodies” when sick and expressed that antibiotics are “like gold” (valuable/effective) and can be used when over-the-counter medicines do not work and when the antibiotics or source of the antibiotics are “trusted.” Table 2 highlights representative participant quotes by theme.Table 1.Sociodemographic characteristics of participants by healthcare system (HCS)Table 2.Representative participant quotes by themeFigure 1.Overview of themes: Reasons to use nonprescription antibiotics by healthcare system (HCS)

Conclusion
Qualitative analyses revealed the beliefs, practices, and healthcare system-related obstacles underlying nonprescription use. The concept of taking antibiotics for symptom relief (including for viral infections and pain) gives antibiotic stewardship programs a new direction with patient education. In addition, promoting more accessible primary care by reducing healthcare-access barriers may reduce patients’ usage of antibiotics outside of a healthcare setting.

Disclosures
Barbara Trautner, MD, PhD, Genentech: Grant/Research Support|Peptilogics: Grant/Research Support
1020. A Novel Quality Control Solution for Gram Stain Through Integration of Deep Learning Vision Technology: A Proof-of-Concept
Authors: Hata Jane , Reed Jessica , Magee Kyle 
Published: November 2023

Abstract

Background
Gram stain (GS) is essential for preliminary bacterial identification. The lack of a standardized quality control method for GS is a significant drawback. By utilizing a deep convolutional neural network (CNN) design, we present a proof-of-concept for a novel solution to GS quality assurance. Using this approach, current manual GS, and potentially automated GS methods, may possess a standardized method of quality control.

Methods
Twenty-nine GS from positive blood cultures encompassing the spectrum of GS quality (acceptable, over/under decolorization, smear thickness, stain artifact) were selected by two expert microbiologists.
A total of 197 images were obtained using a Cognex D-900 camera and Olympus BX-43 microscope at 1000X magnification. Images were classified using deep learning software (Cognex, ViDi Suite 4.1). Eighty-one images were classified as suboptimal and 116 were classified as optimal by expert review.
To address background variation due to manual GS, we implemented a screening classification tool to separate images into 5 distinct classes (pale, rose, orange, indigo, variegated). The training and test sets consisted of 100 and 97 images respectively.
Using a chaining technique, a second classification tool was added after the screening classification tool. The second tool further divided the 197 images into two dataset classes: optimal and suboptimal. The second tool used 105 images for training and 92 images for the test set. Model performance was compared to expert microbiology review, with GS verified by organism identification using MALDI-TOF.

Results
Cognex ViDi Suite 4.1 could discriminate between optimal and suboptimal GS images. The chained classification tool was able to be trained with 100% recall and 100% accuracy, with a resulting F-score of 1.00.
Figure 1
VisionPro GUI with optimal image (MRSA)

Conclusion
Deep learning enabled image analysis is an effective method for sorting GS which are acceptable for further interpretation and suboptimal smears which require rework. Additional study is warranted to develop deep learning image analysis tools for the interpretation of GS on multiple specimen types and incorporate into automated GS systems.

Disclosures
Jane Hata, PhD , D(ABMM), Roche Molecular Systems: Grant/Research Support Kyle Magee, MLS(ASCP), SeluxDx: Employee
1027. At-Home vs. In-Clinic Receipt of Cabotegravir and Rilpivirine Long-Acting: An Implementation Science Trial
Authors: Williams Jamila K , Young Christina , Hanson Rochelle F , Moreland-Johnson Angela , Adekunle Ruth O , Kirk Stephanie , Meissner Eric G 
Published: November 2023

Abstract

Background
Cabotegravir plus rilpivirine long acting (CAB + RPV LA) is administered as an intramuscular injection every 1 or 2 months for treatment of HIV-1 infection. The need for frequent travel to a clinic could impair treatment access. We hypothesized that receiving treatment at-home would be as safe and effective as receiving treatment in clinic and that having different options for where to receive treatment would result in high patient satisfaction.

Methods
Persons prescribed CAB + RPV LA in the Infectious Diseases Clinic at the Medical University of South Carolina (MUSC) were offered enrollment in this implementation science study between August 2021 and December 2022. This study was approved by the MUSC IRB. After receiving the initial injection in clinic, study participants chose to receive each subsequent injection over the 12-month intervention in clinic or at home, with option to switch during the study. For home injections, CAB + RPV LA was shipped to participants’ homes and stored refrigerated until preparation and administration by a home health provider. For clinic injections, CAB + RPV LA was shipped to the clinic and stored until the injection visit. Monthly surveys were completed by study participants.

Results
The thirty-three patients enrolled in the study were primarily Black (64%) and male (73%). Two participants stopped CAB + RPV LA and transitioned to oral therapy due to allergy (n=1) and efficacy (n=1) concerns. Nearly an equal number of participants elected to receive treatment primarily in clinic (n=16) relative to at home (n=14). Contrary to our expectations, switching the primary location of treatment receipt during the study was uncommon (n=2 to date). Most survey responses to date indicated extreme satisfaction (93%) with treatment. Consistent with reported clinical experience, the most common side effect has been injection site pain/soreness (52% of injections). No differences in safety, efficacy, or satisfaction have been observed based on treatment location with results accruing.

Conclusion
Administering CAB + RPV LA at home is associated with high satisfaction and thus far is safe and effective.

Disclosures
Jamila K. Williams, MHA, Viiv Healthcare: Grant/Research Support Stephanie Kirk, PharmD, Viiv Healthcare: Advisor/Consultant|Viiv Healthcare: Grant/Research Support Eric G. Meissner, MD, PhD, Viiv Healthcare: Advisor/Consultant|Viiv Healthcare: Grant/Research Support
1033. Unexpected Allies: Vancomycin and Cefazolin Combination Therapy in Methicillin-Resistant Staphylococcus aureus Bacteremia
Authors: Caniff Kaylee E , Kunz Coyne Ashlan J , Rybak Michael J 
Published: November 2023

Abstract

Background
Vancomycin (VAN) monotherapy is regarded as first-line treatment of bloodstream infections (BSIs) due to methicillin-resistant Staphylococcus aureus (MRSA). However, in vitro and clinical evidence indicate synergy is achieved against MRSA when certain beta-lactam antibiotics are combined with VAN. In 2016, a MRSA BSI treatment pathway was implemented at the Detroit Medical Center (DMC) which incorporates early use of combination therapy with VAN and cefazolin (CFZ). This study assesses clinical outcomes among patients receiving VAN vs. combination therapy with VAN + CFZ in MRSA BSI.

Methods
This is a retrospective, observational cohort study of patients hospitalized with MRSA BSI at the DMC from 2006-2021. Included patients were initiated on VAN within 72 hours of the index culture. Patients were excluded if they received &lt; 5 days of VAN, transferred to an outside hospital, received an alternative anti-MRSA antibiotic, received &gt; 5 days of non-CFZ beta-lactam, or initiated on CFZ &gt; 120 hours after index culture. Patients were compared by VAN therapy (no receipt of CFZ during treatment course) to VAN + CFZ combination therapy (CFZ initiated within 120 hours of index culture). Multivariable logistic regression was performed to identify independent predictors of 30-day mortality.

Results
Overall, 359 patients were included; 145 received VAN + CFZ and 214 received VAN. There were no significant differences between groups when comparing baseline demographics, infectious source, comorbid conditions, MRSA risk factors, or illness severity. However, VAN + CFZ patients were more likely to have an infectious diseases consult (98.6% vs. 82.7%, p &lt; 0.001). VAN + CFZ was associated a lower 30-day mortality rate (3.4% vs. 9.8%, p = 0.022) and shorter duration of bacteremia (49.0 [35.0-74.0] hours vs. 62.0 [42.0-95.8] hours, p = 0.005). After adjusting for confounders, VAN + CFZ receipt was independently associated with reduced 30-day mortality (aOR 0.31, 95% CI 0.11-0.93).

Conclusion
In patients with MRSA BSI, the addition of CFZ to VAN within 120 hours of index culture was associated with improved outcomes. To our knowledge, this is the first study specifically examining VAN + CFZ in this population. Further research is warranted to determine the utility of this therapy combination in MRSA BSI.

Disclosures
Michael J. Rybak, PharmD, PhD, MPH, Abbvie, Merck, Paratek, Shionogi, Entasis, La Jolla, T2 Biosystems: Advisor/Consultant
1098. COVID-19 Reinfections in Older Adults: Risk Factors for Poor Outcomes
Authors: Lando-King Elizabeth , Morris Keeley , Seys Scott , Zirnhelt Zachary , Talsma Elle , Wienkes Haley , Como-Sabetti Kathryn , Meyer Stephanie 
Published: November 2023

Abstract

Background
Older adults are at higher risk for hospitalization and death from COVID-19. The impact of COVID-19 reinfections on older adults is less clear. As more of the population experiences at least one COVID-19 infection, understanding risk factors associated with severe outcomes at reinfection is critical for improving patient care.

Methods
We examined the risk of hospitalization, ICU admission, and death among MN residents aged 65+ experiencing 2nd infections (reinfection) during the Omicron wave (12/26/2021-10/1/2022; n = 9311). We first performed log binomial regressions to examine risk of hospitalization, ICU admission, and death across the entire study period. We then stratified the sample by variant wave at 1st infection (Table 1). All models were adjusted for time from 1st infection to reinfection, gender (male vs. female), vaccination status at reinfection (vaccinated vs. unvaccinated), age group (65-74, 75-84, 85+), metro vs. outstate, and infection severity at 1st infection (hospitalized vs. not hospitalized).

Results
In the full model, people with 1st infections during each of subsequent variant waves were at increased risk of hospitalization during reinfection relative to people whose 1st infection occurred during the initial wild-type wave (Alpha: 1.27, 0.96-1.68, Delta: 1.29, 1.13-1.48, Omicron: 1.93, 1.72-2.18; Table 2). A similar effect was observed for ICU admission. In stratified analyses, age and severity at 1st infection were significant predictors of hospitalization, ICU admission and death across some variant waves (Tables 3 and 4).

Conclusion
In a preliminary examination of all Omicron reinfections, each subsequent variant wave of 1st infection was associated with an increase in hospitalization. However, given the lack of substantial temporal overlap between variant waves, it is not possible to distinguish whether characteristics of the variant or time between 1st and 2nd infections is impacting magnitude of risk. Stratifying by variant wave allowed us to examine whether potential risk factors varied by variant of 1st infection. Our stratified results indicate that greater age and hospitalization at 1st infection significantly increase negative outcomes at reinfection regardless of the variant of 1st infection.

Disclosures
All Authors: No reported disclosures
1110. Why has Utilization of Novel Gram-negative Antibiotics been Sluggish in U.S. Hospitals? A Retrospective Cohort Study to Inform Future Antibiotic Development and Market Entry Rewards
Authors: Strich Jeffrey R , Ullah Mishuk Ahmed , Lawandi Alexander , Diao Guoqing , Warner Sarah , Li Willy , Demirkale Cumhur Y , Mancera Alex , Walker Morgan , Yek Christina , Neupane Maniraj , De Jonge Nathaniel , Kadri Sameer S 
Published: November 2023

Abstract

Background
Sluggish uptake of novel gram-negative antibiotics has jeopardized their future development and supply potentially risking patient lives. Understanding underutilization patterns might better inform unmet needs and market entry rewards. We studied patterns and drivers of use of recently U.S. FDA-approved novel gram-negative agents in patients with gram-negative infections (GNI) displaying difficult-to-treat resistance (DTR; resistance to all first line B-lactams including carbapenems, and fluoroquinolones).

Methods
Using the all-payer PINC-AI database, quarterly percent change in the post-approval use of seven gram-negative agents and secular trends in colistin use were calculated. For inpatients with DTR GNI at microbiology reporting hospitals, we compared novel vs older/reserve agent use by infection site and pathogen. At hospitals that use novel agents, generalized linear mixed models with weighting identified patient and hospital factors associated with the use of any novel (vs older/reserve) agents as targeted therapy against DTR GNI.

Results
At 619 hospitals, while colistin use declined between 2016Q1 and 2021Q2, post-approval use grew variably for each novel agent (Fig1); compared to the first novel anti–Klebsiella pneumoniae carbapenemase (KPC) agent ceftazidime-avibactam (approved 2015), usage was relatively sluggish for subsequently approved anti-KPC-agents meropenem-vaborbactam and imipenem-cilastatin-relebactam and zero for plazomicin. At 302 microbiology reporting hospitals, 44.4% of 2830 overall DTR cases including 70.2% of 627 DTR-A. baumannii cases received only older/reserve agents (Fig2). The odds of use of novel (vs older/novel) agents were greater in patients displaying hemodynamic instability and higher comorbidity burden, but similar across race categories and insurance status, and lower at Western(vs Midwestern) hospitals (Table1).

Conclusion
Nearly half the patients in US hospital with DTR-GNIs are still receiving targeted therapy with older/reserve agents. While the value of novel agents is indicated by clinicians preferring them over older/reserve agents in sicker patients, future agents with distinctly novel mechanisms and activity against DTR-A. baumannii are needed to bridge the utilization gap.

Disclosures
Morgan Walker, MD, Cytovale: Advisor/Consultant