bluuebunny/crossref_metadata_2025_split huggingface dataset:
2340. COVID-19 Vaccine Hesitancy among Faculty Members, College Students and Health Care Workers in Lebanon
Authors: Doumat George , Tfaily Mohamad Ali , Wazzi-Mkahal Rayyan , Kanafani Zeina 
Published: November 2023

Abstract

Background
The COVID-19 pandemic has caused significant morbidity, mortality, and economic losses worldwide. Despite the efficacy of several vaccines in reducing SARS-CoV-2 infections, vaccination hesitancy remains a challenge. This study aimed to examine COVID-19 vaccination perceptions, beliefs, attitudes, and knowledge in Lebanon and identify unique predictors of vaccine hesitancy.

Methods
We conducted a cross-sectional online survey between March and June 2021 at the American University of Beirut and its Medical Center targeting faculty members, students, and healthcare workers. The survey included four sections, covering socio-demographics, COVID-19 perceptions, attitudes, and knowledge, with a primary focus on vaccination intent. We used a multivariate logistic regression model to investigate potential determinants of vaccine hesitancy.

Results
We had 422 respondents with an overall response rate of 94%. A large proportion of the study population were females (69%) and individuals with at least undergraduate college education (93%). Healthcare workers comprised 29.4% of all survey respondents. Of the respondents, 368 (87%) were definitely willing to take the COVID-19 vaccine, and 13% expressed various forms of vaccine hesitancy (1% definitely not willing; 8% undecided likely; 4% undecided unlikely). The most important independent predictors of vaccine hesitancy were the perception that the COVID-19 vaccine is more dangerous that the COVID-19 infection, that the vaccine development was rushed, and being a healthcare worker. Knowledge about COVID-19 infection, level of education, age, and recommendation from the respondent’s healthcare provider were negatively correlated with vaccine hesitancy. The multivariable analysis is shown in the Table.

Conclusion
We found a high COVID-19 vaccine acceptance rate and some of the factors associated with hesitancy were modifiable, including knowledge and perceptions about the disease and the vaccine, and healthcare provider recommendation. Addressing these factors is crucial for successful vaccination programs, as combatting vaccine hesitancy may be as crucial as developing a safe and effective vaccine.

Disclosures
All Authors: No reported disclosures
2362. SARS-CoV-2 Omicron Variants Associated with Less Severe Disease in Hospitalized Patients Irrespective of Baseline Risk Factors and Immunity
Authors: Lee Austin , Kawaguchi Eric , Vu Christina , Ray Brianna , Suh Joy , Vojvodic Vanya , Smith Scotti , Torres Cesar , Stafylis Chrysovalantis , Wald-Dickler Noah , Holtom Paul , Klausner Jeffrey , Khan Saahir 
Published: November 2023

Abstract

Background
The Omicron variant of SARS-CoV-2 saw the highest incidence of cases during the COVID-19 pandemic, yet these cases had less severe outcomes compared to earlier variants. This could be due to increased immunity from vaccination, infection of healthier patients, increased identification of less severe cases, and decreased viral pathogenicity. We examine the relative contribution of these factors to outcomes among hospitalized COVID-19 patients by comparing a cohort from the early pandemic to a cohort from the Omicron wave, subdivided by baseline immunity.

Methods
We retrospectively reviewed electronic medical records of 456 patients hospitalized for COVID during the early pandemic (03/2020 - 05/2020) and 453 patients hospitalized for COVID during the Omicron wave (12/2021 - 01/2022) at a public safety net hospital in Los Angeles, CA. We recorded demographics, clinical data, infection and vaccination history, and hospital outcomes including severe disease, defined as need for supplemental oxygen.

Results
Patients hospitalized during the early pandemic were more likely to have severe disease than those during the Omicron wave (75.9% vs 35.1%, p &lt; 0.001). Within the Omicron cohort, “non-immune” patients without vaccination or prior infection had more severe disease than “immune” patients with prior vaccination or infection (37.8% vs 33.3%, p &lt; 0.001). Patients hospitalized during the early pandemic were older with more medical comorbidities than during the Omicron wave; within the Omicron cohort, immune patients were older with more medical comorbidities than non-immune patients. After controlling for age and medical comorbidities via logistic regression, non-immune Omicron patients were less likely to have severe disease than early pandemic patients (OR = 0.25 [0.17-0.38]); immune Omicron patients had even lower rates of severe disease compared to early pandemic patients (OR = 0.15 [0.10-0.23]).
Characteristics of Patient Cohorts divided by Pandemic Period and Immunity Status
Risk Factors associated with Severe Disease by Logistic Regression

Conclusion
We conclude that the Omicron variant of SARS-CoV-2 produced milder disease than earlier variants irrespective of baseline risk factors and immunity, but vaccination or prior infection further reduced disease severity in the Omicron cohort. The likely presence of undetected prior infection in the Omicron cohort would weaken the first but strengthen the second conclusion.

Disclosures
All Authors: No reported disclosures
128. Validation of a rapid diagnostics platform for detecting extended-spectrum beta-lactamase resistance in gram negative bacteremia
Authors: Andrews Sam , Timbrook Tristan , Fisher Mark , Tritle Brandon 
Published: November 2023

Abstract

Background
Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) bloodstream infections (BSI) are associated with increased cost, morbidity, and mortality compared with BSI by non-ESBL-producing bacteria. Phenotypic susceptibility data from blood cultures can take up to 72 hours to result, leading to delays in appropriate antimicrobial administration and unnecessary carbapenem usage. In April 2021, University of Utah (U of U) Health began utilizing the BIOFIRE® Blood Culture Identification (BCID2) Panel platform for rapid identification of organisms and resistance genes in blood cultures, including CTX-M, the most common ESBL gene in the United States. However, other genetic determinants can lead to third-generation cephalosporin resistance. Therefore, we sought to determine the positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of the BCID2 platform for predicting phenotypic ceftriaxone susceptibility at our institution. Additionally, we sought to determine susceptibility of ertapenem among our isolates as co-resistance has been reported amongst CTX-M containing isolates.

Methods
This was a retrospective observational cohort study evaluating adult patients with bacteremia by select Enterobacterales species (Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group, Proteus, Salmonella). Data collection was performed utilizing the Enterprise Data Warehouse, clinical lab data, and medical chart review.

Results
Between 4/1/2021 and 1/31/2023, 386 isolates (in 386 patients) of Enterobacterales were identified; the majority of isolates were E. coli (280, 72.5%). Ceftriaxone resistance was observed in 45 isolates (11.6%). We found that BCID2 is highly specific (100%) and sensitive (91.1%) for predicting ceftriaxone susceptibility with high NPV (98.8%) and PPV (100%) at the U of U Health. All ceftriaxone-resistant isolates were susceptible to ertapenem.

Conclusion
The BCID2 platform is a highly sensitive and specific rapid diagnostic for determining ceftriaxone resistance at our institution. These findings should be confirmed at individual institutions to account for local resistance epidemiology.

Disclosures
Tristan Timbrook, PharmD, bioMerieux: Employee|bioMerieux: Stocks/Bonds Mark Fisher, PhD, Copan Diagnostics: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support
2428. Association of body mass index and bloodstream infections in patients on extracorporeal membrane oxygenation: A single-center retrospective cohort study
Authors: Lee Eun Hwa , Lee Jung Ah , Ahn Jin Young , Jeong Su Jin , Ku Nam Su , Choi Jun Yong , Yeom Joon-sup , Song Young Goo , Park Se Hee , Kim Jung Ho 
Published: November 2023

Abstract

Background
Obesity is associated with poor clinical outcomes in critically ill patients. However, under some clinical conditions, obesity has protective effects. Bloodstream infections (BSI) are one of the most common nosocomial infections associated with extracorporeal membrane oxygenation (ECMO) support. BSI during ECMO is associated with higher mortality rates and poorer clinical outcomes. This study analyzed whether body mass index (BMI) was associated with BSI during ECMO and in-hospital mortality.

Methods
All adult patients who had received ECMO support for &gt;48 h were included in the analysis. The total duration of ECMO support, in-hospital mortality, and BSI were analyzed according to BMI categories. The Cox proportional hazards model was used to compare the risk of BSI according to different BMI categories.Figure 1.Study flow chart

Results
A total of 473 patients were enrolled in the study. The average age was 56.5 years old and 65.3% were men. The total ECMO duration was approximately 11.8 days with a mortality rate of 47.1 %. The incidence of bacteremia and candidemia were 20.5% and 5.5%, respectively. There was no significant difference in bloodstream infection rates (p=0.784) or mortality rate (p=0.253) among the five groups. The underweight group required ECMO for respiratory support, whereas the overweight and obese groups required cardiogenic support (p&lt; 0.0001). However, there was no significant difference in the development of BSI during ECMO support or in-hospital mortality among any of the five groups.

Conclusion
Patients with higher or lower BMI did not show an increased risk of BSI or in-hospital mortality associated with ECMO support.Figure 2.Forest-plot for risk of bloodstream infection occurrence in different body-mass index categories.Figure 3.Kaplan-Meier analysis comparing the survival rate in different BMI groups.

Disclosures
All Authors: No reported disclosures
2452. Prevalence of Antimicrobial ReSistanCE iN BloodStream Infections in HOspitalized (BSI) PatieNts in BRazil (ASCENSION-BR): Preliminary Results of a Multicenter Study
Authors: Antochevis Laura C , Barth Afonso , Wilhelm Camila , Carrilho Cláudia , Arns Beatriz , Guimarães Luiz Felipe , Starling Carlos E , Coelho Andre , Mendes Elisa , Rocha Verônica , Martins Amanda , Girão Evelyne , Telles João , Sudbrack Letícia , Leão Robson , Zavascki Alexandre 
Published: November 2023

Abstract

Background
Carbapenem-resistant Enterobacterales (CRE), P. aeruginosa (CRPA), A. baumannii (CRAB), methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecium (VRE) are major multidrug-resistant (MDR) bacteria causing healthcare-associated infections. There is no multicenter study addressing the prevalence of these MDR bacteria in Brazil. We report the preliminary results of the ongoing ASCENSION-BR study evaluating the prevalence of these microorganisms in BSI in hospitalized patients in this country.

Methods
This prospective multicenter study has been conducted in 13 hospitals distributed in 4 of 5 Brazilian regions. From 15th August to 31st April (to be finished on 14th August 2023), each hospital recruited patients for a period of up to 6 months. Adult patients hospitalized for at least 48h, with positive blood cultures with Enterobacterales, P. aeruginosa, A. baumannii, S. aureus and Enterococcus spp. were eligible. More than one BSI of the same patients were included if caused by a distinct bacteria. MDR isolates were sent to a central laboratory where isolates were re-identified by MALDI-TOF-MS.

Results
A total of 10 hospitals recruited patients for 6 months(m), 1 for 5m, and 2 for 1m. 1231 bacterias were isolated from 1091 BSI episodes (118 were polymicrobial), and 442 (35.9%) were MDR. Enterobacterales were the most common isolates in BSIs (659, 75.3%), followed by S. aureus (221, 18.0%), A. baumannii (113, 12.9%), Enterococcus spp. (135, 11.0%: 48 [35.6%] E. faecium and 84 [62.2%] E. faecalis) and P. aeruginosa (103, 8.4%). Among Enterobacterales, the most frequent species were K. pneumoniae (275, 41.7%), E. coli (126, 19.1) and Enterobacter spp. (69, 10.5%). A total of 224 (34.0% of Enterobacterales) BSIs were caused by CRE (155 [69.2%] K. pneumoniae, 27 [12.1%] Serratia marcescens, 15 [6,7%] Enterobacter spp., and 27 [12.1%] other 11 species. A total of 100 (88.5% of A. baumannii) isolates recovered in BSIs were CRAB and 38 (36.9% of P. aeruginosa) were CRPA. Among Gram positives, 50 (22.6% of SA) were MRSA, and VRE represented 93.3% of E. faecium and 3.3% of E. faecalis isolates.

Conclusion
High prevalence of MDR in BSI, notably in A. baumannii, were found among hospitalized patients in Brazil.

Disclosures
João Telles, MD, PhD, MSD: Advisor/Consultant|MSD: Speaker|Pfizer: Advisor/Consultant|Pfizer: Speaker|União Química: Advisor/Consultant|União Química: Speaker Alexandre Zavascki, MD, PhD, Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support
2468. The Genomic Epidemiology of Carbapenemase-Producing Enterobacterales (CPE) in Ontario, Canada, 2016
Authors: Jamal Alainna J , Tijet Nathalie , McGeer Allison , Baqi Mahin , Borgia Sergio , Ciccotelli William , Farshait Nataly , Katz Kevin , Mehta Mamta , Goneau Lee , Mertz Dominik , Small Lorne N , Melano Roberto 
Published: November 2023

Abstract

Background
Carbapenemase-producing Enterobacterales (CPE) are among the most urgent of antimicrobial resistance threats. In south-central Ontario, Canada, over one-third of CPE cases are associated with local healthcare and the incidence of such CPE cases is rising steadily. We integrated whole-genome sequencing (WGS) and CPE population-based surveillance data to gain insights into CPE transmission dynamics in Ontario, Canada.

Methods
We included all incident CPE isolates received at the Public Health Ontario Laboratory as part of a voluntary surveillance program from Jan. 1 to Dec. 31, 2016 in Ontario, Canada (population ∼13.5 million). All isolates underwent Illumina WGS. MLST was determined for all isolates, and single nucleotide variant (SNV) analysis was performed by species. SNV analyses were combined with epidemiological data from the Toronto Invasive Bacterial Diseases Network to identify transmission clusters.

Results
There were 206 incident CPE isolates from 176 patients. Most common species were Escherichia coli (95, 46%) and Klebsiella pneumoniae (76, 37%), and most common carbapenemases produced were NDM (77, 37%), OXA-48-like (68, 33%), and KPC (45, 22%). There was variability in MLST, with ST167 being most common among E. coli (10, 11%), and ST147 being most common among K. pneumoniae (13, 17%). There were 14 clusters with 34 (17%) CPE isolates belonging to 33 (20%) unique patients total (Table). Cluster size range was 2-5 patients. Time from first to last identified case in clusters ranged from 0 to 258 days. In 8 clusters, the index case likely acquired CPE during prior hospitalization abroad, with subsequent direct or indirect transmission to other patients in the cluster. In 5 clusters, all patients likely acquired CPE at the Ontario hospital where their CPE was detected.

Conclusion
There was variability in CPE species and MLST as well as carbapenemase produced. Almost one fifth of patients belonged to a transmission cluster, with transmission lasting many months in some clusters. These data highlight challenges with CPE local transmission and a need to intensify control measures.

Disclosures
All Authors: No reported disclosures
2498. An evaluation of a mandatory Hepatitis C Virus screening bill in perinatally exposed infants in Kentucky
Authors: Guy Laura , Yarber-Cambron Lisa , Herring Nicholas , Jennings Hunter , O’Connell Katherine , Scott Traci 
Published: November 2023

Abstract

Background
In the last decade, Hepatitis C virus (HCV) rates have dramatically increased in women of child-bearing age nationally and in Kentucky. Correspondingly, there has been a documented increase in the percentage of infants born with HCV. In response to this alarming increase in HCV cases, Kentucky became the first state nationwide to implement a mandatory universal HCV screening of pregnant women in July of 2018. This study evaluates the efficacy of the mandatory universal HCV screening bill KRS 214.160 SB 250.

Methods
Using laboratory data, a retrospective cohort of HCV-positive women who sought obstetric care at Norton Healthcare between January 1, 2017, and December 31, 2019, and subsequently delivered live infants were identified. Mother-infant dyads were grouped into pre- (before July 1st, 2018) or post-implementation (after July 1st, 2018) groups based on the infant’s date of birth. Manual chart reviews were utilized to identify screenings for HCV in both mothers and infants. Adequate testing was defined by the current CDC recommendations.

Results
1.8% of infants in the study were diagnosed with congenital HCV infection. A modest increase of testing per CDC guidelines occurred during the post-implementation study period. Only 190 infants had at least one HCV laboratory result during the study period (68.1%). Only 55 children in the cohort were adequately tested for HCV during the study period. Fifteen infants (14.71%) born during the pre-implementation period were adequately tested per the guidelines. Only 55 (24.4%) of the infants born during the post-implementation period were tested per CDC guidelines (Fig. 1).

Conclusion
Overall, HCV screening is still inadequate in Kentucky. However, there was a modest increase in the number of adequate HCV infant screenings. 11% of the infants in the cohort had no observable follow-up for HCV although almost all children had documented perinatal exposure to HCV. The documented vertical transmission rate in this cohort is lower than the frequently cited 5.8%. More research is required to evaluate the efficacy of the mandatory HCV screening bill in Kentucky.

Disclosures
Laura Guy, BS, CRCC, Gilead Sciences, Inc: Grant/Research Support Lisa Yarber-Cambron, MSN, RN, AMB-BC, Gilead Sciences, Inc: Grant/Research Support Nicholas Herring, BS, MPH, Gilead Sciences, Inc: Grant/Research Support Hunter Jennings, BS, Gilead Sciences, Inc: Grant/Research Support Katherine O'Connell, BS, MPH, Gilead Sciences, Inc: Grant/Research Support Traci Scott, MD, Gilead Sciences, Inc: Grant/Research Support
2556. A Phase 1, Open-Label, Single Dose Study to Evaluate the Pharmacokinetics (PK), Safety, and Tolerability of Epetraborole Tablets and the Impact of Alcohol Dehydrogenase (ADH) Genotype on the PK of Epetraborole and Metabolite M3 in Healthy Japanese Adult Subjects
Authors: Patel Gina , Castañeda-Ruiz Bibiana , Yoshihara Tatsuya , Krause Kevin M , O’Shea Kevin , Kammerer Linda , Maier Gary , Long Jennifer , Smith Alex , Chanda Sanjay , Moore Stephanie , Eckburg Paul B 
Published: November 2023

Abstract

Background
Epetraborole (EBO), an orally available bacterial leucyl transfer RNA synthetase inhibitor with potent activity against nontuberculous mycobacteria, is under clinical development for treatment-refractory MAC lung disease. Nonclinical studies suggest that metabolism of EBO to metabolite M3 may involve oxidation by ADH. The goal of this study was to evaluate the impact of ADH genotype on the PK of EBO and M3 in healthy Japanese subjects.

Methods
In this open-label trial, a single 500 mg EBO dose was administered to subjects in 3 cohorts defined by ADH1B genotype (*1/*1, *1/*2, or *2/*2). EBO and M3 plasma concentrations were measured by a validated LC-MS/MS method, and plasma EBO and M3 PK were determined using non-compartmental methods. Standard clinical and laboratory evaluations and treatment-emergent adverse events (TEAEs) were assessed.

Results
18 subjects were enrolled (6/cohort). EBO was rapidly absorbed, with M3 subsequently appearing in plasma. After reaching Cmax, EBO and M3 concentrations declined with a geometric mean t1/2 of 10.7 to 11.4 h and 26.7 to 33.1 h, respectively. EBO exposures (Cmax and AUC) were similar between Cohort 1 and Cohort 2, while exposures were 1.2- to 1.4-fold higher in Cohort 3 (Table); however, exposure of M3 was similar across all cohorts. Compared to Cohort 1, M3:EBO ratios for Cohort 3 were generally similar for Cmax and were approximately 26% lower for AUC. No apparent differences in t1/2 were observed across cohorts for either EBO or M3. No TEAEs or clinically significant changes in clinical laboratory parameters, vital signs, physical examinations, or ECGs were reported in this study.

Conclusion
Administration of EBO in Japanese subjects with varying ADH1B genotypes had no meaningful effect on EBO or M3 plasma exposure. The slightly increased EBO exposures associated with the 500 mg dosage in subjects with ADH1B *2/*2 genotype were within the range of tolerable exposures. Oral EBO was well tolerated in this study; no TEAEs were reported. This Phase 1 study did not identify any risk that would preclude evaluation of oral EBO administered 500 mg daily in patients with different ADH1B genotypes, including Japanese patients.

Disclosures
All Authors: No reported disclosures
2565. In vitro synergistic bacterial killing of imipenem and ceftaroline against Mycobacterium abscessus; a static concentration time-kill analysis
Authors: Shin Eunjeong , Nantongo Mary , Holland Steven M , Kreiswirth Barry N , Dousa Khalid M , bonomo Robert A 
Published: November 2023

Abstract

Background
Mycobacterium abscessus (Mab) represents a significant clinical challenge, with a rising incidence in recent times. The current therapeutic approach, which involves prolonged IV administration of amikacin, is associated with notable toxicities. Consequently, there is a pressing need to explore safe alternatives in antibiotic therapy. This study aimed to evaluate the in-vitro synergistic effect of a double β-lactam (DBL) combination which is safe for all ages.

Methods
We conducted static concentration time-kill (SCTK) studies utilizing Mab strain ATCC19977 over 10 days in duplicate. SCTK evaluated the impact of imipenem (IPM) and ceftaroline (CFT) in both monotherapy and combination therapy on bacterial killing (inoculum: 6 log10 CFU/mL). To counteract the recognized extent of thermal degradation of β-lactams, predetermined quantities of IPM and CFT were added every 24 hours. Synergistic killing was estimated in the S-ADAPT software. In addition, the post-antibiotic effect (PAE) was measured following a 2-hour exposure to β-lactams. The β-lactams were removed by exchange with drug-free broth after centrifugation.

Results
DBL of IPM+CFT exhibited synergistic bactericidal activity, surpassing that of monotherapy with rapid regrowth observed in 1-3 days. Monotherapy demonstrated up to ∼1.5 log10 killing followed by near-complete regrowth over a period of 10 days. DBL demonstrated significant synergistic killing, resulting in rapid and the most extensive reduction (∼3.5 Log10 CFU/mL) and suppression of regrowth over 10 days. The addition of a β-lactamase inhibitor reduced the CFT concentration required for bacterial killing, resulting in synergistic bacterial killing at an achievable concentrations in-vivo mouse studies and clinical trials in the future. Furthermore, PAE were 4 minutes for IPM and 2 hours for CFT. Strikingly, the DBL at a concentration of 1xMIC demonstrated noteworthy bacteriostatic activity, with the suppression of bacterial growth lasting up to 14 h.

Conclusion
DBL therapy yielded the most rapid and extensive killing of Mab with limited regrowth. The β-lactamase inhibitor was efficacious in inhibiting a broad-spectrum β-lactamase (blaMab). The prolonged PAE observed in the DBL of IPM plus CFT may prove beneficial for intermittent dosing regimen.

Disclosures
Robert A. bonomo, MD, Entasis, Merck, VenatoRx, Wockhardt: Grant/Research Support