bluuebunny/crossref_metadata_2025_split huggingface dataset:
2469. Comparative Genomics Uncovers Strain Diversity and Possible Unrecognized Transmission of MDROs among Hospitalized Patients
Authors: Koundakjian Dylan , Strudwick Amanda F , Page Alex , Van Riel Julia , Gooden D’Ante , Satola Sarah W , Bombin Andrei , Read Timothy D , Jacob Jesse T , Babiker Ahmed , Woodworth Michael H 
Published: November 2023

Abstract

Background
Contamination of the healthcare environment by colonized patients is an important source of multidrug-resistant organism (MDRO) transmission. We aimed to determine MDRO room contamination of patients with MDRO clinical cultures to test diversity of dominant strains in colonizing isolates and detect possible transmission.

Methods
Inpatient cases with clinical cultures positive for CRE, extended-spectrum cephalosporin resistant Enterobacterales (ESCRE), CR-Pseudomonas and VRE were eligible for inclusion. Patients on the same unit without positive MDRO clinical cultures in the prior 90 days were selected as controls. Participant inguinal and perirectal sites were sampled by E-swab. Three patient room surface composites were sampled with sponge sticks on the same day. Colonies on differential and selective media were identified by MALDI-TOF with Vitek2 antimicrobial susceptibility testing. Isolates underwent genome sequencing. Clustered gene alignment and average nucleotide identity were compared for conspecific isolates. Transmission was defined as isolation of conspecific MDRO strains with &gt; 99.9% ANI in two or more patients.

Results
Twelve cases and 5 controls were included. Among cases, the same clinical MDRO was detected in 91% (10/11, one patient declined sample collection) of patient-site cultures and in 42% (5/12) of environmental cultures. Among controls, an MDRO was detected in 60% (3/5) of patient samples but no MDROs were found in environmental samples. Antibiotic susceptibility was similar between conspecific patient clinical, colonizing, and environmental isolates. Among isolates sequenced, SNP analysis confirmed genetic relatedness between colonizing and invasive strains and revealed unrecognized unit-based MDRO transmission.
Cases and Controls had similar clinical features
Whole genome sequencing demonstrated patient colonization with multiple conspecific strains and uncovered potential unit-based transmission of colonizing isolates

Conclusion
There is significant environmental contamination from hospitalized patients with clinical MDRO culture positivity. Whole genome sequencing demonstrated patient colonization with multiple conspecific strains and uncovered potential unit-based transmission of colonizing isolates, which may be potentiated by environmental contamination. Further research is needed to understand if reducing patient MDRO colonization could reduce environmental contamination and transmission.

Disclosures
Ahmed Babiker, MBBS, Roche: Advisor/Consultant
2473. Rates of Antibiotic Resistant Infections in Hospitalized Patients with Hematologic and Non-Hematologic Cancers, 2019
Authors: McCarthy Natalie , Lutgring Joseph D , Baggs James , Wolford Hannah , Reddy Sujan 
Published: November 2023

Abstract

Background
Patients with cancer have risk factors for developing both hospital-onset (HO) and antibiotic resistant (AR) infections such as high antibiotic use, long lengths of stay, and device utilization. Understanding the epidemiology of AR infections in this population can inform clinical management and prevention strategies. We aimed to describe the rates and proportions of AR infections in hospitalized patients with cancer.

Methods
Using the PINC AI Healthcare Database, we included adult discharges from 2019 among facilities reporting microbiology data. We identified patients with at least one cancer diagnosis from the Healthcare Cost and Utilization Project’s Clinical Classifications Software Refined categories and Elixhauser Comorbidity Software Refined for ICD-10-CM. We calculated age-standardized rates of AR infections among cancer patients per 10,000 discharges, stratified by community-onset (CO: ≤ day 3 of hospitalization) and HO (≥ day 4 of hospitalization), and hematologic and non-hematologic cancer types. Hematologic cancers included lymphoma, leukemia, myeloma and myelodysplastic syndrome. We also examined the proportion of AR infections in patients with cancer among all AR infections in the cohort.

Results
Of &gt;2 million discharges from 277 facilities, 11.4% were patients with cancer. Compared to all patients, cancer patients had higher rates of infection with CO and HO vancomycin resistant Enterococcus (VRE) and carbapenem resistant Enterobacterales (CRE), and HO Enterobacterales with AR phenotypes suggestive of extended-spectrum β-lactamase (ESBL) production (Table 1). Compared to patients with non-hematologic cancer, patients with hematologic cancer had higher rates of all AR infections, except for CO carbapenem resistant Acinetobacter spp. (CRAsp) infections (Table 1). For most AR infections, cancer patients made up a greater proportion of all HO AR infections compared to CO AR infections (Table 2).

Conclusion
Patients with cancer had higher rates of several AR infections compared to all patients. To decrease the burden of AR infections in this population, infection prevention strategies may focus on VRE, ESBL, and CRE pathogens, as well as HO infections, in all cancer patients, particularly those with hematologic cancer.

Disclosures
All Authors: No reported disclosures
2479. Impact of the COVID-19 pandemic on the hospital acquisition of multidrug-resistant organism in two Greek hospitals
Authors: Karakosta Polyxeni , Kousouli Elisavet , Vourli Sophia , Georgiou Panagiota Christina , Mamali Vasiliki , Zarkotou Olympia , Pournaras Spyros 
Published: November 2023

Abstract

Background
COVID-19 pandemic pushed back progress for combating antimicrobial resistance (AR). We aimed to provide a proxy measure for MDRO Hospital Acquisition in two Hospitals following COVID-19 pandemic.

Methods
Active surveillance for MDROs recovered from any specimen collected &gt;3 days post-admission, using laboratory data without patient’s clinical evaluation was conducted from Jan 2019 to Dec 2022 in Attikon & Tzaneio hospitals. MDROs included carbapenem-resistant (CR) Enterobacteriaceae (CRE), CR Acinetobacter baumannii (CRAB), CR Pseudomonas aeruginosa (CRPA), vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). Adult inpatients hospitalized in ICUs or non-ICU wards participated in the study. Surveillance definitions of MDRO Laboratory-Identified (LabID) Event and MDRO Infection/Colonization Incidence Density Rate (IDR) were based on the CDC MDRO/CDI Module criteria (January 2023). Patient days and susceptibility data of isolated CRE were collected monthly. Incidence rate ratio (95% CI) was calculated to examine changes in rates from 2019 (pre-pandemic) to 2020, 2021 and 2022 (pandemic).

Results
During four years, 3,241 hospital-onset LabID Events, with no documented prior evidence of infection/colonization with the specific organism type, were recorded. The Infection/Colonization IDR for non-ICUs and ICUs was 0.59 and 6.69 per 1,000 patient days for CRE, 0.68 and 10.08 for CRAB, 0.19 and 1.41 for CRPA, 0.39 and 1.77 for VRE and 0.20 and 0.39 for MRSA, respectively. Compared to 2019, the CRE Infection/Colonization IDR raised significantly by 52% in 2020, 110% in 2021 and 146% in 2022 only in non-ICUs; non-significant increase was observed in ICUs. CRAB Infection/Colonization IDR increased constantly in non-ICUs after COVID-19 pandemic, but only during 2021 in ICUs. In CRE, KPC was the commoner carbapenemase (54%, 2019; 53%, 2020; 60%, 2021; 63%, 2022). CRPA infection/colonization significantly decreased during 2021 in ICUs (60%) but increased in 2022 in non-ICUs; VRE increased in 2022 in non-ICUs (61%) and MRSA remained unaltered.

Conclusion
MDRO Infection/Colonization IDR has further deteriorated during the pandemic with CRE and CRAB having leading role.

Disclosures
All Authors: No reported disclosures
2487. Which Extended-Spectrum β-Lactamase-Producing Enterobacterales Colonize the Gastrointestinal Tract of High-Risk Patients?
Authors: Stambaugh Haley , Lewis Shawna , Jacobs Emily B , Hareza Dariusz A , Bergman Yehudit , Cosgrove Sara E , Tamma Pranita , Simner Patricia J 
Published: November 2023

Abstract

Background
The epidemic of extended-spectrum β-lactamase producing Enterobacterales (ESBL-E) continues to expand. ESBL-Es commonly colonize the intestinal tract and may propagate the spread of ESBL genes. However, the frequency at which ESBL production occurs in all Enterobacterales (including inducible AmpC-producers) is unknown. This study aims to define the epidemiology of third-generation cephalosporin resistant Enterobacterales (3GC-RE) colonization to understand their burden and contribution to ESBL spread in high-risk populations (e.g., ICU, oncology, transplant).

Methods
Surveillance cultures for 3GC-RE were performed by collecting perirectal swabs among high-risk populations at The Johns Hopkins Hospital. Isolates were identified by MALDI-TOF MS after recovery on 3GC selective chromogenic media. Antimicrobial susceptibility testing was performed using lyophilized broth microdilution panels following Clinical and Laboratory Standards Institute (CLSI) guidelines. 3GC-RE were characterized using the CLSI ESBL disk test among recommended Enterobacterales. For inducible AmpC-producing Enterobacterales, cefepime +/- clavulanic acid disk test was performed. Carbapenem-resistant Enterobacterales (CRE) were tested for carbapenemase-production using the modified carbapenem inactivation method (mCIM) and by the CARBA 5 lateral flow assay, if mCIM positive.

Results
Of 966 surveillance cultures, 99 (10%) were positive for 3GC-RE and 14 (1%) were positive for CRE. Almost all 112 (99%) rectal swabs had a single organism isolated while multiple organisms were isolated from 1 (1%). 114 bacterial isolates were recovered (Table 1). Of the 3GC-RE, 66 (58%) were ESBL-producers with Escherichia coli, Klebsiella pneumoniae and K. oxytoca being the most common ESBL-E. Additionally, 14 (12%) were CRE with K. pneumoniae, E. coli and Enterobacter cloacae complex being the most common CRE. Of CRE, 7 (50%) were carbapenemase producers with 4 (57%) KPC, 2 (29%) NDM and 1 (14%) KPC and NDM.

Conclusion
Colonization with 3GC-RE and CRE occurs in 10% and 1% of rectal swabs collected from high-risk patients, respectively. 58% of 3GC-RE were ESBL producers and ranged between 0-100% among 3GC-RE; including up to 33% from inducible AmpC producing Enterobacterales.

Disclosures
Sara E. Cosgrove, MD, MS, Debiopharm: Advisor/Consultant|Duke Clinical Research Institute: Advisor/Consultant Patricia J. Simner, PhD, Affinity Biosensors: Grant/Research Support|BD Diagnostics: Advisor/Consultant|BD Diagnostics: Grant/Research Support|Entasis: Advisor/Consultant|GeneCapture: Stocks/Bonds|Merck: Advisor/Consultant|OpGen Inc: Board Member|OpGen Inc: Grant/Research Support|OpGen Inc: Honoraria|Qiagen Sciences Inc: Advisor/Consultant|Qiagen Sciences Inc: Grant/Research Support|Shionogi Inc: Advisor/Consultant|T2 Biosystems: Grant/Research Support
2504. Online Clinician Education Results in Performance Changes in Clinical Practice Related to Hepatitis B Vaccination
Authors: Nair Arun S , Larkin Amy , Mehta Nimish 
Published: November 2023

Abstract

Background
This study examined whether online continuing medical education (CME/CE) focused on evidence-based best practices for implementing hepatitis B vaccination guidelines into clinical care would result in the adoption of new clinical practices.

Methods
Clinicians participated in an online, 30-minute CME/CE video discussion among experts with synchronized slides. Performance in the real world was assessed by inviting learners to complete a survey 30-60 days post-education, identifying practice changes and the degree to which clinicians experience barriers to those changes. For each possible practice, learners reported whether they were implementing for the first time or had modified it due to education, they were already doing it prior to education; or they were not doing it before or after education. They also indicated barriers they experience at least “some” of the time for each practice. The data were collected from 5/19/2022 to 10/24/2022.

Results
There were 44 learners consisting of PCPs, Diab/Endos, Ob/Gyns, Nurses, NPs and Pharmacists who completed the survey. Analysis showed that 100% of learners made a practice change or had practices reinforced due to education. Top 5 practice changes modified or implemented as a result of education included:
Some of the main barriers to implementing practice changes identified by the learners include:

Conclusion
The practice changes identified in this assessment provide a compelling evidence that participation in online CME/CE prompts adoption of changes in practice related to hepatitis B vaccination. Future education is needed to address the barriers identified in this assessment.

Disclosures
All Authors: No reported disclosures
2509. Association of Non-Alcoholic Fatty Liver Disease with HBV, HAV, and HEV Exposure
Authors: Vassilopoulos Stephanos , Vassilopoulos Athanasios , Benitez Gregorio , Kaczynski Matthew , Shehadeh Fadi , Kalligeros Markos , Mylonakis Eleftherios 
Published: November 2023

Abstract

Background
Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease. The association between prior hepatitis B virus (HBV), hepatitis A virus (HAV), and hepatitis E virus (HEV) infection and NAFLD has not been elucidated. The National Health and Nutrition Examination Survey (NHANES) aims to assess the health and nutritional status of the population across the United States.

Methods
By using the 2017-2020 NHANES, we evaluated the age-adjusted prevalence of prior HBV, HAV and HEV infection among participants with NAFLD, as well as the age adjusted prevalence of NAFLD, high risk non-alcoholic steatohepatitis (NASH) and liver fibrosis among participants with prior HBV infection. We then performed multivariable logistic regression analyses using adjusted odds ratios (aOR) to examine the association of prior HBV, HAV and HEV infection with NAFLD, high risk NASH, and liver fibrosis.

Results
We identified 2565 individuals with anti-HBc serology results, 1480 unvaccinated participants with anti-HAV results, and 2561 participants with anti-HEV results. Among participants with NAFLD, the age-adjusted prevalence of prior HBV, HAV and HEV infection was 3.48%, 32.08% and 7.45%, respectively. The age-adjusted prevalence of NAFLD, high-risk NASH and fibrosis among participants with prior HBV infection was 33.59%, 3.36%, and 8.00%, respectively. Prior infection with HBV, HAV and HEV was not associated with NAFLD or high-risk NASH. Participants with anti-HBc and anti-HAV seropositivity were more likely to have significant fibrosis compared to participants with negative anti-HBc and anti-HAV serology [aOR: 1.53 (95% CI, 1.05 – 2.23) and 1.69 (95% CI, 1.16 – 2.47), respectively].
Age-adjusted prevalence of NAFLD, high-risk NASH and liver fibrosis among participants with positive anti-HBc serology
Adjusted odds ratio of prior viral hepatitis exposure

Conclusion
Participants with a history of HBV or HAV infection exhibit greater odds of significant liver fibrosis compared to those without HBV or HAV exposure. To limit disease-related outcomes, healthcare providers should prioritize vaccination efforts and use an individualized strategy for NAFLD in patients with prior viral hepatitis, including HBV or HAV infection.

Disclosures
Eleftherios Mylonakis, MD, PhD, BARDA: Grant/Research Support|Basilea: Advisor/Consultant|Chemic Labs/KODA Therapeutics: Grant/Research Support|Cidara: Grant/Research Support|Leidos Biomedical Research Inc./NCI: Grant/Research Support|NIH/NIAID: Grant/Research Support|NIH/NIGMS: Grant/Research Support|Pfizer: Grant/Research Support|Regeneron Pharmaceuticals, Inc.: Grant/Research Support|SciClone Pharmaceuticals: Grant/Research Support
140. Follow-up Blood Cultures for Gram-Negative Bacteremia among Adults with Cancer
Authors: Haak David , Fong Karen , Spivak Emily S , Imlay Hannah 
Published: November 2023

Abstract

Background
Current evidence suggests that performing follow up blood cultures (FUBC) in patients with Gram-negative bacteremia (GNB) may not improve outcomes and can lead to unnecessary healthcare expenditure. However, studies often exclude more fragile patient populations, such as those with active malignancy. In a cohort of patients with active malignancy and GNB, we aimed to quantify the rate of performing FUBCs, the rate of positivity, and to compare characteristics of patients with and without positive FUBCs.

Methods
Patients admitted to University of Utah Health with active malignancy and GNB during 2019 were identified. Manual chart review was performed to collect demographics, clinical characteristics, management and outcome measures. Patients who had positive FUBC were compared to those with negative FUBC. Patients who died or went to comfort care only within 48h of admission were excluded.

Results
56 patients were identified. FUBCs were performed in 51 patients (70 FUBCs total) during the 4 days after initial positive blood culture. 4 FUBCs in 4 patients were positive. Of the positive FUBC, 2 (50%) were collected within 24 hours of the initial blood culture (Figure 1). 1 patient with a positive FUBC (25%) had not had source control achieved (Table 1).
90-day readmission (50% vs 34%) and recurrent GNB with the same organism (25% vs 8.5%) were higher in the positive FUBC group compared to the negative FUBC group. 90-day mortality (25% vs 28%) was similar between the two groups (Table 1).

Conclusion
In hospitalized patients with active malignancy and GNB, FUBC were performed frequently but the majority were negative. Of the positive FUBC, a significant proportion were either collected within 24 hours of starting active antimicrobials, limiting their significance. Prospective studies of standardized blood culture collection are needed to characterize the natural history of GNB and define when positive FUBC are clinically meaningful. These data suggest use of FUBC use could be reduced by limiting use to more than 24 hours after both appropriate antibiotic therapy is initiated and source control is achieved.

Disclosures
All Authors: No reported disclosures
2522. Antisense Antibiotics are Effective Against Pseudomonas aeruginosa Biofilm
Authors: Merville Paul J , Ray Garrett , Greenberg David E , Pybus Christine A , Helaibi Ibrahim 
Published: November 2023

Abstract

Background
P. aeruginosa (PA) causes severe infections in immunocompromised patients and is increasingly antibiotic resistant. In addition, the formation of biofilm by PA makes effective treatment difficult. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) are novel antisense antimicrobials that are designed to target pathogens in a gene-specific way and prevent translation of protein. We have demonstrated in vitro and in vivo activity of lead PPMOs in PA; however, it remains unclear whether PPMOs remain active in the biofilm setting over time and if synergy can be achieved with traditional antibiotics.

Methods
P. aeruginosa (GFP-PAO1) was dosed with a rhodamine-labelled PPMO targeting acpP. Samples were fixed at different time intervals and imaged by fluorescent microscopy. A Pearson’s coefficient was recorded for each dose and time condition. Minimum biofilm eradication concentration plates were used to treat PA biofilm with acpP or rpsJ targeted PPMOs in daily dosing experiments. Fixed synergy assays were performed on mature biofilm via 24-hour Q8 dosing with PPMO, antibiotics or control. Biofilm burden was quantified by CFU enumeration.

Results
PPMOs co-localized with PA in a dose- and time-dependent fashion. Pearson coefficients increased from 0.0583 at the 30-minutes to 0.4118 and 0.4976 at the 3- and 5-hour time points respectively. In addition, biofilm reduction was dose-dependent. In daily dosing experiments, the 3’RXR4-AcpP PPMO resulted in a 5-log reduction in biofilm burden compared to control on day 7 [p&lt; 0.0001]; the 5’RXR4-RpsJ PPMO resulted in a 5.5-log reduction in biofilm burden compared to no treatment control [p&lt; 0.0001]. PPMOs incubated with tobramycin or aztreonam were found to have synergistic (FIC&lt; 0.5) or antagonistic effects (FIC &gt; 1) in biofilm and planktonic killing depending on the combination tested.

Conclusion
Lead PA PPMOs demonstrate dose and time-dependent biofilm eradication over multiple days of therapy. In addition, some PPMOs demonstrate synergy with other small molecule antibiotics that are used to treat certain patients with PA infections. PA PPMOs could be an innovative treatment modality for infection due to Pseudomonas.

Disclosures
David E. Greenberg, MD, University of Texas Southwestern Medical Center: Dr. Greenberg has numerous patents on PPMOs
2529. Population pharmacokinetic models for cefepime and enmetazobactam derived from pooled Phase 1 to Phase 3 clinical studies
Authors: Vollmer Jannik , Belley Adam , Velicitat Patrick , Machacek Matthias 
Published: November 2023

Abstract

Background
The investigational β-lactam/β-lactamase inhibitor combination of cefepime (FEP)/enmetazobactam (ENM) met criteria for non-inferiority and superiority compared to piperacillin/tazobactam in a phase 3 clinical trial of adult patients with complicated urinary tract infections (cUTI)/acute pyelonephritis (AP). In this study, a population pharmacokinetic (PK) model is presented that describes FEP and ENM plasma PK in adult cUTI/AP patients.

Methods
Plasma PK samples were analyzed from participants receiving FEP (n=588) and ENM (n=649) in three phase 1 (n=132), and single phase 2 (n=43) and phase 3 (n=488) clinical trials. Population PK parameters were assessed and the relationship between different covariates and model parameters were investigated. The effect of infection on disposition was assessed by testing disease covariates on fixed and random effects for all PK parameters.

Results
A two-compartment model with linear clearance of FEP (5.95 L/h) and ENM (7.68 L/h) from the central compartment best described the PK of both compounds. Common covariates for both compounds were de-indexed estimated glomerular filtration rate (eGFR), age, and body weight while ENM PK covariates also included cUTI infection and sex. Simulations showed that the only covariate requiring dose adjustment was renal function. The final model simultaneously described FEP and ENM plasma PK, which enabled estimates of the correlation of the random effects between PK parameters. Clearances and volumes of distribution (Vd) were strongly correlated within individuals between the two compounds (correlation coefficients &gt;0.9). Variability was higher in cUTI patients although differences in mean ENM or FEP exposures between healthy subjects and cUTI patients were negligible. The total Vd was 16.9 L for FEP and 20.6 L for ENM. Clearance of both agents was found to depend on de-indexed eGFR (covariate coefficients ≥0.83), suggesting that renal filtration is the predominant clearance mechanism. The terminal elimination half-life was 2.2 h for FEP and 2.0 h for ENM.
Final population PK model population parameter estimates for cefepime and enmetazobactam determined from the pooled phase 1 to phase 3 clinical studies

Conclusion
The population PK models for FEP and ENM predict exposures in cUTI patients, including subjects with renal impairment. These models support Monte-Carlo simulations and target attainment estimations in adult cUTI/AP patients.

Disclosures
Adam Belley, PhD, Allecra Therapeutics SAS: Advisor/Consultant Patrick Velicitat, MD, Allecra Therapeutics SAS: Salary