bluuebunny/crossref_metadata_2025_split huggingface dataset:
219. Clinical Outcomes of Early vs Late Oral Stepdown Therapy in the Management of Uncomplicated Gram-Negative Bacteremia
Authors: Michael Amanda , Vyas Nikunj M , DeRose Joseph 
Published: November 2023

Abstract

Background
Current studies show that oral stepdown antibiotics are safe and effective for patients with gram-negative bacteremia (GNB), but evidence is lacking in appropriate time from IV to oral stepdown therapy. The purpose of this study was to evaluate clinical outcomes in early (EPOS) vs late (LPOS) oral stepdown therapy in patients with GNB.

Methods
This was an IRB-approved retrospective chart review including patients in a three hospital community health system. Patients were included in this study if they were ≥ 18 years old, hospitalized for ≥ 24 hours with a positive blood culture with E. coli, Klebsiella spp., and/or Proteus spp. and transitioned to oral antibiotics prior to discharge. Exclusion criteria included complicated bacteremia and any patients who were pregnant or immunocompromised. The primary endpoint of the study was to evaluate the achievement of clinical cure at the end of therapy (CC) in EPOS (≤ 96 hours) vs LPOS ( &gt; 96 hours) groups. A subgroup analysis included achievement of microbiological cure (MC). The secondary endpoint evaluated the length of stay (LOS) and duration of IV (DIV) and duration of PO (DPO) antibiotics.

Results
Total of 50 patients were included in the primary analysis, with 30 patients in the EPOS group and 20 patients in the LPOS group. The median age and gender stratification between both groups were similar. CC (93.3% vs 100%) and MC (86.7% vs 95%) were similar amongst patients in the EPOS and LPOS groups, respectively. As seen in Table 1, DIV was shorter in the EPOS group (3.27 vs 6.2 days, P=0.0001) and DPO was longer in the EPOS (6.83 vs 4.75 days, P=0.007). Patients in the EPOS group had trends toward shorter LOS compared to the LPOS group (6.67 vs 8.1 days, P=0.08). Patient is the EPOS group were more likely to receive oral cephalosporins compared to LPOS patients (83.3% vs 45%, P=0.006) as seen in figure 1, patients in the LPOS group were more likely to receive amoxicillin/clavulanate than the EPOS patients (30% vs 6.7%, P=0.04).

Conclusion
EPOS may be a viable approach to uncomplicated gram-negative bacteremia with a lot of practical benefits. EPOS may lead to decreased DIV therapy and potentially decreased LOS. Additionally, EPOS with cephalosporins may be considered in most patients with uncomplicated bacteremia with a urinary source.

Disclosures
All Authors: No reported disclosures
221. Performance of risk scores in predicting infective endocarditis Staphylococcus aureus bacteremia in a prospective Asian cohort
Authors: Nicholas Ngiam Jinghao , CY Koh Matthew , GW Goh Wilson , Meng Tham Sai , Archuleta Sophia , Fisher Dale , Chai Louis , Tambyah Paul 
Published: November 2023

Abstract

Background
Several risk scores have been derived to predict the risk of infective endocarditis (IE) amongst patients with Staphylococcus aureus bacteraemia (SAB). This helps to guide clinical management, including the need for transoesophageal echocardiography (TEE).

Methods
We prospectively studied 634 patients admitted with SAB. Baseline clinical characteristics and laboratory results recorded, and patients were followed up prospectively. The cohort was stratified into those with or without IE, and the PREDICT Day 1, Day 5 and VIRSTA scores were tabulated. Area under receiver operating characteristic (AUC) curves were constructed to compare the performance of each score.

Results
Of the 634 patients examined, 36 (5.7%) had IE. These patients were slightly younger (51.6±20.1 vs 59.2±18.0 years, p=0.015), but tended to have community acquisition of bacteraemia (41.7% vs 17.9%, p&lt; 0.001), intravenous drug use (30.6% vs 2.7%, p&lt; 0.001), pre-existing structural heart disease (11.1% vs 2.7%, p=0.005), and persistent bacteraemia beyond 72 hours (19.4% vs 6.0%, p=0.002). There was no significant difference in mortality (8.3% vs 5.7%, p=0.459). The VIRSTA score had the best performance in predicting IE (AUC 0.76, 95%CI 0.66-0.86) compared with PREDICT Day 1 and Day 5. A VIRSTA score of &lt; 3 had the best negative predictive value (97.5%), compared with PREDICT Day 1 (&lt; 4) and Day 5 (&lt; 2) (94.3% and 96.6% respectively).
Receiver operating curves comparing performance of each risk score in predicting IE in patients with SABScore Proportion of cohort Sensitivity (%) Specificity (%) Positive predictive value (%) Negative predictive value (%) PREDICT Day 1 ≥4 4/634 (0.6%) 0.0 99.3 0.0 94.3 PREDICT Day 5 ≥2 192/634 (30.2%) 58.3 71.4 10.9 96.6 VIRSTA ≥3 149/634 (23.5%) 66.7 79.1 16.1 97.5
Comparing performance of each risk score at specified cut-offs in predicting IE in patients with SAB

Conclusion
Overall, the risk scores performed well in our Asian cohort. If applied, 23.5% of the cohort with a VIRSTA ≥ 3 required TEE, and a score of &lt; 3 would have a negative predictive value of 97.5%.

Disclosures
All Authors: No reported disclosures
231. Blood Neutrophil to Lymphocyte Ratio Is Associated with Mortality And Readmission in Gram Negative Bacteremia
Authors: Roldgaard Marcus , Benfield Thomas , Tingsgård Sandra 
Published: November 2023

Abstract

Background
Neutrophil-Lymphocyte Ratio (NLR) in blood has been shown to be able to predict bacteremia in emergency departments and an association with mortality has been shown in patients with sepsis in intensive care units. Its potential in relation to mortality and readmission in gram negative bacteremia (GNB) is unknown.

Methods
Retrospective cohort study of patients with GNB from 2018 through 2022 from four different hospitals in the greater Copenhagen area. Exclusion criteria were immunosuppression and missing NLR values on the day of blood culture. The association between NLR levels and 90-day all-cause mortality were analyzed using logistic regression models, while the association between NLR levels and 60-day readmission was analyzed using the logit link interpretation of the cumulative incidence function. Associations were expressed as odds ratios with 95% confidence intervals.

Results
The study included 1763 patients. The median age was 76.8 years and 51.3% were female. The median NLR was 17.3. Urinary tract infection (UTI) was the most frequent focus and Escherichia coli was the most frequent pathogen. Significant differences in median NLR were found between age groups, pathogens, and patients with/without hypertension, liver disease, COPD, dementia, and alcohol abuse. 378 patients (21.4%) died before 90 days. 526 (29.8%) patients were readmitted to the hospital within 60 days.
The odds ratio for all-cause 90-day mortality per NLR increase by one was 1.008 (1.003-1.013, p:0.002) and for 60-day readmission, it was 1.006 (1.001-1.012, p:0.02) per NLR increase by one, corresponding to odds ratios of 1.15 (1.04-1.27, p: 0.009) and 1.11(1.01-1.23, p: 0.04) per doubling of NLR respectively. NLR was not associated with outcome when stratified for UTI and gastrointestinal infection. Discriminatory ability for mortality was limited and comparable for NLR, neutrophil and lymphocyte count, producing receiver operating characteristic curves with an area under the curve of 0.58 (0.55-0.62), 0.60 (0.55-0.62) and 0.60 (0.57-0.64).
Forest plot depicting adjusted odds ratios and 95% confidence intervals for 90-day mortality and 60-day readmission
Cumulative incidence curves for 60-days readmission and mortality divided by quartiles of blood neutrophil to lymphocyte ratio
Kaplan-Meier curve of the survival probability divided by quartiles of blood neutrophil to lymphocyte ratio

Conclusion
Blood neutrophil-lymphocyte ratio was associated with 90-day all-cause mortality and 60-day readmission in patients with gram negative bacteremia. However, the ratio has limited ability in predicting mortality or readmission.

Disclosures
All Authors: No reported disclosures
234. Risk Factors for Mortality in Patients with Escherichia coli Bloodstream Infections and Influence of the Antimicrobial Resistance Pattern in a Referral Hospital in Nicaragua
Authors: Sánchez-Delgado Mauricio , Marenco-Avilés Sunaya , Porras-Cortés Guillermo D 
Published: November 2023

Abstract

Background
Escherichia coli is the most frequent etiological agent in bloodstream infections, and mortality has increased because of the increasing rates of bacterial resistance. Every healthcare institution has to characterize the epidemiological trend and recognize determinants for adverse outcomes in patients with bacteremia. The aim of this study was to identify risk factors for mortality and identify the influence of the pattern of bacterial resistance, as well as associated clinical characteristics in patients with E. coli bloodstream infections hospitalized at the Dr. Fernando Vélez Paiz Hospital in Managua, Nicaragua.

Methods
It is a retrospective, cross-sectional, and analytical study. The study period was between January 1st, 2020, and December 31st, 2022. A total of 81 patients with bacteremia due to E. coli were analyzed out of the total number of patients with bloodstream infections (Figure 1). The epidemiological trend, clinical variables, and pattern of antimicrobial resistance were analyzed. Risk factors for mortality were identified, and odds ratios and confidence intervals were calculated.Figure 1.Flowchart of Selection of Patients with E. coli Bloodstream Infections

Results
The prevalence of E. coli bacteremia among all bloodstream infections was 13.3%, with a mortality rate of 37.0%. The mean age of the patients was 54.7 ± 17.2 years old. Regarding comorbidities, 43.2% and 42.0% had hypertension and diabetes, respectively. Genitourinary was the main associated site of infection (58.0%) (Table 1). A high rate of E. coli producing ESBL was identified (64.2%). The resistance to ciprofloxacin and carbapenem was 67.9% and 12.3% respectively. Multi-drug resistance was observed in 28.4% of the strains. (Table 2). A history of steroid use was recorded in 40% of non-survivors versus 9.8% of survivors. Resistance to carbapenems was higher in non-survivors (26.7% vs. 3.9%). The main risk factors for mortality were use of a urinary catheter in ≥60 years old, resistance to carbapenems, and abdominal sepsis as source of infection, among others (Table 3).Table 1.Sites of Infection in Survivors and Non-SurvivorsTable 2.Antimicrobial Resistance Pattern in Survivors and Non-SurvivorsTable 3.Risk Factor for Mortality in Patients with E. coli Bloodstream Infections

Conclusion
The main risk factors for mortality in patients with bloodstream infections due to E. coli were use of urinary catheter in older patients, resistance to carbapenems, bacteremia associated with abdominal sepsis, among others. A high rate of resistance to ciprofloxacin, and beta-lactams was observed.

Disclosures
All Authors: No reported disclosures
239. Comparing Alternative Treatment Options for Stenotrophomonas maltophilia bacteremia
Authors: Teran Nicholas S , Zidaru Andrei , Phe Kady 
Published: November 2023

Abstract

Background
Stenotrophomonas maltophilia can cause nosocomial infections in immunocompromised hosts and patients with indwelling devices or broad-spectrum antibiotic exposure. Treatment of S maltophilia infections poses a challenge due to intrinsic resistance mechanisms, including inducible L1 metallo and L2 cephalosporinase beta-lactamases. Trimethoprim-sulfamethoxazole (SXT) is recognized as the agent of choice for S maltophilia infections. Outcomes with alternative antimicrobials are not well described.

Methods
We conducted a retrospective study of adults with positive blood cultures with S maltophilia who received ≥48h of directed antimicrobials at our institution between 3/2013 and 6/2022. Patients were stratified by their antimicrobial treatment, including levofloxacin, SXT, minocycline, ceftazidime, or combination therapy. The primary outcome was 30d all-cause mortality. Secondary outcomes were microbiological and clinical cure. Microbiological failure was defined as blood cultures growing S maltophilia during or within 7d of discontinuing therapy. Clinical failure was defined as a lack of resolution of signs or symptoms of infection requiring therapy adjustment.

Results
Of 67 patients with positive S maltophilia blood cultures, 53 patients treated with levofloxacin (n = 27), SXT (n = 10), minocycline (n = 8), combination (n = 5) or ceftazidime (n = 3) were included. The remaining 14 patients were excluded for receiving &lt; 48h of therapy. The median Charlson comorbidity index was 4 [IQR 3-6]. The most common source of bacteremia was catheter-related (n = 27). Overall, 30d mortality was 26.4%. There was no significant difference in 30d mortality among patients treated with levofloxacin, SXT, minocycline, combination or ceftazidime (p = 0.23). Interestingly, patients with monomicrobial S maltophilia bacteremia had statistically higher 30d mortality (35.3% versus 11.8%, p &lt; 0.05). Microbiological and clinical cure rates were similar between treatment groups (p = 0.06 and p = 0.16, respectively).

Conclusion
Treatment options for S maltophilia bacteremia resulted in similar 30d mortality; however, findings were limited by the small sample size. Larger, prospective studies are warranted to detect differences in treatment alternatives.

Disclosures
All Authors: No reported disclosures
247. Evaluation of the Efficacy and Safety of Cefazolin in Non-Pneumococci Streptococcal Bacteremia
Authors: Wibisono Arya , Rose Dusten T T , Jaso Theresa (Terry) 
Published: November 2023

Abstract

Background
Among the large variation of streptococcal infections, recommended therapies are generally well-defined. There is a lack of efficacy data on alternative therapies, notably in phylogenetic groups that are less studied. The purpose of this study is to quantify the differences in clinical efficacy and safety between recommended antibiotics (penicillins and ceftriaxone) compared to cefazolin for uncomplicated non-pneumococci streptococcal bacteremia.

Methods
This is a multi-center, retrospective cohort study from January 2017 to January 2021. Patients were included if older than 18 years of age and had a non-pneumococci streptococcal isolate recovered on blood cultures. Patients were excluded if they had a polymicrobial bacteremia, diagnosed meningitis or endocarditis, received less than two days of a study drug, or received more than three days of a non-study drug. The primary outcome was treatment failure defined as: 30-day in-hospital all-cause mortality; or the alteration of targeted therapy after at least 48 hours of treatment for (1) concern of clinical failure based on progress notes in the electronic medical record or (2) an adverse drug reaction. Secondary outcomes included 90-day all-cause mortality, intensive care unit length of stay, hospital length of stay, C. difficile infection, adverse events, and 6-month infection related readmissions.

Results
A total of 230 patients were included: 177 in the penicillins/ceftriaxone group and 53 in the cefazolin group. Baseline demographics were balanced between the two groups in regard to age, sex, comorbidity score, infection severity, and infectious disease consultation. The most commonly identified pathogens were S. pyogenes (30.9%), S. agalactiae (26.5%), and S. mitis/oralis (11.7%). Analysis showed no significant difference between treatment failures with recommended antibiotics (6/177, 3.4%) and cefazolin (1/53, 1.9%), p=1.00. No differences were noted in secondary safety outcomes.

Conclusion
Rates of treatment failure with cefazolin were not significantly different compared to recommended antibiotics in the treatment of uncomplicated non-pneumococci streptococcal bacteremia. Cefazolin may be a potential option for treatment in these infections. Further studies are warranted.

Disclosures
All Authors: No reported disclosures
257. Shared antibody sequences reveal novel public clonotypes of antibodies within and between HIV infected and healthy individuals
Authors: Chang Arthur , Hicar Mark D 
Published: November 2023

Abstract

Background
Public clonotypes, antibodies against specific antigens in unrelated individuals that have genetic similarities, have been shown in a variety of infections, including SARS-CoV-2 and HIV. These can be exploited as potential diagnostics and to identify past infections that may be related to post-infectious disorders, such as Kawasaki disease, Multiple Sclerosis or Alzheimer's disease.

Methods
Heavy chain variable sequences were retrieved from public biorepositories (Bioprojects PRJNA486667, PRJNA638224,PRJNA527941) from 270 subjects. These were derived from labeled cohorts: Healthy (116), HIV broadly neutralizing (46), HIV non-broadly-neutralizing (50), HIV-negative (43), and COVID-19 (15). We utilized the Immcantation package of software run on our SUNY Buffalo computational cluster. After PRESTo annotation, duplicate sequences were collapsed and sequences of only single counts were removed. Clonal groups were determined using SCOPer requiring IGHV, IGHJ, and CDR3 amino acid sequence to be perfectly matched. Figures and statistics were generated with immcantation, excel, pandas, and graphpad prism 8.

Results
There were 5.5 million unique heavy chain sequences from 32 million sequences. Defining public clonotypes as completely sharing CDR3 amino acid sequence and having predicted same germline variable, D, and J chains, 6861 (0.12%) shared clones were found. The distributions of CDR3 lengths showed skewing to shorter CDR3s (mean length of 10.5). There were no stringently defined clones noted in all members. Within HIV infected persons the two most shared clones both used VH1-18, JH4, had CDRaa 8, and were immature IGM/D. Three clones were used in near 10% of cases across both non-HIV and HIV datasets with prominent usage of VH 4 family members and were less mutated and IGM/D. There were eight clones solely shared &gt; 10% within non-HIV/non-Covid infected individuals, with the top shared clones all consistent with matured IGG responses with prominent predicted use of VH3-7 and a number of novel CDR3s noted.
Predicted CDR3 length using incantation was compared for cohort of clones that shared predicted V, D, J usage and the exact CDR3 amino acids between individuals. This distribution failed normality testing.

Conclusion
Identification of public clonotypes will show stochastic bias toward shorter CDR3 regions. There were differences between HIV and non-HIV cohorts and a number of novel public clonotypes were found.

Disclosures
Mark D. Hicar, MD/PhD, Pfizer: site investigator for 2 trial
295. Humanized Mice and Convalescent Humans Yield an Antibody Panel against the Highly Immunogenic Decorin Binding Protein A (DbpA) of the Lyme Disease Spirochete, Borrelia Burgdorferi
Authors: Muriuki Beatrice M , Golonka Rachel M , Ma Zepei , Bharadwaj Ravi , Li Qi , Vance David , Willsey Graham G , Lyn Piazza Carol , Rudolph Natalie J , Mantis Nicholas , Wang Yang , Cavacini Lisa 
Published: November 2023

Abstract

Background
Lyme disease is the most commonly diagnosed tick-borne infection, affecting more than 300000 people in the United States annually. The disease is principally caused by the transmission of the spirochete bacteria, by the black-legged (deer) ticks. With a renewed call for interest in a Lyme disease vaccine, antibodies relevance continues due to their efficacy, safety and versatile nature. Humanized mice and humans recovering from the disease have successfully been used to generate therapeutic antibodies against Ebola and SARS-CoV-2 diseases.

Methods
Our study used humanized mice and convalescent patients to generate recombinant human antibodies that recognize decorin-binding protein A (DbpA), a lipoprotein that is proposed to function as spirochete adhesin. The mAbs expressed as human IgG-Fc fragments were characterized for reactivity with recombinant DbpA, native DbpA on the surface of live Borrelia burgdorferi, borreliacidal activity in the presence of human complement and, finally subject to epitope mapping using an array of methodologies.

Results
The predominant lineage of humanized mice antibodies utilized VH5-51, VH3-20, VH3-23 and VH3-53 all paired with VK1-33 families. Other common families included VH4-31 paired with VK1-39, VH4-4 and VH4-8 paired with VK-9. The human derived antibody utilized VH3-30 paired with VK1-33. We observed an overlap in the repertoire of kappa chains between humanized mice and human-derived mAbs.

Conclusion
Combining the humanized mice and human platforms enabled the identification of antibodies with a high binding and specificity to DbpA, which have potential prophylactic and therapeutic properties.

Disclosures
All Authors: No reported disclosures
304. Immunoproteasome Inhibition Augments Endoplasmic Reticulum Stress and Enhances Disease During Coronavirus Respiratory Infection
Authors: Steigmann Jacob C , Suttenberg Lauren , Zhou Xiaofeng , Weinberg Jason 
Published: November 2023

Abstract

Background
Inflammation contributes to disease in patients with SARS-CoV-2 infection. The immunoproteasome (IP), an inducible component of the ubiquitin-proteasome system, contributes to the diversity of T cell epitopes generated during infection and production of antiviral and pro-inflammatory cytokines. Like the standard proteasome, the IP degrades damaged and misfolded proteins to minimize proteotoxic cell damage, which may occur via endoplasmic reticulum (ER) stress pathways. IP subunit expression increases in lungs of patients with SARS-CoV-2 infection. We previously demonstrated increased IP activity in mice infected with murine hepatitis strain 1 (MHV-1), a murine coronavirus. However, specific contributions of the IP to coronavirus pathogenesis are not yet defined. We used MHV-1 to test the hypothesis that increased IP activity is a protective host factor during acute coronavirus infection.

Methods
C3H.HeJ mice infected with MHV-1 were treated with vehicle or ONX-0914 (ONX), an IP inhibitor. We monitored weight loss and survival following infection and harvested organs at multiple times. Bone marrow-derived dendritic cells (BMDC) from C3H.HeJ mice were infected with MHV-1 in the presence of ONX. We used qPCR to assay viral load and expression of cytokines (IFN-β, IFN-γ, TNF-α, IL-6, IL-1β) and genes involved in ER stress pathways (CHOP, BiP, Grp94, Calreticulin, GADD34).

Results
IP inhibition enhanced weight loss and mortality following MHV-1 infection but did not substantially affect viral replication. Virus-induced expression of TNF-α and IL-1β was lower in the lungs of ONX-treated mice, while TNF-α expression was higher in livers. Expression of ER stress pathway genes was significantly greater in both lungs and livers of infected, ONX-treated mice compared to controls early in the course of infection. IP inhibition did not affect viral replication in BMDC, but it did enhance expression of IFN-β, TNF-α, and GADD34.

Conclusion
IP inhibition enhanced MHV-1-induced disease but did not affect viral replication. IP inhibition had modest effects on virus-induced inflammation. Increased evidence of ER stress in mice and cells treated with ONX suggests that the IP minimizes harmful proteotoxic stress, particularly in the liver, during acute coronavirus infection.

Disclosures
All Authors: No reported disclosures