bluuebunny/crossref_metadata_2025_split huggingface dataset:
514. Nirmatrelvir/ritonavir or Molnupiravir for Treatment of Non-hospitalized Patients with COVID-19 at Risk of Disease Progression
Authors: Butt Adeel A , Yan Peng , Shaikh Obaid 
Published: November 2023

Abstract

Background
In randomized controlled trials, Nirmatrelvir/ritonavir (NMV/r) and Molnupiravir (MPV) reduced the risk of severe/fatal COVID-19 disease. Real-world data are limited, particularly studies directly comparing the two agents.

Methods
Using the VA National COVID-19 database, we identified previously uninfected, non-hospitalized individuals with COVID-19 with &gt;1 risk factor for disease progression who were prescribed either NMV/r or MPV within 3 days of a positive test. We used inverse probability of treatment weights (IPTW) to account for providers’ preferences for a specific treatment. Absolute risk difference (ARD) with 95% confidence intervals were determined for those treated with NMV/r vs. MPV. The primary outcome was severe, critical, or fatal disease within 30 days of treatment prescription using the IPTW approach. Analyses were repeated using propensity-score matched groups and 1:1 matched groups.
Cohort construction

Results
Between January 1 and November 30, 2022, 9,172 individuals were eligible for inclusion (6,692 prescribed NMV/r; 2,480 prescribed MPV). The ARD for severe, critical, or fatal disease for NMV/r vs MPV was -0.18 (95% CI -0.45 to 0.09). There was no statistically significant difference in ARD among strata by age, race, sex, comorbidities, or symptoms at baseline. Kaplan-Meier curves did not demonstrate a difference between the two groups (p-value=0.43). Analysis of the propensity-score matched cohort yielded similar results (ARD for NMV/r vs. MPV -0.12, 95% CI -0.71 to 0.47).

Conclusion
We found no significant difference in short term risk of severe, critical or fatal disease in non-hospitalized individuals with COVID-19 at risk of disease progression treated with either NMV/r or MPV.

Disclosures
Adeel A. Butt, MBBS, MS, Gilead Sciences: Grant/Research Support|Merck and Company: Grant/Research Support
520. Polymerized type I collagen as a treatment for COVID-19 in Mexico
Authors: Del Carpio-Orantes Luis , García-Mendez Sergio , Sánchez-Díaz Jesús Salvador , Aguilar-Silva Andrés , Martínez-Rojas Manuel , Jiménez-Flores Oscar Rodrigo , Villalobos-López Luis Roberto , González-Arce América Alejandrina , González-Medel Karem Samantha , Domínguez-Cámara Rubén , Munguía-Sereno Alvaro Efrén , Zamora-Vázquez Violeta Rosalia , Vázquez-Manzano Quiahuitzin Elizabeth , Ortíz-Pérez Diego , Hernández-Martínez Semiramis Itzel , Hernández-Hernández Sara Nohemí , Solís-Sánchez Ishar , Fonseca-Pouchoulen Victor Alejandro , Montano-Montiel Laura Guadalupe , Reich-Sierra Reynaldo 
Published: November 2023

Abstract

Background
In Mexico, Polymerized Type I Collagen (PTIC) has been used as a treatment for patients with moderate to severe COVID-19, who present inflammation, coagulation activation and oxygen requirements, its use being successful both in outpatient and hospital settings, decreasing morbidity and mortality rates. in patients at high risk of complications.

Methods
Descriptive and retrospective study, which analyzes the response to treatment with PTIC throughout the various waves of COVID-19 presented in Mexico, reviewing the inflammation markers and severity indices, as well as the mortality of each group.

Results
250 patients who used PTIC were entered into the study, distributed according to the waves of COVID (2nd wave=35, 3rd wave=65, 4th wave=120 and 5th wave=30), the average age of all the patients was 46 years , being the masculine gender the most prevalent; The main risk factors in this population are: Obesity, Diabetes and Hypertension. Biochemically, all presented lymphocytopenia, mild thrombocytopenia, as well as elevation of inflammatory markers (D-dimer, ferritin, C-reactive protein, neutrophil/lymphocyte index) and high severity scores with data of secondary hypoxemia, highlighting those affected in the 4th wave where the Delta strain predominated. After treatment with PTIC, inflammation and hypoxemia improved significantly, highlighting low mortality rates even during the 4th wave, which was the most aggressive in Mexico and dominated by the Delta-strain. Mortality in each wave was: 2nd wave=2.9%, 3rd wave=3%, 4th wave=6% and 5th wave=0%

Conclusion
PTIC is a good treatment for moderate to severe COVID-19 in patients with a high risk of complications, significantly reducing mortality rates as well as the risks of inflammation and secondary thrombosis.

Disclosures
All Authors: No reported disclosures
525. Comparison of the acceptability and safety of molnupiravir in COVID-19 patients aged over and under 80 years
Authors: Fujita Kohei , Kanai Osamu , Hata Hiroaki , Odagaki Takao , Mio Tadashi 
Published: November 2023

Abstract

Background
Molnupiravir is being widely used as a treatment for coronavirus disease 2019 (COVID-19); however, its acceptability and safety in older patients aged ≥ 80 years in real-world clinical practice is not well understood.

Methods
We conducted a single-centre retrospective study and assessed the outcome of patients with COVID-19 treated with molnupiravir according to the following criteria: (A) discontinuation rate of molnupiravir; (B) type, frequency, and severity of adverse events; (C) all-cause mortality within 30 days of the diagnosis of COVID-19.

Results
Forty-seven patients (46.1%) were aged ≥ 80 years (older patients) and 55 (53.9%) were aged &lt; 80 years (younger patients). There were no significant differences in coexisting diseases and history of vaccination for COVID-19 between older and younger patients. Older patients were significantly more likely to have moderate disease (moderate 1 and 2) according to the Japanese Ministry of Health, Labour and Welfare classification than younger patients. During treatment, 8.5% of older patients and 1.8% of younger patients stopped taking molnupiravir, but the difference was not significant. Adverse events were observed in 39/102 (38.2%) patients. The most common adverse events were diarrhoea (9.8%), exacerbation of coexisting diseases (6.9%), bone marrow suppression (6.9%), liver dysfunction (5.9%), and loss of appetite (4.9%). Most adverse events were minor, ranging from grades 1 to 3. The all-cause mortality rate was 10.8%, and no molnupiravir-related deaths were observed.

Conclusion
Molnupiravir treatment is acceptable and safe in older patients with COVID-19 aged ≥ 80 years.

Disclosures
All Authors: No reported disclosures
531. Clinical efficacy of inhaled corticosteroids in patients with coronavirus disease-2019: an updated systematic review and meta-analysis
Authors: Jeong Su Jin 
Published: November 2023

Abstract

Background
Inhaled corticosteroids (ICS) are known to be relatively safe for long-term use in inflammatory respiratory diseases, and it has been repurposed as one of the potential therapies for outpatients with coronavirus diseases 2019 (COVID-19). However, ICS have not been accepted for COVID-19 as a standard therapy because of its lack of proven benefits. Therefore, this study aimed to evaluate the effectiveness of ICS in patients with COVID-19.

Methods
Randomized controlled trials comparing the efficacy of ICS treatment in patients with COVID-19 were identified through literature electronic databases searches up to March 10, 2023. Meta-analyses were conducted for predefined outcomes, and the certainty of evidence was graded using the grading of recommendations, assessment, development, and evaluation approach.

Results
Overall seven trials (eight articles) were included in this systematic review. Compared with usual care, ICS was associated with significantly improved clinical recovery at 7 and 14 days in patients with COVID-19. In subgroup analysis, only budesonide showed significant efficacy in clinical recovery, whereas no significant benefit was observed for ciclesonide. Moreover, ICS use was not significantly associated with all-cause hospitalization, all-cause mortality, admission to intensive care unit, or the use of mechanical ventilation. Our systematic review used evidence with very low to moderate certainty.

Conclusion
The results of this meta-analysis revealed the clinical efficacy of ICS treatment compared with usual care. Based on limited evidence, our results suggest that ICS treatment, especially budesonide, improves the clinical recovery of patients with COVID-19. The safety of ICS treatment in patients with COVID-19 has not yet been established; however, ICS are relatively safe and widely available. In addition, short-term ICS use in the early stages of COVID-19 did not increase the risk of pulmonary infections or side effects. Subsequent randomized clinical trials with a larger number of patients, as well as meta-analyses, are needed to determine the usefulness of ICS treatment in improving the clinical outcomes of patients with COVID-19.

Disclosures
All Authors: No reported disclosures
572. Growth rate comparisons for clinical Klebsiella pneumoniae (KP) isolates using nutrient-rich and -depleted broth stratified by inner colony production during fosfomycin (FOF) disk diffusion (DD) testing
Authors: Daley Ellora , Bixby Morgan , Collins Lindsey , Salay Jenna , Hirsch Elizabeth B 
Published: November 2023

Abstract

Background
Recent studies have indicated the presence of non-susceptible IC appearing within the zone of inhibition during FOF DD testing. Limited studies focusing on Escherichia coli have demonstrated that observed increases in resistance come with decreased isolate fitness. We sought to compare growth rates of susceptible KP non-IC-producers, IC-producers, and their non-susceptible IC (as determined by broth microdilution) in both nutrient-rich and -depleted broth to understand in vitro fitness differences.

Methods
Two isolates which had never produced IC (254, 275), two susceptible IC-producers (131, 209), and two corresponding resistant IC (131D, 209D) were included. Each isolate was grown in both full and ¼ strength Mueller-Hinton broth (MHB) for 24 hours with samples taken at standard time intervals in two technical replicates, with duplicates performed on separate days. Using the generation time equation (Figure 1) for the logarithmic phase of growth, rates were calculated and compared across three groups: (1) individual parent and IC pairs, (2) non-IC producers and IC-producers, and (3) IC-producers and IC as a whole. Comparisons across the three groups in both nutrient-rich and -depleted conditions were completed using Student’s t-tests.

Results
Average generation time for each isolate in full and ¼ strength MHB are shown in Table 1. Difference in generation time in full-strength MHB for parent and IC pairs were [131/131D] 0.04 hours and [209/209D] 0.05 hours (Table 2). In ¼ strength MHB, difference in generation time for parent and IC pairs were [131/131D] 0.03 hours and [209/209D] 0.01 hours. Average growth rate difference between non-IC-producers and IC-producers was 0.05 hours and 0.01 in full- and ¼ strength, respectively. The average generation time difference between IC-producers and IC was &lt; 0.01 hours and 0.01 in full- and ¼ strength, respectively.

Conclusion
Our data reveal no significant difference in growth rates between these KP isolate types which may signify no in vitro fitness differences for IC or IC-producers in both nutrient-rich and nutrient-depleted conditions. While the findings of this study are limited due to small sample size, they justify further investigation into the fitness of these isolate types through an in vivo mouse model and genetic testing.

Disclosures
Elizabeth B. Hirsch, PharmD, FCCP, FIDSA, Melinta: Honoraria|Merck: Grant/Research Support
576. Comparison of Three Blood Culture Testing Models at a Tertiary Care Hospital: Does Laboratory Centralization Work?
Authors: Haghamad Aya , Streva Vincent , Juretschko Stefan , Lemon Jamie 
Published: November 2023

Abstract

Background
Centralization of laboratory testing has become increasingly common in US hospital systems. One criticism of centralization is increased test turnaround time leading to potential delays in care.

Methods
In this study, we analyzed three microbiology laboratory testing models for blood cultures at a tertiary care hospital. These models were: 1) full workup in a hospital-based microbiology laboratory; 2) incubation, Gram stain (GS), and molecular blood culture identification (BCID) in a hospital-based microbiology laboratory followed by subculture identification and susceptibility testing (AST) at a centralized core laboratory; and 3) full workup in the centralized microbiology laboratory. Blood culture samples were transported 33 miles from the hospital to the core laboratory. We evaluated these three models for time from collection to positivity, time from collection to GS result, time from collection to BCID result, time from collection to organism identification, time from collection to AST, and patient length of hospital stay.

Results
We observed no statistical difference in time to blood culture positivity, time to GS result, or time to BCID result. There were shifts in the median time to AST between Model 1 (53.6h) and Model 2 (73.9h) and Model 2 and Model 3 (63.8h), but these were not statistically significant. Of note, time to AST and time to final result in Model 3 were more uniform, with fewer outliers than in the other two models. This is likely a result of the greater degree of laboratory automation in place at the core laboratory and reduced time spent in transit before culture workup. Finally, there was no difference in length of hospital stay between the hospital and decentralized models, though the hybrid approach (Model 2) resulted in increased length of hospital stay compared to either of the other models.

Conclusion
Our results suggest centralization of blood culture testing does not significantly impact timely reporting of laboratory results and has no impact on length of patient hospital stay. Interestingly, these data demonstrate potential delays when blood culture workups are split between hospital and centralized laboratories. Additional work is needed to fully understand the role of centralization of laboratory testing on treatment decisions and patient outcomes.

Disclosures
All Authors: No reported disclosures
589. Clinical Utility and Patient Characteristics Associated with Positive Whole Blood PCR for Borrelia spp. in an Endemic Area Using Novel High-Definition PCRTM assay: A Case Series
Authors: Mutti Jasmine , Moore Franklin , Paez Armando 
Published: November 2023

Abstract

Background
Current guidelines recommend antibody testing to detect acute borreliosis. Detectable antibody response takes about 2-3 weeks limiting its usefulness in early infection. The ChromaCode High-Definition PCR (HDPCR)™ Tick-Borne Pathogen Panel (TBP) is a research use only qualitative, real-time PCR assay for detection and identification of tick-borne pathogens including Borrelia spp. from whole blood samples.

Methods
HDPCR™ TBP was put in clinical use after this was validated in the laboratory to identify Anaplasma phagocytophilum, Babesia microti, Ehrlichia spp, Borrelia spp. (B. burgdoferi B. mayonii, and B. miyamotoi). Chart review was performed on all (+)Borrelia spp. from 8/1/22 to 12/31/22. Descriptive analysis was performed on each case. All data was captured and stored using RedCap.

Results
Over a period of 5 months, 9 (0.5%) out of 1667 tested were (+) for B. burgdorferi; one (0.06%) was (+) for B. miyamotoi; out of these 6 cases had clinical information for review as described in Table 1. Mean age was 64 years; 4 were white and 2 were Hispanic. All 6 lived in western Massachusetts, and only 1 had a known history of tick bite. All had reported systemic symptoms at the time of testing. 3 had (+) B. burgdorferi IgM antibodies;1 case tested (+) PCR for B. miyamotoi but serology was not performed. 1 case was (+) for B. burgdorferi PCR 28 days after symptom onset and had babesiosis co-infection; 1 with B. burgdorferi mono-infection had a (+) PCR test on day 14 of symptoms. All 6 had symptom improvement after doxycycline treatment for 10-14 days.
Case description

Conclusion
HDPCR™ TBP for Borrelia spp is a low yield test, even in an endemic region. All (+) cases were symptomatic and clinically improved following doxycycline treatment supporting the test’s validity. Two cases had negative IgM antibody testing and diagnosis would be likely missed without PCR testing. None were immunocompromised including 2 with prolonged PCR positivity with 1 case having babesiosis co-infection. Study was limited only to 6 cases excluding analysis of other tick-borne infections as part of syndromic testing. Clinical usefulness and timing of HDPCR™ TBP to diagnose borreliosis and other tickborne illnesses need further study.

Disclosures
All Authors: No reported disclosures
593. Evaluation of the EDTA-modified Carbapenem Inactivation Method (eCIM) with Using the EDTA Blood Collection Tube for Differentiating the Serine- and Metallo-β-lactamase (MBL) Producing Enterobacterales
Authors: Sakanashi Daisuke , Suematsu Hiroyuki , Takayama Mina , Kawamoto Yuzuka , Miyazaki Narimi , Ohno Tomoko , Yamada Atsuko , Nakamura Akiko , Ohta Hirotoshi , Koita Isao , Hirai Jun , Asai Nobuhiro , Mori Nobuaki , Mikamo Hiroshige 
Published: November 2023

Abstract

Background
The rapid and wide spread of carbapenemase-producing Enterobacterales (CPE) has become a global concern. Currently, β-lactams with β-lactamase inhibitors (such as ceftazidime/avibactam, relebactam/imipenem) are used for treatment of CPE infection as one of the effective agents. However, some of combinations do not have activity against MBLs. Thus, we believe that the discriminating between MBL and serine-CPE is important. The eCIM has been published by Clinical & Laboratory Standards Institute (CLSI) to differentiate to MBL from serine-CPE. The eCIM is required EDTA, that is not clinical diagnostic agent. In this study, we examined simplifying the eCIM procedure by using the EDTA blood collection tube (BCT-eCIM).

Methods
A total of 53 CPE (39 MBL and 14 Serin-CPE) were tested. The test population included 39 clinical isolates, and 14 reference strains from NCTC or ATCC (Table 1). The eCIM were performed and interpreted by following CLSI procedures. For BCT-eCIM, whole quantity of 2-mL TSB was inoculated into a BD Vacutainer EDTA Tube (2-mL) (Becton-Dickinson) (Vacutainer-eCIM) or an EDTA-2K Insepack II-D 2-mL tube (Kyokuto Pharmaceutical Industrial, Tokyo, Japan) (Insepack-eCIM); the tubes conform to International Organization for Standardization 6710, hence the 2-mL TSB inoculated tubes obtain final concentration of 4.1 to 6.8 mM EDTA. The BCT-eCIM used these tubes as a substitute for 0.5 mM EDTA TSB tube of eCIM, and any other procedures followed the eCIM procedure. Additionally, we performed the 4 mM- and 7 mM-eCIM to verify the effect of EDTA concentration (variable region of BCT-eCIM).
Table 1
Bacterial strains

Results
Table 2 and Figure 1 show the performance data of each eCIMs and the positive and negative Quality control results, respectively. The sensitivity of 4 mM-eCIM, 5 mM-eCIM, 7 mM-eCIM, Vacutainer-eCIM and Insepack-eCIM were 37/40 (93%), 36/40 (90%), 36/40 (90%), 39/40 (98%) and 39/40 (98%), respectively. The specificity of 4 mM-eCIM, 5 mM-eCIM, 7 mM-eCIM, Vacutainer-eCIM and Insepack-eCIM were 11/13 (85%), 13/13 (100%), 13/13 (100%), 12/13 (92%) and 12/13 (92%), respectively.
Table 2
Results obtained using the eCIM and BCT-eCIM

Conclusion
Our methods (BCT-eCIMs) were superior to sensitivity compared to conventional eCIMs. Therefore, BCT-eCIM may be useful in clinical settings as the simplifying method.

Disclosures
Hiroshige Mikamo, M.D, Ph.D, Asahi Kasei Pharma Corporation: Grant/Research Support|Merck Sharp & Dohme: Honoraria|Pfizer Inc.: Grant/Research Support|Pfizer R&D Japan: Honoraria|Sumitomo Pharma Co., Ltd.: Grant/Research Support|Sumitomo Pharma Co., Ltd.: Honoraria
598. Clinical Characteristics and Characterization of Hafnia Alvei Infections in Cancer Patients
Authors: Thakkar Keval , Shah Heeya , Larsen Matthew , Aslam Sadaf , Greene John 
Published: November 2023

Abstract

Background
There have been documented cases, although rare, of clinically significant infections caused by Hafnia alvei leading to infections such as bacteremia, pneumonia, UTI, meningitis, and empyema. H. alvei infections can be community-acquired or nosocomial. The published data for H. alvei in cancer patients is limited. The aim of this study was to characterize H. alvei infections including patient characteristics, antimicrobial susceptibility patterns, location of isolation, and microbial characteristics of isolates in cancer patients.

Methods
A retrospective cohort study was performed to review records of all consecutive patients with a positive H. alvei culture during the past 7 years. Variables included patient’s age, sex, underlying malignancy, neutrophil count, location and duration of infection, antimicrobial susceptibility patterns, hospital stay, co-isolates, and outcomes.

Results
A total of 15 patients with positive H. alvei cultures were identified at the Moffitt Cancer Center. There were 8 (53%) female and 7 (47%) male patients. The mean patient age was 65.7 ±15.8 yrs. All patients had underlying malignancies, most common type was solid organ malignancy in 11 patients (73%), and hematologic malignancies in 4 patients (27%). Two patients (13%) were neutropenic at the time of positive culture. H. alvei isolates were first identified in patients at a median of 8 days and an average of 11 days after admission to the hospital. Of the 15 isolates, 8 (53%) were monomicrobial and 7 (47%) were polymicrobial cultures (Table 1). Co-isolates and susceptibilities are shown in the Table 2 and 3.
Table 1
Demographic data for all identified patients
Table 2
Characteristics of H. alvei isolations
Table 3
H. alvei antibiotic susceptibility report

Conclusion
This study demonstrated that H. alvei is a truly rare pathogenic organism with only 15 documented cases of isolation over an 80-month time period at an academic cancer center. In patients with underlying malignancies, the organism tends to have a predilection for both the urinary tract and abdominal wounds, and can be isolated from pure cultures in the urine and with co-isolates in all other locations. Our study showed that resistance with H. alvei is usually with ampicillin and most of our isolates were resistant to cefazolin and cefoxitin. When infection does occur, isolates tend to be susceptible to standard antibiotics such as aminoglycosides and ciprofloxacin.

Disclosures
All Authors: No reported disclosures