bluuebunny/crossref_metadata_2025_split huggingface dataset:
LB1580. Efficacy Assessment of MAT2203 Encochleated Oral Formulation of Amphotericin B, in the Neutropenic Mouse Model of Pulmonary Mucormycosis
Authors: Gebremariam Teclegiorgis , Gu Yiyou , Alkhazraji Sondus , Youssef Eman , Matkovits Theresa , Cobb Jenel , Mannino Raphael J , Ibrahim Ashraf S 
Published: December 2022

Abstract

Background
Invasive mucormycosis (IM) is associated with high mortality and morbidity. MAT2203 is an encochleated oral formulation of amphotericin B which has been shown to be safe and effective against murine aspergillosis and murine cryptococcal meningoencephalitis. We sought to compare the efficacy of MAT2203 to liposomal amphotericin B (LAMB) treatment in a neutropenic mouse model of IM.

Methods
ICR mice were immunosuppressed with cyclophosphamide and cortisone acetate on days -2, -3 and +8, relative to infection with intratracheally instilled Rhizopus delemar 99-880 or M. circinelloides f. jenssenii DI15-131. Treatment with placebo (diluent control), oral MAT2203 (5 to 45 mg/kg, given qd or bid for 7 days) or LAMB (10 mg/kg, iv, qd for 4 days), began 16 h post infection. Survival (n=10-20/group from 1/2 experiments) through Day +21 and tissue fungal burden of lungs or brain (n=10/group) euthanized on Day +4 post infection (conidial equivalents using qPCR) served as a primary and secondary endpoint, respectively.

Results
For Rhizopus delemar infection, doses of MAT2203 5,15 mg/kg qd or 7.5 mg/kg bid, significantly prolonged median survival time (MST) and enhanced overall survival vs. placebo-treated mice (MST of 9 Days and 0% survival for placebo-treated mice vs. 13 Days, and 20-40% for MAT2203 doses, P&lt; 0.05 by Log-Rank). Importantly, MAT2203 treatments were as effective as LAMB (MST of 16 days and overall survival of 45%). For mice infected with M. circinelloides, MAT2203 at 15 mg/kg, qd significantly prolonged MST and enhanced overall survival vs. placebo-treated mice (MST of 5 Days and 0% survival, for placebo-treated mice vs. 13.5 Days and 50% survival for MAT2203, P&lt; 0.05). In both infection models MAT2203 treatment of 15 mg/kg or LAMB resulted in significant ∼1.0-1.5 log reduction and ∼2.0-2.2 log reduction in lung and brain fungal burden vs. placebo, respectively (Wilcoxon Rank Sum).

Conclusion
MAT2203 demonstrated in vivo efficacy in treating R. delemar or M. circinelloides pulmonary infection in immunosuppressed mice, which was equivalent to the LAMB current standard of care. Continued investigation and development of MAT2203 as a novel, and oral formulation of amphotericin antifungal agent against mucormycosis is warranted.

Disclosures
Theresa Matkovits, PhD, Matinas BioPharma: Employee Jenel Cobb, PhD, Matinas BioPharma: Employee Raphael J. Mannino, PhD, Matinas BioPharma: Employee Ashraf S. Ibrahim, PhD, Matinas BioPharma: Advisor/Consultant|Matinas BioPharma: Grant/Research Support|SFunga: Grant/Research Support.
131. Carbapenemase-producing Acinetobacter spp. from Israel, 2001-2006: earliest report of blaNDM predating the oldest known blaNDM-positive strains
Authors: Haraoui Louis-Patrick , Grenier Frédéric , Heynemand Félix , Lévesque Simon , Sullivan Richard , Landecker Hannah L , Higgins Paul G , Rodrigue Sébastien 
Published: December 2022

Abstract

Background
Carbapenem-resistant Acinetobacter baumannii (CRAb) is a WHO priority 1 critical pathogen. Despite Israel being affected early by high CRAb rates, limited molecular data are available. We investigated the presence of carbapenemases among 198 Acinetobacter spp. clinical isolates from Israel between 2001 and 2006.

Methods
Strains from 3 archives underwent whole-genome sequencing (Illumina NovaSeq on all, MinION on a subset) and computational analyses: assembly (Unicycler), annotation (prokka), identification (Kraken, 16S rRNA), search for carbapenemases (ResFinder, BLDB curation). Figures were generated in Inkscape, plasmid alignment on AliTV.

Results
A. baumannii (Ab) represented 179/198 (90.4%) Acinetobacter spp. (Figure 1). Annual incidence varied from a minimum of 16 (2001) to a maximum of 62 (2004), with an average of 30. Eighty-four Ab (46.9%) carried a carbapenemase: 38 (45.2%) blaOXA-72 (blaOXA-24-like); 28 (33.3%) blaOXA-23-like (20 blaOXA-23 and 8 blaOXA-225); 18 (21.5%) blaOXA-58 (16 from 2001-2). Annual CRAb rate increased yearly from 2002 (32%) to 2006 (67%).
Eight species of non-baumannii Acinetobacter (NbA) accounted for 19 isolates (9.6%): A. pittii (n=6), lwoffii (n=4), junii (n=3), ursingii (n=2), others n=1: A. gyllenbergii, johnsonnii, schindleri, and variabilis (Figure 1). Two of three A. junii contained blaOXA-58, one of which, Ajun-H1-3, isolated in a blood culture in January 2004, also possessed blaNDM-1. The pNDM-Ajun-H1-3 plasmid matched numerous NDM-positive plasmids reported from 2005 onwards in Acinetobacter spp. as well as Enterobacterales (Figure 2). Figure 1:annual distribution of Acinetobacter baumannii and non-baumannii Acinetobacter in Israel between 2001 and 2006, including their intrinsic oxacillinases and the presence of carbapenemases.Figure 2:plasmid alignment of pNDM-Ajun-H1-3 (Israel, 2004) with other NDM-positive plasmids found globally from 2005 onwards in Acinetobacter spp. and Enterobacterales.

Conclusion
We retrospectively assessed carbapenemase diversity among Acinetobacter spp. in Israel from 2001-2006. Analysis of 179 Ab isolates predate observations elsewhere: rapidly rising CRAb rates, driven by the dissemination of blaOXA-23-like and blaOXA-24-like genes replacing blaOXA-58.
Among 19 NbA, an A. junii isolated in 2004 carried two carbapenemases, blaOXA-58 and blaNDM-1, making it the earliest NDM-positive isolate reported to date, preceding NDM-positive Acinetobacter spp. found in 2005 in India.
Further investigations into the origins of blaNDM are needed to understand the conditions that led to its emergence and prevent similar issues from arising in the future.

Disclosures
Paul G. Higgins, PhD, Coris Bioconcept: Supply antibodies for lateral flow test kits.
163. Assessment of Pneumonia FilmArray Use on the Impact on Antimicrobial De-escalation Within an Integrated Health System
Authors: Weichman Brittani , Bushman Amanda , Terrero Salcedo David A 
Published: December 2022

Abstract

Background
BioFire® FilmArray® Pneumonia Panel (PFA) is a highly sensitive and specific diagnostic tool. PFA has been found to reduce antimicrobial utilization, however, inappropriate use can lead to high positivity rates that often do not correlate with standard cultures. Injudicious PFA utilization has been associated with inappropriate antibiotic use. We aimed to evaluate the inpatient utilization of PFA, establish culture correlation and assess clinical decision by ordering providers based on these results.

Methods
Retrospective review and descriptive analysis of adult patients presenting to an integrated health system in the Des Moines Metro, between March 2021 and September 2021, who had a PFA ordered and collected in their hospitalization. Indication, collection date, identified targets of PFA and cultures, antibiotic use, and trends in antibiotic de-escalation were collected.

Results
A total of 127 PFA were collected, of which 94 were from sputum (74%) and 33 were from BAL (26%). From PFA done in BAL, 42% were collected outpatient. Timing of PFA collection in relation to admission date is shown in Table 1.
Sensitivity of PFA when matched to culture was 90% in sputum vs 67% in BAL, with specificity in sputum of 48% vs 82% in BAL.
The overall relative frequency of timing of PFA orders in relation to admission is shown in Figure 1. Of 127 PFA collected, 39 (31%) were on standard therapy for community acquired pneumonia at time of collection and 24/39 (19%) were collected within the first 48 hours of admission. We found that 27 (21%) patients had appropriate changes in antibiotics after PFA results and 42 (33%) were not changed when it was considered appropriate to do so. Out of 72 patients with negative PFA, 30 (42%) had no change in antibiotics.

Conclusion
PFA collected early in the hospitalization did not result in antibiotic de-escalation when appropriate and many times was ordered when results would not lead to de-escalation due to narrow standard of care therapy already in use. Within our health system, PFA is not adequately utilized to support decisions for antimicrobial de-escalation.

Disclosures
All Authors: No reported disclosures.
165. Biofire pneumonia panel use in severe pneumonia and antibiotic treatment in COVID-19 patients
Authors: Stohs Erica J , McElligott Maureen , Creager Hannah M , Fey Paul D , Van Schooneveld Trevor C 
Published: December 2022

Abstract

Background
Hospitalized COVID-19 patients with severe pneumonia are commonly treated for secondary bacterial pneumonia. The Biofire pneumonia panel, a rapid molecular diagnostic tool with 18 bacterial, 8 viral and 7 resistance gene targets, was made available to critical care and infectious disease clinicians in May 2020 at our institution. We sought to describe its utilization and influence on antibiotic use in patients hospitalized with COVID-19 lower respiratory tract infection (LRTI).

Methods
Eligible patients with COVID-19 LRTI (positive PCR test and abnormal chest imaging) had sputum or bronchoalveolar lavage pneumonia panel (PNP) paired with a respiratory tract culture between May 4 and Dec. 8, 2020, were included. Demographics, comorbidities, clinical data including microbiologic testing, PNP indication(s), and antibiotic use after testing were abstracted through chart review. Descriptive statistics were utilized.

Results
Characteristics of 133 patients are provided in Table 1. Median age was 61 years, 93 (70%) were male, 93 (70%) were mechanically ventilated, and 68 (51%) died within 30 days on PNP testing. PNP results, including culture results are listed in Table 2. No target was identified in 63 (47%) patients. Staphylococcus aureus was the most common bacterial isolate identified (MSSA in 32 [24%], MRSA in 8 [6%]) with culture growth in 21 specimens. More than 1 target was identified in 29 patients (22%). Empiric antibiotics and subsequent modifications within 24h hours of pneumonia panel are provided in Table 3. Vancomycin and cefepime were most frequently prescribed. Antibiotic modifications were made in 71/133 patients. Cessation of the anti-MRSA agent occurred in 39/72 (54%) of eligible patients and the anti-Pseudomonal agent in 21/78 (27%).

Conclusion
The PNP is a useful tool to evaluate secondary bacterial pneumonia in critically ill COVID-19 patients and may assist clinicians and antimicrobial stewardship programs in expedited antibiotic discontinuation or de-escalation particularly where rates of secondary bacterial infection are low, such as COVID-19 LRTI.

Disclosures
Erica J. Stohs, MD, MPH, bioMerieux: Grant/Research Support Paul D. Fey, PhD, BioFire: Advisor/Consultant|BioFire: Grant/Research Support|Merck: Grant/Research Support Trevor C. Van Schooneveld, MD, bioMerieux: Advisor/Consultant|bioMerieux: Grant/Research Support|Insmed: Grant/Research Support|Merck: Grant/Research Support|Thermo-Fischer: Advisor/Consultant.
207. Burden of Post-Transplant Neutropenia and Leukopenia among Kidney Transplant Recipients: A Multi-Institutional Real-World Observational Study
Authors: Raval Amit D , Turzhitsky Vladimir , Fazio-Eynullayeva Elnara , Jin Harry , Merchant Sanjay 
Published: December 2022

Abstract

Background
Kidney transplant recipients (KTRs) are commonly prescribed valganciclovir/ganciclovir (V/G) prophylactically to prevent cytomegalovirus (CMV) infection; however, prolonged exposure to these medications is associated with an increased risk of post-transplant neutropenia (PTN) and leukopenia (PTL). Real-world evidence characterizing the incidence of PTN and PTL and their associated consequences on a national level are limited.

Methods
This retrospective cohort study utilized the TriNetX Dataworks – USA Network, a global federated network of de-identified electronic health record (EHR) data for 82.5 million patients across 49 US healthcare organizations. Adult KTRs who were treated with V/G between January 1, 2012 and September 30, 2020, were included in this analysis. PTN was defined as absolute neutrophil count&lt; 1500/μL and PTL was defined as white blood cell count&lt; 3,500/μL. We estimated the proportion of PTN and PTL among KTRs and examined differences in granulocyte colony-stimulating factor (G-CSF) use and clinical outcomes between KTRs with and without PTN or PTL in the 1-year following KT.

Results
Overall, 8,791 patients included in the analyses had a mean age of 52.8 years, 40.7% were females, 41.6% White and 32.6% Black. 3,383 patients (38.5%) developed PTN and 6,127 patients (69.7%) developed PTL based on the laboratory definitions. The incidence rates of PTN and PTL were 15.5/100 person-days and 53.4/100 person-days, respectively. There were no significant differences between comparison groups with respect to demographic characteristics at baseline. KTRs with PTN had higher G-CSF use compared to those without PTNs (38.9% vs.3.61%). Similarly, those with PTLs had higher G-CSF use compared to those without (22.8% vs. 4.2%). Both PTN and PTL were also associated with increased risk of CMV infection, graft rejection, and loss (Table 1, all p&lt; 0.001).

Conclusion
The results of this large EHR study demonstrate that a sizeable proportion of V/G treated KTRs develop PTN and/or PTL, both of which are associated with increased medication use and suboptimal health outcomes. These findings underscore the importance of taking steps to mitigate the risk of neutropenia and leukopenia where possible to help improve outcomes in KTRs.

Disclosures
Amit D. Raval, PhD, Merck and Co., Inc.: Employee of Merck|Merck and Co., Inc.: Stocks/Bonds Vladimir Turzhitsky, PhD, Merck & Co., Inc.,: Employee|Merck & Co., Inc.,: Stocks/Bonds Sanjay Merchant, PhD, Merck & Co., Inc.: Stocks/Bonds.
240. Antibiotic Overuse Among Children with COVID-19 Hospitalized in a Pediatric Intensive Care Unit
Authors: Gillon Jessica , Garguilo Kathryn , LeBlanc Kerry , Banerjee Ritu 
Published: December 2022

Abstract

Background
Antibiotic overuse has been well described among hospitalized adults with COVID-19 but similar evaluations in children are lacking. We sought to quantify bacterial infection rates and antibiotic utilization among critically ill children hospitalized with COVID-19 to identify opportunities to optimize care.

Methods
We performed a single center retrospective cohort study of all children hospitalized with symptomatic COVID-19 in a pediatric intensive care unit between May 16, 2020 and February 11, 2022 at a tertiary care children’s hospital in the Southeastern U.S. We performed medical record review to abstract demographic and clinical characteristics. This study was approved by the institutional IRB with a waiver of consent.

Results
During the study period there were 92 subjects hospitalized in the intensive care unit with COVID-19. Demographic and clinical characteristics of the cohort are summarized in the Table. Median age was 12.4 years, median length of stay was 6 days, 32% of subjects required mechanical ventilation and 5% died. The vast majority of children had one or more comorbidities and only 1 subject was fully vaccinated against SARS-CoV-2. Thirteen (14%) subjects had bacterial growth from any clinical specimen. Eight subjects had respiratory cultures that may have represented airway colonization; when these were excluded, 5 (5%) subjects had either urinary tract or bloodstream infections. Two of the bloodstream infections were caused by drug-resistant organisms and were hospital-acquired. Despite the low number of subjects with bacterial infections, 45% received antibiotics for &gt;3 days. The antibiotic days of therapy per subject varied widely and ranged from 0 to 61 days.

Conclusion
In this cohort of nearly 100 critically ill children with COVID-19, the rate of culture-confirmed bacterial infection ranged from 5-14% yet nearly half of patients received antibiotics. Limitations include the single center and retrospective study design and the fact that bacterial pneumonia may not be culture-confirmed. Despite these limitations, this work suggests that children with COVID-19 rarely have bacterial co-infections and are often prescribed unnecessary antibiotics.

Disclosures
All Authors: No reported disclosures.
393. Healthcare and Out-of-Pocket Costs Associated With Clostridioides difficile Infection Among US Adults 18–64 Years of Age
Authors: Yu Holly , Alfred Tamuno , Zhou Jingying , Judy Jennifer , Olsen Margaret A A 
Published: December 2022

Abstract

Background
Limited data are available on healthcare costs associated with Clostridioides difficile infection (CDI) among adults &lt; 65 years of age.

Methods
This retrospective cohort study used Optum’s de-identified Clinformatics® Data Mart to identify first CDI episodes from 2016–2019 among individuals 18–64 years of age insured under commercial plans. CDI was defined by ICD9/ICD10 diagnosis codes or a combination of CDI diagnosis/testing with antibiotic treatment. Healthcare costs were evaluated among CDI+ cases and 1:1 propensity score-matched CDI− controls. Both CDI+ cases and controls had continuous database enrollment for ≥12 months prior; follow-up continued through the earliest of death, disenrollment or 12 months post-index. Costs were analyzed by age group, acquisition type, and hospitalization status within 2 months of the CDI index date.

Results
We identified 13,820 CDI+ cases and 4,027,386 potential controls; 12,999 cases (18–49 y, n=6667; 50–64 y, n=6332) were matched to a control. In the 50–64-year matched groups, mean total healthcare costs at 2 months post-index were $18,453 (CDI+) and $6819 (CDI−); $11,634 in excess costs were attributable to CDI (Figure 1A). Mean attributable costs were higher for hospitalized healthcare-associated ($68,745) and hospitalized community-associated ($37,646) cases than non-hospitalized healthcare- or community-associated cases ($8333 and $2953, respectively). The mean attributable out-of-pocket (OOP) cost in the 50–64-year age group was $573 and was higher for community-associated vs healthcare-associated cases (Figure 1B). Overall CDI-attributable costs in the 18–49-year age group trended similarly but were mostly lower for total healthcare costs ($7826 [CDI+, $12,019; CDI−, $4193]; Figure 2A) and slightly higher for OOP healthcare costs ($642 [CDI+, $954; CDI–, $311]; Figure 2B).

Conclusion
CDI-attributable healthcare costs among US individuals 18–64 years of age are substantial, particularly for those hospitalized for CDI. Effective prevention in younger adults may significantly reduce healthcare resource utilization and costs to both the healthcare system and patients.
Funded by Pfizer Inc.

Disclosures
Holly Yu, MSPH, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Tamuno Alfred, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Jingying Zhou, MA, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Jennifer Judy, MS, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Margaret A A. Olsen, PhD, MPH, Pfizer Inc: Advisor/Consultant|Pfizer Inc: Grant/Research Support.
405. Utilization of a novel humble inquiry interview approach in assessing implementation barriers to a Nurse Driven Clostridioides difficile infection (CDI) order set
Authors: Kon Shelley , Fisher Sara , Ngo Nhi , Gunter Christine M , Craig Randi , Vanderburg Rebecca , Bessesen Mary T , Gilmartin Heather 
Published: December 2022

Abstract

Background
Timely diagnosis and use of contact precautions for Clostridioides difficile infection (CDI) is key to prevent spread in hospital settings. Empowering nursing staff to order stool tests and proactively implement precautions has been shown to reduce hospital acquired CDI. Our institution established a nurse driven CDI order set in 2019, however only 1% of tests were ordered by nurses in the past year. The goal of this quality improvement project was to understand current use of the nurse-driven CDI order set using a novel humble inquiry approach.

Methods
We used humble inquiry, an interview approach that poses questions while building relationships with participants through humility, curiosity, and active listening skills to explore barriers to utilization of a nurse driven CDI order set. Two nursing students at a 182-bed Veterans Health Administration (VA) hospital were trained to use humble inquiry and a three-item interview guide. A convenience sample of nurses and nursing assistants were interviewed about a) what they know about the nurse driven CDI order set, b) where there is documentation about the order set and c) barriers to use of the order set (if any). Interviews were conducted from January to April 2022. Demographics were analyzed descriptively. Interview data and the experience of conducting humble inquiry were analyzed using manifest content analysis.

Results
Interviews (n=19) with nurses (n=16) and nursing assistants (n=3) revealed the majority (13/19 = 68%) were not aware of the nurse driven CDI order set. Of those aware, most were able to identify the location of information on their unit and where to document in the electronic medical record. The two most common barriers included lack of awareness of the order set and patient reluctance to disclose their bowel habits. Delay in providers reading notes (3/19=16%) and lack of PPE during COVID (1/19= 5%) were also identified as barriers. The nursing students reported the humble inquiry approach allowed participants to be the “experts” and “teachers”. Table IIllustrative quotes from interview answers and associated demographic information.

Conclusion
The humble inquiry method was valuable in understanding viewpoints and identifying barriers to utilization of a nurse drive CDI order set. Lack of awareness of the order set and patient modesty were identified as barriers and may be targeted for future interventions.

Disclosures
All Authors: No reported disclosures.