bluuebunny/crossref_metadata_2025 huggingface dataset:
2142. Safety and immunogenicity of COVID Influenza Combination Vaccine
Authors: Shinde Vivek , Woo Wayne , Liu Sharon , Cook Sara , Santiago Zenaida , Neal Susan , Plested Joyce S , Vincent Tim , Zhu Mingzhu , Cloney-Clark Shane , Cho Iksung , Fries Lou , Glenn Greg
Published: December 2022

Background

We developed a COVID-Influenza Combination (CIC) vaccine, comprising recombinant SARS-CoV-2 Spike (rS) and quadrivalent influenza hemagglutinin (HA) protein nanoparticles (qNIV), and Matrix-MTM adjuvant. rS/Matrix-M previously demonstrated efficacy against COVID-19 in Phase 3 trials, while qNIV/Matrix-M previously demonstrated induction of broadly cross-reactive antibodies. Here we report preliminary safety and immunogenicity results of a first-ever Phase 1/2 CIC dose-finding trial.

Methods

Seropositive (COVID-19 vaccinated ≥ 8 weeks prior) participants (N=642) aged 50-70 years were randomized equally, to receive two intramuscular doses, 56 days apart, to 1 of 14 different dose/formulations of CIC using a design of experiments approach (dose range: rS 2.5-22.5ug, HA 5-60ug; and 50ug Matrix-M), or to 1 of 2 reference formulations of either standalone rS with Matrix-M [2 doses] or qNIV with Matrix-M [1 dose only]. Pre- and post-vaccination (Days 0, 28, 56, 70, 84, 182) immunogenicity assessments including SARS-CoV-2 anti-S IgG and influenza HAI antibodies to vaccine-homologous strains. Reactogenicity was assessed 7 days following each dose, and safety outcomes assessed through Day 70. Multiple regression was used to create predictive models to assess antibody response surfaces and for dose optimization.

Results

All CIC formulations were well tolerated, with a reactogenicity and safety profile generally comparable to standalone rS or qNIV. Regression modelling of post-first dose responses revealed that both rS and HA antigens in a CIC formulation modestly interfered with each other, however, interference was overcome with dose adjustment across a range of rS/HA doses. Specifically, higher rS dose ( >20ug), in a dose dependent fashion, overcame HA interference, closely matching standalone rS IgG reference responses (GMEU 16,818), whereas lower, intermediate HA dose overcame rS interference, closely matching standalone HA reference HAI responses for H3N2 (GMT 145), H1N1 (GMT 134), and B-Victoria (GMT 66); while modestly (at least 34%) lower than the reference B-Yamagata response (GMT 101).

Conclusion

CIC formulations were well tolerated and immunogenic, with various dose combinations achieving response comparable to standalone vaccines.

Disclosures

Vivek Shinde, MD, MPH, Novavax Inc.: Stocks/Bonds Wayne Woo, MS, Novavax Inc.: Stocks/Bonds Sharon Liu, n/a, Novavax Inc.: Stocks/Bonds Sara Cook, n/a, Novavax Inc.: Stocks/Bonds Zenaida Santiago, n/a, Novavax Inc.: Stocks/Bonds Susan Neal, n/a, Novavax Inc.: Stocks/Bonds Joyce S. Plested, n/a, Novavax Inc.: Stocks/Bonds Tim Vincent, n/a, Novavax Inc.: Stocks/Bonds Mingzhu Zhu, n/a, Novavax Inc.: Stocks/Bonds Shane Cloney-Clark, n/a, Novavax Inc.: Stocks/Bonds Iksung Cho, MS, Novavax Inc.: Stocks/Bonds Lou Fries, n/a, Novavax Inc.: Stocks/Bonds Greg Glenn, n/a, Novavax Inc.: Stocks/Bonds.
2162. Risk Factors Associated with Hospitalization among 0 to 21 Years Old Patients with Active Asthma/Active Airway Disease: Preliminary Findings from Multi-Center Study Across United States.
Authors: Pardasani Sapna , Dallas Ronald H , Ross Hailey S , Ferrolino Jose A , Fisher Brian T , Danziger-Isakov Lara A , Muller William J , Maron Gabriella , Kitt Eimear
Published: December 2022

Background

More data are needed to understand the risk for COVID-19 severity among pediatric asthma patients. We present findings from a national registry characterizing COVID-19 hospitalizations among pediatric asthma patients.

Methods

Data were obtained from the Pediatric COVID-19 US Registry, which included medical records of COVID-19 cases < 21 years old between March 2020 and May 2021. Those with asthma were eligible while immunocompromised and transplant cases were excluded. Descriptive statistics and chi-square tests were performed.

Results

Of the 1089 eligible asthma cases, half were 12 to 17 years old [Figure 1], the majority were male [Figure 2], a third Black African American [Figure 3], and most were Non-Hispanic/Latino 825 (76%). 242 (22%) reported a history of smoking.

A fourth of cases (257 (23.6%) were hospitalized for COVID-19. More than half (54%) reported asthma as their only pre-existing condition. The majority (n=71, 28%) were taking regular inhaled corticosteroids. Almost half (n=120, 47%) had abnormal chest radiographic findings, 20 (7.8%) had abnormal CT findings, and 24 (9%) progressed to lower respiratory infection. About 10% (n=25) needed mechanical ventilation. A third (n=88, 34%) required ICU care with 33% of those receiving inhaled corticosteroids. A quarter needed mechanical ventilation [Figure 5].

Compared to asthma patients not hospitalized for COVID-19, those hospitalized were significantly (P< 0.05) more likely to be non-Hispanic, havemultiple pre-existing conditions, and be obese [Figure 6]. Compared to those not admitted to ICU, ICU cases were significantly more likely to be obeseand be diagnosed with MIS-C [Figure 7].

Demographics

The majority of cases (N=479, 44%) were between 12 and 17 years old, Male (N=610,56%) and Black or African American (N=410, 38%).

Clinical Characteristics

Risk factors assessment

Conclusion

This is one of the first national studies examining COVID-19 among pediatric cases with asthma. Our data suggest that children with asthma who have multiple pre-existing conditions and/or are obese have a higher risk for hospitalization. These early data may aid clinicians in developing future prospective studies to understand COVID-19 risk among this vulnerable population.

Disclosures

Lara A. Danziger-Isakov, MD, Ansun BioPharma: Contracted clinical research|Astellas: Contracted clinical research|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Contracted clinical research|Pfizer: Contracted clinical research|Takeda: Grant/Research Support|Takeda: Contracted clinical research|Viracor: Grant/Research Support.
2190. Characterization of Inhaled Nitric Oxide (iNO) for the treatment of Viral Community Acquired Pneumonia (CAP)
Authors: Tal Asher , Shifer Yehonatan , Wolak Talya , Grossman Alon , Dicker Dror
Published: December 2022

Background

Nitric Oxide (NO) has been previously demonstrated to have antimicrobial, anti-inflammatory, and vasodilator properties. Extensive work has been done in the clinical setting to explore these properties with iNO administered intermittently at high concentrations of 150-250 ppm. While viral CAP has gained major attention with the emergence of COVID-19, treatment methods remain limited and are challenging to develop. The purpose of this study is to assess iNO treatment administered to hospitalized adults with viral CAP.

Methods

This is a randomized, open label multi-center ongoing study. Study population includes subjects aged 18-80, hospitalized for vCAP including COVID-19. Following enrollment, subjects were randomized 1:1 to either iNO [150ppm for 40 minutes, 4 times daily, up to 7 days in addition to standard supportive treatment (SST)], or control [SST alone]. iNO was delivered by LungFitTM, an innovative NO generator under development (Beyond Air, NY, USA). Follow up period is 180 days. Study endpoints include safety and the time to reach a stable saturation of ≥93%. In addition, different other clinical parameters are collected to profile the effect of iNO in this population.

Results

Analyzing the Intent To Treat (ITT) population (n=35, [16 iNO and 19 control]), safety profile of iNO treatment observed so far, was found to be favorable with no treatment related Adverse Events (AEs). Faster clinical improvement was noted in the iNO treatment group, paralleling CRP improvement between baseline to end of treatment (mean 2.7 mg/dl comparing treatment group [n=8] to control group [n=7], data not final).

Conclusion

These data suggest that intermittent treatment with 150ppm iNO is safe and well tolerated and may contribute to faster clinical improvement in viral CAP. Different laboratory parameters may shed some light and help to characterize this observed effect, supporting the further exploration of iNO for the treatment of viral lower respiratory tract infection, including COVID-19.

Preliminary findings were presented at ECCMID 2022

Disclosures

Asher Tal, MD, Beyond Air Inc: Advisor/Consultant|Beyond Air Inc: Stocks/Bonds Talya Wolak, MD, talya wolak: Advisor/Consultant Dror Dicker, MD, AstraZenca: Advisor/Consultant|AstraZenca: Honoraria|Beyond Air: Grant/Research Support|Boehringer Ingelheim: Advisor/Consultant|Boehringer Ingelheim: Honoraria|Eli Lilly: Grant/Research Support|Novo Nordisk: Advisor/Consultant|Novo Nordisk: Grant/Research Support|Novo Nordisk: Honoraria.
2208. Rates of Medically-Attended RSV among US Adults: A Systematic Review and Meta-Analysis
Authors: McLaughlin John M , Khan Farid L , Begier Elizabeth , Swerdlow David , Jodar Luis , Falsey Ann R
Published: December 2022

Background

Adult respiratory syncytial virus (RSV) vaccines are in late stages of development. A comprehensive synthesis of adult RSV burden is needed to inform public health decision-making.

Methods

We performed a systematic review and meta-analysis of studies describing the incidence of medically-attended RSV (MA-RSV) among US adults. We also identified studies reporting nasopharyngeal (NP) or nasal swab RT-PCR results with paired serology (four-fold-rise) or sputum (RT-PCR) to calculate RSV detection ratios quantifying improved diagnostic yield after adding a second specimen type (ie, serology or sputum).

Results

We identified 14 studies with 15 unique MA-RSV incidence estimates, all based on NP or nasal swab RT-PCR testing alone. Pooled annual RSV-associated incidence per 100,000 adults ≥65 years of age was 178 (95%CI: 152‒204; n=8 estimates) hospitalizations (4 prospective studies: 189; 4 model-based studies: 157), 133 (95%CI: 0‒319, n=2) emergency department (ED) admissions, and 1519 (95%CI: 1109‒1929, n=3) outpatient visits. Based on 6 studies, RSV detection was ∼1.5 times higher when adding paired serology or sputum. After adjustment for this increased yield, annual RSV-associated rates per 100,000 adults ≥65 years were 267 hospitalizations (UI: 228‒306) (prospective: 282; model-based: 236), 200 ED admissions (UI: 0‒478), and 2278 outpatient visits (UI: 1663‒2893). Persons < 65 years with chronic medical conditions were 1.2−28 times more likely to be hospitalized for RSV depending on risk condition.

Conclusion

The true burden of RSV has been underestimated and is significant among older adults and individuals with chronic medical conditions. A highly effective adult RSV vaccine would have substantial public-health impact.

Disclosures

John M. McLaughlin, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Farid L. Khan, MPH, Pfizer: Employee|Pfizer: Stocks/Bonds Elizabeth Begier, M.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds David Swerdlow, MD, Pfizer: Advisor/Consultant|Pfizer: Stocks/Bonds Luis Jodar, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Ann R. Falsey, MD, BioFire Diagnostics: Grant/Research Support|Janssen: Grant/Research Support|Merck, Sharp and Dohme: Grant/Research Support|Novavax: Advisor/Consultant|Pfizer: Grant/Research Support.
2216. ROAR ED-SANE: A Retrospective Observational Assessment Review of an Emergency Department Sexual Assault Nurse Examiner Program’s Adherence to CDC Guidelines for Sexually Transmitted Infections
Authors: Nelson Jennifer , Woolever Nathan L , Meyer Lisa M , Hall Scott T , Stakston Jaclyn , Dababneh Ala , Van Sistine Michael , Tempelis Jennifer M , Dierkhising Ross , Lessard Sarah R , Roush Kathleen
Published: December 2022

Background

Sexual assault survivors are at increased risk for sexually transmitted infections. Due to patient vulnerability, institutions have implemented Sexual Assault Nurse Examiner (SANE) protocols to care for these patients. These protocols guide evidence collection, testing, treatment, and medical follow-up to ensure optimization of sexually transmitted infections (STIs) treatment, monitoring and follow-up. Previous gap analyses have identified decreased prescribing of prophylactic STI medications and scheduling follow-up appointments compared to guideline recommendations. The purpose of this study was to assess adherence of medication prescribing and follow-up scheduling practices to Centers for Disease Control (CDC) guidelines.

Methods

This study was a single-center, retrospective, observational, descriptive assessment which evaluated adherence rates to CDC guidelines, to scheduling medical follow-up, and patient attendance at scheduled appointments. Pediatric and adult patients who presented to the emergency department at Mayo Clinic Health System in La Crosse, WI from January 2018 through December 2021 were included. Data collected through chart review included demographics and laboratory data necessary for prescribing prophylactic HIV medications, antibiotics for STIs, emergency contraception, and vaccine administration. Descriptive statistics were used to evaluate results.

Results

One hundred three patients were evaluated. Majority of patients were female and presented within 3 days of assault. Medication adherence to CDC guidelines was ≥ 80% for chlamydia and gonorrhea whereas < 80% was noted for trichomoniasis and HIV prophylaxis. Adherence to post-ED discharge follow-up was 40%.

Conclusion

Opportunities to improve adherence of ED-SANE protocols for medication prescribing and medical follow-up for trichomoniasis and HIV prophylaxis exist.

Disclosures

All Authors: No reported disclosures.
LB746. Safety and Immunogenicity of a Booster Dose of Novavax COVID-19 Vaccine, Adjuvanted (NVX-CoV2373) in Adults from the PREVENT-19 Trial in the United States
Authors: Áñez Germán , Dunkle Lisa M , Gay Cynthia L , Kotloff Karen L , Patel Nita , Plested Joyce S , McGarry Alice , Woo Wayne , Cai Rongman , Cho Iksung
Published: December 2022

Background

Novavax COVID-19 Vaccine, Adjuvanted (5 µg recombinant spike protein/50 µg Matrix-MTM adjuvant; NVX-CoV2373) has received regulatory authorizations for use in adults ≥ 18 years globally.

Methods

Participants from PREVENT-19 (NCT04611802), a phase 3, randomized, observer-blinded, placebo-controlled trial that evaluated the efficacy, safety, and immunogenicity of a primary series of 2 doses of NVX-CoV2373 given 21 days apart, in adults ≥ 18 years in the United States and Mexico, were eligible to receive a booster dose at least 6 months after the initial vaccination series. Short-term safety and immunogenicity of the booster dose was assessed in an ad hoc analysis of 298 participants.

Results

There was an incremental increase compared to the initial vaccination series in local and systemic reactogenicity, which was transient and mostly mild-to-moderate in intensity. Most unsolicited adverse events were also mild-to-moderate in severity; there were no deaths or treatment-related SAEs and 2/298 booster recipients in this analysis reported unrelated SAEs. Neutralizing, anti-S IgG, and hACE2 receptor binding inhibiting antibodies against the ancestral (Wuhan) strain 28 days after booster were higher than those 14 days after primary vaccination (Table). Overall, humoral responses were high regardless of interval between priming and booster vaccination, but a longer interval yielded stronger responses. Higher immune responses against the Omicron BA.1, BA.2, and BA.5 variants were also observed after the booster dose than after the primary series in a subset of 14-18 participants tested. Overall, humoral responses were high and broad regardless of age after any vaccination, but higher responses were observed in adults < 65 years after initial and booster vaccinations. A booster dose induced more robust antibody responses compared with the primary series in adults ≥ 65 years.

Conclusion

A single booster dose of NVX-CoV2373 demonstrated a satisfactory safety profile, and high levels of neutralizing, anti-S IgG, and hACE2 inhibition antibody responses against the SARS-CoV-2 prototype Wuhan as well as against the Omicron variant including recently emerged sub-variants.

Disclosures

Germán Áñez, MD, Novavax Inc.: employer|Novavax Inc.: Stocks/Bonds Lisa M. Dunkle, MD, Novavax, Inc: Employee|Novavax, Inc: Stocks/Bonds Nita Patel, MS, CRP, Novavax, Inc.: employer|Novavax, Inc.: Stocks/Bonds Joyce S. Plested, PhD, Novavax Inc.: employer|Novavax Inc.: Stocks/Bonds|Novavax Inc.: Stocks/Bonds Alice McGarry, MPH, Novavax: Employee|Novavax: Stocks/Bonds Wayne Woo, MS, Novavax: Employee|Novavax: Stocks/Bonds Rongman Cai, PhD, Novavax Inc.: employer|Novavax Inc.: Stocks/Bonds Iksung Cho, MS, Novavax, Inc.: employer|Novavax, Inc.: Stocks/Bonds.
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

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< 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< 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

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

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

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

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< 1500/μL and PTL was defined as white blood cell count< 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< 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

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 >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

Background

Limited data are available on healthcare costs associated with Clostridioides difficile infection (CDI) among adults < 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

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.
444. Effect of multidisciplinary management of CKD on proteinuria in people with HIV
Authors: Bennani Yussef , Richey Lauren , Hasan Hira , Perez Annalisa
Published: December 2022

Background

Optimizing management of chronic kidney disease in people with HIV has become a more pressing priority both to minimize morbidity and preserve HIV antiretroviral options. Part of standard care is employing the beneficial effects of angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARB) in patients with clinically significant proteinuria. Our analysis looks at the proteinuria outcomes of PWH with CKD co-managed by a multidisciplinary team of infectious disease and nephrology physicians nested in a Ryan White-funded clinic in New Orleans.

Methods

Patients with HIV and at least grade 3 CKD or with significant proteinuria were referred to the multidisciplinary clinic. Patients were evaluated by an HIV specialist and nephrologist at the initial visit for a jointly developed management plan. Renal function and proteinuria were measured at baseline and longitudinally per standard of care. Change in proteinuria and GFR over time were calculated. Patients were also assessed for whether they were prescribed ACE/ARB therapy, if appropriate. Patients included in this analysis were evaluated between January 1, 2021 and March 31, 2022.

Results

During the analysis period, 46 patients with at least CKD 3 or proteinuria were evaluated. 35 patients were Black non-Hispanic, 9 were White non-Hispanic, and 2 were Hispanic. 39 were male, and 7 were female. 35 had a previous diagnosis of hypertension, and 10 had diabetes mellitus. Of the 42 with a recorded baseline urine protein measurement, 24 were found to have clinically significant proteinuria. Of those with proteinuria, 16 were on an ACE or ARB at their baseline evaluation. 20 were on ACE/ARB’s the end of the analysis period (p=0.058). Average baseline proteinuria was 1,158 mg/g, while average final was 938 mg/g, which was less but not significantly different (p=0.54). Mean baseline GFR was not significantly different from final GFR (50.8 mL/min vs 50.5 mL/min, p=0.67).

Conclusion

A multidisciplinary model of managing CKD among people with HIV may improve adherence with management guidelines and limit progression of proteinuria and decrease in GFR. In general, the natural history of kidney disease with proteinuria is to worsen over time, so while not significant, proteinuria in this cohort did decrease over time

Disclosures

All Authors: No reported disclosures.
539. Impact of a Rapid Diagnostic Assay for the Detection of Bacterial and Viral Agents on Antimicrobial use in Critically Ill Patients with Pneumonia
Authors: Sielatchom Noubissie Lionel K , Ciochetto Zachary , Willey Emily , Olexia Deanna , Wrzesinski Magdalena , Buchan Blake W , Njeri Wainaina J , Gibble Allison
Published: December 2022

Background

Conventional diagnostic methods for pneumonia have a long turnaround time, and a pathogen is isolated in only 33% of cases. As a result, empiric therapy with broad-spectrum antimicrobials often becomes definitive therapy. Rapid molecular diagnostics paired with antimicrobial stewardship intervention have the potential to improve outcomes for patients with lower respiratory tract infections (LRTIs). However, data to support this hypothesis are scarce. This study examined the influence of a rapid multiplex polymerase-chain-reaction (PCR) test on antimicrobial use in critically ill patients with LRTIs.

Methods

This single-center study consisted of pre-implementation (PrIP, December 1, 2018, to February 28, 2019) and post-implementation periods (PoIP, December 1, 2021, to February 28, 2022). Both groups included intensive-care unit (ICU) patients with respiratory cultures from bronchoalveolar lavage (BAL), mini-BAL, or tracheal aspirates. Interventions during the PoIP included concurrent testing of specimens with the BioFire® Pneumonia Panel and clinical decision support tools to streamline treatment recommendations from ICU pharmacists. The primary outcome was the difference in time to optimal therapy (TTOT). Secondary outcomes included time to effective therapy (TTET) and duration of therapy (DOT) for antipseudomonal and anti-MRSA agents.

Results

A total of 163 patients were included (n = 80, PrIP; n = 83, PoIP). The mean age was 57 + 16 years, and medical ICU patients accounted for 60% (n = 97) of cases. The median APACHE II score was the only significant baseline difference between the two arms (22 vs. 18, interquartile range [IQR] 16, 28 vs. 12, 25, p = 0.01). The median TTOT was 38 hours in the PrIP and 21 hours in the PoIP (p < 0.001). TTET was 5.7 hours in the PrIP and 4.9 hours in the PoIP (p = 0.106). The median DOT for antipseudomonal agents decreased by 52% (4.4 days in the PrIP and 2.1 days in the PoIP, p < 0.001), and anti-MRSA agent DOT was 53% shorter in the PoIP (1.9 days vs. 0.9 days, p < 0.001).

Conclusion

Implementation of a rapid multiplex PCR panel for lower respiratory-tract pathogens significantly reduced the time to optimal therapy in critically ill patients with pneumonia. Clinically meaningful reductions in anti-MRSA and anti-pseudomonal agent duration were also noted.

Disclosures

Blake W. Buchan, PhD, Accelerate: Advisor/Consultant|Accelerate: Honoraria|BioFire: Honoraria|ChromaCode: Advisor/Consultant|ChromaCode: Honoraria|Pattern: Advisor/Consultant|Pattern: Honoraria.
600. Cefiderocol is Not Sequestered in an Ex vivo Extracorporeal Membrane Oxygenation (ECMO) Circuit
Authors: Berry Angela V , Conelius Allison M , Gluck Jason A , Nicolau David P , Kuti Joseph L
Published: December 2022

Background

ECMO is widely used in critically-ill patients that require respiratory and/or cardiac support, but may affect drug exposure by altering pharmacokinetics within patients or sequestering drugs in the circuit. Cefiderocol, a siderophore antibiotic with activity against multi-drug resistant gram-negative bacteria, may be used to treat serious infections in critically-ill patients supported by ECMO. Limited data are available to guide dosing in this population. Herein, we determined the loss of cefiderocol through an ex vivo ECMO circuit.

Methods

A closed-loop ECMO circuit prepared with a Quadrox-i adult oxygenator and primed with Isolyte S was used during all experiments. Fresh whole blood collected from healthy volunteers was pooled, injected to replace priming fluid, and circulated at 4.5 L/min at 37° C. Cefiderocol was administered into the circuit at 0h to obtain peak plasma concentrations of ∼89.7 mg/L. A pre-oxygenator blood sample was taken at 0h to confirm baseline concentration. Post-oxygenator blood samples were collected between 0-24h to determine loss of cefiderocol in the circuit. A control jar of the same pooled matrix spiked with cefiderocol was maintained at 37° C for comparison. Each ECMO/control experiment was performed in triplicate. A general linear model was constructed to compare the rate of loss between the ECMO circuit and controls.

Results

Baseline cefiderocol concentrations in the ECMO circuit and control jar ranged from 51.7-91.8 mg/L and 67.7-100.5 mg/L, respectively. At 0h, the difference in pre- vs post-oxygenator concentration was -4 ± 4% (range: 0-7%). After 24h, cefiderocol % reduction was similar between the ECMO circuits and controls (50% ± 13 vs 50% ± 9, p=1.0). The degradation rate of cefiderocol followed a zero order process and did not differ significantly between the circuit and control (slope: -0.0186 ± 0.0052 vs -0.0201 ± 0.0039, p=0.786).

Conclusion

Cefiderocol was not sequestered in an ex vivo ECMO circuit studied with an adult oxygenator, suggesting insignificant removal from the circuit can be expected. Pharmacokinetic studies in critically ill patients supported by ECMO are warranted to determine final dosing recommendations in this population.

Disclosures

David P. Nicolau, PharmD, Shionogi: Grant/Research Support Joseph L. Kuti, PharmD, Abbvie: Honoraria|bioMeriuex: Advisor/Consultant|bioMeriuex: Grant/Research Support|Contrafect: Grant/Research Support|Entasis: Grant/Research Support|Merck and Co: Grant/Research Support|Roche Diagnostics: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Shionogi: Honoraria|Summit: Grant/Research Support.