bluuebunny/crossref_metadata_2025 huggingface dataset:
354. A Comparison of Different Strategies for Optimizing the Selection of Empiric Antibiotic Therapy for Hospital-Acquired Pneumonia (HAP) and Ventilator-Associated Pneumonia (VAP) Caused by Gram-Negative Bacteria in Intensive Care Units (ICU)
Authors: Wangchinda Walaiporn , Aitken Samuel L , Lephart Paul , Pogue jason M
Published: November 2023

Background

Guidelines for HAP/VAP recommend considering local susceptibility data and patient specific risk factors for empiric therapy. However, data are lacking assessing whether a unit-specific combination antibiogram or a patient-specific factor-based approach will better drive appropriate empiric treatment. This study aims to hypothetically compare the two methods.

Methods

This retrospective study was conducted at Michigan Medicine between 2021-2022. Microbiological data of 221 non-duplicated, first Gram-negative respiratory isolates obtained from 190 patients in the MICU and SICU in 2021 were used to develop unit-specific combination antibiograms (Table 1) and individual patient charts were accessed to identify the impact of the presence/absence of various risk factors on antimicrobial susceptibility to define optimal regimens. Selected empiric regimens based on each approach are shown in Table 2. These two approaches were then hypothetically applied to 129 patients with positive respiratory cultures in 2022. The appropriateness, defined by having at least one in vitro active agent, and the overuse of antibiotics in empiric regimens by the two approaches were then assessed and compared.

Results

The breakdown of different empiric regimens selected based on the two approaches are shown in Table 3. Cefepime was the backbone β-lactam in regimens for both MICU and SICU by unit-specific combination antibiograms and in 83.7% of regimens based on patient-specific risk factors. Empiric regimens based on patient-specific risk factor had a higher rate of appropriateness than those based on antibiograms (89.1% vs 83.7%), with a 33.1% reduction in the rate of inappropriate empiric therapy. Additionally, using combination antibiograms resulted in a higher prevalence of antibiotic overuse than using patient-specific risk factors (72.9% vs. 40.3%), with most inappropriate use due to unnecessary aminoglycoside use. The overuse of other agents was comparable between approaches.

Conclusion

Both approaches were useful and can be applied in empiric antibiotic selection. However, the patient-specific risk factor-based approach offers advantages in reducing rates of inappropriate therapy and decreasing the overuse of combination agents.

Disclosures

jason M. Pogue, PharmD, AbbVie: Advisor/Consultant|Entasis: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Qpex: Advisor/Consultant|Shionogi: Advisor/Consultant
355. Stratification of Patient-Specific Risk Factors for Multidrug-Resistant Gram-Negative Respiratory Pathogens in Intensive Care Units (ICU)
Authors: Wangchinda Walaiporn , Aitken Samuel L , Lephart Paul , Pogue jason M
Published: November 2023

Background

Guidelines for nosocomial pneumonia recommend empiric combination therapy for patients with a risk of infection due to multidrug-resistant Gram-negative pathogens in ICUs. Common risk factors cited include ≥ 5-day duration in the ICU, transfer from other healthcare facilities, recent antibiotic use, and history of a resistant Gram-negative pathogen. However, the interrelation of these factors and which are key drivers remain ill-defined. This study is designed to stratify risk factors to further optimize empiric regimens.

Methods

A total of 190 patients who had a positive Gram-negative respiratory culture obtained from the MICU/SICU of Michigan Medicine in 2021 were included. Patients were classified into subgroups based on the presence/absence of each aforementioned risk factor. Cumulative susceptibility percentages of isolates in each risk group were examined and compared.

Results

Cumulative susceptibility percentages of Gram-negative respiratory isolates from patients with/without each risk factor are shown in Figure 1. Patients with recent antibiotic use or history of a resistant Gram-negative pathogen had noticeably lower susceptibility rates than those without those risk factors, whereas the presence/absence of prolonged ICU stay and/or admission from another facility had minimal impact on susceptibility rates. In patients without recent antibiotic exposure or history of a resistant pathogen, 90% had pathogens that demonstrated in vitro susceptibility to cefepime monotherapy. (Figure 2) In contrast, the susceptibility percentages of any β-lactam monotherapy were < 75% in patients with one or more of these factors and remained < 85% when adding an aminoglycoside or fluoroquinolone. More stratified analyses demonstrated that patients with previous positive carbapenem-resistant P. aeruginosa or Enterobacterales should receive a novel agent. Proposed stratified empiric regimens are summarized in Figure 3.

Conclusion

Recent antibiotic use and previous positive resistant Gram-negative cultures were significant factors for determining antibiotic resistance in Gram-negative respiratory pathogens. Risk stratification based on these two factors can help further optimize empiric antibiotic therapy.

Disclosures

jason M. Pogue, PharmD, AbbVie: Advisor/Consultant|Entasis: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Qpex: Advisor/Consultant|Shionogi: Advisor/Consultant
356. Impact of CLSI Breakpoint Changes on Unit-Specific Combination Antibiograms for Gram-Negative Respiratory Isolates
Authors: Wangchinda Walaiporn , Aitken Samuel L , Pierce Virginia M , Lephart Paul , Pogue jason M
Published: November 2023

Background

In 2023, the CLSI updated aminoglycoside breakpoints for P. aeruginosa and Enterobacterales. The anticipated decrease in aminoglycoside susceptibility rates resulting from these revised breakpoints will impact empiric antibiotic selection for nosocomial pneumonia. This study aims to evaluate the impact of the new breakpoints on the susceptibility rates of various combination antibiotic regimens for Gram-negative pneumonia at Michigan Medicine.

Methods

The susceptibility rates of single and combination antibiotic regimens were determined by applying the CLSI breakpoints to 221 non-duplicated, first Gram-negative respiratory isolates obtained from patients in the MICU and SICU of Michigan Medicine in 2021. Combination antibiograms were developed to compare susceptibility rates of various potential empiric regimens based on the 2022 vs. 2023 aminoglycoside breakpoints. Subgroup analyses for P. aeruginosa vs. non-P. aeruginosa were performed.

Results

Comparisons of unit-specific combination antibiograms against all Gram-negative respiratory isolates using 2022 vs. 2023 breakpoints are shown in Table 1. Based on the 2022 breakpoints, overall susceptibility rates for aminoglycosides were higher than those of anti-pseudomonal β-lactams. The addition of an aminoglycoside improved the susceptibility percentages of a β-lactam up to 23%, allowing similar activity with amikacin-based combination therapy to levofloxacin-based. In contrast, based on 2023 breakpoints, the susceptibility rates of amikacin and gentamicin dropped significantly (85.1 to 58.8% and 81.0 to 56.6%, respectively) and combination with these two agents did not provide additional benefit to the β-lactam backbone. The tobramycin susceptibility rate was minimally affected by the breakpoint changes (82.8% vs. 79.2%). Subgroup analyses demonstrated that the decrease in susceptibility percentages for aminoglycosides was largely driven by the breakpoint changes for P. aeruginosa (Table 1).

Conclusion

The updated 2023 CLSI breakpoints resulted in a substantial decrease in the susceptibility percentages of amikacin and gentamicin which clinicians need to be aware of when choosing empiric antibiotic treatment.

Disclosures

Virginia M. Pierce, MD, FIDSA, UpToDate, Inc.: Authorship royalties jason M. Pogue, PharmD, AbbVie: Advisor/Consultant|Entasis: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Qpex: Advisor/Consultant|Shionogi: Advisor/Consultant
369. The DOOR is open: A Web-based Application for Analyzing the Desirability of Outcome Ranking
Authors: Hamasaki Toshimitsu , He Yijie , Evans Scott R
Published: November 2023

Background

The Antibacterial Resistance Leadership Group (ARLG) has developed the Desirability of Outcome Ranking (DOOR) methodology, a novel paradigm for the design, conduct, analysis and interpretation of clinical trials. The DOOR methodology enables clinicians to effectively evaluate and select treatment strategies by providing an informative way to compare the patient-centered risks and benefits of intervention alternatives. There are two complementary approaches to DOOR analysis. The first approach summarizes DOOR responses between treatments by the probability of a more desirable outcome in one treatment relative to another (DOOR probability) using the concept of pairwise comparisons, The second, “partial credit” analyses, involves grading the DOOR levels on a scale from 0 (least desirable) to 100 (most desirable), allowing for strategic scoring, preferential assignment of relative importance to DOOR levels for personalized analyses, and evaluation of robustness through analysis of different scoring keys.

Methods

The Statistical and Data Management Center of the ARLG is developing interactive web-based applications (apps) with downloadable data presentations, to help clinical researchers conduct DOOR analyses.

Results

Two editions of the apps are available. The Standard Edition (Std) requires entry of summary level data of the DOOR outcome by intervention group. The app generates ARLG-recommended components of comprehensive DOOR analyses, including summary tables and figures of DOOR distributions, forest plot displays of DOOR probability estimates for the DOOR and its components, and partial credit analysis. The Professional Edition (Pro) reads patient-level data. In addition to the analyses provided in the Std, the Pro includes additional functionality and informed visualizations, i.e., inverse probability weighting (IPW)-based analyses, tie-breaker analyses, and the Anthology of Patient Stories plot.

Data Entry Panel of the Application (Standard Edition)

DOOR Frorst Plot Output (Standard Edition)

DOOR Forest Plot Output from DORI-05 study of comparing IV doripenem (DOR) to IV levofloxacin (LVX), with a step-down option of oral levofloxacin in both groups after 3 days of IV therapy (Standard Edition)

Partial credit analysis output from DORI-05 study of comparing IV doripenem (DOR) to IV levofloxacin (LVX), with a step-down option of oral levofloxacin in both groups after 3 days of IV therapy (Standard Edition)

Conclusion

The DOOR apps provide comprehensive tools for researchers to implement the DOOR methodology. The apps are freely available online at https://methods.bsc.gwu.edu/.

Disclosures

All Authors: No reported disclosures
376. Long Term Outcomes of a Pilot Single-Blinded, Randomized Controlled Trial Comparing BNT162b2 vs JNJ-78436735 Vaccine as the Third Dose after Two Doses of BNT162b2 Vaccine in Solid Organ Transplant Recipients
Authors: Natori Yoichiro , Martin Eric F , Mattiazzi Adela , Sota Katherine Alexandra , Viotti Julia Bini , Anjan Shweta , Guerra Giselle
Published: November 2023

Background

Due to immunosuppressive medication, the immunogenicity after COVID-19 vaccination is suboptimal and durability in Solid Organ Transplant (SOT) recipients is still questionable. Thus, booster dose has been studied to improve not only the short but also long-term immunogenicity. However, mix and match method for this purpose was not well studied.

Methods

This was a post hoc analysis of a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs JNJ-78436735 vaccine as the third dose after two doses of BNT162b2 vaccine. We included adult SOT recipients with functional graft who had received two doses of BNT162b2 vaccine and were randomly assigned to receive either vaccine. The outcome included SARS-CoV-2 IgG positivity at six months after the third dose and geometric mean titer.

Results

4 SOT recipients, including 39 kidney, 3 liver, 1 lung, and 1 heart transplants, were analyzed per protocol. Only 1 recipient did not develop IgG after 6 months. Median IgG levels at 6 months were 5893 and 65584 for BNT162b2 vs JNJ-78436735, respectively(p< 0.01). For geometric mean titer from prior to third dose and 6 months after was 4.1 and 62.0 for BNT162b2 vs JNJ-78436735, respectively(p< 0.01).

Conclusion

After 6 months post third dose, BNT162b2 showed significant higher immunogenicity in SOT recipients. BNT162b2 provided a higher IgG titer, and durability. To continue BNT162b2 vaccine boosters should be beneficial in SOT recipients but further study should be required.

Disclosures

Adela Mattiazzi, MD, Care Dx: Advisor/Consultant|Care Dx: Speaker|Kaneka: Advisor/Consultant|Kaneka: Speaker
380. The first two years of the European VACCELERATE volunteer registry
Authors: Salmanton-Garcia Jon , Stewart Fiona A , Heringer Sarah , Leckler Janina , Cornely Oliver A , Pana Zoi Dorothea
Published: November 2023

Background

The VACCELERATE Volunteer Registry is an active single-entry point for European residents interested in clinical trial participation. It has received funding from the European Union’s Horizon 2020 research and innovation programme (grant agreement 101037867), and the German Federal Ministry of Education and Research (grant BMBF01KX2040). As of today, the VACCELERATE Volunteer Registry is active in 17 countries, and associated to two national registries (France, The Netherlands), with 106,869 registered volunteers overall. Participants provide their contact information, including first and last name and e-mail address, age, gender, pre-existing comorbidities, vaccination status for SARS-CoV-2, COVID-19 history, and maximum distance willing to travel to a clinical trial site, if needed. The registry is open to both adults and children, complying with legal consent requirements. The VACCELERATE Volunteer Registry is active since October 2020.

Methods

Once volunteers sign in on www.vaccelerate.eu/volunteer-registry, data are stored until a request is received from entities managing or

performing clinical trials or epidemiological studies. Based on the inclusion criteria of the respective study, number of volunteers

needed, potential delivery of invitation reminders, and turnaround time is set. Afterwards, matching notifications are delivered.

Eventually, if volunteers autonomously decide to participate in the study, they may contact via email the promoters.

Results

So far, the VACCELERATE Volunteer Registry has been approached to match clinical trials and epidemiological studies with volunteers 28 times. Of those, 17 (61%) studies have been focused on different aspects of SARS-CoV-2, such as finding of the best vaccination scheme, new vaccine testing, or infection point-prevalence. Additionally, new vaccinations against Streptococcus pneumoniae have been the research topic of 6 (21%) studies. Overall, 71,758 study participations have been offered to VACCELERATE volunteers of all ages.

Conclusion

After 2 years since its activation, the VACCELERATE Volunteer Registry has become a reference for study sponsors and clinical trial units to speed up volunteer enrolment in trials. We expect a further increase in volunteer registration, and study requests.

Disclosures

Oliver A. Cornely, MD PhD, DZIF: Advisor/Consultant|DZIF: Board Member|DZIF: Grant/Research Support|DZIF: Honoraria|DZIF: Stocks/Bonds
382. A Multifaceted Intervention to Reduce Blood Culture Contamination in Medical and Surgical Wards: A Cluster Randomized Controlled Trial
Authors: Sayabovorn Naruemit , Chongtrakool Piriyaporn , Rachakhom Siriporn , Kaewsomnuck Supaporn , Wejsuwanmanee Rakkan , Khamphimabood Chuthaphorn , Jitmuang Anupop
Published: November 2023

Background

Blood culture (BC) is a standard diagnostic testing of bloodstream infection. Inappropriate blood sampling may lead to BC contamination causing antimicrobial overuse and adverse outcomes. Several individualized interventions during blood sampling are applied to reduce BC contamination. However, the efficacy of a multifaceted intervention applied to nursing staff for reducing the contamination rate has yet to be thoroughly studied.

Methods

From August 2020–January 2021, we conducted a 1:1 cluster-randomized controlled trial in 6 medical and 6 surgery wards. Six wards (3 medical, 3 surgery) as the intervention arm received the multifaceted intervention comprising a multimodal educational program, regular surveillance, and feedback. The other six wards (3 medical, 3 surgery) as the control arm received standard care. Participant nurses responsible for BC collection had to answer the pre- and post-study questionnaires to score their background knowledge on appropriate BC sampling. Clinical data and microbiological results were also collected.

Results

Of 3,630 blood culture bottles, 304 (8.4%) were culture positive, with an equal number of true bacteremia and contaminated bottles in both arms. The pre-study contamination rate was 2.2-2.5%. After applying the interventions, the contamination rate was 2.3% in the intervention arm and 3.2% in the control arm (p=0.535). Coagulase-negative staphylococci were the most common contaminants (12.8%). Factors associated with contaminated BC included pulmonary diseases (p=0.006), length of hospital stay (p=0.004), blood sampling at 7:00-15:00 (p=0.001), and delayed time to positivity (23.49 h, p< 0.001). In addition, nurses who received the interventions achieved overall scores in post-study questionnaires significantly more than nurses who did not (p< 0.001).

Conclusion

The multifaceted intervention can maintain a lower contamination rate throughout the study period. It may be a strategy to improve knowledge of an appropriate BC collection for medical staff. This study demonstrated that comorbidity, length of hospitalization, time of blood sampling, and time to culture positivity likely influenced BC contamination.

Disclosures

All Authors: No reported disclosures
386. Participant Reflections on Their Experiences Participating in Phase 1 and 2 Inpatient Vaccine Trials and Human Challenge Studies
Authors: Wunderlich Bettina , Chang Kathryn , Moulton Lawrence , Kass Nancy , Karron Ruth , Talaat Kawsar R
Published: November 2023

Background

Volunteers are critical for the success of clinical trials but there is still debate on the ethics surrounding recruitment and enrollment of healthy human subjects who are paid for their participation in such research. This study seeks to examine the experiences and perceptions of risks and benefits of participants in early-phase inpatient studies to gain greater insight into how they feel about participating.

Methods

An interviewer-administered survey was conducted with 152 healthy volunteers who participated in at least one Phase 1 or 2 inpatient vaccine or challenge clinical trial at the Johns Hopkins Center for Immunization Research, during the years of 2010-2020. Participant characteristics, study experiences, and perceived risks were analyzed. Poisson regression with robust variance was used to examine factors associated with perception of risk before and after participation.

Results

Most participants who completed the survey were male (62%) and Black or African American (78%). 53% attained at most a high school degree and 42% had an income below $18,500 a year. Compensation was the primary factor for joining a study for 68% of participants; 35% of them relied on clinical trials as a major part of their income. Nevertheless, 32% reported they declined to participate in at least one study and 63% reported that they ask about the side effects before joining a new study. Over 90% of participants agreed or strongly agreed that they enjoyed participating, wanted to participate, and were glad they joined the study. There was a significant reduction in the perceived risk of study participation after study completion compared to perceived risk before joining the study, where before the study 46% thought it was “Not at all risky” compared to 73% afterwards.

Conclusion

Most participants in our early-phase inpatient studies are males of lower income and compensation was the primary motivator for joining. However, side effects do factor in their decision whether to join. The majority of participants indicated that they were glad they joined the study. Despite the studies having risks and expected side effects, there was also a significant decline in perception of risks related to the study following participation, which implies participants feel safer than they anticipated feeling.

Disclosures

Lawrence Moulton, PhD, Pfizer Canada ULC: Employee Kawsar R. Talaat, MD, Intralytix: Advisor/Consultant|Merck: Advisor/Consultant|NIAID: DSMB|Pfizer: Grant/Research Support|Pfizer: Pfizer contract with institution|Sanofi: Grant/Research Support|Takeda: Advisor/Consultant
392. The Impact of Therapeutic Interventions on Post-Acute Sequelae of SARS-CoV-2 (PASC) in COVID-19 Survivors: A Retrospective Analysis
Authors: Calderon Andrea S , Englund Kristin
Published: November 2023

Background

Post-acute sequelae of SARS-CoV-2 (PASC) is a condition characterized by persistent and debilitating symptoms that continue more than 28 days beyond the acute phase of COVID-19. A significant proportion of individuals who have contracted COVID-19 have reported long-term symptoms consistent with PASC. Despite the growing number of reports on PASC, its exact pathophysiology remains unclear, and there are currently no effective treatments available. Although various therapeutic interventions have been developed and used to treat COVID-19 patients, the effectiveness of these interventions in preventing the development of PASC is not yet established. Therefore, there is a pressing need to identify potential long-term health impacts and the relationship between therapeutic interventions and the development of PASC in COVID-19 survivors.

Methods

A retrospective chart review was conducted at the reCOVer Clinic at Cleveland Clinic Foundation from March 2020 to November 2022. The study population consisted of patients diagnosed with PASC, who were matched with controls without PASC at a 1:1 ratio.

Results

We identified 57 patients that were deemed to have PASC in the study period. Multiple interventions that were given at the time of COVID-19 diagnosis were reviewed. Table 1 shows the characteristics of both patient groups. Our analysis did not find any significant differences in the baseline characteristics of patients who did and did not develop PASC, including hospital admission status, need for ICU, and need for intubation. Among those that received nirmatrelvir-ritonavir, tocilizumab, remdesivir and dexamethasone there were no statistical differences found in those that eventually developed PASC (p-values of 0.50, 0.74, 0.07 and 0.06, respectively).

Conclusion

The findings of our study suggest that treatment alone at the time of COVID-19 diagnosis is not protective against the development of PASC. Further studies are needed to identify other potential risk factors for PASC. Clinicians should consider future research focusing on identifying effective treatments for this debilitating condition.

Disclosures

All Authors: No reported disclosures
395. Remdesivir Stewardship Through Criteria for Use Implementation Across a Large System is Associated with Enhanced Outcomes and Efficiency
Authors: Daragjati Florian , Cosimi Reese , Ghosh Subhangi , Moreno Ana Cristina Perez , Miller Collin , Rice Erin , Fakih Mohamad G
Published: November 2023

Background

The National Institute of Health (NIH) COVID-19 Treatment Guidelines support use of remdesivir in hospitalized adults with mild-to-moderate COVID-19 infection for those at risk of progressing to severe COVID-19 and those who require oxygen supplementation, high-flow nasal cannula, or non-invasive ventilation. We implemented a standardized approach for the treatment of COVID-19 infection adopting the NIH criteria for use in a single system.

Methods

Patients ≥ 18 years old admitted with a diagnosis of COVID-19 infection from January 2021 to September 2022 in 94 hospitals from a single health system and 1012 peer hospitals from a large national database were included. Risk-adjusted outcomes in COVID-19 patients were compared, including mortality, readmissions, geometric mean length-of-stay (GMLOS), and mechanical ventilation days. We also compared remdesivir use in the COVID-19 population in the single health system and the large national database.

Results

85,874 and 789,660 COVID-19 patients were included from the single health system and large national database, respectively, during that time frame. Remdesivir use in COVID-19 patients was lower within the single system hospitals compared to external peer hospitals (33.6% vs 43.3% respectively; mean difference 9.7% (CI 8.5%-10.9%); p < 0.001). Risk-adjusted mortality and GMLOS were also lower for the system compared to peer hospitals, while readmissions and mechanical ventilation use were not significantly different (Table).

Conclusion

The adoption of the NIH Criteria for remdesivir use in a single system was associated with lower COVID-19 mortality and lower geometric mean length of stay despite less remdesivir use compared to external peer hospitals. Our findings support optimizing the compliance with the NIH treatment guidelines.

Disclosures

Reese Cosimi, PharmD, Allergen: Advisor/Consultant
396. Clinical Characterization of Long COVID 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

Background

Long COVID is defined as the persistence of symptoms after 4 weeks of an acute picture. There is talk of 65 million people affected in the world. In Mexico there are no statistics or studies that explore this entity in the population.

Methods

A descriptive, cross-sectional, and prospective study was carried out using an online survey, in adults who wish to participate and who are living in Mexico from January to March 2023, whose main objective is to characterize patients who present symptoms of Long COVID

Results

336 participants with an average age of 41 years (range 18-79 years), the most affected gender is female (69%); Risk factors are Obesity 41%, Diabetes 16%, Hypertension 15.8%; 43.5% commented that they were healthy before COVID-19. Cases of acute COVID they have suffered, 42.3% comment that 2 previous infections, 29.5% had one and 28.3% 3 or more. 77% refer to mild COVID, 13% to severe COVID, and 10% both. Regarding vaccination, 45% have 3 or more vaccines, 36% 2 vaccines, 9% have one vaccine and 10% have not been vaccinated against COVID-19. The most prevalent symptoms are Neuropsychiatric 90%, Musculoskeletal 88%, Cardiovascular 82%, Gastrointestinal 78%, and Pulmonary 71%. The most frequent Neuropsychiatric symptoms: fatigue 76%, memory disorder 72%, anxiety 65%; Musculoskeletal symptoms are arthralgia 71.4%, myalgia 40%, arthritis 28%. Cardiovascular symptoms are palpitations 58%, tachycardia 38%, precordial pain 27%. Gastrointestinal symptoms are diarrhea 43%, abdominal pain 41%, Colitis 26%. Pulmonary symptoms are chronic cough 40%, persistent expectoration 29%, dyspnea 23%. Other symptoms are alopecia 53.3%, chronic dermatitis 38%, frequent infections after COVID-19 20%, menstrual disorders 17%, thyroid disease 12%, development of autoimmune diseases 9.5%, sexual dysfunction 9%, COVID tests persistently positive 6%, thrombotic events 3.6% (cerebral 0.9%, pulmonary thromboembolism 0.6%, myocardial infarction 0.3%), myocarditis 3.3%, chronic renal failure 2.4% and cancer 1.8%.

Conclusion

It is important to characterize this population since it has particularities that make it susceptible to this new entity and the creation of clinical guidelines in the country should be encouraged to begin limiting sequelae.

Disclosures

All Authors: No reported disclosures
398. Increased Risk of Severe COVID-19 Outcomes Across all Groups of Individuals with Hematological Malignancies, Solid Tumors, and Solid Organ Transplants Compared with the General Population: Initial Results from INFORM, a Retrospective Health Database Observational Study in England
Authors: McNulty Richard , Dube Sabada , Lu Yi , Graham Sophie , Arnetorp Sofie , Justo Nahila , Yokota Renata , Evans Kathryn , Venkatesan Sudhir , Yates Mark , Taylor Sylvia , Quint Jennifer , Evans Rachael A
Published: November 2023

Background

Despite COVID-19 vaccination, individuals who are immunocompromised due to underlying conditions, such as cancer and organ transplant, are at a greater risk of severe COVID-19 outcomes compared with the general population that is vaccinated. However, there are limited data quantifying this risk during the omicron-predominant period, particularly for important sub-groups that may have variable risk for severe COVID-19 outcomes. We report initial findings from the INFORM study describing the clinical burden and severe COVID-19 outcomes in patients with immunocompromised conditions (IC) in England, UK in 2022.

Methods

This retrospective cohort study utilized National Health Service database in England. The study period was from Jan 1–Dec 31, 2022 and the baseline period for assessment of patient characteristics, including IC, was from Jan 1, 2017–Dec 31, 2021. Definitions of IC sub-groups are provided in Table 1. Severe COVID-19 outcomes were defined as COVID-19–related hospitalization, COVID-19–related intensive care unit (ICU) admission, and/or COVID-related death.

Results

Of the 11,990,730 individuals in the general population sample aged ≥ 12 years, 468,745 (3.9%) were immunocompromised and accounted for approximately one-quarter of severe COVID-19–related outcomes (22% of hospitalizations, 28% of ICU admissions, and 23% of deaths; Table 2). The risk of severe COVID-19 outcomes was higher in well-recognized IC conditions (eg, solid organ transplants, hematological malignancies, and solid tumors) across all the sub-groups compared with the overall population (Table 2).

Conclusion

There is an increased burden in the prevalence of severe COVID-19 outcomes among all individuals with IC, highlighting the need for additional protection to target this population.

Disclosures

Richard McNulty, MD, AstraZeneca: Employee Sabada Dube, PhD, AstraZeneca: Employee Yi Lu, PhD, Evidera: Employee Sophie Graham, MSc, Evidera: Employee Sofie Arnetorp, MS, AstraZeneca: Employee Nahila Justo, PhD, MBA, Evidera: Employee|Karolinska Institute: Employee Renata Yokota, PhD, AstraZeneca: Employee Kathryn Evans, MPH, Evidera: Employee Sudhir Venkatesan, MPH, PhD, AstraZeneca: Employee Mark Yates, PhD, Evidera: Employee Sylvia Taylor, PhD, MPH, MBA, AstraZeneca: Stocks/Bonds Jennifer Quint, PhD, AstraZeneca: Grant/Research Support|Evidera: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Insmed: Grant/Research Support Rachael A. Evans, PhD FRCP, AstraZeneca: Advisor/Consultant|Boehringer: Advisor/Consultant|Evidera: Advisor/Consultant
407. Prevalence of Post-COVID Sequelae Amongst Fully Vaccinated and Unvaccinated US Hospitalized Veterans
Authors: Jeyapalina Sujee , Wei Guo , Stoddard Greg , Millier Aaron , Agarwal Jayant
Published: November 2023

Background

Post-Acute Sequelae of COVID-19, also known as long COVID, refers to a wide range of ongoing health symptoms and illnesses that persist for weeks or months after the acute phase of the COVID-19 illness has resolved. Based on the overwhelming reports of multiple health symptoms, the ICD-10 code U09.9 became effective on October 1, 2021, for coding ongoing symptoms or health problems related to COVID-19, a range of prevalence for long-COVID is reported. Thus, we hypothesized that among veterans who experienced a COVID-19 infection that required hospitalization, with follow-up beginning with the first hospitalization and assigning vaccination status on first hospital admission date, subsequent long COVID prevalence would be greater in the unvaccinated.

Methods

The deidentified veterans' data were accessed from the VA COVID-19 Shared Data Resources with local ethical approvals. The Veterans Affairs Informatics and Computing Infrastructure was used to extract patient health records for all U.S. veterans above the age of 18 who had tested positive for COVID-19. The primary outcome was the prevalence of reported U09.9 code after a single COVID-19 infection. The prevalence rates were calculated as the proportion of long-COVID within veterans who tested positive for COVID-19 disease between 10/01/2021 to 03/30/2023.

Results

In total, 468,620 veterans who were older than 18 reported being positive for COVID-19 within the studied period. Also, 68,125 veterans had reported multiple COVID-19 infections and were excluded from the study. Within this cohort, 15,772 veterans had the U09.09 code assigned, indicating a long-COVID prevalence rate of 3.93%. Although no significant difference was found between the prevalence of long-COVID between the vaccinated (3.98%) and unvaccinated (3.87%) veterans, post-hospitalization, vaccinated veterans had a much-reduced prevalence rate (3.50%) than that of the unvaccinated group (8.78%). This trend was mirrored by the requirement for mechanical ventilation.

Conclusion

Although the prevalence of long-COVID is 3.93% within the entire Veteran population, the prevalence of reported long-COVID was ∼three-fold greater in unvaccinated hospitalized veterans, with a ∼2.5-fold greater requirement for mechanical ventilation in the unvaccinated

Disclosures

All Authors: No reported disclosures
408. Clinical Spectrum of Pediatric Long COVID and Impact of COVID-19 Vaccines on the Clinical Course
Authors: Kamel Dina , Bender Jeffrey , Warburton David , Wood John C , Mohandas Sindhu
Published: November 2023

Background

Long COVID is a well-recognized, emerging health problem following COVID-19 infection. It presents with a wide range of ongoing, new, or returning symptoms following COVID-19 infection. Symptoms can last from weeks to months, significantly impacting patients’ quality of life. There is no precise definition for long COVID making it difficult to diagnose. Little is known about long COVID in children and the effect of COVID-19 vaccine on its course. This study aims to describe the most common symptoms in pediatric patients and to study the impact of vaccination on the course of long COVID.

Methods

A retrospective analysis of all children aged 0-21 years seen in the COVID Recovery Clinic at Children’s Hospital of Los Angeles from August 2021 to April 2023. Data were abstracted using a standardized tool and analyzed using SPSS 28.

Results

Overall, 107 patients were identified with long COVID. Of these, 51 (47.7%) were females with a median age of 14.1 years (IQR 11.1-15.9). Data regarding race and ethnicity were limited. The most commonly reported symptoms were fatigue (94.4%), headache (73.6%), exercise intolerance (57%), dizziness (49.5%), brain fog (41.1%), shortness of breath (31.8%), musculoskeletal pain (30.8%), chest pain and palpitations (29%). Symptoms developed immediately after COVID-19 infection in 56 (52.3%) of patients, within 1-4 weeks in 37 (34.7%), and after 4 weeks in 14 (13%) of them. At the time of presentation to the clinic, 57 (53.3%) were vaccinated against COVID-19, and 35 (61.4%) of them received the vaccine after the onset of long COVID symptoms. Of those 35 patients, 51.4% reported no change in symptoms after vaccine administration, 42.9% reported symptom improvement and 5.7% had progression of symptoms.

Figure (1)

Figure (2)

Conclusion

Long COVID is a growing well-recognized problem in children after COVID-19 infection. In our large cohort of pediatric patients, we identified fatigue and headache as the predominant presenting symptoms. COVID-19 vaccine led to symptomatic improvement in a proportion of patients. Longer prospective follow-up is needed to help better understand the impact of long COVID on children. COVID-19 vaccines should be further investigated in a systematic fashion as a possible therapeutic intervention in children with long COVID.

Disclosures

All Authors: No reported disclosures
409. Unvaccinated Adolescents Bear the Majority of Disease Burden of Severe COVID-19 Among Those Admitted to the Intensive Care Unit (ICU)
Authors: Kaushik Ashlesha , Thieman Corey , Gupta Sandeep
Published: November 2023

Background

COVID-19 vaccination is one of the most important public health tools to prevent severe COVID-19.

Methods

COVID-19 vaccine (Pfizer-BioNTech) first received the U.S. Food and Drug Administration (FDA) Emergency use authorization (EUA) for individuals 16 years of age and older on 12/11/2020 and for 12-15 years of age on 5/10/2021. We evaluated clinical and epidemiologic characteristics of critically ill adolescents with COVID-19 admitted to the intensive care unit (ICU) at our tertiary-care centers in Northwestern Iowa (encompassing Sioux City and Sergeant Bluff locations) during the 1-year post-vaccination approval period from June 1, 2021- May 31, 2022. Adolescence was defined as age-group 12-21 years per WHO definition.

Results

Twenty-one adolescents were admitted to the ICU with a median age of 16 years (IQR 12-20 years) and male: female ratio of 1:1.3. The majority (77%) were admitted with COVID-19 related pneumonia and 10 developed hypoxemic respiratory failure; 19 of 21 (90%) adolescent patients admitted to the ICU during this period were unvaccinated and all adolescents developing respiratory failure (10/10, 100%) were unvaccinated. Majority of patients with respiratory failure (70%) required mechanical ventilation (MV). Seventy % of patients with respiratory failure were obese (BMI of >30); 40% of patients had two or more pre-existing comorbidities; those with BMI >40 were 4.3 times more likely to develop respiratory failure (p< 0.0001). Inflammatory markers were 5-20 times higher among patients with respiratory failure (p< 0.05); 60% of those with respiratory failure developed complications including ARDS, acute renal injury and cerebral anoxic encephalopathy. All with respiratory failure required parenteral steroids. Mean duration of ICU stay was significantly longer for patients with respiratory failure [14.6 (±1.7) days versus 7.5 (± 2.6) days, p< 0.0001)]. None of the patients died. After hospital discharge, 30% patients reported post COVID-19 fatigue at 3-month follow up.

Conclusion

Our results showed that all of the critically ill adolescent patients with COVID-19 associated hypoxemic respiratory failure were unvaccinated and majority developed complications. These results further emphasize importance of COVID-19 vaccination efforts for adolescents.

Disclosures

All Authors: No reported disclosures
410. Acinetobacter baumannii Infections During COVID: Molecular Epidemiology and Outcomes at a Tertiary Hospital in Dallas
Authors: Khazi-Syed Afeefah F , Pybus Christine A , Clark Andrew E , Kim Jiwoong , Zhan Xiaowei , Desai Dhara , Barth Jackson , Greenberg David E
Published: November 2023

Background

Acinetobacter baumannii (AB) is a significant human pathogen that is frequently antibiotic resistant and has been associated with post-COVID-19 infections.

Methods

In this study, we performed whole-genome sequencing on AB isolates collected at an academic medical center in Dallas, TX between January 2020 and June 2021. We extracted clinical and laboratory data and analyzed both outcomes and molecular epidemiology of AB isolates in patients with and without COVID-19.

Results

Nineteen isolates collected from 17 AB-infected patients were included in this study. Most isolates were cultured from the respiratory tract (58%), followed by urine (16%), blood (10.5%), wound (10.5%), and catheter tips (5%). 4/17 patients were COVID-19 positive. The average Charlson Comorbidity Index at admission was lower for patients with COVID-19 (2.75) compared to counterparts (4.46). Using Fisher’s exact test, no statistical significance was observed in hospital events: ICU Admission (0.08), Ventilation (1.0), and Sepsis (0.23). The mortality rate during admission was 50% for COVID-19 patients and 23% for patients without COVID-19 (Odds Ratio: 3.33, p-value: 0.54, 95% CI: [0.32, 34.83]). All 19 isolates were carbapenem-resistant (CRAB) and multi-drug resistant (MDR) per definitions established by Magiarkos et al. 67% of isolates from COVID-19 patients were extensively-drug resistant (XDR) compared to 33% of isolates from non-COVID-19 patients. MIC data for cefiderocol was available for 9/19 isolates. Values ranged from 0.5 – 16 μM with 4/9 isolates being < 4 μM. Meropenem MIC values for all isolates were ≥ 64 μM. Many isolates contained at least one carbapenemase: OXA-72 (15/19), OXA-23 (3/19), OXA-95 (3/19), OXA-24 (1/19). MLST analysis revealed ST2 as the most common in all patients (15/19), followed by ST499 (3/19) and ST406 (1/19).

Conclusion

COVID-19 patients infected with AB trended towards a significant difference in mortality compared to AB patients without documented COVID-19 during the same period. All AB isolates were CRAB, and isolates from COVID-19 patients were more likely to be XDR.

Disclosures

David E. Greenberg, MD, University of Texas Southwestern Medical Center: Dr. Greenberg has numerous patents on PPMOs
411. Comparison of clinical outcomes between early and delayed transplantation after SARS-CoV-2 infection
Authors: Reum Kim A , Chang Eui Jin , Bae SeongMan , Jung Jiwon , Kim Min Jae , Chong Yong Pil , Lee Sang-Oh , Choi Sang-Ho , Kim Yang Soo , Kim Sung-Han
Published: November 2023

Background

Thera is limited data comparing the clinical outcomes between early and delayed transplantation after SARS-CoV-2 infection. We thus compared the clinical outcomes in solid organ transplant (SOT) and hematopoietic stem cell transplant (HCT) recipients who recently experienced SARS-CoV-2 infection depending on the timing after SARS-CoV-2 infection.

Methods

We retrospectively reviewed the medical records of adult patients who underwent SOT or HCT with a history of COVID-19 infection prior to transplantation at a tertiary hospital, Seoul, South Korea from January 2021 to August 2022. Patients transplanted within 3 months after COVID-19 infection were classified into the early transplantation group, and those transplanted after 3 months were classified into the delayed transplantation group.

Results

A total of 53 patients who underwent SOT and 28 patients underwent HCT with a history of COVID-19 infection prior to transplantation were reviewed. Of the SOT patients, 48 (91%) were classified in the early group (median 50.0, range 12.0-89.0 days) and 5 (9%) in the delayed group (median 105.0, range 93.0-117.0 days). In the early group, 45 patients were uneventful, 2 patients had rejection, and 2 patients died. In the delayed group, 4 patients were uneventful, and 1 patient. Of the HCT patients, 19 (68%) were identified in the early group (median 34.0, range 2.0-90.0 days) and 9 (32%) in the delayed group (median 102.0, range 92.0-188.0 days). In the early group, 15 patients were uneventful, 2 patients relapsed, and 2 patients died. In the delayed group, 4 patients were uneventful, 3 patients had acute graft-versus-host disease, 1 patient relapsed, and 1 patient died. A total of 6 patients died among SOT and HCT recipients, 5 of whom died due to bacteremia caused by multidrug-resistant bacteria and 1 from acute rejection. None of the patients who underwent SOT and HCT developed COVID-19 PCR re-positivity or COVID-19 compatible symptoms after transplant.

Conclusion

Our data suggest that the early transplantation after SARS-CoV-2 infection may be performed without increased risk of COVID-19-associated complications.

Disclosures

All Authors: No reported disclosures
412. Comparison of Outcomes in Pneumonia Patients Hospitalized with COVID-19 and Influenza in Connecticut, 2015-2020
Authors: Kim Daewi , Yousey-Hindes Kimberly
Published: November 2023

Background

Since the start of the Coronavirus Disease 2019 (COVID-19) pandemic, comparisons between hospitalized COVID-19 and influenza patients diagnosed with pneumonia are scarce. The objective of this study was to compare characteristics and outcomes among the two.

Methods

Cases for this analysis came from FluSurv-NET and COVID-NET, population-based surveillance platforms of the Connecticut Emerging Infections program for laboratory-confirmed influenza and COVID-19 hospitalizations. FluSurv-NET pneumonia cases occurred during 4 seasons (2015-16 – 2018-19), COVID-NET cases occurred during March-December 2020. Chart reviews were completed for all FluSurv-NET cases and a sample of all COVID-NET cases. Pneumonia was defined as having radiographic key terms on chest x-ray/CT and a discharge diagnosis of pneumonia in the medical record. Outcomes used for comparison included length of stay, intensive care unit (ICU) admission, death, and the following 3 discharge diagnoses: acute respiratory distress syndrome (ARDS), respiratory failure and sepsis.

Results

A total of 1361 pneumonia cases were identified, 652 from COVID-NET (COVID-19 pneumonia[C-19-pna]) and 709 from FluSurv-NET (Influenza pneumonia [I-pna]). C-19-pna cases had a longer median length of stay compared to I-pna cases (9 days vs 5 days; p< .001) and were more likely to have a diagnosis of acute respiratory failure (64% vs 26.3%, p< .001) across all adult age groups (≥18 years). C-19-pna cases were also more likely to die and have an ARDS diagnosis compared to I-pna cases (25% vs 6.1%, p< .001; 10.8% vs 1.7%, p< .001 respectively); this was observed across age groups ≥ 50 years (p < .001). C-19-pna cases ≥65 years were more likely to be admitted to the ICU compared to I-pna cases ≥65 years (35.8% vs 22.2%, respectively p< .001). Conversely, a greater proportion of I-pna cases ≥65 years had a sepsis diagnosis compared to C-19-pna cases in the same age group (24% vs 16.9%, respectively p< .001).

Conclusion

C-19-pna cases were younger, more obese and had more chronic metabolic disease than I-pna cases. I-pna cases were more likely to have chronic lung disease and be immunocompromised than C-19-pna cases. C-19-pna resulted in a significantly longer median length of stay, greater in-hospital mortality, and greater morbidity.

Disclosures

All Authors: No reported disclosures