bluuebunny/crossref_metadata_2025 huggingface dataset:
P-1775. Impact of a Stewardship Intervention Targeting Prolonged Antibiotic Use ( >15 Days) on Antibiotic Utilization, Resistance Patterns, and Costs
Authors: Heo Eunjeong , Lee Yeonju , Kim Hyung-Sook , Lee Ju-Yeun , Choi Seong Jin , Moon Song Mi , Kim Hong Bin , Kim Eu Suk , Song Kyoung-Ho
Published: January 2025

Background

Inappropriate antibiotic use, particularly prolonged courses, is a significant driver of antibiotic resistance. This study aimed to evaluate the impact of a targeted antimicrobial stewardship program (ASP) intervention on antibiotic utilization, resistance, and costs in patients receiving antibiotics for more than 15 days.

Monthly changes in DOT per 1000 patient-days over the span of 5 years

Methods

We employed an intervention targeted adult inpatients receiving antibiotics for more than 15 days since August 2018. An ASP team of pharmacists and infectious disease physicians implemented interventions through direct communication via messengers, visits, and EHR records. The intensive intervention period lasted seven months (August 2018 - February 2019) and continued alongside other stewardship activities afterward. We assessed the changes in antibiotic utilization (days of therapy per 1000 patient-days; DOT, length of therapy per 100 discharges; LOT), length of stay (LOS), resistance rate, and antibiotic costs before (January 2016 - July 2018) and after (August 2018 - January 2020) the intervention, using Interrupted time series analysis, retrospectively.

Results

A total of 193,492 patients were admitted and 587 interventions were conducted over the study period. The intervention resulted in a sustained decrease in DOT (-3.02 DOT; 95% CI: -3.71 to -2.33) and LOT (-1.32 LOT; -1.72 to -0.92). Additionally, a significant reduction was observed in the use of broad-spectrum antibiotics, including third-generation cephalosporins (-0.74 DOT; -1.1 to -0.38) and carbapenems (-0.48 DOT; -0.63 to -0.33). Furthermore, the significant upward trend (0.3% per month; 0.2 to 0.4) in the resistance rate of E. coli and Klebsiella to third-generation cephalosporins waned (-0.03% per month; 0 to -0.03). Finally, antibiotic costs decreased by $695.9 per 1000 admissions (-889.1 to -502.7). However, no significant change in LOS was associated with the intervention.

Conclusion

This study demonstrates that an ASP intervention focusing on optimizing antibiotic duration can effectively reduce the utilization of broad-spectrum antibiotics, the burden of resistance, and antibiotic costs in a hospital setting.

Disclosures

All Authors: No reported disclosures
P-1776. Impact of Sepsis Recognition Tools and Pharmacy Workflow on Sepsis Management and Outcomes
Authors: Abdelmahab Salma , Dubrovskaya Yanina , Marsh Kassandra , Merchan Cristian , Siegfried Justin , Papadopoulos John , Smalley Samantha
Published: January 2025

Background

CDC 2023 Hospital Sepsis Program Core Elements prioritizes protocolized care, timely and effective antibiotics and de-escalation. At NYULH, robust sepsis tools integrated into Epic since July 2021 include the Sepsis Indicator Column on the Emergency Department (ED) Track Board for patient identification, nurse and physician-driven Best Practice Advisory (BPA), ED Sepsis Quick List for antimicrobial orders, and Sepsis Guidelines. Sepsis antibiotics in the ED are administered as IV push over 3 minutes followed by IV piggyback since March 2021.

Methods

We conducted a retrospective review of adult patients with community-onset sepsis and confirmed bacteremia who presented to ED between 9/2022 and 5/2023. The primary outcomes were time to antibiotics and the percent of patients with ineffective empiric antibiotics. Secondary outcomes included time to de-escalation and sepsis outcomes. As a process measure, we evaluated sepsis guidelines adherence and pharmacy interventions.

Results

During 9/2022 to 8/2023, 1682 ED sepsis cases were recorded, and 22% had bacteremia. Among 109 included patients, median Charlson Comorbidity Index was 6 (IQR 3-8) and Pitt bacteremia score 0 (IQR 0-1). Median time from ED sepsis recognition to antibiotic verification by pharmacy was 9 min (IQR 0-27) with median time to antibiotic administration of 29 min (IQR 15-50). Ineffective initial therapy occurred in 11% of cases with median time to effective antibiotics at 24 h. De-escalation was seen in 84% of cases with median time of 2 days for both MRSA and atypical coverage discontinuation and 4 days for Pseudomonas coverage. Initial therapy adhered to guidelines in 70.6% of cases, and deviation primarily occurred due to the administration of vancomycin in the absence of MRSA risk factors. Antibiotic-related pharmacy and stewardship (ASP) recommendations were made in 40% of patients while in ED and 96% of patients during hospital stay. In-hospital mortality, ICU admission, 30-day infection related re-admission and C. difficile infection within 6 months were 8.3%, 42.2%, 8.3% and 1.8%, respectively.

Conclusion

The integration of Epic sepsis recognition tools with ASP and pharmacy workflows led to high rates of timely and effective antibiotic administration in the ED and de-escalation during hospitalization.

Disclosures

All Authors: No reported disclosures
P-1778. Factors Underlying Infection-Related Mortality: Learnings from an Academic Institution with Antimicrobial Stewardship Practices
Authors: Issac Aleena , Sreeraj V , Puthoor Deljo , Adarsh A K , Sabu Tabitha Merium , Prathibha V K , Geethalakshmi V , Thomas Maridas Tom , Joseph Thomas , Mohan Gopika P , Johnson Mariya , Thomas Alga P , Santhosh Sneha , Lubaina P R
Published: January 2025

Background

Limited research has explored the efficacy of Antimicrobial Stewardship (AMS) interventions in reducing Infection-Related Mortality (IRM). This study aims to evaluate the impact of AMS practices on IRM and its associated factors.

Methods

A retrospective case-cohort study was conducted on inpatients who expired during hospitalization between May 1, 2022, and April 30, 2023, in a tertiary hospital. The case group comprised patients with infection-related mortalities, defined as deaths caused by any potential life-threatening infection, such as sepsis, pneumonia, infective endocarditis, peritonitis, encephalitis, abscesses, meningitis, empyema, pyelonephritis, and cholecystitis. Patients who expired without such infections constituted the control group. The primary exposure variable was adherence to AMS practices during the hospital stay. A Binomial Logistic Regression model was employed to identify risk factors (e.g., age, sex, recent multi-drug-resistant organism culture positivity) for infection-related mortality in both AMS-adherent and non-adherent groups.

Results

Among the 1225 total mortalities, 41.3% (=506) represents the case group. It was found that only recent multi-drug resistant organism culture positivity has a significant association with AMS adherence (odds ratio =0.328 & p =0.003). The statistical modeling of both groups depicted in figure 1&2.

Conclusion

Despite adherence to AMS practices, the presence of multi-drug-resistant organism culture positivity predisposes individuals to infection-related mortality.

Disclosures

All Authors: No reported disclosures
P-1780. Compliance Assessment of Antimicrobial Stewardship Program Activities within a Long Term Acute Care (LTAC) System
Authors: Hobbs Athena L V , VanCura Jennifer , Shea Katherine M
Published: January 2025

Background

Long Term Acute Care (LTAC) hospitals encounter a unique challenge in that despite fewer resources, they are required to comply with CMS and TJC antibiotic stewardship programs (ASPs) Conditions of Participation for hospitals. In June 2023, completion of an antimicrobial stewardship gap analysis survey was required throughout a national LTAC system to assess compliance and identify areas for improvement.

Methods

This was a 173 question, multi-site survey consisting of four phases with questions about implementation of progressively more difficult ASP interventions; regulatory (n=55 questions), basic (n=45 questions), intermediate (n=41 questions), and advanced (n=32 questions) interventions. Compliance was defined as a “yes” or a “not-applicable” response. A chi-square test was used to assess responses between different phases and average monthly acute patient days (APD).

Results

All 26 LTAC hospitals in the system completed the survey. The average compliance within all hospitals was 84% for phase one, 86% for phase two, 73% for phase three, and 62% for phase four. There was a significant difference in compliance between the phases (p< 0.0001) and based on APD per facility (Table 1, p< 0.0001). When assessing compliance with individual questions, a total of 13 questions (7.5%) had low compliance (less than 50%), which were flagged as particular areas for opportunity. Low compliance questions were grouped based on CDC Core Elements, six of which pertained to Action, three to Tracking, two to Education, and one each to Reporting and Hospital Leadership Commitment. As expected, the majority (n=8) of low compliance questions were in phase four.

Conclusion

This standardized survey was used as a tool to ensure regulatory compliance and identify additional opportunities for ASP advancement in a system of LTACs. Overall, we report high rates of compliance, especially in the regulatory phase 1, likely due to support from a System ASP and dedicated ID pharmacist. Our evaluation suggests that smaller or less busy facilities with fewer average monthly APDs may have more resources to ensure compliance with ASP initiatives. It is important to recognize that some phase 4 advanced ASP interventions may not be feasible in the LTAC setting.

Disclosures

Katherine M. Shea, PharmD, BCIDP, T2 Biosystems: Advisor/Consultant
P-1782. Antimicrobial Stewardship Program Resourcing across Hospitals over Time: A Repeated Cross-Sectional Study
Authors: Leung Valerie , Thomas Sera , Brown Kevin , Daneman Nick , Schwartz Kevin , Langford Bradley J
Published: January 2025

Background

Antimicrobial stewardship programs (ASP) are a crucial component of an overarching One Health approach to mitigate antimicrobial resistance (AMR). Adequate resourcing is a predictor of success for hospital ASPs. To understand the progress of hospital ASPs, we conducted periodic surveys tracking the level of resourcing over time.

Methods

Public Health Ontario’s Hospital ASP Landscape survey is conducted every 2-3 years, beginning in 2016 and most recently in 2023. This online survey is disseminated using a targeted distribution list to reach antimicrobial stewardship practitioners in acute care and complex continuing care & rehabilitation hospitals. Descriptive analysis was performed at an aggregate level and by hospital type. Full-time equivalent (FTE) staffing ratios were compared to Association of Medical Microbiology and Infectious Disease (AMMI) Canada recommendations for 2021 & 2023.

Results

In 2023, the survey response rate was 70% (90/129) of hospitals with 98% reporting the presence of a formal ASP. Response rate of previous surveys ranged from 55-78%. In 2023, the proportion of organizations reporting any designated resources to support their program was 60%; this was 50% in 2016, 57% in 2018 and 53% in 2021. The proportion of hospitals meeting the AMMI resourcing recommendations for physician and pharmacist FTE in 2023 was 10% and 21% compared with 7% and 13% in 2021. For teaching hospitals, the average physician FTE/100 beds was 0.045 in 2023 and 0.044 in 2021; the average pharmacist FTE/100 beds was 0.183 in 2023 and 0.173 in 2021. For large & medium hospitals, average physician FTE/100 beds was 0.049 in 2023 and 0.046 in 2021; the average pharmacist FTE/100 beds was 0.261 in 2023 and 0.210 in 2021. For small & rehabilitation hospitals, the average physician FTE was 0.009 in 2023 and 0.024 in 2021; the average pharmacist FTE was 0.113 in 2023 and 0.071 in 2021. (Table 1)

Conclusion

The proportion of hospitals reporting any designated resources to support their ASP is relatively unchanged since 2016. Resource allocation continues to be below national recommendations for physician and pharmacist FTEs, especially for smaller institutions.

Disclosures

All Authors: No reported disclosures
P-1803. Why We Do What We Do: A Survey of ID Providers About Oral Antibiotics
Authors: Witt Lucy S , Suchindran Sujit , Winkler Marisa
Published: January 2025

Background

Multiple studies have shown the efficacy of oral antibiotics for serious infections. Despite this, many infectious disease (ID) providers continue to solely use intravenous (IV) antibiotics. To understand current practices among ID providers in our healthcare system, we conducted a survey to observe practice patterns, comfort level, and beliefs around oral antibiotics.Table 1.Respondent Demographics and Responses

Methods

Our survey was distributed via email to 137 local ID providers at nine hospitals. The survey included questions about demographics, practice characteristics, and comfort with as well as barriers to prescribing oral antibiotics. Also included were five clinical cases for which respondents were asked to choose definitive therapy from a selection of IV and oral options. Based on responses, providers were classified as either high- or low-oral antibiotic prescribers (HOAP or LOAP). Categorical variables were analyzed using chi-square or Fischer’s exact test as appropriate.Table 2.Respondent Answers to Clinical Cases

Results

A total of 60 clinicians (44%) completed our survey. 87% were academic affiliated (52/60), while 13.3% (8/60) identified as private practice (Table 1). Half of respondents were categorized as LOAP. All respondents chose an oral step-down therapy for a case of E. coli bacteremia, while only one provider chose an oral option for step-down therapy for left-sided native valve endocarditis caused by E. faecalis (Table 2). 73.3% of HOAP chose oral antibiotics as definitive therapy for the case of an uncomplicated MSSA central line associated bloodstream infection compared to no LOAP (Table 2). The only statistically significant predictor of LOAP was type of practice; with all private practice providers classified as LOAP. HOAP were more likely to cite supervisor concerns with oral antibiotics as a barrier to prescribing oral antibiotics. Interestingly, similar numbers of HOAP and LOAP expressed they had no concerns about prescribing oral antibiotics.

Conclusion

In this survey of ID providers regarding oral antibiotics, most demographics did not predict HOAP or LOAP. Certain clinical scenarios, such as Gram-negative bacteremia, led to oral antibiotic use in both LOAP and HOAP. This information can be used by stewardship programs to target interventions to encourage oral antibiotic step-down therapy in LOAP.

Disclosures

Marisa Winkler, MD, PhD, Element Iowa City (JMI Laboratories) was contracted to perform services in 2023 for > 30 biotech and pharmaceutical companies: Grant/Research Support
P-1821. Patient-Derived Airway Organoids for Modelling and Modulating Rhinovirus infection
Authors: Merenda Alessandra , Ehsani Nilofar , Gkogkou Foteini , Pott Johanna , Bezhaeva Taya , Vries Robert G J , Boj Sylvia F
Published: January 2025

Background

HUB’s patient-derived organoids (PDOs) are unique in vitro 3D models derived from adult stem cells that closely resemble the architecture and physiology of the tissue of origin. PDOs established from the airway epithelium are instrumental in investigating the pathogenesis of respiratory infections as well as testing strategies to counter such diseases. Because in vivo pathogens attack the luminal surface of the epithelium, HUB has established monolayers from airway PDOs, where the luminal side is accessible for mimicking host-pathogen interactions.

Viruses such as Rhinovirus type 16 (RV16) are among the most common respiratory pathogens affecting the airway tract. As an entry receptor, RV16 recognises the intercellular adhesion molecule-1 (ICAM-1) on the surface of epithelial cells, making it an attractive target for inhibiting RV16 infection.

Methods

In this study we conducted experiments to assess the effect of an anti-ICAM-1 monoclonal antibody (mAb) on RV-16 infection. PDO-derived monolayers were pre-treated with different mAb concentrations before infection with RV16. Transepithelial electrical resistance (TEER) and monolayer integrity were monitored daily, and the viral titre was quantified at different time points post-infection (PI) by calculating the 50% tissue culture infectious dose (TCID50). Production of IP-10, an inflammatory cytokine released by the epithelium in response to infections, was also measured at 48 h PI.

Results

Our data showed that viral titre increased over time when no pre-treatment was applied, indicating that RV16 could propagate in airway PDO monolayers. A significant decrease in viral titre was observed in monolayers treated with the highest ICAM-1 mAb doses. Such an inhibitory effect on viral titre was accompanied by a total suppression of IP-10 release upon mAb treatment, suggesting a potential role for ICAM-1 inhibition in immune response modulation during RV16 infections.

Conclusion

Overall, this study not only revealed the value of PDO-derived monolayers as a platform for gaining insights into viral infection mechanisms but also demonstrated the potential of preclinically testing novel antiviral strategies. This findings have significant implications for the development of effective treatments for respiratory infections.

Disclosures

All Authors: No reported disclosures
636. Pneumocystis Pneumonia Outcomes in Solid Organ Transplant Recipients and Patients Living with HIV: A Population-Based Study Over 20 Years (2002-2022) in Ontario, Canada
Authors: Lo Carson , Fridman Daniel , Kwong Jeffrey , Hosseini-Moghaddam Seyed M
Published: January 2025

Background

While it is well established that HIV-positive and non-HIV immunocompromised patients are susceptible to Pneumocystis pneumonia (PCP), comparing PCP outcomes between patients with different underlying immunocompromising conditions is critically important to optimize chemoprophylaxis strategies.

Methods

In this population-based cohort, we determined contributing factors to 90-day all-cause mortality following PCP diagnosis among patients living with HIV (PLWH) and solid organ transplant recipients (SOTRs) hospitalized in Ontario, Canada between Apr/1/2002 and Dec/31/2022. We linked data from provincial health administrative databases using unique encoded identifiers and included all adult patients hospitalized with PCP based on diagnostic codes from hospital discharge abstracts. We used logistic regression models to estimate unadjusted and adjusted odds ratios (uOR and aOR) and 95% confidence intervals (95%CI) for the associations between underlying immunocompromising conditions and PCP outcomes.

Results

A total of 879 patients were hospitalized with PCP, including 121 SOTRs (13.7%) and 758 PLWH (86.2%). 90-day mortality rates were 19.8% in SOTRs and 13.2% in PLWH. In the unadjusted model, 90-day mortality was not significantly associated with organ transplantation (OR=1.58; 95%CI, 0.96-2.62) or HIV infection (OR=0.62; 95%CI, 0.38-1.03). Comparing HIV patients to liver SOTRs, liver SOTRs experienced higher mortality (uOR=8.54, 95%CI=3.11-23.46). In the adjusted model, liver transplantation was associated with an increased risk of 90-day mortality (aOR=4.36; 95%CI, 1.40-13.59). Among SOTRs, in the unadjusted analysis, liver transplant recipients had an increased risk of 90-day mortality (uOR=9.18; 95%CI, 3.00-28.09).

Conclusion

Among SOTRs, liver transplant recipients are at particularly higher risk of mortality following PCP diagnosis. Our findings may prompt a re-evaluation of current PCP prophylactic strategies in liver transplant patients.

Disclosures

All Authors: No reported disclosures
637. Stable bloodstream infection rates despite rising colonization: Insights from a hospital system using in-house PCR screening for Candida auris
Authors: Rosa Rossana M , Rosello Gemma , Manzanillo Kelley , Martinez Octavio , Abbo Lilian M
Published: January 2025

Background

Candida auris (C. auris) is spreading in the United States at a rapid pace. At our facilities, risk-based admission screening for colonization with C. auris using PCR has been a cost-effective tool for guiding infection prevention (IP) practices. We describe the observed trends in incidence of detection of colonization present on admission and hospital-onset cultures at our facilities since deploying in-house PCR testing.Figure 1:A. Candida auris 2-step screening process B: Sample Candida auris screening questionnaire

Methods

Study conducted at an integrated healthcare system in Miami, Florida, consisting of a large tertiary care center, three community hospitals and one inpatient rehabilitation hospital. The study period went from August 2021 to December 2023. In August 2021 we implemented admission screening for C. auris with PCR performed in-house. Screening criteria, testing and isolation protocols are presented in Figure 1A-B. Patients testing negative on admission were not routinely re-tested. Joinpoint regression was used to estimate changes in the incidence rates of C. auris newly present on admission surveillance (CA-POA), hospital-onset (HO) clinical cultures from any source and bloodstream infections (BSI). Definitions used are presented in Table 1.

Results

We identified 292 patients with CA-POA, for a crude rate of 9.1 per 10,000 patient-admissions. Between August 2021 and June 2023, the monthly percent change in the incidence rate of CA-POA significantly increased by 4.9% (95% CI 2.6-7.2; p< 0.01) and decreased by 17.4% (95% CI -30.8 to -1.5; p=0.03) between July 2023 and December 2023. There were 124 patients with HO clinical cultures, including 72 hospital-onset BSIs, for a crude BSI rate of 0.59 per 10,000 patient-days. There were no statistically significant changes in the trends of incidence of these infections during the study period. Incidence rates for the different outcomes of interest are displayed in Figure 2A-2D.

Incidence rates for outcomes of interest

Conclusion

We found that despite rising rates of patients newly identified as already colonized with C. auris upon admission, the rates of HO cultures and most importantly of bloodstream infections have remained stable at our facilities. Admission screening using in-house PCR can lead to a more precise deployment of IP resources, mitigation of horizontal transmission and raising public health awareness on spread occurring outside hospitals.

Disclosures

All Authors: No reported disclosures
P-1898. Reduction of Blood Culture Contamination Rates and Associated Healthcare Costs Through Implementation of Certified Phlebotomist-Drawn Blood Cultures at a Community Teaching Hospital
Authors: Mishra Shikha , Valdez Michael , Mejia Danna , Vickers Adonica , Johnson Royce H , D’Assumpcao Carlos M , Kuran Rasha , Fang Michelle
Published: January 2025

Background

Blood culture contamination (BCC) is a drain on healthcare resources, with clinical implications such as delayed diagnosis. At Kern Medical (KM), a safety net teaching hospital in Bakersfield, CA, BCC in some areas had continually exceeded the 3% recommended maximum, with 59% of new positive blood cultures per patient representing contamination in early 2023. In response, a quality improvement initiative was launched in 2023 to reduce BCC through certified phlebotomist-drawn blood cultures (PDBC).

Methods

A retrospective cohort study was conducted to assess the clinical and financial impact of BCC reduction through PDBC. Any blood culture with growth of a common commensal organism during the first 2 months of 2024 was reviewed for attributable hospital length of stay (LOS) and ED, laboratory, procedure and pharmacy resources associated with BCC. Patients were excluded if blood culture growth was indicative of true infection or if the patient was still admitted at the time of review or transferred to another hospital. Costs were calculated based on literature and institution-specific charges.

Results

BCC was identified in 35 patients over the study period, with coagulase-negative Staphylococcus (CoNS) species isolated in 71% of patients and polymicrobial growth in 34% of cases. Forty percent of patients had been admitted with a non-infectious principal diagnosis, and 14% of patients had been discharged at the time of blood culture positivity and were readmitted or called back to the ED for management of possible bacteremia. Transthoracic echocardiogram had been performed for assessment of infective endocarditis in 34% of all patients and 40% of patients with CoNS prior to final identification of the blood culture isolate(s), which required 5.5 days on average. Sixty-six percent of patients received vancomycin, including 43% of patients admitted for noninfectious diagnoses. Twenty-three percent of patients had new or additional LOS due to BCC, with an average of 1.4 days. The average additional cost associated with a BCC event at KM was $2931.

Conclusion

Given that BCC rates decreased at KM from 4.6% with non-certified phlebotomy staff collection compared to 1.2% with certified phlebotomist collection, introduction of PDBC resulted in an estimated cost avoidance of $778,596 per year.

Disclosures

All Authors: No reported disclosures
645. Rapid Versus Conservative Tuberculosis De-isolation Policy Impact Assessment: Province-wide Retrospective Review of 2017-2020, British Columbia, Canada
Authors: Alhekail Othman Zeyad O , Singh Navneet , Hansen Elisabeth , Johnston James , Cook Victoria J , Connors William J
Published: January 2025

Background

Tuberculosis (TB) remains a significant global health threat. Upon diagnosis, patients with pulmonary TB are required to undergo specific isolation precautions to prevent further disease transmission. Current practice typically mandates isolation for at least two weeks post-diagnosis, with extended periods for those found to have positive sputum acid fast bacilli (AFB) smear results. The most recent Canadian Tuberculosis Standards (2022) and other international groups have suggested that the decision to discontinue TB airborne isolation should be made based on length of effective treatment rather than bacteriological endpoint (i.e. Sputum AFB results and culture results).

Sputum-based (Conservative) de-isolation determination

Methods

This is a retrospective analysis of newly diagnosed drug susceptible pulmonary TB cases between 2017 and 2020 in British Columbia, Canada. By comparing rapid (defined in Table 1) and conservative (defined in Table 2) isolation determination policies, and estimating recommended isolation periods for each, we aim to quantify isolation periods and assess whether adopting the rapid de-isolation determination protocol would significantly reduce airborne isolation durations.

Treatment based (Rapid) de-isolation determination

Results

We identified a total of 952 cases with drug susceptible pulmonary TB. Among the 952, the mean age was 54 years (SD 22). With regards to sputum AFB smear status, 351 (37%) had a negative AFB smear at baseline and 355 (37%) remained sputum AFB smear positive for over 90 days (did not meet conservative de-isolation criteria). Among the remaining 246 cases, 82 converted their AFB smear status to negative within less than 28 days from the first positive sputum AFB smear sample. Based on sputum AFB smear status alone, we found that rapid de-isolation determination would have resulted in a median of 10 (IQR 62) fewer days of isolation.

Conclusion

Adopting a rapid de-isolation determination protocol would result in substantial reductions of isolation durations for patients with drug-susceptible pulmonary TB. Updated evidence-based TB de-isolation guidelines emphasizing effective treatment duration, such as the new recommendation from the National TB Coalition of America, can significantly reduce patients' harm and health system costs of unnecessarily prolonged isolation.

Disclosures

All Authors: No reported disclosures
P-1948. Differential Patterns of Protection from Natural Infection against SARS-CoV-2 Reinfection in the Pre-Omicron and Omicron Eras
Authors: Chemaitelly Hiam , Ayoub Houssein H , Abu-Raddad Laith J
Published: January 2025

Background

SARS-CoV-2 infection protection against reinfection can be compromised by emergence of immune-evasive variants.

Methods

A national, matched, test-negative, case-control study was conducted on Qatar's population between February 5, 2020-February 12, 2024, to assess the level and durability of protection offered by omicron infection against omicron reinfection, compared to the protection provided by pre-omicron infection against pre-omicron reinfection. Subgroup and sensitivity analyses were performed.

Results

Effectiveness of pre-omicron infection against pre-omicron reinfection was 81.1% (95% CI: 80.4-81.8%). Effectiveness was 81.3% (95% CI: 80.6-82.1%) in the first year after the previous infection and 79.5% (95% CI: 77.1-81.5%) thereafter. In contrast, effectiveness of omicron infection against omicron reinfection was only 53.6% (95% CI: 52.1-55.0%) and demonstrated rapid waning. Effectiveness declined from 81.3% (95% CI: 79.6-82.9%) within the first 3-6 months post-infection to 59.8% (95% CI: 57.8-61.7%) in the subsequent 3 months, further dropping to 27.5% (95% CI: 22.7-32.0%) within the next 3 months, and reaching only 4.8% (95% CI: -2.7-11.8%) after one year. Effectiveness against symptomatic reinfection and for both unvaccinated and vaccinated individuals mirrored these patterns. Effectiveness of infection in preventing severe, critical, or fatal COVID-19 upon reinfection remained nearly 100% in both pre-omicron and omicron eras, showing no signs of waning over time.

Conclusion

SARS-CoV-2 natural immunity shows a dynamic interplay between host immunity and viral evolution, resulting in contrasting reinfection patterns before and after omicron emergence. These patterns suggest a shift in evolutionary pressures, with intrinsic transmissibility driving adaptation pre-omicron and immune escape becoming dominant post-omicron.

Disclosures

All Authors: No reported disclosures
P-2002. Incidence and Risk of COVID-19 Hospitalization Among Unvaccinated Children
Authors: Zerbo Ousseny , Timbol Julius , Hansen John R , Goddard Kristin , Layefsky Evan , Ross Pat , Fireman Bruce , Nguyen Dao , Greenhow Tara L , Klein Nicola P
Published: January 2025

Background

Although most children often experience mild illness following SARS-CoV-2 infection, some can develop severe disease requiring hospitalization, admission into an intensive care unit (ICU), or die.

Methods

Children aged 0 - < 18 years, members of Kaiser Permanente Northern California (KPNC), an integrated healthcare organization with more than 4 more million members, were followed from March 1, 2020, until the earliest occurrence of: chart-confirmed COVID-19 hospitalization, disenrollment from KPNC, age 18 years, receipt of COVID-19 vaccine, death, or study end (December 31, 2022). We calculated the incidence rate of hospitalization by SARS-CoV-2 variant period and by age group. We determined risk factors for hospitalization using Poisson regression. We also conducted descriptive analyses of hospitalized cases.

Results

Among 1,107,799 children, 423 were hospitalized for COVID-19 during follow-up. The incidence of hospitalization increased with each new SARS-CoV-2 variant and was highest among children aged < 6 months. Among the < 6-month-olds, the incidence rate per 100,000 person-months was 7 during pre-delta, 13.3 during delta and 22.4 during omicron. Black (RR= 2.05, 95% CI: 1.33 – 3.16) and Hispanic children (RR = 1.82, 95% CI: 1.34 – 2.46) and children with any comorbidities were at high risk of hospitalization (RR = 3.81, 95% CI: 2.94 – 4.95). Overall, 20.3% of hospitalized children were admitted to an intensive care unit (ICU), but ICU admission was 36.1% among 12 - < 18-year-olds. The majority of ICU admits (91.8%) had no comorbidities.

Conclusion

Children too young to be vaccinated had the highest incidence of COVID-19 hospitalization, while adolescents had the highest proportion of ICU admissions. To prevent severe disease in children and adolescents, everyone eligible should be vaccinated.

Disclosures

Nicola P. Klein, MD, PhD, CSL Seqirus: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support
P-5. Human Papillomavirus Vaccination Coverage Among Girls and Boys in the United States: A Birth Year Cohort Analysis of the National Immunization Survey-Teen, 2016–2022
Authors: Meyer Sarah , Nmn Yankey David , Elam-Evans Laurie , Pingali Sandy , Stokley Shannon K , Singleton James A , Nyika Ponesai
Published: January 2025

Background

Human papillomavirus (HPV) causes approximately 37,000 cancers in the United States annually. HPV vaccine, recommended by CDC at age 11 or 12 years, prevents more than 90% of HPV-attributable cancers. We aim to identify coverage gaps to guide targeted interventions.

Methods

We conducted a birth cohort analysis among adolescents born 1999-2009 using National Immunization Survey-Teen (NIS-Teen), a random-digit dialed telephone survey which also collects vaccination data from providers. We analyzed 131,553 records from 2016 to 2022 NIS-Teen data to determine: 1) trends in coverage with ≥ 1 HPV vaccine dose before age 13 years (on-time initiation), 2) cumulative coverage from 13 to 17 years (catch-up), 3) on-time HPV vaccination up to date status (all recommended doses before age 13 years), 4) missed vaccination opportunities (provider visits before age 13 years where HPV unvaccinated adolescents received other recommended vaccine but not HPV vaccine), and achievable coverage if HPV vaccination opportunities were not missed. Regression analysis provided the average percentage increase in coverage across birth cohorts. Kaplan-Meier method provided cumulative HPV vaccination coverage from age 13 to 17 years, stratified by birth cohorts.

Results

HPV vaccination coverage before 13 years increased from 27.0% among adolescents born in 1999 to 69.8% among those born in 2009. Coverage for girls increased from 37.4% to 73.4%; coverage for boys increased from 16.9% to 65.9%. Overall, coverage increased from 33.1% before age 13 years to 74.9% before age 18 years. HPV vaccination up to date status increase from 10.3% among adolescents in 1999 to 42.2% among those born in 2009. Among the 38,568 (29.3%) who had not received any HPV vaccination, 31,513 (82.5%) had ≥ 1 missed HPV vaccination opportunity. The potential achievable vaccination coverage if opportunities were not missed was 94.8%.

Conclusion

Coverage with on-time HPV vaccination and HPV up to date increased by birth cohort among adolescents born 1999–2009 but remains suboptimal. Low uptake increases risk for HPV cancers. Opportunities for HPV vaccination before age 13 years are being missed and can be reduced by effective provider recommendations for HPV vaccination and by administering all recommended vaccines during the same visit.

Disclosures

All Authors: No reported disclosures
P-2007. Prognosis of COVID-19 Patients with Preexisting Dementia: Findings from a Comprehensive Multicenter Propensity-Matched Cohort Study in Brazil
Authors: Chagas Victor Schulthais , Ramos Lucas Emanuel F , Pires Magda Carvalho , da Silva Rosa Patryk Marques , Reis Gomes Virginia Mara , de Alvarenga Joice Coutinho , Meira Karina Cardoso , Romero Aliberti Márlon Juliano , Camargos Bicalho Maria Aparecida , Marcolino Milena S
Published: January 2025

Background

Despite the increasing knowledge about Covid-19 manifestations, there is still a lack of studies regarding the impact of the pandemic in patients with dementia. This study aims to evaluate clinical characteristics and outcomes of patients with dementia hospitalized due to Covid-19.

Methods

This retrospective observational study is part of a multicentric cohort that analyzed data from 38 hospitals from 19 Brazilian cities. Patients were included if they were ≥ 60 years old and hospitalized due to laboratory-confirmed Covid-19 between March 2020 and March 2022. Demographics data, clinical characteristics at admission, laboratory findings and outcomes were collected. Patients were matched in a propensity score analysis according to the presence or absence of dementia and stratified by age, sex, number of comorbidities, hospital, and year. A logistic regression model to estimate the propensity score was employed.

Results

Overall, 1,556 patients were included (median age 82 [interquartile range [IQR] 76-87 years], 58.7% women). A total of 405 had dementia diagnosed in medical records or by statement. Dementia group presented a higher prevalence of dyspnoea, cough, myalgia, headache, anosmia and ageusia compared to those without dementia. At hospital admission, dementia group had a higher prevalence of delirium (38.5% vs. 22.5%; p< 0.001), fever (49.4% vs. 41.7%; p=0.009), sensory impairment (57.3% vs. 25.6%; p< 0.001) and lower frequency of invasive mechanical ventilation support (23% vs. 37.8%; p< 0.0001). Palliative care was more frequent in dementia patients when compared to controls (39.8% vs. 19.7%; p< 0.001). There were no clinically relevant differences in laboratory results. Regarding outcomes, those with dementia had shorter length of stay in hospital (7.0 vs. 9.0 days; p=0.026), lower frequency of sepsis (17.0% vs. 24.0%; p=0.005) and kidney replacement therapy (6.4% vs. 9.8; p=0.002). There was no difference observed in hospital mortality between groups.

Conclusion

Clinical characteristics of Covid-19 differ between older patients with and without dementia. Dementia alone cannot explain the higher short-term mortality due to Covid-19. Other risk factors such as frailty and acute morbidity should be considered.

Disclosures

All Authors: No reported disclosures
P-2009. COVID-19 in Children with Hematological/Oncological Diagnoses – Exploring Reasons for Better Clinical Outcomes
Authors: Pinninti Swetha , Trieu Connie , Knoppova Barbora , Pati Sunil , Barley Avangelos , Latting Misty , Halima Sama , Ridings Alexis , Poulson Sydney , Whelan Kimberly , Bemrich-Stolz Christina , Britt William , Boppana Suresh
Published: January 2025

Background

The majority of COVID-19 infections in children, including in those with underlying hematological and oncological (Heme-Onc) diagnoses are mild with good outcome compared to adults. Postulated reasons include cross-protection from immunity against seasonal coronaviruses (HCoV’s), subdued inflammatory responses in children than in adults and differences in humoral and T-cell responses. The objectives of this study are to compare antibody responses against HCoV’s, anti-SARS-CoV-2 humoral, T-cell, and inflammatory profiles between Heme-Onc children with COVID-19 and control groups.

Methods

Binding IgG antibodies against Spike (S) of SARS-CoV-2, four HCoV’s (HKU1, OC43, NL63 and 229E), quantitative levels of 21 cytokines and 9 chemokines (multiplexed solid-phase electrochemiluminescence assay by Meso Scale Diagnostics/MSD) were compared among five cohorts: 1) children with Heme-Onc diagnoses and COVID-19 (n = 41) 2) healthy children with COVID-19 (n = 21) 3) adults with COVID-19 (n = 14) 4) children with multisystem inflammatory syndrome (MIS-C) [n = 23] and 5) healthy children without COVID-19 (n = 12). Additionally, T-cell responses against S and nucleocapsid (N) proteins of SARS-CoV-2 was assessed using ELISpot in Heme-Onc children a group of healthy children COVID-19.

Results

Anti-S antibodies and neutralizing antibodies against SARS-CoV-2 and HCoV were significantly lower in children in Heme-Onc and healthy children with COVID-19 compared to adults with COVID-19 (Figure 1). The concentration of eight pro-inflammatory cytokines and chemokines were significantly lower in Heme-Onc and healthy children compared to adults with COVID-19 and children with MIS-C. The responder T-cell frequency varied between 0 and 860/100,000 PBMC at study enrollment in children with Heme-Onc diagnoses.

Conclusion

In this single-center study, cross-protection from HCoV antibodies is an unlikely mechanism to explain mild COVID-19 in children, including in those with underlying hematological and oncological diagnoses. Subdued inflammatory responses to SARS-CoV-2 could be one of the factors for the mild COVID-19 disease phenotype in children.

Disclosures

Swetha Pinninti, MD, Moderna: Grant/Research Support|Pfizer: Grant/Research Support Suresh Boppana, MD, GSK: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support
P-2056. Modelling the Relative Vaccine Effectiveness of ARCT-154 versus BNT162b2 using Immunogenicity Data
Authors: Nguyen Van , Crepey Pascal , Pivette Jean Marie , Settembre Ettan , Rajaran Sankarasubramanian , Youhanna John , Ferraro Aimee , Chang Cheng , Van Boxmeer Josephine , Mould-Quevedo Joaquin F
Published: January 2025

Background

Vaccination has become an essential weapon in the global battle against COVID-19. While showing high effectiveness against the original Wuhan-Hu-1 strain and early SARS-CoV-2 variants, questions have surfaced regarding the duration of immunity they provide, especially with the emergence of new viral strains. The innovative self-amplifying (SA)mRNA vaccine, ARCT-154, has demonstrated clinical improvements in extending duration of immune response. Our objective was to compare the long-term efficacy of ARCT-154 with BNT162b2 in an adult population by assessing relative vaccine effectiveness (rVE) over time.

Methods

rVE was estimated using a two-step approach. First, we used geometric mean titer data (Days 29, 91, and 181 post-vaccination) from a phase 3 double-blind controlled clinical trial comparing the immune response of ARCT-154 and BNT162b2 against Wuhan-Hu-1 and Omicron BA.4/5 in healthy 18–77-year-olds (Japan Registry for Clinical Trials identifier: jRCT2071220080). We then incorporated this information into a published model correlating immunogenicity and efficacy to calculate the rVE of ARCT-154 versus BNT162b2 in symptomatic and severe cases.

Results

ARCT-154 exhibited an increasing rVE against symptomatic infection with Wuhan-Hu-1 over time, ranging from 2.11% on Day 29 to 8.51% on Day 181 post-vaccination. rVE against symptomatic Omicron infection was 0% on Day 29 but increased to 13.85% by Day 91 and 20.25% by Day 181. rVE against severe illness ranging from 1% to 4% for Wuhan-Hu-1 and 1% to 13% for Omicron across all measured time points.

Conclusion

ARCT-154 showed longer-lasting protection than BNT162b2 against symptomatic and severe COVID-19 for both the original Wuhan-Hu-1 and Omicron BA.4/BA.5 strains.

Disclosures

Van Nguyen, PhD, CSL Seqirus USA: Advisor/Consultant Pascal Crepey, n/a, CSL Seqirus USA: Advisor/Consultant Jean Marie Pivette, n/a, CSL Seqirus USA: Advisor/Consultant Ettan Settembre, n/a, CSL Seqirus USA: Stocks/Bonds (Private Company) Sankarasubramanian Rajaran, n/a, CSL Seqirus UK: Stocks/Bonds (Private Company) John Youhanna, n/a, CSL Seqirus USA: Stocks/Bonds (Private Company) Aimee Ferraro, n/a, CSL Seqirus USA: Stocks/Bonds (Private Company) Cheng Chang, n/a, CSL Seqirus USA: Stocks/Bonds (Private Company) Josephine Van Boxmeer, n/a, CSL Seqirus Amsterdam: Stocks/Bonds (Private Company) Joaquin F. Mould-Quevedo, PhD, CSL Seqirus USA: Stocks/Bonds (Private Company)
P-2073. COVID-19 Vaccine Effectiveness in Patients with Lung Cancer and Mesothelioma in the Omicron Era
Authors: Hosseini-Moghaddam Seyed M , Shepherd Frances A , Swayze Sarah , Kwong Jeffrey
Published: January 2025

Background

Since the Omicron variant emerged, uptake of booster doses of COVID-19 vaccines has gradually decreased both in the general population and among individuals at increased risk of severe COVID-19, such as patients with lung cancer. COVID-19 vaccine effectiveness (VE) has not been estimated in patients with lung cancer in the Omicron era.

Methods

In this test-negative design study using linked population-based cancer registry, health administrative, vaccination, and public health surveillance databases, we included all patients with active lung cancer or mesothelioma living in Ontario, Canada, who were tested for SARS-CoV-2 by RT-PCR from January 2, 2022, to August 31, 2023. We estimated VE against COVID-19-related severe outcomes (hospitalization or death) 7-179 days and ≥180 days following vaccination.

Results

During the study period, 13,622 patients with active lung cancer or mesothelioma underwent SARS-CoV-2 testing, with 1,371 (10.1%) positive. After exclusions, we analyzed 6,037 testing episodes, including 1,354 test-positive and 4,683 randomly selected test-negative episodes. Overall, COVID-19-associated hospitalization and mortality rates were 7.3% and 4.0%, respectively. Across both groups, 126/439 hospitalized patients (28.7%) and 116/5,598 non-hospitalized patients died (2.1%) (p=0.001). After multivariable adjustment, VE against severe COVID-19 was 56% (95%CI, 29%, 72%) 7-179 after vaccination and 10% (-45%, 44%) ≥180 days after vaccination.

Conclusion

Overall, COVID-19 VE against severe outcomes appears to be considerably lower for patients with active lung cancer or mesothelioma than the general population and decreases substantially beyond 180 days after vaccination. Our finding supports administration of COVID-19 booster doses in patients with lung cancer and mesothelioma every 6 months.

Disclosures

All Authors: No reported disclosures
P-2082. Shifting Susceptibility: MIC Assessment in RPMI versus MHB for Daptomycin Non-Susceptible MRSA Isolates
Authors: Bleick Callan , Vader Samantha , Lawal Aminah , Avery Shaylyn , Rybak Michael J
Published: January 2025

Background

Traditional minimum inhibitory concentration (MIC) screening, widely adopted in clinical microbiology labs, utilize Mueller-Hinton broth (MHB) to determine susceptibility breakpoints for bacterial organisms. The Roswell Park Memorial Institute (RPMI) medium supplemented with 5% Luria-Bertani Broth (LB) is commonly used in cell culture research to maintain cell health and improve viability. Additionally, it has been demonstrated to better mimic physiological conditions in humans. This study seeks to elucidate differences in MICs in 25 daptomycin non-susceptible (DNS) methicillin-resistant Staphylococcus aureus (MRSA) isolates.

Methods

Twenty-five DNS-MRSA bacterial strains were utilized. Variations in daptomycin MICs between RPMI and MHB were determined via triplicate microbroth dilution (MBD). After 24 hours, 50 µL of resazurin was added to each 96-well plate, and MICs recorded. Both RPMI and MHB were supplemented with 50 mg/L of calcium, and pH levels verified (pH 7.30-7.50). We assessed differences in MICs between RPMI and MHB using the Mann-Whitney U test (P < 0.05).

Results

The comparison of daptomycin MICs between RPMI and MHB revealed significant differences (P < 0.05) for the 25 DNS-MRSA bacterial strains examined. Specifically, in RPMI, MIC values ranged from 0.0125 to 2, whereas in MHB, MIC values ranged from 2 to 4. This suggests a notable impact of culture medium on the effectiveness of daptomycin against the tested bacterial strains. The study's findings underscore the importance of considering culture conditions when evaluating antimicrobial susceptibility, particularly for DNS-MRSA strains.

Conclusion

Our comparative assessment of MICs using RPMI versus MHB revealed statistically significant differences in antimicrobial activity. These differences warrant further investigation across additional strains and antibiotics. Notably, while the breakpoint for daptomycin is 1 mg/liter for S. aureus, our MICs done in RPMI indicated susceptibility of previously recorded DNS strains with a MIC < 1 mg/L according to CLSI guidelines. These findings highlight the importance of considering potential shifts in MICs based on testing media differences and suggest a need for reevaluation of traditional susceptibility testing methods.

Disclosures

Michael J. Rybak, PharmD, PhD, MPH, Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Advisor/Consultant|Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Grant/Research Support|Abbvie, Melinta, Sionogi, Merck, T2Biosystems: Speaker