bluuebunny/crossref_metadata_2025 huggingface dataset:
P-582. Long-term effectiveness and tolerability of Dolutegravir/Lamivudine in Korea: 3 year follow up
Authors: Seong Jae Eun , Ahn Sangmin , Han Min , Lee Yongseop , Ah Lee Jung , Ho Kim Jung , Ahn Jin Young , Jeong Su Jin , Su Ku Nam , Choi Jun Yong , Yeom Joon-sup
Published: January 2025

Background

Many studies have revealed the real-world effectiveness and tolerability of Dolutegravir/Lamivudine (DTG/3TC). However, most studies were conducted in Western countries, and data from Asian countries are still lacking; in particular, the results from long-term use have not been reported in Asian countries. As DTG/3TC has been introduced and is becoming increasingly widespread in Asia, it is necessary to investigate the maintenance rate, reasons for discontinuation, long-term effectiveness, and metabolic parameter changes.

Methods

We performed a retrospective cohort study with adult people with HIV treated with DTG/3TC specific combination at a tertiary hospital in Korea. Among them, those who were followed up for more than 36 months were included. Both treatment-naïve and those who switched from other antiretroviral therapies to DTG/3TC were included. Baseline characteristics, DTG/3TC maintenance rates, effectiveness, and metabolic parameters changes over 36 months were investigated.

Results

From July 2020 to April 2024, 305 people with HIV started DTG/3TC. Among them, 134 people with HIV followed for more than 36 months were included (16 treatment-naïve and 118 switching). Most were male (N=126, 94%), and the median age was 45.5 years. There were no cases of switching from DTG/3TC to other ARTs during the 36-month follow-up after starting DTG/3TC. All of the treatment-naïve group maintained HIV RNA < 50 copies/mL from 6 to 36 months after starting DTG/3TC. The rate of HIV RNA < 50 copies/mL at the 36 months in the switching group was 99.2% (117/118). In the treatment-naïve group, CD4 cell count increased from a median of 494 cells/uL at baseline to 795 cells/uL at 36 months (p=0.005). During the 36-month follow-up, there were no significant changes in lipid profile and body weight in both treatment-naïve and switching groups except for an increase in HDL cholesterol in the switching group (from median 45 mg/dL at baseline to median 49 mg/dL at 36-month, p=0.001).

Effectiveness of Dolutegravir/Lamivudine for the treatments-naive and switching groups

Conclusion

In our long-term follow-up study conducted in South Korea, DTG/3TC worked effectively in viral suppression and CD4 count maintenance, and no significant adverse effects were observed on lipid profiles and body weight gain in both treatment-naïve and switching groups.

Tolerability of Dolutegravir/Lamivudine for the treatments-naive and switching groups

Disclosures

All Authors: No reported disclosures
P-591. Injecting Hope: A Long-Acting Injectable Program to Treat HIV Using Cabotegravir/Rilpivirine at a Ryan-White Funded HIV Clinic
Authors: Vega Victoria , Aragon Kelsea , Azimi Sara , Snyder Jeremy , Iandiorio Michelle , Jakeman Bernadette
Published: January 2025

Background

Cabotegravir/rilpivirine (CAB/RPV) was approved as the first long-acting injectable (LAI) antiretroviral (ART) switch regimen. While clinical trials demonstrate CAB/RPV safety and efficacy, access and clinical workflow challenges have hindered implementation in practice. The objective of this study was to describe use of CAB/RPV in a Ryan-White funded clinic.

Methods

A retrospective chart review was conducted on the first 40 patients, aged > 18 years, referred to the pharmacist CAB/RPV clinic. Referral criteria included HIV-1 RNA < 50 copies/mL and no baseline CAB/RPV resistance.

Results

The majority of patients were male (90%) and white (85%), with a median age of 48 years (range 20-79), BMI of 28 (range 21-48), and use of 6 non-HIV medications (range 0-25). 73% had prior non-adherence to appointments. A DNA archive genotype was obtained for 8 patients due to lack of data. 4 patients had baseline RPV mutations, 2 were identified post-DNA archive genotyping. 14 patients did not start CAB/RPV (6 opted against, 4 had resistance, 2 had insurance denial, 1 had a high copay, 1 moved). The age of those who opted against LAI was not different from those who switched (p=0.2). Pharmacists devoted significant time to patient evaluation and coordination. 26 patients started CAB/RPV; 50% covered by medical benefit, 46% aged > 50 years. Psychological stress/stigma of daily ART was the main reason for switching. 1 patient travelled 228 miles for injections and 1 was homeless. By month 12, 24 patients (92%), including 1 unhoused patient, maintained control on CAB/RPV. No HBV reactivations occurred. 1 patient discontinued due to soreness. 1 patient (BMI < 30, no baseline resistance) had ongoing viremia of < 200 and was switched back to oral ART; post-CAB/RPV DNA archive genotype revealed no mutations.

Conclusion

CBV/RPV offers a switch option for patients, even those with unstable housing or history of missed appointments. Older patients on multiple medications still sought LAI CAB/RPV. Our experience shows that DNA archive genotype testing was valuable in guiding treatment decisions for patients lacking prior data and that proper evaluation and coordination identifies appropriate patients for CAB/RPV, resulting in high continuation rates

Disclosures

All Authors: No reported disclosures
P-592. Rapid initiation of antiretroviral therapy under the Treat-All policy reduces loss to follow-up and virological failure in routine HIV care settings in China: A retrospective cohort study (2016-2022)
Authors: Xia Huan , Ma Ping
Published: January 2025

Background

Following the World Health Organization's guidelines for rapid antiretroviral therapy (ART) initiation [≤ 7 days after human immunodeficiency virus (HIV) diagnosis], China implemented Treat-All in 2016 and has made significant efforts to provide timely ART since 2017. The purpose of this study was to evaluate the effects of rapid ART on loss to follow-up (LTFU) and virological failure compared to those of delayed ART.

Trends in rapid ART initiation (A) and time from HIV diagnosis to treatment initiation (B) from June 2016 to December 2022.

Methods

This research included newly diagnosed HIV-infected adults from Tianjin, China between June 2016 and December 2022. Our primary outcome was LTFU (more than 90 days after the prior drug pick-up or clinical visit) at 12 months following enrollment. The secondary outcome was 12-month virological failure after treatment initiation. Furthermore, Kaplan-Meier estimators were utilized to examine the LTFU time for rapid and delayed ART initiation. Moreover, the correlation between rapid ART initiation and LTFU was evaluated using univariate and multivariable Cox regression, whereas the relationship between rapid ART and 12-month virological failure was investigated via logistic regression.

Kaplan-Meier survival curve of loss to follow-up in ART initiation group.

Results

A total of 896 (19.1%) of 4688 participants received ART ≤ 7 days post-HIV diagnosis. The rate of rapid ART initiation has increased from 7.5% in 2016 to 33.3% by 2022. Rapid ART was less common in persons with baseline CD4 counts of 350 - 499 and ≥ 500 compared to those < 200. Furthermore, it was also less prevalent in individuals who were diagnosed with tuberculosis or had an unknown route of HIV infection, while was more common in people who used Medicare/self-paid medications. The rapid ART group had an LTFU rate of 3.3%, as opposed to 5.0% in the delayed initiation group. Moreover, the rapid ART group had a much reduced virological failure rate (0.6% vs. 1.8%). Rapid ART individuals had a reduced likelihood of LTFU (adjusted hazard ratio: 0.65, 95% CI: 0.44 - 0.96) and virological failure (adjusted odd ratio: 0.35, 95% CI: 0.12 - 0.80).

Conclusion

Under China's Treat-All policy, rapid ART initiation reduced the risk of LTFU and virological failure. The real-world data indicated that rapid ART initiation is practicable and beneficial for Chinese people with HIV, providing evidence and guide for its widespread implementation and scaling up.

Disclosures

All Authors: No reported disclosures
P-594. Temperature Stability of BPL-1357, a BPL-Inactivated, Whole-Virus, Universal Influenza Vaccine
Authors: Banerjee Camellia , Giurgea Luca Tudor , Cervantes-Medina Adriana , Taubenberger Jeffery , Memoli Matthew J
Published: January 2025

Background

Influenza A viruses (IAV) present a constant public health threat from seasonal epidemics to potential pandemics. Currently approved vaccines perform poorly against mismatched seasonal influenza strains and are unlikely to provide any protection against a pandemic potential influenza such as avian influenza. We have developed a vaccine composed of four β-propiolactone-inactivated (BPL-inactivated) low-pathogenicity avian IAV subtypes (H1N9, H3N8, H5N1 and H7N3) which demonstrated protection against lethal challenge with a wide variety of influenza subtypes in mice and ferrets. Human trials are ongoing but even with a promising vaccine, thermal stability can still be an issue that could limit use in resource-poor settings.

Methods

The four components of BPL-inactivated vaccine were stored individually at four different conditions, -80°C, -20°C, 4°C, and room temperature. Hemagglutination (HA), neuraminidase activity (NA), and protein assays were done for each temperature condition after 7 and 28 days of storage.

Results

Baseline protein concentrations were similar across vaccine components. After 28 day incubation, protein concentrations remained stable at room temperature and at 4°C for H1N9 and H7N3, but decreased for H3N8 and H5N1, more at room temperature to 52.1% and 56.1% of Day 0 concentration respectively. At 4°C there was less loss of protein for those components. Activity of NA and HA varied at baseline; for example H3 and H5 had much higher activity (1280) than H1 (160) and H7 (320) and NA activity was highest for N1 (482.22 mU/ml) and lowest for N9 (33.65 mU/ml). HA and NA activity was stable for 28 days at room temperature and 4°C. At -20°C, HA activity showed marked declines within 7 days. Overall, our data shows stability of protein and HA and NA activity at 4°C for up to 28 days, and some short-term stability at room temperature.

Conclusion

Developing a universal flu vaccine would contribute greatly to preventing future pandemics. However, for global use, this vaccine would need to be stable and distributable. Here we show that we may potentially have a vaccine that is both efficacious and shelf stable at 4°C. Further evaluation of immunogenicity at different temperature conditions should be performed, especially to resolve discordance between protein and activity assays.

Disclosures

All Authors: No reported disclosures
P-599. 6-Valent, OspA-Based VLA15 Lyme Disease Vaccine Candidate Against Lyme Borreliosis in a Healthy Pediatric and Adult Study Population: A Phase 2 Study Update
Authors: Messier Marc D , Wagner Laura , Hochreiter Romana , Lamberth Erik , Larcher-Senn Julian , Simon Raphael , groark James , Stark James H
Published: January 2025

Background

Lyme borreliosis (LB) is the most common tick-borne disease in the US, with approximately 476,000 cases diagnosed and treated annually and nearly 90 million individuals living in high incidence jurisdictions. Vector-focused prevention measures have varying levels of effectiveness due to low utilization, poor adherence, or high cost. A safe and efficacious vaccine to prevent LB is warranted. We provide an update on the Pfizer-Valneva VLA15 vaccine clinical development program, specifically the safety and immunogenicity booster data of the phase 2 trial (NCT04801420).

Methods

A randomized, observer-blinded, multi-centre Phase 2 study investigated the safety and immunogenicity of VLA15 in adult and pediatric study populations. A total of 625 participants aged 5-65 years were enrolled in three age groups (5-11 years, 12-17 years, and 18-65 years) and randomized 1:1:1 to receive VLA15 180 mcg with alum in a three-dose (Month 0-2-6) or a two-dose schedule (Month 0-6), or three injections of placebo (Month 0-2-6) followed by booster doses at Month 18 and Month 30. Safety and immunogenicity data up to one month after completion of the primary vaccination series and yearly booster doses are presented.

Results

Up to Month 19, VLA15 was safe and well tolerated in all age groups after all doses. Most adverse reactions were mild or moderate in severity. No related SAEs or other safety concerns were reported. The VLA15 booster dose induced a robust, anamnestic immune response against all six OspA vaccine serotypes in all age groups. Immune responses in children were higher than in adults across both schedules.

Conclusion

The Month 18 VLA15-221 booster dose was safe and immunogenic in both adults and children. The Month 30 booster data is under analysis. The ongoing blinded Phase 3 trials in Europe and North America will provide additional data which may support use of this vaccine as the primary preventative measure to protect against LB.

Disclosures

Marc D. Messier, PhD, SOBI: Advisor/Consultant|Valneva: employee|Valneva: Ownership Interest Laura Wagner, M.Sc., Valneva: employee Romana Hochreiter, PhD, Valneva Austria GmbH: WO2021/207615 A1|Valneva Austria GmbH: Employee, owner of stock options Erik Lamberth, MD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Julian Larcher-Senn, PhD, Valneva: Advisor/Consultant Raphael Simon, PhD, Pfizer: Stocks/Bonds (Private Company) James groark, MD, Pfizer: Stocks/Bonds (Public Company) James H. Stark, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company)
P-610. HPV vaccine knowledge, attitudes and practices among healthcare providers before introduction to the national schedule, Almaty, Kazakhstan - 2023
Authors: Ablimitova Feruza , Nabirova Dilyara , Horth Roberta , Kirpicheva Ulyana , Gazezova Saya , Smagul Manar
Published: January 2025

Background

Healthcare providers play a vital role in the success of new vaccine uptake. In 2024, Kazakhstan will introduce the human papillomavirus (HPV) vaccine into the immunization schedule after a 2013 pilot was unsuccessful due largely to widespread misinformation. We aimed to establish baseline knowledge, attitudes, and practices (KAP) related to HPV vaccination among providers to prepare for vaccine rollout.

Methods

We conducted a cross-sectional study in April-May 2023 of healthcare providers responsible for vaccinations in all 34 polyclinics that conduct vaccinations in Almaty. Providers completed anonymous questionnaires in group sessions. KAP domain scores >70% were considered adequate. We used multinomial logistic regression to assess factors associated with intent to recommend HPV vaccines; we presented odds ratios and 95% confidence intervals (95%CI).

Results

Of 832 participants, 68% were nurses and 41% had at least one < 18-year-old child (Table 1). One-third (33%) had adequate knowledge about HPV; specifically, 71% correctly believed HPV is not airborne, and 22% knew HPV infection is not currently curable. One-fifth (20%) had adequate attitudes towards HPV; and 39% knew that HPV vaccines don’t cause infertility. On questions related to routine childhood immunizations, 61% could not correctly dispel common myths. One-quarter (28%) would recommend the HPV vaccine to patients and to their own or friends’ children. The odds of recommending the HPV vaccine were lower for nurses compared to physicians (OR=0.5, 95%CI=0.3, 0.9), for providers with inadequate HPV knowledge compared to adequate (0.6, 95%CI=0.4, 1.0), and for those who believed common myths compared to those who didn’t (0.6, 95%CI=0.4, 1.0) (Table 2). The odds of recommending the vaccine were higher for providers with adequate attitudes towards HPV vaccine myths compared to those without (1.4, 95%CI=0.8, 2.5) and for those with adequate knowledge of childhood vaccine safety compared to those without (2.3, 95%CI= 1.3, 4.0).

Conclusion

We found suboptimal KAP towards HPV vaccines. Results demonstrate the need to prioritize the rollout of a vaccine education, communication, and advocacy strategy to healthcare providers before the national HPV vaccine rollout.

Disclosures

Ulyana Kirpicheva, M.Sc. in FIeld Epidemiology, Abbott Laboratories: Grant/Research Support
P-634. Effect of Pre-existing OPV-induced immunity on development of canonical and non-canonical poliovirus virulence mutations
Authors: Carrington Yuan J , Zhou Frank , Altamirano Jonathan , Maldonado Yvonne A
Published: January 2025

Background

Preventing vaccine-derived polio is crucial, yet polio evolution and transmission mechanisms remain unclear. Our previous study in Mayan infants found that preexisting OPV-induced polio antibodies did not affect S3 immunogenicity. We now explore if viral mutations differ in those with and without preexisting antibodies. Using NGS, we identify and characterize vaccine poliovirus’ mutation patterns from stool sample isolates post one and two OPV doses. We hypothesize that OPV-induced intestinal immunity will correlate with increased mutations after the 2nd dose compared to the 1st.

S1 Canonical Mutations vs. Mutation Rates Post 1st and 2nd Dose of 116 OPV Isolates

Methods

179 OPV samples from a previous study were used. Participants received an OPV dose at study weeks 1 and 9 with stool samples collected at weeks 0, 1, 2, 4, 6, 8, 9, 10, 14, 16, and 17. A multiplex qPCR was used to determine serotype positivity. PCR amplicons created from stool viral RNA were purified and sequenced. Sequences were analyzed using the Illumina workflow nf-core/viralrecon (ver 2.5) and R (ver. 4.2.2).

S2 Canonical Mutations vs. Mutation Rates Post 1st and 2nd Dose of 82 OPV Isolates

Results

303 isolates were sequenced: 127 serotype 1 (S1), 91 serotype 2 (S2) and 85 serotype 3 (S3); 35 from week 0, 187 from weeks 1-8 (post dose 1: D1) and 81 from weeks 9-17 (post dose 2: D2). S1 and S2 in D2 showed significantly higher mutation rates (% of samples with mutation(s) at a given genome location) at all positions (S1 p = 0.0014, S2 p < 2.2e-16), while S3 showed no difference (p = 0.9899). For canonical mutations, S1 D2 had higher mutations at G480A (D1 65.3% vs. D2 68.6%) and A2795G (D1 8.5% vs. D2 10.5%), but 0% at A2438T while D1 had 6%; no mutations were seen at T525C and T2879C. For S2, D2 had higher mutations at A481G (D1 11.4% vs. D2 16.7%), with no mutations at T2909C in either set. In S3, D2 showed higher mutations at T472C (D1 36.6% vs. D2 46.4%), but lower mutations at C2493T (D1 26.9% vs. D2 16.7%) and T2034C (D1 3.8% vs. D2 0%).

S3 Canonical Mutations vs. Mutation Rates Post 1st and 2nd Dose of 70 OPV Isolates

Conclusion

Overall, isolates post the 2nd OPV dose showed significantly higher mutation rates for S1 and S2, but not for S3. Preexisting antibodies may be associated with higher mutation rates and long-term likelihood of neurovirulent reversion. Serotype differences may be related to shedding patterns and other serotype specific characteristics. Further studies are planned to understand the impact of pre-existing intestinal immunity on polio viral mutation and evolution.

Disclosures

Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Member, DSMB
P-646. Culture Positive Pneumococcal Pneumonia Requiring Hospital Admission from 2017-2022 at Eight US Children’s Hospitals
Authors: Engstrom Eric , Hulten Kristina G , Barson William J , Lin Philana L , Dahl Steven , Ramirez Kacy A , Bradley John S , Pannaraj Pia , Tan Tina Q , Dien Bard Jennifer , Kaplan Sheldon L
Published: January 2025

Background

The incidence of pneumococcal pneumonia (PP) has decreased significantly since the introduction of pneumococcal conjugate vaccines (PCV7, PCV13), however, pneumococci still remain the most common cause of bacterial pneumonia in children. We evaluated the current clinical presentation, isolate serotypes, and isolate antibiotic susceptibility of PP cases from 2017-2022.

Methods

We collected pneumococcal isolates and limited clinical data prospectively from patients with invasive pneumococcal disease ages ≤18 years at 8 children’s hospitals in the United States. Serotyping was performed at a central research laboratory. Patients with PP were identified and further clinical and laboratory data for each episode of pneumonia was collected retrospectively with a standardized case report form.

Results

We collected 159 pneumococcal isolates and clinical data from patients with PP over the study period; extended clinical data was available for 95 patients (Figure 1). 9/159 (5.8%) isolates were non-susceptible to ceftriaxone (MIC > 1.0 µg/mL; 7/9 were 19A), and 10/159 (6.5%) were non-susceptible to penicillin (MIC > 2.0 µg/mL; 10/10 were 19A). 20/159 (12.6%) patients were completely unimmunized, while 108/159 (67.9%) were fully immunized with PCV7 or PCV13. Serotypes unique to PCV20 caused 34 episodes (21.4% of all isolates) (Figure 2). The risk ratio of a patient having PCV13 vaccine serotypes vs non-vaccine serotypes was not different between fully immunized and unimmunized (p=0.23), fully immunized and under-immunized by age (p=0.59), or any vaccination and unimmunized (p=0.11) patients. Of patients with extended clinical data, 40% had uncomplicated pneumonia, 31% had empyema (14/29-serotype 3, 6/29-19A, 1/29-19F), and 24% had necrotizing pneumonia (15/23-serotype 3, 4/23-19F, 0/23-19A). 78/95 (82.1%) patients had respiratory viral testing, of which 57.1% were positive for at least one virus (Table 1 and 2).

Conclusion

PP continues to be an important cause of morbidity in the United States. Antibiotic resistance is a major concern for serotype 19A, but overall antibiotic resistance in pneumococcal pneumonia is low. The introduction of PCV20 in 2023 for routine administration to infants may modestly reduce incidence of PP.

Disclosures

Kristina G. Hulten, PhD, Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support William J. Barson, MD, Pfizer: Grant/Research Support Pia Pannaraj, MD, MPH, AstraZeneca: Grant/Research Support|Pfizer: Grant/Research Support Tina Q. Tan, MD, Astra Zeneca: Grant/Research Support|GSK: Grant/Research Support|Iliad: Advisor/Consultant|Merck: Advisor/Consultant|Moderna: Advisor/Consultant|Novavax: Advisor/Consultant|Pfizer: Advisor/Consultant|Sanofi Pasteur: Advisor/Consultant Sheldon L. Kaplan, MD, Pfizer: Grant/Research Support
P-649. Unusual Increase in Bordetella parapertussis Cases Detected in Pediatric Reference Centers in Mexico and Colombia During 2023: Is this Trend Emerging Elsewhere?
Authors: Gutiérrez Tobar Ivan Felipe , Carbajal-César Ana C , Londono-Ruiz Juan Pablo , Antonio-González Viviana , Salinas-Morales Daniel A , Robledo-Vega Carolina , Cuéllar Nicolás , Gutiérrez-Reyes Gloria M , de la Garza Eduardo Arias , Saltigeral Simental Leonor Patricia , Manzano-Arredonda Dámaris , Díaz-Jiménez Virginia
Published: January 2025

Background

Bordetella parapertussis infections clinically present with symptoms similar to Bordetella pertussis, albeit less severe and less frequent. We describe a multinational experience of an increase in cases from three pediatric reference centers in Mexico and Colombia

Graph 1

Distribution of B. parapertussis cases by date and country

Methods

Observational, retrospective study conducted at 3 pediatric reference centers, 2 in Mexico and 1 in Colombia. We included patients positive for Bordetella parapertussis via multiplex PCR respiratory assays from January 2023 to April 2024. Analysis focused on clinical characteristics and outcomes. Descriptive statistics were utilized and statistical comparisons were performed with the Mann-Whitney U test and Fisher's exact or chi-squared tests, significance was set at p < 0.05

Graph 2

Age distribution by PICU admission status

Results

The study involved 61 patients, 42 from Mexico and 19 from Colombia, with initial cases originating in Colombia (Graph 1). Median age was 3 years (1 month to 13 years), with no significant age differences between countries. Males accounted for 59% of cases. Approximately 70.49% of children were fully vaccinated, and 26.23% had contact with individuals displaying respiratory symptoms. Common symptoms included cough (90.16%), rhinorrhea(60.66%), respiratory distress (59.02%), fever (59.02%), and paroxysms (22.95%). Coinfections were prevalent in 85.25% of cases, mainly rhinovirus (45.9%) and RSV (18.0%). Laboratory findings showed median leukocyte count of 9,450 (IQR: 7,250-14,922.5).Chest X-rays indicated interstitial patterns in 58.33% and consolidation in 8.33% of cases. The PICU admitted 24.59% of patients, with 6.56% requiring intubation. A significant age difference was observed between PICU admissions (median 0.58 years) and non-admissions (median 4 years), p = 0.037 (Graph 2). No fatalities occurred.

Conclusion

The increase in cases occurred in two countries, initially emerging and then subsiding in Colombia. Most patients had viral co-detection, mainly with Rhinovirus. Despite typically mild descriptions in the literature, around a quarter required ICU admission, particularly among younger patients, suggesting increased vulnerability in this group. Continuous monitoring of evolving circulation patterns is vital locally and regionally, as similar phenomena may be happening elsewhere.

Disclosures

All Authors: No reported disclosures
P-659. Active Surveillance of Mucosal Pneumococcal Infections to Predict the Potential Added Benefits of Extended-Spectrum PCVs in Children < 24 Months in Southern Israel
Authors: Dagan Ron , Benisty Rachel , van der Beek Bart Adriaan
Published: January 2025

Background

Although mucosal infections, such as otitis media (OM) and acute conjunctivitis (AC) are the most common manifestations of pneumococcal disease in young children, surveillances have been based mainly on invasive pneumococcal disease (IPD) due to paucity of serotype-specific data on mucosal infection rates. We present rates and serotype dynamics of OM and AC as a means for assessing potential added benefits of the new PCVs, (PCV15/PCV20) against OM and AC in children < 24m.

Annual incidence rates of P-OM and P-AC episodes, children <24 months of age*,

southern Israel, July 2004 through June 2023

Methods

A retrospective analysis of two prospective, population-based surveillance projects on OM (Ben-Shimol CID 63:611, 2016) and AC (Dagan CID 72:1200, 2021) in southern Israel. All episodes in children < 24m with OM and/or AC with cultures in southern Israel have been included. All middle-ear fluid (MEF) and conjunctival cultures in the region are processed in a single laboratory of the hospital where ∼95% of all children are born and treated, permitting incidence calculations. The current analysis covers all pneumococcal OM and AC (P-OM, P-AC) from July 2004 through June 2023.

Distribution of individual serotypes in P-AC and P-OM episodes, children <24 months of age*,

southern Israel, July 2015 through June 2023 (late PCV13 period)

Results

A total of 2,312 and 1,039 episodes of P-OM and P-AC, respectively, were observed. The P-OM and P-AC annual rates are presented in Figure 1. The respective incidence rate ratios (95% CI) for 2017-2023 (excluding Corona year 2020-2021) vs. 2004-2008 were 0.12 (0.09-0.16) and 0.37 (0.26-0.53). During the stable PCV13 period (2015-2023), 32% and 24% of all P-OM and P-AC, respectively, were PCV20 serotypes (Figure 2). In both diseases, the PCV13 serotypes 19A, 19F, 3, and 14, and the PCV20-non-PCV13 serotypes 10A, 11A, 33F, and 15 B/C, predominated. PCV13 serotypes 1, 4, 5, 6A, 6B, 7F, 9V, 18C, 23F (grouped) constituted only 0.6% and 1.7% of all P-OM and P-AC, respectively.

Conclusion

1) PCV13 implementation resulted in a rapid and steep decline in both P-OM and P-AC rates, stabilizing within 3-4 years; 2) during the late PCV13 period, only 4 PCV13 serotypes persisted: PCV7 serotypes 19F and 14, and PCV13 non-PCV7 serotypes 3 and 19A; and 3) the non-PCV13 PCV20 serotypes constitute approximately one quarter and one third of P-AC and P-OM, respectively, in children < 24m in southern Israel. Implementation of PCV20 has the potential to add benefit against pneumococcal mucosal disease.

Disclosures

Ron Dagan, Professor MD, GSK: Advisor/Consultant|GSK: Honoraria|MedIMmune/AstraZeneca: Grant/Research Support|MedIMmune/AstraZeneca: Honoraria|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Sanofi Pasteur: Honoraria
P-677. Title: Estimation of Respiratory Syncytial Virus-attributable Hospitalizations among Older Adults in Japan between 2015 and 2018: an Administrative Health Claims Database Analysis
Authors: Seki Masafumi , Kobayashi Yasuhiro , Meroc Estelle , Kitano Takahiro , Polkowska-Kramek Aleksandra , Yoshida Asuka , Liang Caihua , Bruyndonckx Robin , Molalign Moges Solomon , Conde-Sousa Eduardo , Nuttens Charles , Gessner Bradford D , Begier Elizabeth
Published: January 2025

Background

Respiratory Syncytial Virus (RSV) incidence in adults is often underestimated, mainly because of infrequent testing, nonspecific symptoms and lower diagnostic test sensitivity compared to infants. We estimated population-based incidence rates (IRs) of RSV-attributable hospitalizations in adults ≥60 years in Japan using a retrospective time-series model-based approach.

Methods

We obtained hospitalization data from the Medical Data Vision (MDV) database, which is restricted to Diagnosis Procedure Combination (DPC) hospitals; data were included for 01/01/2015-31/12/2018, with 2018 the last complete year available before COVID-19. We estimated the yearly and age-specific RSV-attributable IR of hospitalizations for five cardiorespiratory outcomes defined based on selected ICD-10 codes. We used a quasi-Poisson regression model accounting for periodic and aperiodic time trends, as well as viral activity proxies. An offset was included in the model to account for the increase of the source database size. We extrapolated our results to all DPC hospitals in Japan.

Results

In adults aged ≥60 years, the IRs of RSV-attributable cardiorespiratory hospitalizations were 100-124 per 100,000 person-years (up to 7% of selected cardiorespiratory hospitalizations) and 69-85 per 100,000 person-years for respiratory-specific hospitalizations (up to 8% of all respiratory hospitalizations). IRs for all outcomes were higher in adults aged ≥80 years compared to those aged 60-79 years (Table 1).

Conclusion

Modeled RSV-attributable IRs in Japan were lower than in most other developed countries, likely due to the MDV database only including advanced treatment hospitals. Taking this into account, our results indicate a high burden of RSV-attributable hospitalizations in older adults in Japan, highlighting the need to implement effective RSV prevention strategies. Future work will include a sensitivity analysis extrapolating IRs to all hospitals in Japan.

Disclosures

Yasuhiro Kobayashi, MS, Pfizer Japan Inc: employee of Pfizer Japan Inc.|Pfizer Japan Inc: Stocks/Bonds (Private Company) Aleksandra Polkowska-Kramek, n/a, Pfizer: employee of P95 which received funding from Pfizer to conduct this study Caihua Liang, MD, PhD, Pfizer: Stocks/Bonds (Private Company) Charles Nuttens, n/a, Pfizer: Stocks/Bonds (Private Company) Bradford D. Gessner, M.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Elizabeth Begier, MD, M.P.H., Pfizer Vaccines: Employee|Pfizer Vaccines: Stocks/Bonds (Private Company)
P-685. Investigation of Influenza antibody transfer following maternal vaccination using the PREVAIL Birth Cohort
Authors: Cline Allison R , Conrey Shannon C , Morrow Ardythe L , Staat Mary A , Fayad Danielle , Olson Samantha M , Payne Daniel C , Campbell Angela P
Published: January 2025

Background

Seasonal influenza vaccine is recommended during pregnancy; however, data are limited on transplacental antibody transfer. We used the PREVAIL Cohort of healthy, term infants and their mothers in Cincinnati, Ohio, to describe hemagglutination-inhibition (HAI) titers in pregnancy and measure the association between maternal and cord HAI relative to maternal vaccination during pregnancy.Table 1.Maternal GMT by Vaccination Status and by Influenza A Subtypes and Influenza B Lineages

Methods

Maternal immunization status was abstracted from medical charts/state registries. HAI titers were measured in maternal blood collected in the third trimester, and in cord blood. HAI > 1:40 were considered seroprotective. Paired T tests (log normal distribution) and Fisher’s exact tests were used to compare geometric mean titers (GMT) and proportion of participants with seroprotective HAI, respectively, for each influenza subtype/lineage by vaccination status. Association between maternal and cord HAI was assessed using Spearman correlation and Maternal HAI/Cord HAI ratios.Table 2.Maternal Seroprotection by Vaccination Status and by Influenza A Subtypes and Influenza B Lineages

Results

155 mothers were included and delivered in the 2017-2018 influenza season (July 1st 2017-June 30st 2018); H3N2, H1N1 and B viruses circulated this season. 105 mothers received influenza vaccine during or 4 months prior to pregnancy. Vaccinated mothers had significantly higher GMTs for all influenza subtype/lineage compared to unvaccinated mothers (p< 0.005) (Table 1). A significantly higher proportion of vaccinated mothers exhibited seroprotective titers against influenza subtype/lineage H3N2 and B-Victoria compared to unvaccinated mothers (p< 0.05) (Table 2). There was a significant correlation between maternal and cord blood HAI for all subtype/lineage (r > 0.85, p< 0.05) (Figure 1). Cord GMTs tended to exceed maternal GMTs, with statistically significant differences in Influenza B lineage (p< 0.05) (Table 3). More than 75% of the mother-infant pairs exhibited transplacental antibody transfer ratios ≤ 1.Table 3.Maternal GMT and Cord GMT by Influenza A Subtypes and Influenza B Lineages

Conclusion

Vaccinated mothers displayed protective influenza antibodies levels which were significantly higher than those found in unvaccinated mothers. Maternal HAI was strongly correlated with cord HAI, suggesting efficient transplacental transfer. Moving forward, investigation of factors influencing this transfer will be undertaken.Figure 1.Scatter plots of maternal vs cord log-transformed HAI titers

Disclosures

Mary A. Staat, MD, MPH, Cepheid: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Up-To-Date: Honoraria
P-688. Pediatric Pneumonia trapped in ‘NET’ (Neutrophil Extracellular Traps)
Authors: Mitra Barnali , Mitra Debdeep
Published: January 2025

Background

Neutrophil extracellular traps (NETs) were initially recognized for their role in the immune system, primarily immobilizing and sometimes killing microorganisms. However, further research has revealed their involvement in various diseases due to the harmful effects of their components on surrounding tissues. The innate immune system's role in pneumonia pathogenesis has been emphasized in several studies. Investigating the involvement of NETs in pulmonary infections and their potential as biomarkers for community-acquired pneumonia (CAP) outcomes has been explored in adult patients. Current data suggests that controlled NET release and clearance are beneficial in pneumonia, but any imbalance in this process could lead to harmful inflammation or increased risk of infection dissemination and sepsis.

However, there is a gap in understanding NET activity in pediatric lung infections. Therefore, this study aimed to assess NET activity in pediatric pneumonia patients and correlate it with blood culture results and viral panels for respiratory infections.

Methods

It was a Cross sectional Observational study at a tertiary care hospital and all children diagnosed to be suffering from pnuemonia. 30 Pediatric pneumonia patients were assessed at the time of presentation and evaluated clinically, radiologically and severity was scored based on Modified respiratory distress assessment instrument score (mRDAI). NET values were checked at the time of presentation and at the time of recovery. These values of NET were correlated with blood culture results, Respiratory viral panel and mRDAI score.

Results

Higher levels of Neutrophil extracellular traps (NETs) correlated with increased disease severity (mRDAI score) and with a poor prognosis and higher hospital stay and increased mortality. There was no statistical significance in the NET score of bacterial and viral pneumonia.

Conclusion

An increase in Neutrophil extracellular traps (NETs) levels is a common occurrence during severe respiratory infections. It is plausible to hypothesize that their migration to the lungs and subsequent activation could worsen tissue damage and contribute to the progression of the disease. NET has been identified as one of the markers linked with poor prognosis and severe pediatric respiratory symptoms.

Disclosures

All Authors: No reported disclosures
P-691. Characteristics Associated with the Presence of One or More Risk Factors for Severe Respiratory Syncytial Virus Disease among Adults in the United States
Authors: Horn Emily K , Singer David , Booth Alison , Saiontz-Martinez Cynthia , Berger Ariel
Published: January 2025

Background

Respiratory syncytial virus (RSV) can cause severe disease in older adults and adults with certain medical conditions. In June 2023, RSV vaccination was recommended for United States (US) adults ≥60 years of age (YoA) using shared clinical decision-making. This study explored factors associated with having diagnosed and undiagnosed risk factors (RFs) for severe RSV disease among US adults.

Methods

A retrospective analysis of pooled National Health and Nutrition Examination Survey data from 4 survey waves (January 2011 - March 2020) was conducted, comprising adult respondents (≥20 YoA), and weighted to allow extrapolation to all non-institutionalized US adults (Table 1). Diagnosed RFs were identified via self-report; undiagnosed RFs were assessed via lab test/exam results (limited to diabetes and renal disease). Multivariable logistic regression models were developed to assess associations between respondents’ sociodemographic characteristics and presence of ≥1 RF for severe RSV disease (cardiopulmonary, endocrine, and metabolic conditions).

Results

After extrapolation to the US population, 35.5% of adults ≥20 YoA (n=82,715,916/233,102,301) had ≥1 RF (diagnosed or undiagnosed) for severe RSV disease. For both diagnosed and undiagnosed RFs, older age, lower income, being a smoker, and obesity were associated with significantly higher odds of having ≥1 RF (Table 2). Adults with government insurance had a higher likelihood of having ≥1 diagnosed RF compared with those with private insurance (p < 0.05). Adults from racial and ethnic minority groups were more likely than non-Hispanic White adults to have ≥1 undiagnosed RF (p < 0.01). Compared to adults whose routine place for healthcare was doctors’ offices, adults with no routine place were less likely to have ≥1 diagnosed RF (p < 0.001), while those whose routine place was the emergency room were less likely to have ≥1 undiagnosed RF (p < 0.05).

Conclusion

Among US adults, several social determinants of health are associated with the presence of ≥1 diagnosed and undiagnosed RF for severe RSV disease. Understanding characteristics associated with RFs for severe RSV disease can help to ensure RSV vaccination among these higher risk groups.

Funding: GSK (GSK study identifier: VEO-000686)

Disclosures

Emily K. Horn, MSc, GSK: employee|GSK: Stocks/Bonds (Private Company) David Singer, PharmD, MS, GSK: employee|GSK: Stocks/Bonds (Public Company) Alison Booth, MSc, GSK: Grant/Research Support|Other pharmaceutical, biotech, and medical device companies: Grant/Research Support Cynthia Saiontz-Martinez, MSc, GSK: Grant/Research Support|Other pharmaceutical, biotech, and medical device companies: Grant/Research Support Ariel Berger, MPH, GSK: Grant/Research Support|Other pharmaceutical, biotech, and medical device companies: Grant/Research Support
P-735. Acute Bacterial Skin and Skin Structure Infections: A Comparison of Outpatient One-Hour Infusion Oritavancin and Inpatient Vancomycin Use
Authors: Lindley William , Whittaker Cristen , Szymborski Shana , Reilly Joseph , Trivedi Manish
Published: January 2025

Background

Patients with acute bacterial skin and skin structure infections (ABSSSI) who present to the emergency department (ED) are commonly admitted for intravenous (IV) antibiotic treatment. At AtlantiCare Regional Medical Center (ARMC), oritavancin is utilized in the ED as a single 1200 mg dose to prevent ABSSSI admissions. The purpose of this study is to compare 30-day ABSSSI readmission rates between one-hour ED oritavancin infusion and inpatient vancomycin therapy transitioned to oral antibiotics. A financial assessment of both groups will also be presented.Table 1.Patient characteristics and outcomes analyzed via Student’s t-test or χ2 test.

Methods

Subjects with ABSSSI were included in this retrospective study if they were administered oritavancin in the ARMC ED between November 2022 and August 2023, or given IV vancomycin as an inpatient between January and August 2023. Data collection included patient demographics, history of ABSSSI, injection drug use, and length of stay (LOS). A financial analysis was performed based on diagnosis-related group (DRG) reimbursement and hospital-specific expenditures. Collected data were analyzed using a Student’s t-test or χ2 test as appropriate.

Results

A total of 191 patients were included in this study with 140 and 51 in the oritavancin and vancomycin arms, respectively (Table 1). The 30-day ABSSSI readmission rates were significantly lower in the oritavancin arm (n=8, 5.7%) compared to the vancomycin arm (n=10, 19.6%), p=.004. Amongst the 8 oritavancin readmissions, only 4 (2.9%) were considered oritavancin candidates based on our hospital protocol criteria which defines appropriate patients. The estimated cost after DRG-based reimbursement for a single patient in the vancomycin arm was approximately $10,300. The estimated cost avoidance for each oritavancin patient, not accounting for drug reimbursement or the subsequent decrease in readmissions, was approximately $7,240.

Conclusion

Oritavancin as a one-hour infusion in our ED appears to be an effective treatment option in preventing admissions and significantly decreasing 30-day ABSSSI readmissions. The financial benefits of preventing hospital admissions with single-dose oritavancin should be considered when treating ABSSSI patients in the ED setting.

Disclosures

Joseph Reilly, B.S., Pharm.D., Melinta Therapeutics: Advisor/Consultant
P-746. Characterizing Deep Neck Infections (DNI) at a Tertiary Care Center in Philadelphia with a High Population of People Who Inject Drugs (PWID)
Authors: Patel Kaya , Spivack Stephanie , Yan Flora , Thorntan Noah , Whitley Karl , Soliman Ahmed , Schultz Sara K
Published: January 2025

Background

Acute bacterial skin and skin structure infections (ABSSSI) including cellulitis and abscess are common complications of intravenous drug use (IVDU). With the widespread introduction of xylazine in the Philadelphia drug supply since 2019, more patients are injecting into their neck due to limited peripheral access from vein sclerosis or xylazine wounds. Herein, we have characterized DNI in PWID and their outcomes.

Figure 1

Injection behavior

Methods

The IRB approved this study. We conducted a retrospective chart review of patients with documented opioid use disorder (OUD) with injection behavior and a diagnosis of DNI from January 2016 through December 2022. We collected data on demographics, microbiology, drug use and treatment to characterize infection, surgical intervention, and outcomes.Figure 2.Substances used

Results

We identified 153 patients with OUD and injection behavior who were diagnosed with DNI. 80 (52%) patients were male and 73 (48%) were female. 101 (66%) were experiencing homelessness. 139 (91%) patients reported injecting into their neck and 25 (16%) patients reported using their neck as the only site of injection due to limited peripheral access. Figure 1. 83 (54%) endorsed polysubstance drug use with cocaine or amphetamines. Figure 2. Types of infection include: 131 (86%) neck abscess, 22 (14%) neck phlegmon, 14 (9%) internal jugular (IJ) septic thrombophlebitis, 3 (2%) sternoclavicular septic arthritis, 3 (2%) with mediastinal involvement, and 2 (1%) osteomyelitis (OM) of clavicle or mandible.

124 (81%) patients underwent drainage. 103 (83%) of these patients had cultures sent from the abscess. The predominant organisms were MRSA (47, 46%), MSSA (15, 15%), GAS (23, 22%), and alpha-hemolytic Strep (26, 25%). Figure 3. 137 (90%) patients had blood cultures sent, 115 (84%) without growth, 10 (7%) MRSA, 10 (7%) GAS, and 3 (2%) MSSA. 21 (17%) required repeat intervention. Within 30 days there were 48 (31%) readmissions and 1 (0.5%) death.Figure 3.Microbiologic data from abscess cultures

Conclusion

Since 2016, there has been a sixfold increase in incidence of DNI in PWID. Figure 4. The complications of neck infection can be catastrophic with extension into mediastinum, septic thrombophlebitis, bloodstream infections, or bone and joint infections. It is important to recognize neck infections early and intervene as soon as possible before further complications occur.

Figure 4. Neck abscess incidence

Disclosures

Sara K. Schultz, MD FACP FIDSA, AbbVie: Advisor/Consultant
P-748. Evaluation of Risk Factors for Short Inpatient Hospital Stays for the Treatment of Cellulitis
Authors: Orlikowski Cole , Schmidt Kyle , Jameson Andrew , Dumkow Lisa E
Published: January 2025

Background

Cellulitis is a common cause of hospitalization and imposes significant financial burden on healthcare systems. This study aimed to identify patient risk factors associated with short-stay hospitalizations for cellulitis with a goal to develop a dalbavancin protocol for use in the emergency department (ED) to mitigate short hospital stays.

Methods

A retrospective cohort study was conducted at a 350-bed community teaching hospital in Michigan evaluating adult patients diagnosed with cellulitis February 1, 2020 - August 1, 2023, who received initial treatment with monotherapy targeting beta-hemolytic streptococci or Staphylococcus aureus. Three cohorts were identified based on length of hospitalization or ED discharge. The primary outcome was to identify risk factors associated with short-stay (< 72 hour) hospitalizations. Multivariate logistic regression was used to identify independent patient factors associated with short-stay hospitalization in contrast to long-stay (≥ 72 hours) or ED discharge. Patients were excluded if they required surgical intervention, received polymicrobial therapy, required ICU admission, received cellulitis treatment in the past 90 days, or were being treated for multiple infections.

Results

A total of 161 patients were included (ED discharge, n = 75; Short-stay, n = 46; and Long-stay, n = 40). Patient and treatment characteristics are summarized in Table 1. Logistic regression demonstrated that need for incision and drainage (I&D) (OR 7.23; 95% CI 1.69-38.04), Charlson Comorbidity Index ≥ 3 (OR 1.23; 95% CI 1.04-1.46), or presenting with fever (OR 31.62; 95% CI 5.67 – 596.30) were independent risk factors for short-stay hospitalization compared to ED discharge. Charlson Comorbidity Index > 3 (OR 1.25, 95% CI 1.06-1.48) and purulent cellulitis (OR 4.29, 95% CI 1.22-15.38) were predictive of long-stay hospitalizations. Characteristics such as fever, recurrent cellulitis, history of MRSA, and BMI were not associated with longer hospital stays.

Conclusion

A protocol to evaluate ED patients with cellulitis for dalbavancin use could reduce unnecessary hospitalizations and healthcare cost. Patients with more comorbidities, purulent cellulitis needing I&D, and those with unstable vital signs may be less ideal candidates for ED dalbavancin use.

Disclosures

All Authors: No reported disclosures