bluuebunny/crossref_metadata_2025 huggingface dataset:
2138. Evaluating the Safety and Immunogenicity of the rZIKV/D4Δ30-713 Live Attenuated Chimeric Zika Candidate Vaccine in Healthy Flavivirus-Naïve Adults
Authors: Zhong Diana , Kirkpatrick Beth , Pierce Kristen , Patel Urvi , Blunt Madeleine R , Durbin Anna
Published: December 2022

Background

Zika virus (ZIKV) is a flavivirus associated with a serious congenital Zika syndrome, with a recent epidemic originating in Brazil in 2015. Novel ZIKV vaccine candidates are in development. We report results of a phase I study of the first live attenuated ZIKV vaccine for use in humans. rZIKV/D4Δ30-713 is a chimeric Zika vaccine, expressing the premembrane (prM) and envelope (E) genes of a contemporary ZIKV strain within a dengue DEN4Δ30 background.

Methods

We conducted a phase I, randomized, placebo-controlled double-blind trial, evaluating two different doses, 103 PFU and 104 PFU, of rZIKV/D4Δ30 in healthy adult subjects 18 – 50. Between October 2018 and August 2021, 28 subjects were enrolled in each dose cohort (20 to vaccine; 8 to placebo) at the Johns Hopkins Center for Immunization Research and the University of Vermont Vaccine Testing Center. Subjects were followed 26 weeks post-vaccination. Primary outcomes included safety and reactogenicity (adverse events graded by severity) and immunogenicity assessed by seroconversion by day 90 post-vaccination (ZIKV peak titer ≥ 1:10). The study was IRB approved (WCG 20181303, UVM CHRMS 18-0566).

Results

Fifty-five of 56 enrolled subjects completed the study. One volunteer (104 PFU group) withdrew before study day 28 due to work conflicts. The most common adverse events were headache, fatigue, and myalgias. These events did not occur significantly more frequently in vaccine recipients compared with placebo recipients. One severe adverse event was deemed unrelated to study product (new breast cancer diagnosis). In the 103 PFU group, 9 of 20 (45%) seroconverted. In the 104 PFU group, 7 of 19 (37%) seroconverted (Figure 1). ZIKV could not be recovered by culture or PCR in the blood, saliva, or urine from any subject.

Conclusion

The vaccine appears to be safe and well-tolerated in healthy flavivirus-naïve adults. The seroconversion proportion was similar between the two dosing groups, with higher peak titers in the 104 PFU group. Given the lack of dose effect on seroconversion, further dose increases are unlikely to improve seroconversion. Chimerization can be highly attenuating to viruses. Our results suggest rZIKV/DEN4Δ30 is over-attenuated and thus will not be further developed as a candidate ZIKV vaccine.

Disclosures

Anna Durbin, MD, Merck & Co.: Advisor/Consultant.
2140. INO-4800, a DNA Plasmid Vaccine Encoding the Ancestral SARS-CoV-2 Spike Protein, Is Stable Over a Range of Temperatures Not Requiring Ultra-Cold Chain Storage
Authors: Juba Robert J , Samawova Anthony , Seals Katherine , Kinney Peggy , Brandreth E J
Published: December 2022

Background

Effective vaccines deployable globally are needed to control the COVID-19 pandemic. INO-4800, a plasmid DNA vaccine encoding the ancestral SARS-CoV-2 spike (S) protein, has demonstrated safety and immunogenicity. We report the stability of multiple INO-4800 lots used in Phase 3 clinical trials.

Methods

Lots of INO-4800 stored at the test temperatures (storage temperature [2–8°C] and accelerated temperature [25 ± 2°C]) were sampled every 3 months. Sample stability at each timepoint was assessed in terms of 2 parameters: i) purity as measured by DNA isoform homogeneity by capillary gel electrophoresis (CGE) to quantify relative proportions of different plasmid topologies (supercoiled, open circular, and linear), and ii) potency as measured by a cell-based assay for flow cytometric detection of fluorescently labeled S protein.

Results

At 2–8°C, all tested lots of INO-4800 retained structural homogeneity for ≥12 months (Fig. 1A). Proportions of circular and supercoiled plasmid isoforms were ≥96% and ≥89%, respectively, remaining above minimum regulatory authority-approved specifications (≥85% for circular and ≥80% for supercoiled isoforms). At 25 ± 2°C, all tested lots retained structural homogeneity within specifications for ≥6 months (Fig. 1B), with proportions of circular and supercoiled plasmid isoforms being ≥96% and ≥81%, respectively. Moreover, structural homogeneity of 1/2 (50%) lots was within specification at 9 months at 25 ± 2°C. Potency of all tested lots was ≥84% for ≥6 months at both 2–8°C and 25 ± 2°C, remaining above the regulatory authority-approved minimum of 77% (Figs. 1C and 1D). Moreover, 3/3 (100%) of tested lots were within potency specification at 12 months at 2–8°C and 2 lots and 1 lot, respectively, were within specification at 9 and 12 months at 25 ± 2°C. Data from additional timepoints are accruing and will be presented. Figure 1:Stability of INO-4800 lots used in Phase 3 trials as measured by isoform homogeneity (A and B) and potency (C and D). Shaded areas represent regulatory authority-approved specifications.

Conclusion

INO-4800 is stable across temperatures ranging from 2°C to 25 ± 2°C and does not require ultra-cold storage. This demonstrated stability confers upon INO-4800 the potential to be deployed globally even in resource-constrained settings lacking cold chain infrastructure, thereby contributing to pandemic preparedness and control.

Disclosures

Robert J. Juba, Jr., MS Chemical Engineering Practice, BS Chemical Engineering, Inovio Pharmaceuticals: Employee|Inovio Pharmaceuticals: Stocks/Bonds Katherine Seals, n/a, Inovio Pharmaceuticals: Employee|Inovio Pharmaceuticals: Stocks/Bonds Peggy Kinney, MS Quality Management, Inovio Pharmaceuticals: Employee|Inovio Pharmaceuticals: Stocks/Bonds.
2152. Types and Resistance Patterns of Gram-negative Bacteria (GNB) causing Bloodstream Infections (BSIs) in a Neonatal ICU (NICU), 2010-2019
Authors: Frantzis Irene , Paul Anshu , Gentzler Eliza , Solowey Kyra , Manickam Surya , Hill-Ricciuti Alexandra , Messina Maria , Alba Luis , Johnson Candace L , Brachio Sandhya S , Saiman Lisa
Published: December 2022

Background

BSIs caused by GNB, particularly with multidrug resistance, cause substantial morbidity and mortality in NICUs worldwide1. We previously reported low overall rates of gentamicin resistance in commonly isolated GNB, i.e., Escherichia coli and Klebsiella species, supporting gentamicin as empiric therapy in our NICU2. Over a decade later, we sought to assess GNB BSI rates and potential changes in GNB resistance patterns.

References:

< ! 1.Dramowski A, et al. Paediatr Int Child Health. 2015;35:265-72.

2.Smith A, et al. Pediatr Infect Dis J 2010;29:831–35.

Methods

We retrospectively reviewed GNB BSIs that occurred in infants > 3 days old admitted to a level IV academically affiliated NICU from 2010-2019. Pre-approval for broad spectrum antibiotics was in place throughout the study period. Post-prescription review began in 2017. We collected the types of GNB and resistance to gentamicin, 3rd/4th generation cephalosporin agents, and meropenem. Data analysis included frequency of GNB type per year, incidence per 1000 admissions, and regression analysis

Results

Admissions were generally stable during the study period (range 855-1057). The types of GNB causing BSIs each year and BSI incidence are shown (Figure 1). Incidence ranged from 8-26 per 1000 admissions and during the 10-year period, GNB BSI incidence decreased (p< 0.001). The most common GNB were E. coli (n=21) and Klebsiella spp. (n=25) followed by Enterobacter spp. (n=15) and Serratia marcescens (n=12). GNB resistance trends are shown (Figure 2). Overall, resistance to gentamicin appeared stable (14.5%), while resistance to ceftriaxone increased (19.1%) and resistance to cefepime (3.8%) and meropenem (2.3%) was rare.

Conclusion

GNB BSIs have decreased in our NICU with low rates of gentamicin resistance, supporting the continued use of gentamicin for empiric antibiotic therapy. To maintain low resistance rates, antimicrobial stewardship efforts should continue. NICU-specific antibiograms should be considered to facilitate assessment of resistance trends.

Funding

IF supported by NIAID T32 AI007531.

Disclosures

Lisa Saiman, MD MPH, Merck & Co., Inc.: Advisor/Consultant|Merck & Co., Inc.: Grant/Research Support.
101. Effect of Human Papillomavirus Vaccine to Interrupt Recurrence of Vulvar and Anal Neoplasia (VIVA): A Randomized, Placebo-Controlled Trial
Authors: Stankiewicz Karita Helen C , Magaret Amalia , Magaret Amalia , Schouten Jeffrey , Mao Constance , Huh Warner , Grieco Verena , Seymour Matthew , Varon Dana , Doody David , Fu xi Long , Galloway Denise , Wald Anna , Madeleine Margaret
Published: December 2022

Background

Anal and vulvar high-grade intraepithelial lesions (HSIL) often recur after primary treatment, with 30%-50% recurrence in the 5-years following treatment. Treatment for recurrent lesions can be uncomfortable, debilitating, and costly. The VIVA trial evaluated the effects of the nonavalent human papillomavirus (HPV) vaccine (9vHPV) on recurrent anal or vulvar HSIL.

Methods

We conducted a randomized, double-blinded, placebo-controlled trial of the 9vHPV in vaccine-naïve persons aged 27-69 years who were previously treated for anal or vulvar HSIL and HSIL-free at enrollment. Participants had high-resolution anoscopy or vulvoscopy at screening, month 18 and 36 visits. Eligible participants were randomly assigned (1:1) to receive 9vHPV or placebo on day 1, month 2 and 6. We hypothesized that 9vHPV leads to a 50% reduction of HSIL recurrence. The primary endpoint was anal or vulvar HSIL recurrence, which was assessed in the intent-to-treat (ITT) population.

Results

Between July 2017 and December 2021, 187participants (99 cis-men, 86 cis-women, 2 transgender persons) with a history of anal (104, 56%) or vulvar (83, 44%) HSIL enrolled in the trial. 181 (97%) participants were included in the ITT analysis. Median age was 55 years (IQR 48-63); 71 out of 181 participants (39%) had well-controlled HIV infection. The DSMB recommended stopping the study early because it met specified futility boundaries at interim analysis. Predictive power to show a significant difference in the primary endpoint was 6.4% should the study continue to accrue. With 46% of planned information accrued, the vaccine was not significantly more efficacious than the placebo in preventing recurrent HSIL, with 15 cases in the 9vHPV arm versus 18 cases in placebo (incidence 9.1 versus 10.0/100 person-years; p= 0.83 by log-rank test). We found no differences in HSIL recurrences among vaccine versus placebo recipients by anatomical site or HIV status. The 9vHPV was safe and well-tolerated.

Kaplan-Meier Curve for overall high-grade squamous intra-epithelial neoplasia (HSIL) recurrences for nonavalent-HPV vaccine vs placebo recipients

Conclusion

We found no benefit of the 9vHPV vaccine for prevention of recurrent anal or vulvar HSIL. Our study underlines the importance of HPV prevention with prophylactic HPV vaccines and the need for novel therapeutic vaccines and antivirals to manage prevalent HSIL that have a high potential to recur.

Disclosures

Denise Galloway, PhD, Merck: Grant/Research Support Anna Wald, MD, MPH, Aicuris: Advisor/Consultant|Auritec: Advisor/Consultant|Crozet: Advisor/Consultant|DXNow: Advisor/Consultant|GSK: Grant/Research Support|Merck: Advisor/Consultant|sanofi: Grant/Research Support|VIR: Advisor/Consultant|X-Vax: Advisor/Consultant.
2172. Closing the CAP Gap: Improving the Management of Community Acquired Pneumonia (CAP)
Authors: Hoffman Paige A , Son Andrea H , Hoeprich Stephanie L , Hecker Michelle T
Published: December 2022

Background

In October 2019 updated community acquired pneumonia (CAP) guidelines were published, highlighting indications for empiric anti-MRSA and antipseudomonal antibiotics and use of MRSA nares screens. During a review of patients receiving vancomycin and piperacillin-tazobactam at our institution in 2020 we noted frequent use of anti-MRSA and antipseudomonal antibiotics and infrequent use of MRSA nares screens for CAP. In May 2020 we initiated a multifaceted intervention, including prospective audit and feedback, an updated pneumonia order set, and system-wide education. In this study we sought to describe gaps in the care of patients with CAP at our institution and to evaluate the impact of a multifaceted intervention on those gaps in care.

Methods

We performed a retrospective cohort study on a random sample of unique adult patients admitted with pneumonia from January 1, 2020 through June 30, 2021. Exclusion criteria included COVID infection within 4 weeks of admission, no antibiotics for pneumonia given during admission, immunocompromised condition, and diagnosis of hospital-acquired or ventilator-associated pneumonia. The primary objective was to describe the percentage of patients receiving appropriate anti-MRSA and antipseudomonal therapy and MRSA nares testing during the study period. The secondary objective was to compare appropriateness of these outcomes before and after the intervention.

Study groups

Results

For the 126 patients reviewed, 68.3% received the appropriate empiric spectrum of activity for MRSA and Pseudomonas aeruginosa, improving from 60% to 80% before and after the intervention respectively. The percentage of patients screened for MRSA increased from 6 to 34%; however, the percentage of appropriate MRSA screens decreased from 71 to 54% because screens were often collected despite absence of MRSA risk factors.

Results

Conclusion

The percentage of patients receiving appropriate anti-MRSA and antipseudomonal therapy for CAP improved after a multifaceted stewardship intervention. The percentage of patients for whom appropriate MRSA nares screens was performed worsened, mainly due to use of MRSA nares screens when not needed.

Disclosures

All Authors: No reported disclosures.
102. Efficacy and Effectiveness of High-Dose Influenza Vaccine in Older Adults by Age and Seasonal Characteristics: An Updated Systematic Review and Meta-Analysis
Authors: Lee Jason K , Lam Gary K , Vaisman Rolan , Yin Kevin J , Seet Bruce T , Loiacono Matthew M , Samson Sandrine I
Published: December 2022

Background

High-dose influenza vaccine (HD-IIV) has been used extensively in older adults since its approval in 2009. Studies comparing HD-IIV to standard-dose influenza vaccines (SD-IIV) have demonstrated protection beyond influenza, including reduction of outcomes like cardiorespiratory and all-cause hospitalizations. This study is an update of previously-conducted reviews of the relative vaccine efficacy/effectiveness (rVE) of HD-IIV vs. SD-IIV in adults ≥65 years against influenza-associated outcomes from 2009-2020, with sub-analyses by seasonal and recipient characteristics.

Methods

An updated systematic review and meta-analysis was conducted for studies assessing the rVE of HD-IIV against probable/laboratory-confirmed influenza-like illness (ILI), emergency department (ED) and/or hospital admissions in adults ≥65 years. Results from individual seasons – stratified by outcome, subject characteristics, and influenza season, were meta-analyzed to estimate pooled rVEs of HD-IIV.

Results

19 studies from 11 consecutive seasons with over 45 million HD-IIV or SD-IIV recipients were meta-analyzed. Overall, HD-IIV demonstrated improved protection vs. SD-IIV against ILI (rVE=14.3%, 95%CI:4.2-23.3%), HD-IIV was more effective at preventing hospital/ED visits due to influenza (rVE=10.4%, 95%CI:6.8-13.9%), and hospitalizations due to influenza (rVE=11.2%, 95%CI:7.4-14.8%), pneumonia (rVE=27.3%, 95%CI:15.3-37.6%); pneumonia and influenza (rVE=13.4%, 95%CI:7.3-19.2%); respiratory (rVE=14.3%, 95%CI:8.5-20.0%), cardiovascular (rVE=13.1%, 95%CI:10.5-15.7%), and cardiorespiratory events (rVE=17.9%, 95%CI:15.0-20.8%); and all-causes (rVE=8.4%, 95%CI:5.7-11.0%). Pooled rVEs were similar in sub-analyses by dominant strain, antigenic match, and study type/setting. While all adults 65+ benefited from the use of HD-IIV, age-stratified analyses of the rVE of HD-IIV suggested additional relative benefit with increasing age.

Conclusion

Evidence over 11 consecutive influenza seasons from both randomized and observational studies suggests HD-IIV was consistently more effective than SD-IIV at reducing influenza and associated serious outcomes irrespective of recipient age and characteristics of the influenza season.

Disclosures

Jason K. Lee, MS, MBiotech, Sanofi: Employee|Sanofi: Stocks/Bonds Gary K. Lam, PharmD, RPh, Sanofi: Employee Rolan Vaisman, PharmD, RPh, Sanofi: Employee Kevin J. Yin, MD, MPH, PhD, Sanofi: Employee|Sanofi: Stocks/Bonds Bruce T. Seet, PhD, MBA, Sanofi: Employee|Sanofi: Stocks/Bonds Matthew M. Loiacono, PhD, MSc, Sanofi: Employee|Sanofi: Stocks/Bonds Sandrine I. Samson, PhD, Sanofi: Employee|Sanofi: Stocks/Bonds.
2186. Risk Factors to predict one-year Community-Acquired Pneumonia in a Low-Middle Income Country: A Prospective Cohort Study
Authors: Ibáñez-Prada Elsa D D , Serrano-Mayorga Cristian C , Lozada Julian , Bustos Ingrid G G , Mendez Lina , Crispin Ana M , Reyes Luis Felipe F
Published: December 2022

Background

Community-acquired pneumonia (CAP) is the principal cause of mortality due to infectious diseases globally. Some risk factors have been identified for CAP, such as age, smoking, environmental exposures, malnutrition, previous CAP, chronic bronchitis/chronic obstructive pulmonary disease (COPD), asthma, functional impairment, poor dental health, and immunosuppressive therapy, among others. However, these studies were conducted in high-income countries and patients without comorbid conditions. Therefore, we aimed to identify the risk factors associated with CAP development within a one-year follow-up in a prospective cohort of patients with comorbid conditions in Colombia. Table 1.Logistic Regression Analysis

Methods

This prospective cohort of adult patients with chronic comorbidities between 2020-and 2022 in Bogotá, Colombia. Univariate analysis and multivariate logistic regression model were developed to identify the variables associated with CAP development within a one-year follow-up. The logistic regression model included variables with a p-value<0.20 in the univariate analysis.

Results

A total of 810 patients were included in the program. Median [IQR] age was 63 [53-62] and the most common comorbidities were 52.2% [423/810] arterial hypertension, 21.7% [176/810] coronary disease, and 19.0% [154/810] congestive heart failure. To date, 678 follow-ups have been made. Thirty-four patients died before the 6-month follow-up, and 46 were lost, leaving 598 patients included in the analysis. The cumulative incidence of CAP was 4.3% [26/598] during one year. After adjusting the logistic regression model, the main risk factors associated with pneumonia development were COPD [OR 4.30, 95% CI 1.66-11.11, p< 0.01], and previous antibiotic treatment [OR 4.08, 95% CI 1.08-15.29, p=0.04] (Table 1).

Conclusion

Patients with a history of COPD or previous antibiotic treatment have a more than 300% higher risk of developing pneumonia within one year. Robust vaccination programs for adults are needed in Colombia.

Disclosures

All Authors: No reported disclosures.
103. Evaluating The Appropriateness of Vaccine Administration in Patients with Splenectomy
Authors: Barsoum Barbara , Rayn Anan , Gozar Martin , Jain Sumeet , Ha Lawrence , Donaghy Henry , Doan Thien-Ly
Published: December 2022

Background

The spleen removes microorganisms from the bloodstream and produces antibodies for enhanced immune response. Patients with asplenia are at increased risk for infections caused by encapsulated organisms and have a 6-fold increased risk of sepsis compared to the general population. Those that acquire an infection have a mortality rate of 80%. The CDC recommends administering the meningococcal, influenza, pneumococcal, and Haemophilus influenzae type B (Hib) vaccine at least 2 weeks before or after splenectomy.

Methods

This retrospective chart review evaluated the appropriateness of vaccine administration for patients undergoing splenectomy at Long Island Jewish Medical Center (LIJMC) from January 2016 to June 2020. Patients were included if they were admitted to LIJMC, 18 years or older, and had splenectomy at LIJMC within previous 7 years. Patients were excluded if they were pregnant, admitted to an outside hospital for splenectomy, or had an unknown time of splenectomy. The primary objective was appropriateness of vaccine administration. Inappropriateness was defined as having at least 1 error with administration, including vaccine omissions, timing of vaccine, sequencing (Pneumovax®23 given before Prevnar13®), vaccine interaction (Menactra® given with Prevnar13®), or duplicated vaccines.

Results

Of the 174 patients screened, 29 patients were included in analysis, with a mean age of 58.2 ± 20.6 years. The splenectomy was elective in 69% of patients and emergent in 31% of patients. The vaccine regimen was given inappropriately in 96.6% of patients. The reasons for inappropriateness were vaccine selection (100%), timing (39.3%), vaccine sequence (39.3%), vaccine interaction (14.3%), and duplicate vaccines (7.1%). Excluding emergent splenectomies, 100% of patients received an inappropriate vaccine regimen. The vaccines were given at least 2 weeks before elective splenectomies in 40% of patients, peri-operatively in 30% of patients, and not given in 25% of patients.

Conclusion

Patients undergoing splenectomy received inappropriate vaccine regimens mainly due to omissions, timing, and sequencing. Prevnar13® should be given before Pneumovax®23 when both are indicated and vaccines should be administered at least 2 weeks before splenectomy.

An orderset was created to mitigate errors with vaccine selection for patients undergoing splenectomy.

Disclosures

All Authors: No reported disclosures.
2193. Epidemiology and clinical characteristics of Human adenovirus in Korean children over the past 12 years (2008-2019)
Authors: Ahn Bin , Song Seungha , Kim Ye Kyung , Yun Ki Wook , Choi Eun Hwa
Published: December 2022

Background

Human adenovirus (HAdV) is a common cause of respiratory tract infection (RTI) and clinical presentation varies by serotype. Serotypes 7 and 55 caused severe pneumonia in children during the early 2000s and in soldiers from 2014 to 2018, respectively, in South Korea. Recent data for the epidemiologic and clinical features of HAdV in Korean children are scarce.

Methods

Nasal aspirates were collected from patients aged 18 years or younger with suspected RTIs at Seoul National University Children's Hospital from 2008 to 2019. HAdV serotype was determined by partial sequencing of hexon gene. The demographics and clinical features were reviewed through medical records.

Results

A total of 186 HAdVs were randomly selected for serotyping among 503 isolates obtained for 12 years. The median age was 2.1 years (range 1 month -17.9 years) with a slight male dominance (60.8%). Ten different serotypes were identified, which included 1-7, 31, 34, 35, and 55. The most predominant serotype was HAdV-3 (n=73, 39.3%) followed by HAdV-2 (n=42, 22.6%). Lower RTI was common in children infected with HAdV-3 (n=40, 54.8%) and HAdV-2 (n=18, 42.9%). HAdV-3 showed an epidemic every three years. HAdV-7 which previously caused severe pneumonia, has not been detected since 2008. HAdV-55 (n=9, 4.9%) was sporadically detected by each one case in 2008, 2009, and 2014, while six cases were detected in 2017-18. Among children with HAdV-55 detected, most (66.7%) had upper RTI as clinical diagnosis and only two (22.2%) had a clinically considerable pneumonia.

Conclusion

Over the past 12 years, HAdV-3 and 2 were prevalent and played an important role in RTIs of Korean children. HAdV-55 infection in children was not clinically significant in comparison to the recent Korean military outbreak cases.

Disclosures

All Authors: No reported disclosures.
2194. Epidemiology, Clinical Features and Outcomes of Hospitalized Adult Patients with Respiratory Syncytial Virus Infections
Authors: Malik Ambreen , Sharma Mamta , Bhargava Ashish , Johnson Leonard B
Published: December 2022

Background

Respiratory Syncytial Virus (RSV) is a common cause of respiratory tract infection (RTI) in all age groups. In general, RSV causes more severe disease in the elderly and adults with underlying comorbidities. There are limited studies evaluating RSV disease among inpatient adults. Our study objective was to assess the epidemiology, clinical features and outcomes of RSV RTIs among hospitalized adults.

Methods

A multicenter retrospective cohort study was conducted on adult patients hospitalized for RSV RTIs in southeast Michigan from 1/1/19-12/31/21. Hospitalized patients were identified using ICD 10 codes for RSV related diseases. Electronic medical records were reviewed. We collected the following data: demographics, comorbid conditions, laboratory and radiology results, treatment received and outcomes (death, discharge, 30 day readmission).

Results

A total of 102 patients were identified and included for analysis. The mean (SD) age of the cohort was 68.8 ± 14.2 yrs, 61 (60%) were female and 60 (59%) were white. The mean body mass index of the cohort was 31 ± 9.5 kg/m2. The common comorbidities were chronic lung disease (75%), hypertension (69%), obesity (38%) and congestive heart failure (30%). The mean Charlson weighted index of comorbidity was 2.28 ± 2. Fever and hypotension were noted in 13% and 15% on admission respectively. Admission CXR were abnormal in 47% cases. RSV upper and lower RTI were present in 23 (22.5%) and 79 (77.5%) respectively. Antibiotics were given in 63% of patients. Infectious diseases consultation was obtained in 41% cases. Mechanical ventilation was required in 11%, intensive care in 23.5% patients and length of stay was 6.5 + 5.6 days. Other complications were encephalopathy in 17%, acute kidney injury in 21% and liver injury in 5%. Seven (6.8%) patients died.

Conclusion

Our study found that adults admitted with RSV tended to be elderly, have multiple comorbid conditions and a high incidence of lower RTIs. Admissions were frequently complicated by need for ICU stay, mechanical ventilation and death. Our study supports a need for RSV immunizations once available for this high risk population.

Disclosures

All Authors: No reported disclosures.
2198. Healthcare Utilization During Acute Medically Attended Respiratory Syncytial Virus (RSV) Episodes among Infants in the United States
Authors: Gantenberg Jason , van Aalst Robertus , Diakun David R , Limone Brendan L , Nelson Christopher B , Savitz David A , Zullo Andrew R
Published: December 2022

Background

Healthcare utilization during acute medically attended (MA) RSV-associated lower respiratory tract infection (LRTI) episodes remains poorly characterized, particularly among term infants without comorbidities. Describing the care incurred during these episodes may provide important information regarding the impact of MA RSV LRTI.

Objective: Estimate the occurrence and average number of outpatient, emergency department (ED), and inpatient visits during infants' first RSV season.

Methods

Using deidentified insurance claims data (MarketScan Commercial ®, MSC; MarketScan Medicaid ®, MSM; Optum Clinformatics ®, OC), we assembled a cohort of infants born in the United States between April 1, 2016 and February 29, 2020 and identified their first MA RSV LRTI episode during their first RSV season. We defined an RSV episode as the 7 days following an index RSV diagnosis (inclusive of the diagnosis date), allowing for two alternative definitions of the index diagnosis—a specific definition, based on ICD-10 codes explicitly indicating RSV, and a sensitive definition, including codes for unspecified bronchiolitis. We calculated the average number of outpatient, ED, and inpatient visits during this episode, stratifying estimates by gestational age and the presence/absence of comorbidities. We also calculated the proportion of episodes involving a given place of service.

Results

Using the specific (sensitive) definitions, infants averaged 1.11 (1.19), 0.90 (0.89), and 1.56 (1.39) outpatient visits during their first acute RSV episode, in the MSC, MSM, and OC datasets, respectively (Table). They averaged 0.35 (0.23), 0.51 (0.47), and 0.39 (0.23) visits to the ED and 0.28 (0.14), 0.25 (0.14), and 0.23 (0.11) inpatient stays. While MA RSV LRTI episodes among infants who were preterm and/or had other comorbidities (comorbidity groups B and C) were more likely to involve an ED or inpatient visit, up to 21% (10%) of episodes among otherwise healthy term infants involved an inpatient stay.

Conclusion

Up to 1 in 5 infants experiencing an MA RSV LRTI episode during their first RSV season visited an inpatient setting, including between 9% and 21% of otherwise healthy term infants.

This study was funded by Sanofi and AstraZeneca.

Disclosures

Jason Gantenberg, PhD, MPH, Sanofi: Grant/Research Support Robertus van Aalst, PhD, MSc, Sanofi: Stocks/Bonds David R. Diakun, BS, Sanofi: Employed by IBM Watson Health which was contracted by Sanofi to perfom outcomes research|Sobi: Employed by IBM Watson Health which was contracted by Sobi to conduct the study Christopher B. Nelson, PhD MPH, Sanofi: employee|Sanofi: Stocks/Bonds David A. Savitz, PhD, Sanofi-Pasteur: Grant/Research Support|Sanofi-Pasteur: Honoraria Andrew R. Zullo, PharmD, PhD, Sanofi: Grant/Research Support.
2211. High prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae identified through routine screening for rectal, pharyngeal, and urethral infections within a HIV pre-exposure prophylaxis program in Hanoi, Vietnam
Authors: Adamson Paul C , Bui Hao , Pham Loc , Le Hai , Nguyen Trung , Le Giang , Klausner Jeffrey
Published: December 2022

Background

Pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention and is being scaled up globally. Patients on PrEP have high rates of bacterial STIs, like Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), thus routine screening is recommended. However, access to screening tests for STIs are limited in many low-resource settings. The objectives of this study were to determine the prevalence of CT and NG among participants in Vietnam’s first PrEP program.

Methods

From January through April 2022 participants in the PrEP program at the Sexual Health Promotion Clinic in Hanoi, Vietnam were recruited to study STI prevalence. Study participants completed a survey collecting demographic, behavioral and clinical characteristics. Participants self-collected urine, rectal, and pharyngeal specimens for nucleic-acid testing. Participants positive for NG had an additional specimen collected for culture and antibiotic susceptibility.

Results

In total, 108 participants were enrolled, median age was 24 years (IQR: 22– 28). All were male and reported having sex with men in the prior 12 months. The median number of sex partners in the prior 1 month was 1 (IQR: 1 – 2). Symptoms within the prior week were reported by 41.7% (45/108) – 19.4% reported rectal, 15.7% reported urethral, and 26.9% reported pharyngeal symptoms. The overall prevalence of CT or NG infections was 31.5% (34/108). The prevalence of CT was 24.1% (26/108); by anatomic site, there were 17 (15.7%) rectal, 10 (9.3%) pharyngeal, and 6 (5.6%) urethral infections. The prevalence of NG was 13.0% (14/108); there were 12 (11.1%) pharyngeal, 9 (8.3%) rectal, and 0 urethral infections. Among participants reporting any symptoms, CT prevalence was 26.7% (12/45) and NG prevalence 13.3% (6/45). All infections were treated.

Conclusion

The prevalence of CT and NG was very high among this population of young MSM in a PrEP program in Hanoi, Vietnam. A high proportion of CT infections were rectal (65%) and 86% of NG infections were pharyngeal. These findings highlight the need for expanded access to extragenital nucleic-acid testing among PrEP programs in low- and middle-income countries. Studies demonstrating the benefit of CT/NG screening and treatment within PrEP programs are urgently needed.

Disclosures

Jeffrey Klausner, MD MPH, Cepheid: Advisor/Consultant|Cepheid: Grant/Research Support|Cepheid: Research equipment and supplies.
106. High Maternal Tdap Vaccine Uptake During Early Part of Vaccination Window: Implications for Future Maternal Vaccines
Authors: Law Amy W , Judy Jennifer , Willis Sarah J , Shea Kimberly M
Published: December 2022

Background

Maternal vaccines to prevent respiratory syncytial virus (RSV) among infants are in development. Uptake of existing maternal vaccines can be used to predict uptake of future maternal RSV vaccines and may be used to inform vaccine policy decisions. Previous reports of maternal vaccination rates do not estimate vaccine uptake by gestational week (wGA) of pregnancy, which is needed for precise estimation of vaccine impact. This study estimated the uptake of maternal Tdap vaccination overall and by wGA in a large electronic health records (EHR) database representing both privately and publicly insured patients over a recent 5-year period.

Methods

We identified pregnant women aged 15 – 44 years who had a live birth delivery between 01/01/2017 – 9/29/2021 in the Optum EHR database. Continuous activity for 6 months pre-conception through 1 day after delivery were required. Patients with >1 type of pregnancy outcome within 7 days and/or unidentifiable wGA were excluded. We utilized recently published gestational age algorithms to estimate the uptake of maternal Tdap vaccination overall and by wGA of pregnancy. Results were reported by year.

Results

The population included 1,056,488 live births among 919,510 pregnant women during the study period. The average age at delivery was 29.7 years (SD: 5.6), 72% were white, 82% were non-Hispanic; 58% had private insurance, and 38% had Medicaid. Overall, 56% of the pregnancies included a Tdap vaccine during their pregnancy. Among vaccinated pregnancies, the majority (68%) of Tdap vaccines were administered during the first 6 weeks of the recommended 10-week vaccination window (CDC recommends Tdap vaccination from 27-36 wGA) (Table). Table.Timing of Maternal Tdap Vaccination among Pregnant Women, by Year

Conclusion

In this analysis using a large EHR database, the overall uptake of maternal Tdap vaccination was consistent with previously published estimates. Notably, the majority of Tdap vaccination occurred during the earliest weeks of the recommended vaccination period. These results may have important implications for estimating potential impact of future maternal vaccines.

Disclosures

Amy W. Law, PharmD, Pfizer: Employment|Pfizer: Stocks/Bonds Jennifer Judy, MS, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Sarah J. Willis, PhD, MPH, Pfizer: Pfizer supported research at Harvard Pilgrim Health Care Institute (paid to Institute)|Pfizer: Employment Kimberly M. Shea, Ph.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds.
2222. 3-Day Ceftriaxone vs. Longer Durations of Therapy For Inpatient Treatment of Uncomplicated UTI
Authors: Elajouz Balsam , Dumkow Lisa E , VanLangen Kali , Worden Lacy , Jameson Andrew
Published: December 2022

Background

In the outpatient setting, IDSA guidelines recommend a 3-day course of highly bioavailable oral antibiotics (abx) for treatment of uncomplicated urinary tract infections(uUTI); however, hospitalized patients often receive IV abx and longer durations. Ceftriaxone (CRO) is well tolerated and has a favorable spectrum of activity making it an ideal antibiotic for inpatient uUTI treatment. The purpose of this study was to compare a short, 3-day course of ceftriaxone with longer durations of therapy for inpatients with uUTI.

Methods

This retrospective cohort study included adult inpatients receiving abx for symptomatic uUTI with a positive urine culture between July 1, 2015 and June 30, 2021. The primary objective was to compare clinical cure between patients treated with 3-days of CRO (CRO 3-day) vs longer durations of abx therapy (Longer DOT). Clinical cure was defined as resolution of uUTI symptoms at completion of abx and no new documented symptoms within 24 hours following completion. Secondary outcomes included comparing hospital length of stay (LOS), 30-day return visit due to UTI, and development of Clostridiodes difficile within 30 days of abx treatment. Patients empirically treated with an anti-pseudomonal abx, microbiological resistance to CRO, co-infection, or complicated UTI were excluded.

Results

A total of 100 patients were included in the study (CRO 3-days, n=51; Longer DOT, n=49). Baseline characteristics were similar between groups. There was no difference in the primary endpoint between groups as all patients in the sample population achieved clinical cure (p=1.0). Additionally, no differences in median hospital LOS (5 [4-7] vs 4 [3-6.5] days, p=0.372), 30-day return visit due to UTI (13.7% vs 6.1%, p=0.319), or development of C. difficile within 30 days of treatment (2% vs 6.1%, p=0.357) were observed between the CRO 3-days vs Longer DOT groups, respectively.

Conclusion

There were no differences in efficacy or safety endpoints between short-course CRO and longer durations of therapy. Short-course IV CRO is likely an effective treatment strategy for inpatient treatment of uUTI and may limit prolonged antibiotic durations.

Disclosures

All Authors: No reported disclosures.
2229. Antibiotic Resistance in Gram-Negative Community-Onset Urinary Tract Infections Among Adults Presenting to Hospitals, United States, 2012-2020
Authors: Li Deana , Baggs James , Wolford Hannah , Kutty Preeta K , McDonald L C
Published: December 2022

Background

Choosing empiric therapy for patients with community-onset urinary tract infections (CO-UTI) presenting to hospitals for treatment is challenging without understanding local antimicrobial susceptibility patterns. We investigated changes over time in antimicrobial resistance among CO-UTI pathogens and identified patient-level factors associated with higher levels of resistance.

Methods

We used non-duplicate positive urine cultures in the 2012-2020 Premier Healthcare Database as a proxy for CO-UTI in patients ≥ 18 years old presenting to hospitals receiving care categorized as community-onset inpatient (CO-INPT) or observation/emergency department (OBS/ED). We included cultures positive for Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa obtained within 3 days of admission. Phenotypes investigated include resistance to extended-spectrum cephalosporins (ESC), fluoroquinolones (FLQ), and trimethoprim-sulfamethoxazole (TMP-SX). Logistic regression analyses were performed.

Results

Among 1,987,605 urine cultures meeting study criteria from 432 hospitals, > 66% were E. coli. Antibiotic resistance (AR) was highest to FLQ among CO-INPT E. coli (31.7%) and P. mirabilis (29.3%) in 2020. ESC resistance increased from 2012 to 2020 among E. coli and K. pneumoniae in both CO-INPT and OBS/ED (p< 0.001). TMP-SX resistance remained > 20% among E. coli in CO-INPT and OBS/ED and P. mirabilis in CO-INPT throughout the study period. All AR phenotypes were significantly higher among CO-INPT than OBS/ED (p< 0.001), and higher among males than females (p< 0.001). FLQ resistance among E. coli, P. mirabilis, and P. aeruginosa was > 20% among males (28.2%, 30.4%, 21.9% respectively) but not females (17.5%, 15.1%, 14.5%) in OBS/ED, while it was > 20% among both males (37.2%, 37.3%, 24.6%) and females (31.2%, 33.9%, 21.9%) in CO-INPT. Figure 1.% Resistance to extended-spectrum cephalosporins by year and acute care setting.Figure 2.% Resistance to fluoroquinolones by year and acute care setting.Figure 3.% Resistance to trimethoprim-sulfamethoxazole by year and acute care setting.

Conclusion

Resistance to TMP-SX in both CO-INPT and OBS/ED, and FLQ in CO-INPT, was elevated suggesting alternative empiric therapy might be necessary for CO-UTI presenting to hospitals. Increasing resistance to ESC among pathogens in CO-INPT cultures warrants further evaluation of local resistance levels. Gender and need for inpatient therapy are factors to consider in developing local treatment recommendations.

Disclosures

All Authors: No reported disclosures.
2240. Implementation of a Clinical Decision Support Panel for Urine Culture Ordering
Authors: Yarrington Michael E , McClellan Fabienne , Dunkerson Tray , Reynolds Staci S , Polage Christopher R , Smith Becky A , Seidelman Jessica , Lewis Sarah S , Advani Sonali D
Published: December 2022

Background

Standard urine culture collection techniques have a high risk of false positive results in catheterized patients. IDSA guidelines recommend replacing long-term catheters before specimen collection for cultures. Our goal was to evaluate the impact of clinical decision support (CDS) during the urine culture computerized provider order entry (CPOE) on test use and patient-level outcomes.

Methods

In March 2021, CDS was added to the urine culture CPOE in the electronic health record (EHR). The order panel includes education regarding appropriate clinical indications for urine culturing, and protocolizes urine collection to determine (A) if a urinalysis was ordered, (B) if special patient population (i.e., PICU), (C) the presence and duration of an indwelling urinary catheter, and (D) whether the catheter had difficulty with placement. Depending on the criteria identified in A, B, C, and D, the panel recommends catheter removal prior to urine culture (Figure 1). We retrospectively evaluated the impact of panel implementation in our pre- (7/2020- 3/2021) and post-intervention periods (4/2021- 3/2022) using an interrupted time series analysis with Poisson regression. Outcomes included urine cultures/1000 patient days (pd), number of catheter removal orders, catheter-associated urinary tract infection (CAUTI)/1000 catheter days, and days of antibiotic therapy with urinary tract infection (UTI) indication/1000pd

Order Panel Framework

Results

Clinicians selected catheter removal in 183 of 2133 (8.5%) instances of ordering a urine culture when a catheter was detected by the panel (Figure 2). Analysis revealed a significant decrease in urine culture orders (1.1% decrease/month, p< 0.05), a decreasing trend of antibiotic use with UTI indications (Figure 3, 2.8% decrease/month, p< 0.05), but no significant change in CAUTI rates (Figure 4). Evaluation of the safety reporting system revealed no identifiable increase in safety events related to catheter removal or reinsertion.

Catheter Associated Urinary Tract Infections

Black boxes indicate Poisson regression model estimates

Black boxes indicate Poisson regression model estimates

Conclusion

CDS can aid in improving urine culture practice habits, including removal of long-standing catheters before urine culture. The decreasing trend in total urine culture orders (Figure 5) may reflect a ”culture change” over time to avoid urine cultures in inappropriate instances.

Total Urine Cultures Ordered

Black boxes indicate Poisson regression model estimates. Red circles indicate predicted outcome without ‘intervention’.

Disclosures

Sonali D. Advani, MBBS, MPH, FIDSA, Locus Biosciences: Advisor/Consultant|Locus Biosciences: Honoraria|Sysmex America: Advisor/Consultant.
108. Immune Status of Indian Pediatric Health Care Workers against Various Vaccine Preventable Diseases
Authors: Verma Sanjay , Sachdeva Ravinder Kaur , Mahajan Vidushi , Rawat Amit , Nehra Urvashi , Subramani Vignesh , Jassal Monika , Bharti Bhavneet
Published: December 2022

Background

Health care workers (HCWs) possess a potential risk to acquire and spread various infections. This study was planned to assess the immune status of HCWs in pediatric departments of two tertiary care hospitals in Northern India.

Methods

In this cross-sectional study, HCW’s (Indians), working in pediatric departments of these hospitals, over 6-months period (July18-Dec18) were enrolled after taking written consent and their 5-ml venous blood sample was collected. Ethical clearance was obtained from Institute Ethics committee, before enrolling subjects. Serum were tested for antibodies against diphtheria-toxin (DT), pertussis-toxin (PT), measles, mumps, rubella, varicella, hepatitis-B (HbsAb) and hepatitis-A using commercial IgG (quantitative) ELISA kits.

Results

A total of 160 HCW’s (M:F=77:83), having mean age 30.6±7.8 years, were enrolled. Out of them 106 (66.3%) were resident doctors, 31 (19.4%) nursing-staff, 18 (11.3%) faculty members, 3 (1.9%) research-staff and 2 (1.3%) paramedical-staff. In our study, antibodies (IgG) against DT were between 0.01 to 0.1 IU/ml in 78.1% (120/160); requiring a Tdap booster; while 7 out of 125 had titers < 0.01 IU/ml, which needed 3-doses of primary vaccination. Antibodies (IgG) against PT < 30 IU/ml were seen in 60.6% (97/160), which were considered as seronegative, as per kit recommendations.

A total of 3% (5/160), 13.1% (21/160), 10% (16/160), 17.5% (28/160) had titers < 12 IU/ml for IgG antibodies against measles, mumps, rubella and varicella respectively; were considered unprotected. A total of 25% (40/160) had Anti-HBs antibody titers < 20 mIU/ml; which were low, therefore were advised to take one booster dose of Hep-B vaccine. A total of 15.6% (25/160) had IgG antibodies against hepatitis-A < 10 mIU/ml; were unprotected.

Conclusion

Alarming proportions of pediatric-HCWs had low antibody titres against DT (78.1%) and PT (60.6%), necessitating a dose of Tdap. A total of 10%, 17.5% and 15.6% lacked protective antibodies against rubella, varicella and hepatitis-A. A quarter of screened population had low anti-Hbs titres, requiring boosting of immunity. Our study emphasizes the urgent need for improving immunization status of pediatric HCW’s; as they continue to remain susceptible to various vaccine preventable infectious diseases.

Disclosures

All Authors: No reported disclosures.