bluuebunny/crossref_metadata_2025_split huggingface dataset:
392. Antiretroviral Prophylaxis to Prevent Perinatal HIV Infection in Medicaid-Insured Infants, 2009-2021
Authors: Lu Mingyue , Inagaki Kengo 
Published: January 2025

Abstract

Background
All infants born to people living with human immunodeficiency virus (HIV) should receive postnatal antiretroviral prophylaxis. National policy surrounding perinatal HIV transmission has evolved over time, while real-life data on the effects of such policies are lacking.
HIV Infection within One Year of Life among Newborn Infants with or without Perinatal Antiretroviral Prophylaxis

Methods
We performed a population-based retrospective study using the MarketScan Multi-Sate Medicaid Database from 2009 to 2021. We identified antiretroviral drug use among infants and classified them into prophylactic and therapeutic use. A linear regression model was developed to identify the temporal trend of the use of the zidovudine single prophylaxis among infants receiving postnatal HIV prophylaxis.

Results
We identified 3,147,318 newborn infants during the study period. Among them, 2304 received postnatal antiretroviral prophylaxis, with 2123 receiving zidovudine single prophylaxis in 2009, the rate dropped to 71.7% of such infants by 2021 as a result of the adoption of double and triple prophylactic regimens (P for trend &lt; 0.001). Triple prophylaxis became more commonly used than double prophylaxis by 2018. During the study period, 52 infants had HIV infection within 1 year of life. Among them, 27 (51.9%) infants did not receive perinatal prophylaxis.

Conclusion
Postnatal HIV prophylaxis strategies have evolved over time, reflecting the shifts in healthcare policy. Importantly, more than half of infants diagnosed with HIV during the first year of life did not receive perinatal prophylaxis, suggesting missed maternal infections. Healthcare policy is well-adopted in perinatal HIV infection prevention, but continued evaluation of its adequacy is necessary.

Disclosures
Kengo Inagaki, MD, AstraZeneka: Grant/Research Support
P-1087. Novel Antisense Wide-Range Peptide Nucleic Acids Coated on Polystyrene Plates to Prevent Bacterial Biofilm
Authors: Karp Hannah , Nowak Elizabeth , Su Gillian , Akguc Nihan , Schulz Michael , Sriranganathan Nammalwar , Rao Jayasimha 
Published: January 2025

Abstract

Background
Biofilms are three dimensional communities of microorganisms that are encased in self-produced extracellular polymeric substances. Biofilms play a key role in device-associated infections, including catheter-associated urinary tract infections, largely because they protect microorganisms from standard antimicrobial therapies. Antisense synthetic peptide nucleic acids (PNAs) are an emerging approach to inhibiting specific components of gene expression. Several regulatory and motility genes are relatively conserved across biofilm forming Gram-negative bacilli, such as rpoS, amrZ, rsmA, and motA. In the present study, wide range PNAs (wrPNAs) were developed by our group to exploit these conserved targets, offering a mechanism for precise, yet broad, biofilm inhibition. The impact of wrPNAs on Gram-negative biofilms and bacterial viability were investigated.

Methods
wrPNAs: Antisense-wrPNAs (patent pending) were designed using NCBI Blast to select a region inclusive of the start codon. The wrPNAs ranged from 12 to 14 basepairs, conjugated with a cell-penetrating peptide and O-linker, and were synthesized by PNA Bio (Figure 1).
Quantify biofilm biomass: Bacterial isolates were grown in a 96-well polystyrene plate in minimal salt medium with wrPNA treatment (10 µM each) and incubated at 30˚C for 24hr in a humid chamber. Biofilms were stained with 0.1% crystal violet, solubilized in 33% glacial acetic acid, and measured at OD590 nm.
Quantify bacterial viability: 10-fold serial dilutions and direct stamping onto agar plates.
Statistical analysis: P values were determined using unpaired t-tests or one-way ANOVA with followup tests comparing the mean of each column to the control column (alpha = 0.05).

Results
wrPNA treatment significantly reduced biofilm biomass for their intended species (Figure 2). A cocktail of PNAs had a bactericidal effect on Pseudomonas aeruginosa, but wrPNA treatment had minimal effect on bacterial viability for the other Gram-negative bacilli tested (Figure 2).

Conclusion
wrPNAs against global regulator genes and a motility regular gene reduced biofilm biomass for their intended species. Future work will look at combination therapy to improve bactericidal effects as well as methods for coating treatments onto catheter and device surfaces.

Disclosures
All Authors: No reported disclosures
P-1103. In Vitro Activity of Zoliflodacin Against Baseline Neisseria gonorrhoeae Isolates from US Participants in a Global Phase 3 Randomized Controlled Trial
Authors: McLeod Sarah , Elango Varalakshmi , Bettiol Esther , Luckey Alison 
Published: January 2025

Abstract

Background
Zoliflodacin is an oral, single-dose, first-in-class spiropyrimidinetrione bacterial topoisomerase inhibitor with activity against multidrug-resistant strains of Neisseria gonorrhoeae. Efficacy and safety of zoliflodacin for the treatment of uncomplicated gonorrhea was studied in a global Phase 3 trial that demonstrated non-inferiority to ceftriaxone plus azithromycin. In this study, the antibiotic susceptibility of baseline N. gonorrhoeae isolates from US participants in the Phase 3 trial was characterized.

Methods
Overall, 163 N. gonorrhoeae baseline isolates (139 urogenital, 13 pharyngeal, 11 rectal) were cultured from participants enrolled at 5 US clinical sites. Isolates were speciated using MALDI-TOF. MICs were performed using agar dilution according to CLSI guidelines. CLSI interpretive criteria were applied where available.

Results
The zoliflodacin MIC50/90 was 0.06/0.12 µg/mL (MIC range ≤0.008 – 0.25 µg/mL) against 139 baseline urogenital N. gonorrhoeae isolates, which is consistent with that seen among pharyngeal and rectal US isolates and the global set of baseline isolates from the Phase 3 trial (Table 1). Azithromycin susceptibility rates were lower for the US isolates (69-91% depending on the body site of infection) compared to the global isolates (89-95%); however, susceptibility to ciprofloxacin was higher (62-73% vs 17-28%). For all isolates, susceptibility to tetracycline was low (0-12%) while ceftriaxone susceptibility was high ( &gt;99%). There was 1 ceftriaxone resistant isolate from a US patient (MIC &gt;0.5 µg/mL). This was a pharyngeal isolate also resistant to ciprofloxacin and tetracycline, but susceptible to azithromycin. Zoliflodacin demonstrated an MIC of 0.12 µg/mL against this isolate.

Conclusion
Against N. gonorrhoeae baseline isolates from US participants from a Phase 3 trial for uncomplicated gonorrhea, the in vitro potency of zoliflodacin was consistent with that observed against the global set of baseline isolates and US surveillance studies. Zoliflodacin maintained activity against multidrug-resistant isolates. These data complement the recent Phase 3 results and support the continued development of zoliflodacin for patients with uncomplicated gonorrhea.

Disclosures
Sarah McLeod, PhD, Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Stocks/Bonds (Public Company) Alison Luckey, MD, GARDP: Employee of GARDP, a non-profit Swiss-based foundation, which receives government and private-funded institutional grants/research support
416. Impact of clinical diagnostic stewardship of respiratory cultures across a multicenter PICU collaborative
Authors: Sick-Samuels Anna , Kelly Daniel , Woods-Hill Charlotte , Arthur Abigail , Kumar Urmi , Koontz Danielle W , Xie Anping , Marsteller Jill A , Xiao Shaoming , Colantuoni Elizabeth , Milstone Aaron 
Published: January 2025

Abstract

Background
Respiratory culture practices for critically ill patients with artificial airways vary across and within institutions. Over-testing contributes to unnecessary antibiotic treatment. This study aimed to evaluate the efficacy and safety of implementing clinical decision support to standardize indications of respiratory cultures across a multicenter PICU collaborative.
Monthly Respiratory Culture Rate per 100 Ventilator-Days Before and After Implementing Diagnostic Stewardship Programs
The monthly respiratory culture rate is shown for 15 pediatric intensive care units participating in BrighT STAR Respiratory, a multicenter diagnostic stewardship quality improvement collaborative, 24 months before and 18 months after implementing diagnostic stewardship programs. The mean monthly average rate over time was estimated using a smoothing spline.

Methods
15 U.S. PICUs participated in the BrighT STAR Respiratory Collaborative, a prospective multicenter quality improvement program (QI) from 2019-2023. Each hospital executed local QI programs to improve respiratory culture practices, facilitated by the larger collaborative. The primary outcome was the monthly rate of respiratory cultures per 100 ventilator-days. Process and safety measures included the proportion of cultures repeated within 3 days, bronchoalveolar lavage (BAL) cultures per 100 ventilator-days, and ventilator-associated events (VAE) per 100 ventilator-days among 3 centers conducting this surveillance. We analyzed rates 24 months pre- and 18 months post-intervention using a Poisson generalized linear mixed model with random intercept for sites, robust variance estimates and adjustment for seasonality. Site leads surveyed local faculty for patient safety concerns.

Results
Across 15 PICUs, the monthly average respiratory culture rate was 7.80 per 100 ventilator-days pre-implementation and 6.55 per 100 ventilator-days post-implementation, a 16% rate ratio (RR) reduction (95% confidence interval (CI) 0.78-0.90, P&lt; 0.001). Cultures repeated within 3 days declined 22% from 13% to 10% (95%CI 0.68-0.89, P&lt; 0.001). The BAL culture rate did not change from 0.67 to 0.72 (RR 1.07, 95% 0.85-1.34, P=0.57). The VAE rate did not change from 0.21 to 0.25 (RR 1.17, 95%CI 0.87-1.58, P=0.28). Among 2,525 inquiries to attendings about safety concerns, 2348 replied (93%); 2 concerns were reported (0.08%) regarding perceived delay to cultures with no resulting patient harm.

Conclusion
Standardizing respiratory culture ordering practices may be an effective diagnostic stewardship approach for pediatric patients with artificial airways. We plan to assess impact on clinical outcomes and antibiotic use and to assess facilitators and barriers to implementation.

Disclosures
Aaron Milstone, MD, MHS, Merck: Grant/Research Support
P-1127. Outcomes of Guideline Discordant Tracheal Aspirate Cultures in the Pediatric ICU
Authors: Iles Kerry , Picciarelli Zachary , Rapsinski Glenn J , Aldewereld Zachary 
Published: January 2025

Abstract

Background
Life-saving mechanical ventilation is associated with risk of ventilator-associated infections, though diagnosis of such infections can be difficult. Diagnostic respiratory cultures are often obtained via tracheal aspirate. These cultures can be misleading due to the non-sterile nature of the respiratory tract and the potential for chronic colonization of endotracheal and tracheostomy tubes by pathogenic bacteria which are not actively causing infection. Consequently, growth does not necessarily reflect infection. Misinterpretation of inappropriately collected cultures results in unintended consequences including unnecessary use of antibiotics, antibiotic resistance, and prolonged hospital stay.

Methods
We created a clinical decision support tool as part of the BrightStar2 initiative using signs of acute respiratory infection with the aim to safely minimize collection of cultures lacking diagnostic utility. We completed a retrospective study of tracheal aspirate cultures (TAC) collected in a 36-bed ICU at a pediatric tertiary care hospital from January to December 2022. We determined whether cultures met support tool criteria for collection, including signs of infection, respiratory change, and lack of previous TAC within 48 hours. We then investigated results of unsupported cultures to determine whether cultures provided clinically actionable information.

Results
Of 200 tracheal aspirate cultures, 133 cultures (67%) did not meet criteria for collection, most commonly due to lack of change in respiratory status. A total of 27 unsupported TACs grew new organisms (20%) of which only one organism had clinical significance, accounting for less than 1% of unsupported cultures.

Conclusion
This data suggests our clinical decision support tool is effective in identifying patients in whom a TAC will not yield useful clinical information.

Disclosures
All Authors: No reported disclosures
P-1132. Patient Pre-Selection Improves Efficiency and Acceptability of Antimicrobial Audit-and-Feedback Rounds in a Neonatal Intensive Care Unit
Authors: Lefebvre Marie-Astrid , Girard Gabrielle , Karatzios Christos , Rubin Earl , McDonald Jane 
Published: January 2025

Abstract

Background
Audit-and-Feedback Rounds (AFR) are an effective way of evaluating the appropriateness of antimicrobials in inpatient settings, but they are time- and resource-intensive. In our 52-bed tertiary care neonatal intensive care unit (NICU), AFR methodology was modified in that pharmacists would pre-select patients to be discussed, in order to focus on value-added discussions. This observational study describes the impact of this intervention on key AFR metrics.Figure 1.Percentage of NICU patients on systemic antimicrobials who were discussed at audit-and-feedback rounds, pre- and post-intervention.

Methods
Since October 2019, the NICU team and an Infectious Diseases (ID) physician met weekly to review all patients on systemic antimicrobials at the time of AFR. The ID physician assessed the appropriateness of antimicrobials and made recommendations to the team. Pharmacists prospectively collected data on the duration of AFR, reasons for inappropriate prescriptions, recommendations made, and adherence to recommendations 24 hours later. To improve efficiency, from September 2021 on, it was agreed that pharmacists would select out some patients from the discussion list as they were considered by default to be on appropriate therapy: those followed by the ID service; neonates on empiric ampicillin and an aminoglycoside for early-onset sepsis; and those on prophylactic antimicrobials if already reviewed once before.Figure 2.Percentage of antimicrobial stewardship recommendations accepted by NICU team, assessed 24 hours post-rounds.

Results
In the pre-intervention period (Oct 2019 - Oct 2020), 92% (n = 226) of patients on systemic antimicrobials were reviewed, and AFR lasted 27 minutes on average. Antimicrobial use was considered appropriate for 88% of patients and 75% (n=55) of recommendations were accepted by the NICU team. In the initial post-intervention period (Oct 2021- Oct 2022), 30 % (n = 101) of patients on antimicrobials were discussed at AFR (Figure 1), and usage was considered appropriate in 80% (n = 123). Between Oct 2022 and Oct 2023, mean duration of AFR had decreased to 13 minutes, and adherence to recommendations increased to 92% (n=36).

Conclusion
Patient pre-selection for AFR was associated with shorter rounds and increased uptake of recommendations by clinical teams. This method could be used to conduct AFR in other busy inpatient settings.

Disclosures
All Authors: No reported disclosures
P-1133. Preferred (Spoken) Language was a Major Correlate of Disparate Antibiotic Prescribing in the Pediatric Outpatient Setting Throughout the COVID-19 Pandemic
Authors: Day Melissa E , Duan Qing , Markham Justin , Courter Joshua D , Risma Kimberly , Beck Andrew F , Haslam David 
Published: January 2025

Abstract

Background
No studies have explored sociodemographic variation in antibiotic prescribing across phases of the COVID-19 pandemic. We explored relationships between race, language, socioeconomic measures, and outpatient antibiotic prescribing patterns at our institution before and during the pandemic.

Methods
Data were obtained across all Cincinnati Children’s outpatient primary care centers, urgent cares, and emergency departments (n = 24) from 2018-2023. Outpatients aged 0-18 years with an acute respiratory tract infection were included. Our primary outcomes were the proportion of encounters with antibiotics prescribed. Sociodemographic factors included race, ethnicity, primary language, insurance status, and a socioeconomic deprivation index (SDI) linked to a child’s geocoded home address (with higher scores showing more deprivation). We examined associations between such factors and antibiotic prescribing before (2018-19) and during (2020-21 and 2022-23) the COVID-19 pandemic. Chi-square analyses evaluated associations of proportions across groups.

Results
A total of 185,338 clinical encounters of 99,037 children with median age 3.6 years (IQR 1.3-7.5), 58% White, 9% Hispanic, and 93% English-speaking were captured from 2018-2023. Table 1 shows associations of sociodemographic variables and antibiotic prescribing. While only small differences were noted in prescribing across race and insurance, patients preferring languages other than English had significantly more antibiotic use (Spanish (79%), Nepali (78%), Arabic (77%), Other (74%)) than those who preferred English (69%, p&lt; 0.001). No clinically significant differences (≥5%) were found across SDI quartiles. Antibiotic use decreased early in the COVID-19 pandemic among all sociodemographic groups, rebounding to or above prior pre-pandemic levels and maintaining sociodemographic differences later in the pandemic (Table 2).

Conclusion
At our institution, contrary to prior studies, children who preferred languages other than English received more antibiotics than English-speaking peers, associations which persisted across the COVID-19 pandemic. Next steps include investigating language-based differences in infectious diagnoses and antibiotic prescribing across individual outpatient sites.

Disclosures
All Authors: No reported disclosures
P-1135. Influence of Antibiotic and Laxative Use on Clostridioides difficile Testing in Post-Operative Children
Authors: Negi Ruchita , Deshpande Abhishek , Worley Sarah , Arakoni Venkatraman , Foster Charles B 
Published: January 2025

Abstract

Background
Antibiotic exposure in surgical patients poses risks, contributing both to Clostridioides difficile infection (CDI) and to antibiotic associated diarrhea. While CDI may cause diarrhea, we hypothesized that negative CDT could be a proxy for non-infectious diarrhea and aimed to discern if broad-spectrum (BS) antibiotics or laxatives influenced negative CDT.
Broad Spectrum Antibiotics and Laxative Use In Post-Operative Children with Negative C difficile Test Compared to Matched Controls
CDT: C difficile Testing, DOT: Days of Therapy, SAAR: Standardized Antibiotic Administration Ratio

Methods
A matched case-control study (Jan 2013-Feb 2022) examined risk factors for negative CDT in children (2-18 years) undergoing sedated procedures with preoperative antibiotic prophylaxis at a large referral hospital. Perioperative data was merged with antibiotic and laxative data from the Electronic Medication Administration Record (eMAR). Cases with PCR-negative CDT on postoperative days 3-90 were matched with untested controls based on age, gender, year of testing, and procedure category. We assessed Days of Therapy (DOT) of antibiotics or laxatives for various periods.

Results
Among 14,229 children (mean age 10 ± 5.2 years) undergoing 18,705 procedures, 108 cases and 108 controls were selected. Children with negative CDT received more BS antibiotics 3 days before the test date (1000DOT/LOS = 410) than controls (1000DOT/LOS = 271; OR 1.9 (1.06 – 3.5); P =0.031). Conversely, cases received fewer laxatives postoperatively and 3 days before CDT (1000DOT/LOS =148) than controls (1000DOT/LOS = 346; OR 0.35 (0.17-0.73); P=0.005). No difference was observed in pre-operative laxative use.

Conclusion
Our data suggests that BS antibiotics are a more important contributor to post-operative non-infectious diarrhea in children than laxatives. Antimicrobial stewardship efforts targeting BS antibiotic use in post-operative children could mitigate diarrhea and unnecessary CDT.

Disclosures
Abhishek Deshpande, MD, PhD, AHRQ: Grant/Research Support|Clorox Healthcare: Grant/Research Support
P-1136. Enhancing Pediatric Care: Antimicrobial Stewardship Through 24/7 Pharmacist-Driven Rapid Diagnostics for Gram-Negative Bacteremia
Authors: Huynh Anthony , Gavaza Paul , Tompkins Noreen Chan 
Published: January 2025

Abstract

Background
Rapid diagnostic testing (RDT) in adult bacteremic patients (pts) provides quick organism identification, including resistance genes and can improve time to optimal antibiotic therapy (OAT). Pharmacist-driven RDT (Rx-RDT) interventions [24 hours/day and 7 days/week (24/7)] for pediatric gram-negative bacteremia GNB is limited. Objective was to evaluate outcomes before and after implementation a 24/7 Rx-RDT interventions (INT) for treatment of pediatric GNB.

Methods
Retrospective cohort study analyzed pediatric pts (age &lt; 18 years) with GNB secondary to Escherichia coli, Klebsiella pneumoniae or Klebsiella oxytoca admitted to the Children’s Hospital comparing outcomes before and after implementation of 24/7 Rx-RDT INT. Pre-RDT group included pts admitted from 1/1/14-12/31/14; Pre-RDT 24/7 group embodied weekday antimicrobial stewardship (AMS) duties from 1/1/19-7/5/21; and Post-RDT 24/7 from 7/6/21-8/31/22. Polymicrobial bacteremia or concomitant fungemia were excluded.

Results
A total of 132 pts were included in 3 groups: Pre-RDT (n=35); Pre-RDT 24/7 (n=55); Post-RDT 24/7 (n=42). Baseline demographics were mainly similar with Hispanic predominance (Table 1). In Pre-RDT, Pre-RDT 24/7, and Post-RDT 24/7, respectively, E. coli was most common (65.7% vs 60% vs 54.8%; p=0.666) with CTX-M gene detection (associated with the extended spectrum beta-lactamase (ESBL) phenotype) in latter 2 groups (9.1% vs 26.1%; p=0.013) followed by K. pneumoniae (28.6% vs 25.5% vs 33.3%; p=0.666) with ESBL 21.4% in latter groups; p &gt;0.05). Pts were on OAT at the time of gram-stain (GS) results in 85.7% vs 74.5% vs 59.5%; p=0.034. For pts who were not on OAT at GS results, time to OAT from blood culture collection was lowest in the Post-RDT 24/7 group (85.6 vs 26.2 vs 15.7 hours; p=0.156); time to OAT was faster from time of RDT results Post-24/7 RDT (7.9 vs 2.4 hours; p=0.028). Length of stay (19.5 vs 12.9 vs 13.3 days; p=0.601) and 30-day mortality were similar (11.4% vs 14.5% vs 9.5%; p=0.746); 30-day mortality occurred with Hispanics in all groups (18.2% vs 16.7% vs 14.4%). Night/Weekend pharmacists performed 44% of the Post-RDT 24/7 INT.

Conclusion
Implementation of Rx-RDT interventions 24/7 reduced time to OAT by 30% for pediatric GNB. Night/Weekend pharmacists were integral to our AMS program.

Disclosures
All Authors: No reported disclosures