bluuebunny/crossref_metadata_2025 huggingface dataset:
384. National Trends and Racial Disparities in Sepsis-Related Mortality in Children in the United States, 1999-2019
Authors: Boasiako Ladonna , pappoe Patricia , Asante-Darko Manye Ami , Saka Allotey Felix Nii , Peseo Jennifer , Ononogbu Chidinma S , Dapaah-Siakwan Fredrick
Published: January 2025

Background

There is conflicting data on the racial differences in sepsis-related mortality rate (SRMR) in children and little is known about the trends in SRMR in children in the United States (US). We examined the national trends and racial disparities in SRMR in children in the US from 1999 to 2019.

Sepsis-related mortality rate in US children stratified by age, gender, race, and geographic region.

Sepsis-related mortality rate in US children stratified by age, gender, race, and geographic region.

Methods

This was a retrospective cross-sectional analysis of national death certificate data from the CDC WONDER database from 1999-2019. We used ICD-10 codes to identify children aged 0-18 years who had bacterial sepsis as the underlying cause of death. We excluded deaths from viral, fungal, parasitic, tuberculous, and rickettsial illnesses. The crude SRMR was calculated per 100,000 population and further stratified by age, gender, race, and census region. Racial disparity was evaluated by the NHB-to-NHW SRMR ratio. The Mann-Whitney U test was used to compare two groups and P < 0 .05 defined statistical significance. We evaluated temporal trends with Joinpoint regression, expressed as average annual percentage change (AAPC) with 95% confidence intervals (CI). Next, we repeated the analysis with any mention of bacterial sepsis as a cause of death.Figure 1.Trends in sepsis-related mortality rate in children in the US, 1999-2019.

Results

Among 1.6 billion children, 23,466 had bacterial sepsis as the underlying cause of death [1.4 per 100,000; CI, 1.4 -1.5)]. The SRMR differed by age, gender, race, and geographic region (Table 1). The overall SRMR decreased from 1.7 in 1999 to 1.2 in 2019 (AAPC -1.9%; CI: -2.4, -1.3%) [Figure 1]. The SRMR decreased in males (1.9 to 1.2; AAPC -2.2%, CI: -2.5, -1.9), females (AAPC -2%, CI: -2.5, -1.6), NHB (AAPC -1.7%, CI: -2.3, -0.9); NHW (AAPC -2.1%, CI: -2.4, -1.6), rural (AAPC -2.5%, CI: -3.4, -1.5) and urban areas (AAPC -1.9%, CI: -2.3, -1.5), and in all census regions. The overall NHB-to-NHW SRMR ratio was 2.7 and there was no significant change during the study period. When limited to any mention of sepsis as the cause of death, the differences and trends in SRMR remained unchanged (Figure 1B).

Conclusion

The SRMR declined significantly overall and for all demographic groups. The persistent disparity in SRMR between NHB and NHW suggests differential access to care, recognition and prompt treatment of sepsis. Future studies should unravel the underlying causes of this disparity in mortality outcomes.

Disclosures

All Authors: No reported disclosures
P-1017. Key Fungal Secreted Proteases in Coccidioidomycosis
Authors: Homer Christina , Ochoa Elena , Voorhies Mark , Sil Anita
Published: January 2025

Background

Coccidioides, a dimorphic fungus endemic to the Southwest United States, causes unacceptably high morbidity/mortality. Coccidioides’ virulence stems from its unique and poorly understood host form, the spherule. Spores are inhaled by the host and develop into spherules, which mature until they fill with hundreds of endospores and then rupture, disseminating endospores throughout the host. This entire process is known as spherulation. As spherules are unique to Coccidioides, most spherule biology remains unknown. Coccidioides genomes encode 2 expanded families of proteases, subtilases and deuterolysins, that we hypothesize are involved in spherulation and are promising treatment targets.

Methods

We took 3 approaches to characterize proteases in spherule biology. We studied spherulation by microscopy in the presence of AEBSF (serine protease inhibitor) and 1,10-phenanthroline (metalloprotease inhibitor). We profiled the Coccidioides transcriptome during spherulation, in Converse media, at 39˚C, 10% CO2, or during hyphal growth, in Converse media at room temperature. Using multiplex substrate profiling-mass spectrometry on supernatants from protease deletion mutants or wildtype, we characterized the total amount of secreted protease activity and amino acid preferences around sites of proteolysis.

Results

Treatment of Coccidioides with a protease inhibitor that blocks subtilase activity prevented spherule formation, indicating a role for subtilases in spherulation. Subtilase and deuterolysin expression is induced upon spherule formation in 4 patterns: 1) during early spherule formation, 2) continuous increase over spherulation, 3) 2 peaks of expression in arthroconidia and endospores, or 4) dramatic increase during endospore release. The subtilase Sub1 fits the 4th pattern and is a top 10 most abundant transcript in spherules during endospore release. Sub1 is a major contributor to secreted protease activity in spherules and exhibits a preference for hydrophobic substrates. Phenotypic characterization of this mutant is underway, including virulence studies.

Conclusion

By linking protease activity to spherulation, we have demonstrated the importance of further dissecting the role of these 2 expanded protease families in Coccidioides virulence.

Disclosures

All Authors: No reported disclosures
P-1020. Randomized control trial to study the effectiveness of tablet Fluconazole, capsule Itraconazole and tablet Terbinafine in superficial dermatophytosis
Authors: Mitra Debdeep
Published: January 2025

Background

According to the World Health Organization, dermatophytosis is a relatively frequent superficial fungal infection of the keratinizing structures of the body with a prevalence of 20% - 25% worldwide. The organism is more widespread in tropical areas, with India acting as the main infection hub, because it prefers a hot and humid climate. Tinea corporis is the most common kind of superficial dermatophytic infection, second most common is tinea cruris followed by tinea capitis, tinea unguium, tinea faciei, tinea manuum and tinea pedis. Hot, humid weather, overcrowding, poverty, poor cleanliness, lack of health-care facilities, immunosuppression, and irrational drug use are all risk factors for dermatophytosis.

Fungal skin infection responding to Oral Itraconazole

Clinical response of Dermatophyte infection to Oral Itraconazole at 4 and 8 weeks as compared to baseline

Methods

Total of 180 patients were included in the study and divided into 3 groups based on the day of visit to the hospital and antifungals Fluconazolee, itraconazole or Terbinafine were randomly prescribed to them (60 patients in each group). Patients were followed up at 4th and 8th week for therapy response.

Results

At the end of 8th week KOH (Potassium hydroxide) mount was found to be negative in 86.67%, 73.33% and 63.33% among Itraconazole Fluconazole and Terbinafine groups respectively which was highly significant.

Conclusion

Dermatophytosis is comparatively more commonly seen in physically active age group. Clinical features waned off quicker and better with Itraconazole in comparison to Fluconazole and Terbinafine. Again fluconazole was found to be yielding better clinical outcome than Terbinafine. Overall outcome of patients with dermatophytosis was found to be more satisfactory with a 4 week oral dose of itraconazole. So from this study we conclude that Itraconazole is a better choice of drug for Dermatophytosis compared to Fluconazole and Terbinafine. Also fluconazole is comparatively a better choice than Terbinafine for the same.

Disclosures

All Authors: No reported disclosures
P-1022. Ventricular Shunt Failure in Patients with Coccidioidal Meningitis in Central California, A Single Center Experience
Authors: Hyser Elise , Sivasubramanian Geetha , Fox Kenneth , Hughes Alyssa , Sandhu Jasmine , Yan Yueqi , Diaz Pavel
Published: January 2025

Background

Coccidioidal meningitis (CM) represents the most deleterious form of disseminated coccidioidomycosis and warrants lifelong antifungal therapy. Communicating hydrocephalus is a well-known complication of CM. Antifungal therapy and lumbar drain placement is typically insufficient treatment for CM-related hydrocephalus, often requiring shunt placement. Shunt failures and repetitive surgical revisions have been described in patients with CM. We aimed to characterize shunt outcomes in patients with CM with ventricular shunts in our center.

Methods

We performed a retrospective study of patients above the age of 18 with CM requiring shunt placement in our center from 2014-2024. Data pertaining to demographics, comorbidities, clinical presentation, laboratory and imaging data, shunt characteristics, management and outcomes were collected. Descriptive statistics were used to analyze the sample characteristics. Fisher’s exact or Chi-square test was used to compare outcomes using categorical variables and T-test for continuous variables.

Results

We identified 65 patients with CM and shunt placement. Of these, 27 (42%) did not have shunt failure while 38 (58%) had one or more shunt failure events (ranging 1-14 times, total of 198 events in the whole cohort). Mean age of patients in was 41 years, 55% were Hispanic and 38% had outdoor occupational exposure (Table 1). The average number of days between shunt placement and initial shunt failure was 46 days (0-174). Change in mentation was noted in patients during 27% of shunt failure events (Table 2). Infections and shunt malfunction were major reasons for shunt failure (Figure 1). Patients that suffered shunt failure events, had a statistically significant higher risk of death (p value 0.01).

Conclusion

CM related hydrocephalus, a common complication of this infection, remains a difficult condition to manage. Even with availability of potent anti-fungal agents, 58% of our patients developed shunt failure needing repeated hospitalizations and shunt revision surgeries. Patients who developed shunt failure in our cohort had a higher risk of death. More studies are needed to identify modifiable risk factors which may help prevent this complication and further reduce morbidity and mortality.

Disclosures

All Authors: No reported disclosures
387. High Rates of Bacteremia and Fluoroquinolone Resistance during an Outbreak of Shigellosis among People Experiencing Homelessness and Opioid Use Disorder in Philadelphia, PA
Authors: Stedman Eleanor , Molin Andrea , Oglesby Valencia , Torpey Erin , Spivack Stephanie , Schultz Sara K
Published: January 2025

Background

In October 2023, the city of Philadelphia, PA reported a dramatic rise in shigellosis cases from Shigella flexneri, leading to widespread diarrheal illness and many hospitalizations. Notable qualities of this outbreak included high antibiotic resistance, high rates of bacteremia in hospitalized patients, a death due to invasive shigellosis, and extensive housing insecurity and opioid use disorder (OUD) among those affected.

Rates of antibiotic susceptibility and resistance among tested isolates of Shigella flexneri.

Methods

All patients hospitalized at Temple University Health Systems (TUHS) with confirmed shigellosis between October 2023 and April 2024 were included in the study. Diagnosis was made via stool culture, blood culture, and/or polymerase chain reaction (PCR) stool pathogen panel. Charts were reviewed for patient age, sex, housing status, history of OUD, stool and blood culture data, stool pathogen panel data, antibiotic susceptibility data, and any death due to shigellosis.

Hospitalizations and Bacteremia Over Time

Number of patients hospitalized and number of patients with documented Shigella flexneri bacteremia per month during an outbreak of shigellosis.

Results

Sixty-seven patients were hospitalized at TUHS from October 2023 to April 2024 with confirmed shigellosis. The average age of patients was 43 and 60% were male. Bacteremia was documented in 21 patients (31.3%). Among cultured isolates, 0% were ampicillin or ciprofloxacin susceptible, 2.1% were levofloxacin susceptible, 4.8% were ceftriaxone susceptible, and 89.6% were trimethoprim-sulfamethoxazole (TMP-SMX) susceptible. One patient died from shigellosis, a 1.5% mortality rate in hospitalized patients. Housing insecurity was documented for 67% of patients, and 68.7% of patients had OUD.

Conclusion

This shigellosis outbreak in Philadelphia saw an unprecedented rate of bacteremia among hospitalized patients. Cultured isolates were highly beta-lactam and fluoroquinolone resistant. TMP-SMX was the only oral antibiotic with reliable susceptibility. Most hospitalized patients had housing insecurity and OUD. Due to the fecal-oral route of infection, outbreak containment challenges reflect the insufficient sanitation facilities for people experiencing homelessness.

Disclosures

Sara K. Schultz, MD FACP FIDSA, AbbVie: Advisor/Consultant
P-1042. Comparison of clinical characteristics and outcomes of patients with candidemia caused by Candida auris versus other Candida species – A retrospective case-control study at a community hospital in the Bronx
Authors: Ahmed Nada , Cani Eris , Raymond Lendelle , Zeana Cosmina
Published: January 2025

Background

Conflicting data exists on the mortality rate of Candida auris fungemia compared to other Candida species. The purpose of this study was to compare the clinical outcomes and characteristics of hospitalized patients with candidemia due to C. auris versus non-C. auris species.

Methods

This retrospective case-control study included adult patients with microbiologically confirmed candidemia at an urban hospital in New York City from January 2018 to August 2023. Data collected included demographics, medical history, microbiology data, antifungal treatment, in-hospital mortality, length of hospital stay (LoS), recurrence rate, mycological eradication, and discharge status. Descriptive statistics and t test were utilized for continuous variables, and categorical data was analyzed by Fischer’s exact test with significance set at a p-value < 0.05.

Results

Out of 171 candidemia cases, 17% were due to C. auris and 83% were due to other Candida species, mainly C. albicans (29%) and C. glabrata (19%). Average patient age was 65 years and majority were of Hispanic descent (49%) with common comorbidities including diabetes (55% vs. 43%; p = 0.044) and chronic kidney disease (14% vs. 25%; p = 0.093) in C. auris vs. non-C auris groups, respectively. More C. auris patients required mechanical ventilation (86% vs. 63%; p = 0.019), and had central lines placed (93% vs. 67%; p = 0.002). All C. auris isolates were susceptible to echinocandins but resistant to fluconazole. C. auris patients had a non-significantly higher crude rate of in-hospital mortality (62% vs. 49%; p = 0.075) with a longer mycological eradication time (mean 5 vs. 3 days; p = 0.196). Median time to mortality was longer in C. auris patients (76 days vs. 30 days, p < 0.0006). These patients also had longer hospital stays (median 111 vs. 40 days, p < 0.002) and nonsignificant higher recurrence rates (14% vs. 6%; p = 0.091). More C. auris survivors were discharged to long-term care facilities (78% vs. 56%).

Conclusion

Patients with C. auris fungemia had a significantly longer median time to mortality and LoS, in addition to a non-significantly higher rate of recurrence and mortality.

Disclosures

All Authors: No reported disclosures
P-1048. Coccidioides immitis Fungemia in Central California: A 10 Year Experience
Authors: Hwang Sang Jo , Fayed Mohamed , Mitchell Marilyn , Sivasubramanian Geetha
Published: January 2025

Background

Coccidioides immitis is a soil-borne fungus endemic to Southwestern United States. While about 40% of patients develop symptomatic infections, disseminated infections remain rare (1-3%). Coccidioides fungemia is extremely uncommon and associated with high mortality. Previous reports on Coccidioides fungemia in the 90’s to early 2000’s, mostly from Arizona, showed affected patients had underlying immunocompromising conditions such as HIV/AIDS, and survival was poor. We aim to characterize Coccidioides immitis fungemia in our Central California population in recent years.

Methods

We performed a retrospective analysis of patients with Coccidioides fungemia in a major 750-bed referral center in Central California between the years of 2014 – 2024. Data was collected pertaining to demographics, comorbidities, clinical presentation, management, and outcomes. Descriptive statistics were used to analyze sample characteristics.

Results

We identified 11 patients with Coccidioides fungemia during the study period. The mean age of affected patients was 40 years (Table 1). Mortality was extremely high with death occurring in an overwhelming 82% of patients. Duration of symptoms was less than 1 week in 6/11 (55%) of patients. Death occurred in 44%, even before blood cultures came back positive (Table 2). Cultures returned positive within 7 days of plating in 7/11(64%) patients. Notably, 9 out of 11 patients had acute Coccidioides infection. Only 1 patient had no underlying comorbid condition (Table 3). All patients received anti-fungal therapy with either liposomal amphotericin B or fluconazole.

Conclusion

Coccidioides immitis fungemia continues to be a rare and fatal form of disseminated disease. The majority of patients in our cohort had acute infection, rapid progression of disease and death. Only 27% of patients in our study had HIV/AIDS, which is less than what has been documented in previous studies (which were done in the early 80s-90s). However, many patients in our cohort had other underlying immunocompromising conditions such as SLE, diabetes mellitus). Despite the advances in management of HIV/AIDS, due to increase in other immunocompromising conditions and use of immunomodulatory agents, Coccidioides fungemia remains a threat.

Disclosures

All Authors: No reported disclosures
P-1049. Retrospective Analysis on the Efficacy and Adverse Effects of Antifungal Prophylaxis in Patients with Peritoneal Dialysis-Associated Peritonitis
Authors: Luchana Vidal , Gandhi Shivanthidevi , Doan Thien-Ly , Kamel Barbara , Jain Sumeet , Sohail Rubab , Sison Cristina , Donaghy Henry
Published: January 2025

Background

Fungal peritonitis causes significant mortality for patients on peritoneal dialysis (PD). Antibiotic exposure is a major risk factor for fungal peritonitis amongst PD patients. The 2016 and 2022 International Society for Peritoneal Dialysis (ISPD) Guideline recommends the use of antifungal prophylaxis in PD patients on antibiotics. There is still no consensus on the optimal approach to prevent secondary fungal peritonitis. This study's objective was to evaluate the impact of antifungal prophylaxis on patients with PD-associated peritonitis as secondary prevention for fungal peritonitis.

Methods

This is a retrospective cohort study of patients on concomitant antifungal prophylaxis and those with no antifungal prophylaxis who had confirmed or suspected PD-associated peritonitis while on antibiotic therapy from 2018 to 2023. Descriptive analysis was used to compare the outcome of development of secondary fungal peritonitis. Side effects such as QTc prolongation are also described.

Results

Of the 101 patients with PD-associated peritonitis, there were 36 (35.6%) gram-positive infections, 24 (23.8%) gram-negative infections, 6 (5.9%) fungal infections, and 41 (40.6%) culture negative peritonitis. The most common isolates were Coagulase-negative Staphylococcus (14), eight of which were Staphylococcus epidermidis, followed by Pseudomonas aeruginosa (6). Among the 101 patients, 33 (32.7%) were co-prescribed with antifungal prophylaxis while 68 (67.3%) did not. Fluconazole 100 mg daily was the most common antifungal agent used (84.8%). Over a 1-year period, two patients developed secondary fungal peritonitis in patients with concomitant antifungal prophylaxis (6.1%; 95% CI: 0.74% to 20.23%), compared to 1 patient (1.5%; 95% CI: 0.037% to 7.92%) in patients without antifungal prophylaxis. Among 28 patients on fluconazole, 10 had repeat ECGs. Of these, 7 patients had a QTc greater than 460 ms (70%; 95% CI: 34.8% to 93.3%), and 3 were greater than 500 ms (30%; 95% CI: 6.7% to 65.2%).

Conclusion

Antifungal prophylaxis in the setting of PD-associated peritonitis does not correlate to fewer episodes of secondary fungal peritonitis. Increased QTc with azole use is a potential risk factor for cardiac arrhythmia.

Disclosures

All Authors: No reported disclosures
392. Antiretroviral Prophylaxis to Prevent Perinatal HIV Infection in Medicaid-Insured Infants, 2009-2021
Authors: Lu Mingyue , Inagaki Kengo
Published: January 2025

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 < 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

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

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 ( >99%). There was 1 ceftriaxone resistant isolate from a US patient (MIC >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

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< 0.001). Cultures repeated within 3 days declined 22% from 13% to 10% (95%CI 0.68-0.89, P< 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

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

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

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< 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

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

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 < 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 >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
P-1138. Quantifying Antibiotic Prescribing in Children with Tracheostomies
Authors: Steuart Rebecca , Slone Austin , Courter Joshua D , Benscoter Dan , Pan Amy , Shah Samir S , Thomson Joanna
Published: January 2025

Background

Prolonged or unnecessary antibiotic prescribing is associated with adverse outcomes. Children with tracheostomies are at risk for antibiotic overprescribing. We sought to quantify and characterize systemic antibiotic prescribing among children with tracheostomies, and to identify predictors of higher prescribing.

Methods

This single-center retrospective cohort study included children with tracheostomies 2 months-18 years old cared for between 2010-2018. Detailed demographic, clinical, and antibiotic prescribing data were extracted from the medical record. Patient-level antibiotic prescribing was quantified using antibiotic courses initiated and DOT per child per year of enrollment. Group-level prescribing was summarized using total antibiotic courses and days of therapy (DOT) per 1000 person-days. Antibiotics prescribed for > 1 day were classified by spectrum of activity and stratified by setting and year. Clinical predictors of patient-level prescribing were identified using backward stepwise multivariable analyses within a generalized linear model.

Results

The 548 children with tracheostomies (47.6% with baseline ventilator use) were prescribed a median 8 antibiotic courses per child per year (IQR: 4-16) for a total median exposure of 49.3 DOT per child per year (IQR: 22.6-123.2) or 183.7 DOTs per 1000 person-days. Most courses (73.9%) were broad-spectrum, with vancomycin, piperacillin-tazobactam, and ampicillin-clavulanate being the top 3 most frequently-prescribed antibiotic courses. Azithromycin and gentamicin represented a high proportion of all DOTs (azithromycin 25.4%, gentamicin 13.0%). Annual antibiotic prescribing decreased 34.5% from 2010-2018. In adjusted analysis to identify predictors, ventilator use at baseline was associated with fewer DOT per child per year, while higher patient complexity and more ICU hospital days were risk factors for higher DOT.

Conclusion

Children with tracheostomies have high antibiotic use, and are predominantly prescribed broad-spectrum antibiotics. Chronic ventilator use was a protective factor against higher prescribing. This data may inform antimicrobial stewardship work.

Disclosures

All Authors: No reported disclosures