bluuebunny/crossref_metadata_2025 huggingface dataset:
P-1124. Implementation and Evaluation of a Pediatric Tele-Antimicrobial Stewardship Program in an Integrated Healthcare System
Authors: Stallsmith Jena , Olson Jared , Hersh Adam , Valentine Marilyn E , Thorell Emily A
Published: January 2025

Background

Intermountain Health (IH) has had a successful adult telehealth antimicrobial stewardship program (ASP) since 2016, and Primary Children’s Hospital has also had a longstanding ASP. With 298 pediatric beds throughout the other 23 hospitals within IH, there was an opportunity to expand to these patients that were not previously reviewed. The purpose of this study is to describe the implementation and outcomes of a pediatric tele-antimicrobial stewardship program (PT-ASP) in these hospitals throughout an integrated healthcare system.Figure 1:U chart of antimicrobial days of therapy per patient day

Methods

This is a quasi-experimental, pre- post- analysis of a prospective audit and feedback PT-ASP across 23 medical centers throughout Intermountain Health in Utah. The pre-intervention group included patients < 18 years of age who had antibiotics at any of these 23 hospitals between January 1, 2018, and December 31, 2019. The post-intervention group included patients < 18 years of age who had antibiotics ordered between January 1, 2021, and December 31, 2022. Post-intervention patients were reviewed by a pediatric ASP pharmacist for a descriptive analysis of the daily census and interventions made. The primary outcome was antibiotic days of therapy/patient day (DOT) pre- and post-intervention. The secondary outcomes were to describe the types of interventions and the acceptance rates.Figure 2:U chart of IV antimicrobial days of therapy per patient day

Results

During the first two years of the PT-ASP implementation, 14,999 hospital census days with active antibiotic orders were reviewed. Compared to the pre-intervention period, there was a 21% decrease in total antimicrobial DOT per patient day and a 24% decrease in IV antimicrobial DOT per patient day during the intervention period. The census had a majority of NICU patients (51%). A total of 1,970 interventions were made on 1,287 unique patients, with 13% of the charts reviewed leading to an intervention. The acceptance rate of these interventions was 62%. The two most common types of interventions made were to change the antibiotic regimen and to discontinue antibiotics.Table 1:Pediatric tele-antimicrobial stewardship program intervention acceptance rates by type of intervention

Conclusion

The PT-ASP made over 1,900 interventions leading to a decrease in both total antimicrobial DOT and IV antimicrobial DOT per patient day throughout 23 hospitals in an integrated health system. A PT-ASP is a strategy to steward pediatric beds outside of a stand-alone children’s hospital.

Disclosures

All Authors: No reported disclosures
P-1141. Antibiotic administration for Staphylococcus aureus infections in US children's hospitals, 2015-2023
Authors: Walsh Tyler , Shambhavi Fnu , Newland Jason G , Fritz Stephanie A
Published: January 2025

Background

The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) infections in children has changed. In response to the introduction of new antibiotics published clinical data, treatment strategies have evolved. The objective of this study is to describe the antimicrobial treatment regimens for children hospitalized with this important pathogen.Table 1.Type of Infections by MRSA vs. MSSA

Methods

A retrospective observational study was performed using the Pediatric Health Information System (PHIS) data, including all patients discharged from a PHIS-member hospital from October 1, 2015 to June 31, 2023. Patients with ICD 10 codes identifying an MRSA or MSSA infection and indicating the type of infection were included (Table 1): bacteremia, endovascular, pneumonia, skin and soft tissue infection (SSTI), osteomyelitis, and myositis. The proportion of anti-staphylococcal antibiotics of interest received by all patients, patients with MRSA infections, and patients with MSSA infections were calculated by year.Figure 1.Percent of Antibiotics Prescribed for All Patients with Staphylococcus aureus

Results

21,206 patients met eligibility criteria and were included in the final data set. Infections due to MRSA and MSSA were 9,561 and 11,645, respectively (Table 1). The proportion of patients with S. aureus infections caused by MRSA decreased from 2015 (55%) to 2023 (41%). The most frequent infections were bacteremia (32%), SSTI (27%), and pneumonia (23%, Table 1). The most common antibiotics prescribed for all S. aureus infections in 2015 were clindamycin (53%), vancomycin (49%), and cefazolin (27%) and in 2023 were vancomycin (56%), cefazolin (48%), and ceftriaxone (34%, Figure 1). While vancomycin prescriptions remained consistent over the study period, clindamycin administration decreased 20% (Figure 1). Daptomycin and ceftaroline, the newest MRSA agents, increased from 2% and 3% to 7% and 8%, respectively, of agents prescribed for MRSA infections (Figure 2). For MSSA infections, cefazolin increased in use while oxacillin/nafcillin use remained consistent (Figure 3).

Conclusion

Clindamycin administration has substantially decreased, likely a result of increased resistance prevalence in both MSSA and MRSA. Cefazolin use increased commensurate with the increasing incidence of MSSA infection.

Disclosures

Jason G. Newland, MD, MEd, Moderna: Grant/Research Support|Pfizer: Grant/Research Support
419. Changing Epidemiology of Pediatric Invasive Group A Streptococcus Infections in the United States, 2004-2022
Authors: Ramachandran Veena , Okaro Jennifer , McGee Lesley , Gregory Christopher , Anderson Bridget J , Harrison Lee , Houston Jessica , Lynfield Ruth , Youngkin Erin , Tunali Amy , Thomas Ann , Schaffner William , Petit Susan , Chai Shua
Published: January 2025

Background

Recent reports from children’s hospitals of increasing pediatric invasive Group A Streptococcus (iGAS) infections triggered national concern. Clindamycin and penicillin dual therapy is often recommended for iGAS, which is life-threatening. We used active, population and laboratory-based surveillance to assess changes in pediatric iGAS disease incidence, clinical outcomes, and bacterial strain characteristics between 2004–2022.

Methods

Using CDC’s Active Bacterial Core surveillance network, we identified pediatric iGAS cases (GAS isolation from a normally sterile site in persons aged ≤17 years) from 2004–2022. CDC Streptococcus laboratory characterized available isolates by emm typing and antimicrobial susceptibility using conventional and genomic methods. We compared annual incidence during 2004–2019 (pre-COVID-19 pandemic), 2021 (mid COVID-19 pandemic), and 2022 (relaxation of pandemic mitigation measures). Case fatality ratio (CFR), intensive care unit (ICU) admission, and clindamycin non-susceptibility trends (2011-2022) were assessed with the Cochran-Armitage test.

Results

We identified 2,522 pediatric iGAS cases during 2004–2022. Incidence decreased from 1.9 cases per 100,000 persons (2004–2019) to 0.5 (2021) (Incidence Rate Ratio: 0.29 [95% CI: 0.25-0.32]; P< .001) but increased in 2022 to 1.5 (2021 vs 2022 IRR: 2.9 [95% CI: 2.6-3.2]; P< .001). Thirty-four percent of cases were admitted to the ICU; admission increased from 28.9% (2011) to 36.1% (2022) (P = .04). CFR (3.1%) remained stable (P = .69). All isolates were penicillin susceptible; clindamycin non-susceptibility increased from 3.8% (2011) to 28.1% (2021), before declining to 8.4% (2022) (2011 vs 2022 P = .01). emm1, which accounted for 44.8% of ICU admissions (2011-2022) and 38.5% of fatal cases, decreased to 3.1% of isolates in 2021.

Conclusion

Pediatric iGAS incidence was stable for 15 years before declining substantially in 2021. Infections due to emm1, the most identified emm type in children with severe disease, almost disappeared in 2021, potentially due to initiation of COVID-19 mitigation measures; however, clindamycin non-susceptibility continued to increase. Rising iGAS incidence in 2022 necessitates close monitoring for rises in emm1 infections and antimicrobial resistance.

Disclosures

Lee Harrison, MD, GSK: Advisor/Consultant|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant|Sanofi: Advisor/Consultant
P-1145. Geographic and Genetic Similarities between Sporadic Haemophilus influenzae Type b Pediatric Meningitis Cases in New York City
Authors: Ewing Anne T , Otto Caitlin , Ratner Adam J , Haldeman Sydney , Job Megan
Published: January 2025

Background

Two unvaccinated infants residing in Brooklyn, NY presented to our hospital with Haemophilus influenzae type b (Hib) meningitis within one year of each other. Prior outbreak data suggest that communities with low vaccination rates may have circulation of genetically similar Hib strains. We sought to understand the genomic epidemiology of these geographically related cases, hypothesizing that the strains would be closely related.

Mash tree of Hib genomes. One non-typeable H. influenzae (NTHi) genome is included as an outgroup. Study cases described are highlighted.

Methods

We performed a retrospective chart review of pediatric patients (0-5 years) seen at our multi-center health system between 2013-2023 with a sterile-site culture positive for Hib. Whole genome sequencing (WGS) was performed on Hib isolates from blood and cerebral spinal fluid (CSF) samples from the 2 identified cases. Multi-locus sequence type (MLST) was determined using the PubMLST database. Single nucleotide polymorphisms (SNPs) and indels were detected with snippy. A genetic distance tree (mashtree) including 75 Hib genomes from GenBank was constructed.

Results

No additional invasive Hib cases were detected over the past 10 years of data. We generated high-quality closed genome sequences from the 2 meningitis cases. Notably, the strains both belonged to a novel MLST, sequence type (ST)-2832, part of the ST-6 complex. Bacterial genetic sequences were identical across sample type (blood vs. CSF) for each patient. Strains from the 2 patients differed at 262 sites (SNPs+indels). A genetic distance tree (Figure) demonstrates that the 2 isolates are more closely related to each other than to any other Hib genomes in the dataset.

Conclusion

The 2 recent meningitis cases represented an increase in incidence of invasive Hib disease at our institution and were both geographically and genetically linked, sharing a novel MLST. Sporadic cases of closely related Hib strains suggest that an under-vaccinated population serves as a reservoir for community strain circulation. Understanding Hib epidemiology can help target public health campaigns, including vaccination efforts.

Disclosures

All Authors: No reported disclosures
P-1151. Clinical Impact of Susceptibility Testing in Anaerobic Infections from Pediatric Patients
Authors: Cruz Vidal Diego A , Benson Raimey , Wang Huanyu , Oyeniran Sophonie J
Published: January 2025

Background

Anaerobic infections are rarely described in pediatric populations, where routine use of anaerobic blood cultures remains controversial. Due to rising resistance, susceptibility to some anti-anaerobic drugs is unpredictable, yet anaerobic antimicrobial susceptibility testing (AST) is not widely available.

Herein we characterize anaerobic isolates recovered from subjects treated at Nationwide Children's Hospital (NCH) and describe the impact of anaerobic culture and AST on prescribing practices.

Methods

All anaerobic cultures from non-blood sources (ANAC) and blood cultures with obligate anaerobic organisms (AnaBC) during 2023 were identified. At NCH, anaerobic bottles are collected for all BC. Anaerobic isolates are identified by molecular methods and AST performed on sterile sites or by request. Prescribing practices for subjects with anaerobic isolates and AST performed were reviewed.

Results

In 2023, AST was performed on 74 ANAC isolates (25% positive cultures) and 22 AnaBC isolates (70%) from 72 distinct infectious episodes. ANAC isolates were mostly from superficial wounds/abscesses (40%) and intra-abdominal sources (22%), while most AnaBC isolates were from peripheral cultures (52%). Bacteroides fragilis group (43%) and Clostridium spp. (28%) were the most frequent organisms in ANAC and AnaBC, respectively. Time to identification (89 h) and time to AST (143 h) did not differ between groups (Table 1).

Of the 72 infectious episodes, 38 (54%) were from males with a median age of 14.7 years; 22 (31%) were admitted to the intensive care unit (ICU) and 7 (10%) had immunocompromise at baseline. In comparing infectious episodes from AnaBC or ANAC, episodes from AnaBC had significantly younger subjects (3.5 vs. 15.6 years), longer lengths of stay (13 vs. 6 days) and were more commonly mono-microbial (95% vs. 40%). While not significant, episodes from AnaBC tended to have higher rates of effective empiric (91% vs. 71%) and targeted (100% vs. 73%) therapy than those from ANAC (Table 2).

Conclusion

Gaps in antimicrobial optimization were observed for ANAC infectious episodes. Low rates of effective empiric therapy in these settings indicates the need for timely anaerobic AST. Rapid availability of results may improve rates of effectively treated anaerobic infections.

Disclosures

All Authors: No reported disclosures
P-1162. Colonization Rates and Antimicrobial Susceptibility of Mycoplasma hominis and Ureaplasma urealyticum in Adolescent Girls: Comparison with Young Adults
Authors: Choi Soo-Han , Choi Soo-Han
Published: January 2025

Background

Sexually transmitted infection rates are increasing among adolescents and young adults and remain a serious health problem worldwide. Mycoplasma hominis and Ureaplasma species are sexually transmitted and considered etiologic agents causing various urogenital diseases. This study aimed to estimate the prevalence and antimicrobial susceptibility of M. hominis and U. urealyticum in adolescent girls and to compare them with young women.

Methods

We evaluated the results of M. hominis and U. urealyticum isolated from vaginal swab culture between January 2011 and August 2023. The data were selected from young women aged 12-26 and analyzed by dividing the two groups into adolescents (12-18 years) and young adults (19-26 years).

Results

Among 66 adolescent girls, 58 (87.9%) were positive for mycoplasma culture. Twenty-nine (43.9%) had both M. hominis and U. urealyticum. Compared with the young adult group, colonization rates of M. hominis (45.5% [30/66] vs. 21.7% [64/295], P=0.0002) and U. urealyticum (86.4% [57/66] vs. 79.4% [219/295], P=0.0373) were significantly higher in the adolescent group. As age increased, colonization rates of M. hominis (rho = -0.6703; 95% confidence interval [CI], -0.8840 to -0.2248) and U. urealyticum (rho = -0.5993; 95% CI, -0.8550 to -0.1091) tended to decrease. Macrolides (azithromycin, clarithromycin, and erythromycin) susceptibility rate of M. hominis was less than 10% in both groups. Of M. hominis isolates from adolescents, susceptibility rates to azithromycin, clarithromycin, and erythromycin were 0.0%, 6.7%, and 0.0%, respectively. Ninety percent and 76.7% of M. hominis isolates from adolescents were susceptible to doxycycline and tetracycline. Compared with the young adult group, the macrolides susceptibility rate of U. urealyticum was significantly lower in the adolescent group: azithromycin (36.8% vs. 53.4%, P=0.0368), clarithromycin (47.4% vs. 68.9%, P=0.0031), and erythromycin (38.6% vs. 54.3%, P=0.038). Susceptibility rates of U. urealyticum to doxycycline and tetracycline were 94.7% and 87.7% in the adolescent group.

Conclusion

Compared with young adults, higher rates of colonization and resistance to macrolides for both M. hominis and U. urealyticum were more frequently observed in adolescent girls.

Disclosures

All Authors: No reported disclosures
P-1167. Pediatric Coccidioidal Meningitis: a 39-year Single-Center Retrospective Cohort
Authors: Chan Lienna Y , Gotwalt Jordan , Lacy Marian , Price Nathan B , Olson Scott C , Ampel Neil M , Shehab Kareem W
Published: January 2025

Background

Coccidioidal meningitis (CM) is a rare complication of coccidioidomycosis, an endemic mycosis of the southwestern United States. CM is associated with significant morbidity and mortality, but its clinical characteristics and outcomes are poorly described in children. Herein we present a 39-year retrospective cohort of pediatric CM at a single academic center in the endemic area.

Methods

We conducted retrospective chart review with IRB approval of all patients from birth to 18 years of age with CM from 1981-2010 and 2013-2023. Demographic and clinical data, including presenting signs/symptoms, initial lab and imaging results, treatment course, and complications were collected and summarized.

Results

Sixteen patients with CM were identified. The most common presenting symptoms included headache (50%), fever (44%), nausea/vomiting (38%), weight loss (31%), and cough (19%). Ten patients (63%) initially presented with CM, while 6 patients (38%) presented with CM between 2 weeks to 4 years after initial diagnosis of primary pulmonary coccidioidomycosis. Of 14 patients with serologies, 100% had a positive IgG and 43.8% had positive IgM. Of 14 with an initial CSF sample, 12 (86%) had pleocytosis (median 114.5, range 7-690 WBC/mm3). Of 13 with initial complete blood counts, four (30.7%) had leukocytosis and one had eosinophilia. Hydrocephalus requiring ventriculoperitoneal shunt (VPS) developed in 13 patients (81.3%); two died before a VPS could be placed and one developed CM without hydrocephalus 4 years after initial diagnosis. Of 15 patients prescribed lifelong therapy, 14 received fluconazole and one received voriconazole. Two received IV amphotericin B during their course.

Conclusion

Most children with CM presented without recognized primary pulmonary coccidioidomycosis, with 50% presenting with headache and fewer than 50% with fever. Most patients had CSF pleocytosis without peripheral leukocytosis. Nearly all were treated with fluconazole. Death occurred in two patients; all survivors required VPS. Future prospective trials examining higher doses of fluconazole and use of mold-active azoles are needed to assess their efficacy in preventing hydrocephalus in children with CM.

Disclosures

Nathan B. Price, MD, DSM-Firmenrich: Advisor/Consultant
P-1175. Healthcare-Associated Respiratory Viral Infection Outbreak in a Neonatal Intensive Care Unit
Authors: Marrero Elizabeth , Honeycutt Michele , Henthorne Jennifer , Pool Kristin , Del Valle Penella Ana
Published: January 2025

Background

Healthcare-associated respiratory viral infections (HARVIs) have the potential to cause considerable harm including increased morbidity and mortality in patients in neonatal intensive care units (NICUs). We report an HAVRI outbreak in an open pod 104 bed Level IV NICU at a standalone children’s hospital in the south-central region of the United States and the control measures implemented to contain the outbreak.

Methods

An outbreak was identified through a 255% increase in HARVI rates over four months (figure 1). An interdisciplinary team was formed to address the outbreak.

Interventions included: 1) universal masking, 2) isolation of positive patients and pod-mates with a total of three pods being closed for a total of two weeks from the date of last exposure, 3) visitor restrictions with symptom screening at unit entrance, 4) enhanced environmental measures such as equipment cohorting, baseline deep clean, and increased cleaning frequency, 5) infection prevention practices such as hand hygiene, bare below the elbows, and isolation practices were reinforced with the staff.

Results

Post-interventions, the HARVI rate dropped by 70% over a five month period. During the outbreak, several patients experienced longer hospital stays, three patients required escalation of care, and no deaths occurred (Figure 1).

Conclusion

Rapid identification and response are crucial in managing HARVIs in NICUs. The collaborative efforts between NICU leadership, infection prevention, and hospital administration played a key role in promptly controlling the outbreak.

Disclosures

All Authors: No reported disclosures
P-1198. Molecular and Microbiome/Metagenome Correlates of Illness in Respiratory Syncytial Virus (RSV) Infected Infants
Authors: Caserta Mary T , Mariani Thomas , Gill Steven R , Gill Ann Lindley , Walsh Edward E , Corbett Anthony , Chu Chin-Yi , Qiu Xing
Published: January 2025

Background

Respiratory syncytial virus (RSV) epidemics are a leading cause of hospitalization in infants. Those infants with severe illness appear more likely to develop recurrent wheeze. We aimed to test if airway gene expression and microbiome/metagenome composition in the nasal epithelium during primary RSV infection are associated with illness severity and can identify infants with recurrent wheeze.Table 1.Subject Characteristics

Methods

Healthy infants with PCR confirmed RSV were prospectively recruited from inpatient and outpatient locations over three seasons (Dec 2019 to Dec 2023). Clinical and demographic data, 2 anterior nasal swabs and a nasal wash were collected. Microbiome/metagenome analysis and transcriptome/RNA sequencing were performed on the nasal biospecimens. Disease severity was measured by the Global Respiratory Severity Score (GRSS) and retrained improved Global Respiratory Severity Score (iGRSS). Subjects were followed for 12 months to identify recurrent wheezing.Figure 1.Top 20 genes associated with iGRSS

Results

100 (80 hospitalized) infants were enrolled. Two children were found to be ineligible leaving 98 for analysis. The average age was 3.2 (2.3 SD) months. 60 (61%) were male. A multivariate linear regression model was used to associate gene expression profiles with GRSS and iGRSS. After controlling false discovery rate (FDR) at 0.10 level, 283 genes were significantly associated with iGRSS (95 at 0.05). Gene expression changes involved both Innate Immune and Interleukin Signaling pathways. Metagenome analysis identified microbial species and the microbial metabolic state of the nares during acute infection. We found an abundance of Moraxella in the anterior nares was inversely associated with iGRSS while the abundance of Haemophilus was directly associated with iGRSS. We also identified 29 metabolic pathways associated with the iGRSS including coenzyme A biosynthesis I (procaryotic), mixed acid fermentation, Cavin-Benson-Bassham cycle and superpathways of branched chain amino acid biosynthesis.Figure 2.Bacterial Abundance vs. iGRSS

Conclusion

We enrolled a cohort of previously healthy infants with primary RSV infection and identified associations between host nasal gene expression, nasal microbiome/metagenome composition/activity and disease severity. We are currently testing for associations between these biomarkers and recurrent wheeze.Figure 3.Metabolic Pathways associated with iGRSS

Disclosures

Mary T. Caserta, MD, Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Edward E. Walsh, MD, Enanta: Advisor/Consultant|Enanta: Honoraria|GSK: Advisor/Consultant|Janssen: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support
P-1199. The burden of respiratory syncytial virus among Brazilian infants (BONSAI study): preliminary results
Authors: Ribeiro Manoel , da Silva Rodrigo C , Ribeiro Karina , Tolardo Aline , Homsani Sheila , Barata Rita
Published: January 2025

Background

Respiratory syncytial virus (RSV) is a leading cause of global morbidity and mortality in children < 1 year. Recent data have shown the burden of the disease among full-term babies. RSV surveillance system in Brazil does not capture information about gestational age. We aimed to estimate the incidence of hospitalization due to RSV according to gestational age among infants in Brazil.

Methods

Retrospective cohort study linking (deterministic and probabilistic, based on date of birth, city of residence, and mother´s name) the National Influenza Surveillance System (SIVEP-Gripe) and the National Information System on Live Births (SINASC). All children aged ≤24 months, living in São Paulo state, Brazil, admitted to hospitals clinically presenting with severe acute respiratory illness (SARI) tested for RSV from 2017 to 2019 were included. Incidence rates (IR) were calculated per 10,000 live births/year. Relative risk and corresponding 95% confidence intervals were estimated.

Results

During the study period, 1,807,703 live births were registered in São Paulo state and 11,003 cases of SARI, with 1,801 cases positive for RSV (16.4%). We successfully linked 1,436 RSV cases with SINASC (79.7%). IR was 7.94/10,000 live births/year, peaking in April and May. Eighty-one percent of cases (n=1,166) were registered in full-term infants (37+ weeks) (IR=7.28 cases/10,000 live births/year). IR for infants born < 29, 29-31, 32-36 weeks (w) were 12.68, 19.74, and 12.84 cases/10,000 live births/year, respectively (RR, premature vs full-term=1.83; 95% CI 1.60-2.10). Forty-nine percent of full-term infants with RSV were admitted to ICU (n=570), while the figures for the other gestational age categories were: < 29 (76.5%), 29-31 (60%), 32-36 w (51.8%). The case-fatality rate was 0.8% overall (4% for premature and 0.4% for full-term infants).

Conclusion

Our results showed that the burden of RSV among full-term infants is high (81% of hospitalized cases). Although the risk is higher among premature, a significant proportion of full-term infants can have unfavorable prognoses needing ICU admission, generating an overload of the healthcare system during seasonality. Preventive strategies for all infants are crucial to reduce the burden of RSV in Brazil.

Disclosures

Manoel Ribeiro, MD, PhD, Sanofi: Grant/Research Support Rodrigo C. da Silva, MSc, Sanofi: Grant/Research Support Karina Ribeiro, DDS, PhD, Sanofi: Employee|Sanofi: Stocks/Bonds (Private Company) Aline Tolardo, PhD, Sanofi: Employee|Sanofi: Stocks/Bonds (Private Company) Sheila Homsani, MD, Sanofi: Employee|Sanofi: Stocks/Bonds (Private Company) Rita Barata, MD, PhD, Sanofi: Grant/Research Support
P-1225. The population Pharmacodynamics study of Ganciclovir in Thai kidney transplant recipients with cytomegalovirus infection
Authors: Chantharit Prawat , Sutharattanapong Napun , Chatupho Wasin
Published: January 2025

Background

The aim of this study was to describe the population pharmacodynamic (PPD) of intravenous Ganciclovir for preemptive and treatment in Thai kidney transplant recipients (KT) with cytomegalovirus (CMV) infection who were not during hemodialysis or KT-related systemic lupus erythematous.

Simulations of CMV viral load overtime according to recommended dose

Methods

A retrospective study was conducted by collecting data from medical records, from 1 January 2020-31 December 2022. The estimated pharmacokinetic (PK) parameters derived from published model were applied to link with PPD, subsequently simulate the changes of blood CMV viral load overtime according to recommended dosage, stratified by glomerular filtration rate (GFR). PK/PPD modelling, and simulation were performed with parametric methodology using Phoenix® software, version 8.4, Certara.

Visual Predictive Check

Results

Twelve patients were included. The PPD model was developed by mechanistic indirect response equation, applying Emax model to stimulate the rate of CMV clearance. There were not any significant clinical and laboratory covariates affecting CMV dynamic. Goodness-of-fit plots were acceptable. A visual predictive check showed good consistency with observed data, whereas 1000 times-bootstrapping analysis was completed with 100% success rate. Ten thousand times-simulation indicated the time required for achieving 1-log10 and 2-log10 reduction of CMV viral load by recommended dose were 7-8 days and 15.8-18.5 days respectively. Viral decline was delayed in patients with lowered GFR.

Goodness-of-fit plot

Conclusion

The developed model described Ganciclovir-CMV viral load relationship and simulation result indicating the longer time for CMV viral load reduction in patients who had lower GFR. Our analysis demonstrated that the current recommended dose is required to be reconsidered and further systematic PD study is needed.

Disclosures

All Authors: No reported disclosures
P-1235. HPLC-UV method to establish rapid therapeutic drug monitoring of voriconazole in outpatients
Authors: Yagi Yusuke , Jobu Kohei , Ishida Tomoaki , Yanagisawa Narika , Okazaki Moemi , Arakawa Yu , Yamagishi Yuka , Matsunaga Nobuaki , Hamada Yukihiro
Published: January 2025

Background

Voriconazole (VRCZ) has non-linear pharmacokinetics, so personalized dosing based on pharmacokinetics is important. Approximately 20% of Asians are poor metabolizers of CYP2C19. In Japan, challenges include rapid measurement of VRCZ blood levels, feedback of results to physicians, and rapid therapeutic drug monitoring (TDM). The aim of this study was to evaluate the rapid TDM implementation system for VRCZ in outpatients.

Methods

Measurement of outpatient VRCZ TDM was started at Kochi medical school Hospital in January 2024 based on the blood concentration measurement flow by LM1010 high performance liquid chromatograph (HPLC-UV, Hitachi High-Tech Science Corporation). From January to April 2024, we compared the trough values of VRCZ and the reporting time of blood concentration measurement results after sample collection using the conventional externally requested measurement method (Method A) and the measurement method we constructed (Method B). In addition, we investigated the occurrence of hepatotoxicity from the perspective of preventing adverse events.

Results

The trough concentration of VRCZ were 2.97±1.15 mg/L for method A (n=7) and 3.15±1.25 mg/L for method B (n=15) ,p=0.75. The time required to report VRCZ blood concentration measurement results was significantly shorter (Method A (n=7): 78.9±10.4 h vs. Method B (n=7): 0.44±0.02 h (p< 0.05). No hepatotoxicity was observed during treatment in TDM outpatients who underwent rapid VRCZ measurement.

Conclusion

It is suggested that rapid determination of blood concentration of VRCZ by HPLC-UV will be an effective tool for TDM implementation and medical care support.

Disclosures

All Authors: No reported disclosures
P-1239. Systemic Exposure of Olorofim in Children with Invasive Fungal Infections
Authors: Cornelissen Karen , Rex John H , Zinzi Daniela , Bruggemann Roger , Wright James
Published: January 2025

Background

Olorofim (OLO) is a novel antifungal active vs. Aspergillus (including azole-resistant strains), resistant moulds (e.g., Lomentospora prolificans [LoPro]), and dimorphic moulds. Treatment with OLO in children with invasive fungal infection (IFI) is permitted under the Managed Access Program (MAP), where monitoring of trough concentrations is required due to sparsity of data in this population.

Methods

To be eligible for the MAP, children were aged 6 to 17 years, had an IFI infection that was shown to be or expected to be susceptible to OLO and had limited or no treatment options. Trough plasma samples (collected after an overnight fast) were sent to the central laboratory for analysis of OLO using a validated mass spectrometry assay. As a minimum, samples were taken after at least 7 days dosing and following any dose changes.

The paediatric dose was informed by a population pharmacokinetic (PK) model built using PK data from 52 adult patients with IFI. This model was used to predict systemic exposure in children aged 6 to 17 years based on PK parameters adjusted by weight. Paediatric doses were chosen based on a goal of Cmin ≥ 0.1µg/mL in over 90% of population, whilst Cmax and AUC were to be kept as low as possible. A further dose adjustment was required if OLO was given with strong cytochrome P450 3A4 inhibitors or inducers.

Results

To date, 22 children have received OLO, aged 6 to 17 years (mean = 11.0 y), with body weights of 20 to 80 kg (mean = 37.4 kg). IFIs treated include: IA (7), LoPro (4), Scedosporium spp. (4), coccidiomycosis (2), and other rare fungi (5). Trough level data are available for 19 subjects; the predicted maintenance dose resulted in trough levels ≥ 0.1 µg/mL in 15 subjects (79%). For the remaining 4 subjects (21%) OLO dose was increased. After dose adjustment (if required), observed trough plasma concentrations exceeded the threshold needed for efficacy (i.e., > 0.1 µg/mL) on all sampling occasions.

Conclusion

With the relatively small population and sparse PK sampling data available, the predicted body-weight dependent doses for children aged 6 to 17 y are considered reasonable. The dose predictions will be updated as the PopPK model is refined and trough levels will continue to be monitored pending conduct of a formal paediatric study.

Disclosures

Karen Cornelissen, PhD, F2G: Stocks/Bonds (Private Company) John H. Rex, MD, F2G: Employee Daniela Zinzi, MD. Infectious Diseases Specialist, VP Clinical R&D at F2G: Stocks/Bonds (Private Company) Roger Bruggemann, Pharm, PhD, F2G: Advisor/Consultant|F2G: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support James Wright, n/a, F2G: Advisor/Consultant
P-1255. Dosing of Piperacillin in Altered Renal Function with and without Renal Replacement Therapy for Required Increased Exposition
Authors: Surat Güzin , Dohmann Emma , Scherf-Clavel Oliver , Kurlbaum Max , Hagel Stefan
Published: January 2025

Background

Piperacillin/ Tazobactam [TZP] is a commonly used antibiotic in critically ill and non-critically ill patients, but not lot is known about TZP pharmacokinetics in non-critically ill patients needing dose reduction due to renal impairment. While Summary of Product Characteristics [SoPC] suggests 16 g Piperacillin daily for severe infections, patients with renal impairment (CrCl < 40 ml/min) are advised by the SoPC to only 8-12 g Piperacillin per day. The aim of this study was to determine the probability of target attainment (PTA), with the PK/PD target being set to unbound concentrations ≥60% of the time above 16 mg/L (MIC of increased exposure pathogen) in patients with decreased renal function especially in consideration of changed definitions on the susceptibility testing by EUCAST advising higher treatment dosing regimens for infections with Pseudomonas aeruginosa.

Methods

In this prospective two center study we measured 135 piperacillin serum concentration from 49 patients with decreased renal function to determine peak, trough and concentrations between peak and trough. Specific designed software (Monolix 2023R1) was used to develop a population pharmacokinetic model. The PTA was calculated for four groups (eGFR 40, 30 and 20 ml/min and 10 ml/min with intermitted hemodialysis) with different dosing strategies using Monte Carlo simulation (1000 patients per eGFR group). Covariates like age, sex, height, weight, eGFR, body mass index and body surface area (BSA) were evaluated.

Results

Patients with eGFR 40 and 30 ml/min reached a PTA of over 90% when following the SoPC (eGFR 20-40 ml/min: q8h, 30 min infusions) and increased their PTA to almost 100% when switching to prolonged (over 3h infusions). Patients with eGFR 20 ml/min reached a PTA of almost 90% with a q12h/ 30 min infusion dosage regimen recommended by SoPC for patients with eGFR < 20 ml/min and increased their PTA by about 5% when receiving prolonged infusions (3h). Patients with eGFR of 10 ml/min and intermitted hemodialysis reached a PTA of about 93% (q12h, 30 min infusions) and would reach a PTA of almost 100 % when switching to 3h infusions.

Conclusion

Prolonged infusions increased the PTA in all groups. The results indicate adjustments for Piperacillin infusions in renal impairment.

Disclosures

All Authors: No reported disclosures
P-1260. Validation of Modified First-Order Kinetic Equation for Vancomycin Area Under the Curve Calculation in Neonatal Patients
Authors: Lien Tsung-Chi , Wei She-Yi , Husted Harlan , Taha Sahar , Ip Alice , Covarrubias Laurie , Rongkavilit Chokechai
Published: January 2025

Background

Current guideline emphasizes a ratio of 24 hour-area under the curve (AUC) to minimum inhibitory concentration (MIC) of ≥ 400 mg.h/L as the primary pharmacokinetic and pharmacodynamics predictor of vancomycin activity against serious methicillin-resistant S. aureus (MRSA) infections. Premature infants admitted to neonatal intensive care unit (NICU) are at high risk of Staphylococcal infections due to immunocompromised state and frequent procedures; however, the availability of vancomycin AUC calculator for this population is limited.

Methods

Neonates received vancomycin for at least 4 days between January 2018 and December 2023 with steady-state trough level were included. The modified first-order kinetic equation using population-based distributive volume (Vdf) of 0.7 L/kg and trough level were compared to the Vanc App program validated in infants aged 0 to 90 days with post-menstrual age (PMA) ≥ 25 weeks and weight ≥ 500 grams. Ratio and percentage difference of calculated AUCs between the two models were assessed, as were safety parameters, including urine output < 0.5 mL/kg/hr over at least 6 hours, serum creatinine increases by 0.3 mg/dL or 1.5 times baseline, duration of culture positivity, and recurrence of same infection within 14 days.

Results

We identified 95 neonates with 56% male. The median (range) PMA was 30.1 (24.2 - 44.3) weeks, age was 21 (1 - 137) days, and weight was 1.2 (0.54 - 4.30) kg. Five cases had culture-proven MRSA infections. The average vancomycin dose was 37 mg/kg/day with median (range) duration of 7 (4 - 45) days. Acute kidney injury was identified in 2.1% of patients. Target AUC was achieved in 78% of cases. The average duration of culture positivity was 2.2 days, and no patients exhibited recurrent infections within 14 days after stopping vancomycin. The median (IQR) accuracy was 0.98 (0.95 - 1.01), and bias was -0.02 (-0.05 - 0.01). To obtain concordant AUC results, the mean (SD) Vdf was 0.67 (0.09) L/kg. No statistically significant differences between the two models in identifying AUC outside of therapeutic range (p=0.083).

Conclusion

The modified first-order kinetic equations can achieve comparable AUC estimates in neonates by incorporating a population PK-based VDf of 0.7 and single trough level, eliminating the need for additional blood draws.

Disclosures

All Authors: No reported disclosures
P-1277. Impact of Common Biases on Simulated Relative Vaccine Effectiveness Estimates: Implications for Evidence Synthesis, Decision Making, and Real-World Studies
Authors: Harris Daniel , Loiacono Matthew M , Chit Ayman , Oganisian Arman , van Aalst Robertus
Published: January 2025

Background

A growing number of real-world studies are using health administrative data to estimate relative vaccine effectiveness (rVE) due to ease of access and lower cost. To inform evidence-based decision making, meta-analyses of rVE estimates are often employed to summarize the volume of studies; however, low statistical power, unmeasured confounding, and publication bias threaten the validity of meta-analyzed estimates. Our objective was to demonstrate the impact of these biases on meta-analyzed rVE estimates using simulation.

Methods

We simulated a binary, enhanced vs. standard influenza vaccination strategy (allocated ∼1:1) and rare binary outcome (< 1.0%). True rVE was 20% (1–risk ratio [RR]=0.80). To simulate observational studies, weak negative confounding due to age (RR=1.02) and strong negative confounding by indication (RR=2.0) were introduced as measured and “unmeasured” confounders, respectively. Generalized linear models (link=log; distribution=binomial) estimated RRs and 95% profile confidence intervals (CI). To assess statistical power, small (N=5,000-10,000) and large (N=100,000-150,000) “studies” were conducted. Meta-analysis pooled rVEs by study design and size (randomized [30 small; 30 large]; observational [30 small; 30 large]). To emulate publication bias, statistically significant rVEs were pooled separately.

Results

Vaccine effectiveness point estimates varied widely in small samples (e.g., randomized rVE range = 42% to -18%; observational rVE range = 36% to -78%). Large, randomized studies were unbiased and precise on average (pooled rVE=21%; 95%CI=20-23), while large observational studies were biased and precise (pooled rVE = -4%; 95%CI=-2 to -6). Pooled rVE estimates from small and statistically significant randomized studies overestimated true rVE (n=2; pooled rVE=41%; 95%CI=19-57). Pooling all studies underestimated true rVE (n=120; pooled rVE=4%; 95%CI=3-5).

Conclusion

Low statistical power, confounding, and publication biases contributed to biased, pooled rVE estimates in this simulation. Public health decision-makers using meta-analyses should be aware of these threats to validity. Additional guidance to identify/address these potential biases in meta-analysis are needed.

Disclosures

Daniel Harris, PhD, MPH, Sanofi Vaccines: Advisor/Consultant Matthew M. Loiacono, PhD, MSc, Sanofi: full-time employee|Sanofi: Stocks/Bonds (Public Company) Ayman Chit, MBiotech, PhD, Sanofi: I am an employee of Sanofi|Sanofi: Stocks/Bonds (Public Company) Robertus van Aalst, PhD, MSc, Sanofi: Employee|Sanofi: Stocks/Bonds (Public Company)
P-1281. A Novel Substance Use Disorder-Focused Infectious Diseases Consultation Service: Our Experience with Xylazine-Related Ulcers
Authors: Novick Elizabeth , Kramer Carolyn , Zurlo John , Coppock Dagan , Seval Nikhil , Tucker Mollie
Published: January 2025

Background

Xylazine is a non-opioid analgesic that has become a prevalent additive in the illicit drug supply due to its low cost and synergistic effect with opioids. It is associated with soft tissue ulcers that become necrotic and can lead to infection, amputation, and death. Our hospital created a novel Infectious Diseases (ID) consultation service to help manage xylazine-related ulcers and other infectious sequelae of substance use disorder (SUD). Herein we describe characteristics of patients with SUD who presented to our hospital with xylazine-related soft tissue ulcers.

Methods

Using data extracted from our electronic health record, we generated a database of patients seen on our ID-SUD service between October 10, 2023 and January 1, 2024. We identified patients ≥ 18 years with documented SUD and conducted a retrospective chart review to identify patients with ulcers. Ulcers were defined based on documentation within the physical examination of a provider’s note or under the photographic media section. Patient demographics and clinical characteristics were collected and described using simple counts and frequencies.

Results

We identified 193 patients with SUD seen by the ID consult team during the study period. 73 patients (38%) had skin ulcers. The ulcer group was younger with a median age of 40, more likely to be white (78%) or Hispanic (18%), more likely to have tested positive for fentanyl (96%), more likely to inject (99%), and more likely to leave the hospital against medical advice (38%) compared to the non-ulcer patients, as shown in Table 1. Of patients with ulcers, 39 (53%) had ulcers >10cm in size, 55 (75%) had multiple ulcers, 10 (14%) had fever on admission, 17 (23%) developed bacteremia during hospitalization, and 72 (99%) received antibiotics during hospitalization, as shown in Table 2.

Conclusion

Xylazine-related skin ulcers have become common in patients with SUD, in particular intravenous opioid use. In our adult population in a large city with high rates of SUD, we demonstrated that many patients develop multiple large ulcers. Additionally, many patients with ulcers had evidence of systemic infection with fever, leukocytosis, and/or bacteremia. We anticipate an improvement in clinical outcomes as more is learned about pathophysiology and treatment of xylazine-related ulcers.

Disclosures

All Authors: No reported disclosures
P-1321. The Infectious Disease Needs of Adult Ukrainian Refugees in a Tertiary Centre in the West of Ireland
Authors: Quirke Siobhan , Duffy Lisa , Walsh Ellen , Keane Mary Bohan , Scarry Margaret , Boyle Nicola , Langan Catherine , McDonough Katie , Tuite Helen , Gallagher David , Moloney Geraldine , Lee John , Fleming Catherine
Published: January 2025

Background

Since February 2022 6.5 million have fled Ukraine; 104’ 870 to Ireland (2% of Irish population) [1, 2] The surge in those seeking temporary protection, coupled with infectious disease epidemiology in Ukraine; high prevalence of blood borne viruses and TB has placed strain on host countries' health services. [3, 4] 18 ‘840 (18% of National total, 0.37% of Irish population) are accommodated within our catchment area. The objective of this study was to evaluate case complexity, barriers to access and impact on service by this population.

HIV, HCV and HBV prevalence, control and management

Methods

We performed a retrospective chart review using our electronic patient record, compiled data on a protected spreadsheet and results were collated.

Tuberculosis prevalence, susceptibility, site and management

Results

123 adult Ukrainian refugees have newly attended our service since February 2022 - April 2024, 2.03 new patients weekly; 63/123 (51.2%) are female. The mean age is 44.7 years (18 - 79). 76 (61.8%) have HIV (PLWH); 68 (89.5%) known diagnoses; 39 (57.3%) of whom were virally suppressed on ART and 27 (40%) were viraemic as a result of treatment interruption, 2 (2.9%) had no blood testing with us. 7 (5.7%) were newly diagnosed following arrival to Ireland; 4 (57%) with advanced disease (mean CD4 Count 285 IU/mL [28 - 753]). Thirty two (42%) PLWH are co-infected with HCV, 4 (5.3%) with HBV. 37 (30%) attended with HCV mono-infection, 9 (7.3%) with HBV mono-infection. 17 PLWH (22.4%) report previously treated TB. We have seen 4 (3.25%) cases of active TB; three of MDR pulmonary disease and results are pending for the fourth case. 4, 10.5% of women living with HIV in this cohort have had pregnancies; 2 (5.3% of WLH) are currently pregnant (both live in Donegal; average 165.6 miles from clinic). The average distance traveled to our clinic is 64.6 miles (Range 0.62 - 189); based on current geographic distribution of the group 50.4% (62/123) can access public transport that would allow them to reach our clinic within 2 hours. There was no significant association between access to public transport and missed clinic appointments (p = 0.64). 115/123 (93.5%) have a need for an interpreter. Since February 2022 26 (21%) have required hospital admission with an average length of stay of 22.9 days and a total of 597 bed days used.

Conclusion

We have identified significant case complexity and ongoing high ID service need for this cohort.

Cohort Demographics

Disclosures

All Authors: No reported disclosures