bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1171. C. the Difference: A Daily Review of Clostridioides difficile Order Appropriateness in a Pediatric Acute Care Hospital
Authors: Czernikowski Dara M , Karunakaran Sharon , Stein Margot , Regier Jillian , Jockel Christina , Kozinski Rhianna , Creager Hannah M , Green Michael D , Montoya Lindsay 
Published: January 2025

Abstract

Background
Clostridioides difficile (CD) infections (I) are prevalent and costly healthcare-associated infections (HAIs). High rates of CD colonization in younger children make differentiation between colonization and infection challenging. Assessing for presence of CDI risk factors and absence of alternative causes of diarrhea can help to optimize diagnosis and avoid unnecessary CD testing.
Goal: Optimize HA CD testing and reduce HA CDIs at a pediatric acute care hospital.

Methods
Beginning mid-March 2023, CD tests were shifted to batch testing once daily to allow for pre-review of pending HAI timeframe (collected on or after the 3rd calendar day of admission) test orders. Orders were first identified through a prompted report and associated charts were reviewed using standardized criteria to determine appropriateness: presence of risk factors and relevant symptoms in the absence of other explanations for diarrhea (laxatives, enemas, underlying conditions, etc.). Discussions with clinical teams were initiated when testing was deemed inappropriate. Orders were canceled if teams agreed with reviewer’s feedback. Outcome and process data were retrospectively compared with one year of pre-implementation data. The Health System QI Committee approved this project.

Results
From April 1, 2023 – April 30, 2024, 216 pending HAI timeframe CD tests were reviewed: 83 (39%) were deemed inappropriate; 60 (72%) were canceled by the ordering physicians. Of the total 159 HAI timeframe orders run, 23 (19%) resulted positive. The number of completed HAI timeframe CD tests, average monthly HA CDI rate, and reported HA CDIs all decreased post-implementation (Table 1). The observed HA CDI rate also decreased post-implementation (Fig 1). Using the number of canceled orders and 18% HA CDI positivity rate observed in 2022, we estimate avoidance of 11 misdiagnosed CDIs in CD colonized children from this initiative.

Conclusion
Implementation of the daily review protocol decreased the number of HAI tests performed and the HA CDI rate. Next steps to advance this work include implementing electronic initiatives such as blocking CD tests with recent laxative use, and pop-up reminders for providers to consider testing patients admitted with CD symptoms & risk factors.

Disclosures
Michael D. Green, MD, MPH, ADMA: Advisor/Consultant|Bristol Myers Squibb: Advisor/Consultant|ITB-MED: Advisor/Consultant|kamada: Honoraria
P-1172. Staphylococcus Aureus Long-Term Catheter-Related Bloodstream Infection in Children: Clinical Features and Outcome
Authors: Perez Guadalupe , Merñiez Mariel , Padilla Emilia , Taicz Moira , Berrondo Fernando , Arias Ana Paula , Reijtman Vanesa 
Published: January 2025

Abstract

Background
Staphylococcus aureus long-term catheter-related bloodstream infection (LT-CRBI) are a frequent cause of morbidity and mortality. In Staphylococcus aureus LT-CRBI, it is recommended to remove the catheter. However, in pediatrics, management without catheter removal is often necessary.

Aims
to describe the clinical characteristics and outcome of Staphylococcus aureus LT- CRBI, to cmpare the clinical features and outcome according to removal or retention of the catheter

Methods
Retrospective cohort study. All patients with Staphylococcus aureus LT-CRBI from 1/1/2018 to 12/31/2022 in a pediatric hospital were included. Episodes of relapse of bacteremia were excluded. LT-CRBI was defined according to CDC criteria.

Results
Forty-five patients were included. Median age was 80 months (IQR 27-137). All patients had any underlying disease. Most common comorbidities were onco-hematological disease 27 patients (60%), intestinal failure 5 (11%), chronic kidney disease 3 (7%). Thirty-three were under immunosuppressive treatment (73%).
Median length of bacteremia was 4 days (IQR 3-5) Five patients presented metastatic infection (11%) including 2 patients with pneumonia, 2 thrombophlebitis and 1 soft tissue infection. Twenty-two catheters (49%) were removed. Reasons for removal were: mechanical dysfunction in 6 patients, catheter was not being used in 5 patients, tunnel or pocket infection in 5, septic shock 3 and persistent bacteremia in 3. Two patients died related to infection (4%). Staphylococcus aureus methicillin sensitive predominated (78%). Comparing patients with catheter removal vs retained: there were no differences in epidemiological, clinical features and outcome (metastatic infection 13% vs 9%, intensive care admission 3% vs 3%, length of bacteremia 4 days in both groups, mortality 20% vs 17%, respectively)

Conclusion
In this cohort of children with Staphylococcus aureus LT- CRBI, catheters were maintained in 51% of patients. No difference in outcome or complications was observed.

Disclosures
All Authors: No reported disclosures
P-1176. Optimal Agent and Timing of Surgical Antibiotic Prophylaxis and Surgical Site Infection in Pediatrics
Authors: Tran Martin T , Erickson Shasta , Ashouri Negar , Powell Melissa , Moore Laurie , Morphew Tricia 
Published: January 2025

Abstract

Background
Surgical site infections (SSI) make up ∼20% of all healthcare-associated infections (HAI), with 75% of SSI-associated deaths directly attributable to the SSI. Beta-lactams (BL) including cefazolin (CFZ) and cefoxitin (CFO) are recommended as surgical antibiotic prophylaxis (SAP). Cephalosporins are often avoided in patients with reported BL allergies despite cross-reactivity with penicillin at &lt; 1%. Guidelines recommend giving SAP 60 min prior to incision. Cefazolin and cefoxitin pharmacokinetics (PK) exhibit rapid time to peak serum level and short elimination half-life. We aim to evaluate differences in SSI rate in patients who received CFZ or CFO vs. non-BL alternatives (BLA) and administration of preop BL dose at different time interval prior to incision.

Methods
Retrospective observational study included patients aged 0 – 17 years who received SAP at CHOC from Jul 2021 – Jun 2023. Outcomes include differences in SSI rate within 90 days of surgery between patients receiving recommended BL (CFZ, CFO) vs BLA (clindamycin, gentamicin, metronidazole, vancomycin). Rate of SSI in patients who received pre-op CFZ or CFO at different time interval (0-20 min, 21-40 min, 41-60 min) will be examined. Wound classification (I to IV) as defined by CDC. SSIs were defined according to National Healthcare Safety Network. Bivariate logistic regression analyses compare the odds of experiencing an SSI between study groups.

Results
Median age was 9.0 years [IQR: 3.0, 14.0], 58.8% males. Wound classification is as follows: 37.6% (Class I), 34.1% (Class II), 22.9% (Class III), and 5.1% (Class IV). Overall SSI occurred in 1.0% (92/9054) of procedures. Beta-lactams were used as SAP in 96% of procedures, with 89.8% receiving pre-op dose within 20 min of incision. Laparoscopic appendectomy was the most common procedure at 10.9%. Age &lt; 1 year, use of non-BL SAP and administration of SAP &gt;20 min from incision was associated with significant increase in SSI (p&lt; 0.05, Table 1). No difference in SSI rate observed in patients who continued receiving post-op SAP for class I-II procedures.

Conclusion
Our study supports the continued use of CFZ, CFO compared to BLA for SAP. Pre-op doses of CFZ or CFO within 20 min of incision time were associated with decreased risk of SSI, likely due to their PK characteristics.

Disclosures
All Authors: No reported disclosures
P-1177. Impact of Staphyloccocus aureus Surveillance and Decolonization on MRSA and MSSA Infections in a Neonatal Intensive Care Unit
Authors: Hiermandi Nahid , Foster Catherine , Campbell Judith R , Purnell Krystal , Tocco Elizabeth , Marquez Lucila , Davis Andrea 
Published: January 2025

Abstract

Background
Staphyloccus aureus (SA) infection causes significant morbidity and mortality in NICU patients. Colonization by SA is a risk factor for infection. Surveillance and decolonization aims to curb the transmission of SA isolates thereby reducing rates of SA infection.
Figure 1. Epidemic Curve of MRSA Colonization and Infections 2012-2023

Methods
This retrospective study from 2012-2023 takes place in a 42-bed level-three NICU in Texas Children’s Hospital (Houston, Texas). Neonates are admitted to a private room and undergo weekly surveillance from admission/birth until discharge. Surveillance cultures for MRSA and subsequent decolonization of MRSA-positive neonates began in Oct. 2016. MRSA surveillance was changed to PCR (with reflex to culture if positive) in June 2017. Surveillance PCR (with reflex to culture if positive) and decolonization for MSSA began in Oct. 2021. Colonization is defined as detection by PCR or isolation by culture of SA from nares, umbilicus, or groin. Colonized neonates are treated with mupirocin twice daily for five days and if at least 4 weeks chronologic age or 36 weeks gestational age, topical 2% chlorhexidine wipes daily for five days. Infection is defined by the isolation of SA from cultures in the context of illness. Multiple positive specimens from the same site are considered the same infection if isolated within a 14-day window. Epidemic curves compare colonization and infections before and after the protocol. This study was approved by the Baylor College of Medicine Institutional Review Board.
Figure 2. Epidemic Curve of MSSA Colonization and Infections 2012-2023

Results
Surveillance and decolonization of MRSA-colonized neonates reduced the number of MRSA infections from its peak in 2016 (Figure 1). We continue to see SA-colonized infants especially with a substantial MSSA colonization burden. Despite the high rate of MSSA colonization, the number of MSSA infections remains low (Figure 2). Control charts (Figure 3 and 4) demonstrate rate, mean and upper limit of infection rates calculated per 1000 patient days.
Figure 3. Control Chart for MRSA Infections

Conclusion
The implementation of surveillance and targeted decolonization has been shown to decrease the number of MRSA infection even with ongoing colonization. Despite the high burden of MSSA-colonization, we do not see major peaks of MSSA infections. Further studies should explore if the presence of resistance genes to mupirocin and/or chlorhexidine explains ongoing colonization.
Figure 4. Control Chart for MSSA Infections

Disclosures
All Authors: No reported disclosures
P-1193. Epidemiology of Respiratory Syncytial Virus in Young, Hospitalized Children in Jordan: A Prospective Viral Surveillance Study
Authors: Amarin Justin Z , Hayek Haya , Hamdan Olla , Qwaider Yasmeen Z , Khraise Tala , Khader Ahmad , Odeh Qusai , Salim Rami , Shalabi Hadeel , Alhajajra Ahmad , Khader Yousef , Al-Zoubi Basim , Khuri-Bulos Najwa , Spieker Andrew J , Howard Leigh M , Chappell James , Halasa Natasha B 
Published: January 2025

Abstract

Background
Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections in young children worldwide. With the recent wave of regulatory approvals and authorizations for nirsevimab and maternal RSV vaccines across several countries, understanding the current burden and seasonality of RSV is crucial for implementing effective preventive strategies globally. We aimed to determine the burden, seasonality, and co-detections of RSV in hospitalized children &lt; 2 years old in Amman, Jordan.Figure 1.Monthly proportion of respiratory syncytial virus detections among children &lt;2 years old hospitalized at Al-Bashir Hospital with fever or respiratory symptoms (N=5,922), described by (A) season and disaggregated by (B) co-detection status.

Methods
We analyzed data from four prospective viral surveillance studies conducted at Al-Bashir Hospital collected during 2007, 2010–2013, 2020, and 2023–2024. We included children under 2 years old hospitalized with fever or respiratory symptoms who had a nasal or throat sample tested in the research laboratory for RSV and other common respiratory viruses using real-time polymerase chain reaction. Demographic and clinical data were collected through parental interviews and medical chart abstractions.

Results
Among 5,922 children, 2,540 (42.9%) tested positive for RSV. The median age of children with RSV among this age-restricted cohort was 3.2 months (IQR, 1.6–6.8), and males represented 57.6% (n=1,463). RSV circulation showed seasonal peaks during winter months (Figure 1), with the highest proportions observed in January 2011 (90.1%), 2024 (87.9%), and 2013 (85.8%). The burden and seasonality of RSV during the 2023–2024 season appeared to normalize compared with the disrupted pattern observed in the preceding season. Co-detection of RSV with other respiratory viruses was observed in 41.5% of RSV-positive cases (Table 1), with the most common co-detected virus being human rhinovirus/enterovirus (22.4%), followed by adenovirus (5.0%).

Conclusion
Our findings highlight the substantial burden of RSV among hospitalized young children in Amman, Jordan, and provide valuable insights into the current seasonality of RSV in a resource-limited setting. The normalizing circulation pattern has important implications for the timing and implementation of preventive strategies. The high proportion of RSV co-detections underscores the need for further research to elucidate the clinical significance of respiratory viral co-detection.

Disclosures
James Chappell, MD, PhD, Merck: Grant/Research Support Natasha B. Halasa, MD, MPH, Merck: Grant/Research Support
P-1210. Resurgence of Parechovirus-A3 Infection in Neonates and Young Infants after the Coronavirus Disease 2019 Pandemic in Japan
Authors: Aizawa Yuta , Tachikawa Jun , Yamanaka Takayuki , Shoji Takayo , Ito kenta , Kasai Masashi , Sakurai Hiroki , Minami Kisei , Hoshino Tadashi , Shibata Meiwa , Kondo Kenji , Funaki Takanori , Terauchi Yoshihiko , Furuno Kenji , Cho Yoshiaki , Saitoh Akihiko 
Published: January 2025

Abstract

Background
Parechovirus-A (PeV-A), especially PeV-A3, is a common cause of viral sepsis and encephalitis in neonates and young infants (age &lt; 4 months). The strict infection control measures and non-pharmaceutical interventions of the coronavirus disease 2019 (COVID-19) pandemic affected the epidemiological profiles of community-acquired diseases. However, the effects of the pandemic on the epidemiology of PeV-A infection in this age group are unknown.

Methods
This prospective multicenter observational study was conducted between 2019 and 2023 in 12 Japanese prefectures. Neonates and young infants hospitalized for suspected sepsis and/or meningoencephalitis were included. Samples were sent to the laboratory of Niigata University, and PeV-A was detected by real-time PCR. The 7 hospitals introduced the BioFire Filmarray meningitis/encephalitis (FA/ME) panel in 2020. Genotype was determined by direct sequencing and BLAST analysis, and the phylogenetic tree of viral protein 1 region of PeV-A3 was constructed.

Results
131 patients with PeV-A infection were identified (n = 36 in 2019, n = 7 in 2020, n = 1 in 2021, n = 27 in 2022, and n = 60 in 2023). Genotype was PeV-A3 in 124 cases and PeV-A4 in 2 cases in 2022 and unknown in 5 cases in 2019. Seasonal peaks and other characteristics were similar before and after the COVID-19 pandemic (i.e., in 2019 vs. 2023). Body temperature, fever duration, and the proportion of patients with rash declined; however, the proportion of those with abdominal distention increased. The FA/ME panel was more frequently used after the start of the pandemic (3.2% vs. 53.3%, P &lt; 0.001). The proportion of those with sepsis declined from 83.9% to 63.3% (P = 0.04), but the proportions of those with encephalitis and those requiring ICU admission were similar. No patient had sequelae at discharge. PeV-A3 has evolved within a single clade with two branches.

Conclusion
The number of PeV-A3 infections was higher after the start of the COVID-19 pandemic, possibly because low PeV-A3 activity early in the pandemic increased the number of susceptible pregnant women, thus leading to a decline in maternally derived antibodies. In addition, use of the FA/ME panel might help detect mild cases.

Disclosures
All Authors: No reported disclosures
P-1238. Assessment of Body Weight upon PK of Olorofim in Patients with Invasive Mould Infections
Authors: Cornelissen Karen , Rex John H , Zinzi Daniela , Galbraith Hal , Burt Howard 
Published: January 2025

Abstract

Background
Olorofim (OLO) is a novel antifungal active vs. Aspergillus (including azole-resistant strains), resistant moulds (e.g., Lomentospora prolificans [LoPro]), and dimorphic moulds. Potential impact of bodyweight upon systemic exposure was explored using pharmacokinetic (PK) data from a Phase IIb study and PB (physiologically-based) PK modelling.

Methods
Adult patients in the Phase IIb study (N=203) received OLO (30 mg tablets) at a nominal dose of 90 mg BID and OLO PK profiles were determined over 1 or 2 dosing intervals after 7 to 14 days dosing, with an additional 8 to 9 scheduled pre-dose samples taken over the initial 84 days.
A PBPK model was developed using both in vitro and in vivo data where oxidative cytochrome P450 (CYP)-mediated metabolism was determined to be the major pathway of olorofim clearance. The model was verified via demonstration of good independent recovery of observed systemic exposure in the presence and absence of CYP inhibitors and inducers and applied to the prediction of exposure in obese and morbidly obese subjects.

Results
Of the 168 patients with Invasive Fungal Infection (IFI), known body mass index (BMI) and full PK data over a dosing interval, 48% were normal body weight, 13 to 21% were classed as underweight, overweight or obese, with 1.8% classified as morbidly obese. Steady state systemic exposure (as determined by non-compartmental PK analysis) was similar across all BMI ranges (Table 1), apart from morbidly obese. The apparently higher mean exposure for morbidly obese is based on N=3 and values fall within the range seen for all other groups.
These results agree with PBPK modelling which predicted negligible to mild increases in total plasma olorofim AUC and Cmax values in obese subjects (geometric mean ratios for normal to obese of up to 1.25-fold), whereas a negligible change was predicted in morbidly obese subjects (which further suggests that the observed elevation in exposure in morbidly obese is artefactual likely driven by limited number for this subject population).

Conclusion
As systemic exposure in adults with IFI was similar across a range of BMIs, dose adjustment based on body weight is not required when treating obese or morbidly obese patients.

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)
P-1244. Optimizing Dosing of Penicillin in Combination with Ceftriaxone Against Enterococcus faecalis: An in vitro Pharmacodynamic Model
Authors: Funk Olivia G , Abulmagd Nadine , Cusumano Jaclyn A 
Published: January 2025

Abstract

Background
Penicillin may replace ampicillin in combination with ceftriaxone against Enterococcus faecalis endocarditis due to ampicillin stability, but optimal penicillin dosing is unknown. Penicillin pharmacodynamic (PD) optimization is especially important against borderline-penicillin-resistant, ampicillin-susceptible E. faecalis isolates (“borderline-PRASEF”; MIC 4-8 µg/mL; CLSI breakpoint ≤8 µg/mL) where, in vitro, ampicillin/penicillin-ceftriaxone has shown less activity.
Table 1
Combination therapy change in log10 CFU/mL against two E. faecalis isolates via in vitro one-compartment PD models

Methods
Penicillin intermittent infusion was compared to continuous infusion (CI) alone and with ceftriaxone against a penicillin-susceptible (e2122; MICs [µg/mL]: ampicillin 1, penicillin 2, ceftriaxone 256) and a borderline-PRASEF (e2095; MICs [µg/mL]: ampicillin 1, penicillin 4, ceftriaxone 2048) isolate via 48-hour in vitro one-compartment PD models, in duplicate, with a starting inoculum of 106 CFU/mL. The max penicillin intermittent dose, 5 MU every 4 hours (fT&gt;MIC: e2122, 53.1%; e2095, 40.7%) and most utilized CI dose, 24 MU/day (fT&gt;MIC: e2122 and e2095, 100.0%) were tested. Ampicillin 2 g every 4 hours (fT&gt;MIC: e2122 and e2095, 100.0%) alone and with ceftriaxone 2 g every 12 hours was used as a comparator. Therapeutic enhancement was ≥2-log10 CFU/mL decrease from the most active single agent. Adequate activity was a ≥2-log10 CFU/mL decrease from starting inoculum of 106 CFU/mL.

Results
No antibiotic alone achieved adequate activity. Against e2122, when combined with ceftriaxone, ampicillin and penicillin CI 24 MU/day achieved adequate activity and therapeutic enhancement whereas penicillin 5 MU intermittent infusion plus ceftriaxone did not. Against e2095, no combination achieved adequate activity or therapeutic enhancement. Due to insufficient activity, we tested e2095 against the highest penicillin CI dose of 30 MU/day plus ceftriaxone which did not achieve either outcome.

Conclusion
Optimizing penicillin fT&gt;MIC via CI dosing is needed to achieve similar antibacterial kill to ampicillin-ceftriaxone against penicillin-susceptible E. faecalis. Conversely, even the max penicillin dose of 30 MU/day (fT&gt;MIC 100.0%) as well as standard of care ampicillin-ceftriaxone was unable to maintain activity against borderline-PRASEF.

Disclosures
Jaclyn A. Cusumano, PharmD, BCIDP, Basilea Pharmaceutica: Grant/Research Support