bluuebunny/crossref_metadata_2025 huggingface dataset:
P-1123. Characterization of microbiological isolates in the newborn unit of the San Ignacio university hospital between 2018 and 2022
Authors: Perez Monica Maria , Bertolotto Ana Maria , Del Pilar Montealegre Adriana , Lopez Juan Carlos , Vargas Yaris Anzully , Suarez Maria Alejandra , Gomez Ingrid Mayerly , Cortes Gloria Cecilia
Published: January 2025

Background

Identifying local microbial profiles and antibiotic sensitivities is an important part of antimicrobial stewardship programs in order to prevent overuse of antibiotics. The purpose of this study was to characterize the microbiological isolates from patients hospitalized in the newborn care unit of the Hospital Universitario San Ignacio from January 1, 2018 to December 31, 2022.

Total number of microorganisms isolated

1

Methods

An observational, descriptive, historical single cohort study was conducted. Positive cultures of sterile samples (blood, urine, spinal fluid) from patients hospitalized. Demographic, clinical, and microbiological data of patients with positive cultures were also collected.

Results

A total of 207 positive cultures of sterile samples were identified (97 blood, 108 urines, 2 spinal fluid). The most frequent pathogens isolated were E. coli 28.9%, S. epidermidis 27%, Enterococcus faecalis 11.5%, Klebsiella pneumoniae 8.2% and Staphylococcus aureus 4.8%. E. coli and S. epidermidis being the main microorganisms isolated 28% each were the main pathogens associated with neonatal sepsis (NS). NS was predominantly late-onset >72 hours 94.6%. Early-onset sepsis was less common 5.3% and was associated with E. coli 5.4% and S. agalactiae 18.1%.

Healthcare-associated infections (34.7%), and catheter-associated bloodstream infections (CLABSI) were the most common. Congenital heart disease (P = .000) was the main comorbidity related to CLABSI, as well as gastroschisis (P = 0.002) and intestinal atresia (P = 0.033)

Multidrug-resistant (MDR) microorganisms were isolated in 12 instances (5.8%). Extended Spectrum Beta-Lactamase (ESBL) was 50%. Congenital heart disease was the only comorbidity with a statistically significant relationship with infection by MDR microorganisms (P = 0.026).

Clinical and sociodemographic characteristics of the multidrug-resistant microorganism population.

Conclusion

This is the first study in our environment to know the basal factors of infections in a population at risk, the patterns of resistance and possible association with the most prevalent pathologies and, based on this, to define the strategies of antimicrobial stewardship.

Disclosures

All Authors: No reported disclosures
P-1128. Pilot Cross Sectional Demographic Study of Pediatric Patients with Reported Penicillin Allergy in a Tertiary Rural Regional Health Center
Authors: Feldhaus Kevin , Richter John , Lim Peter Paul , Sass Emily , Reedstrom Hannah , Meeissner Tobias , Deaton McKenna , Borgmann Michael
Published: January 2025

Background

Penicillins remain reliable agents and are considered drugs of choice for select infections.1-3 Approximately 10% of the US population report a penicillin allergy with majority of the labels placed in childhood.4,5 There is a paucity of data describing the role of socio-demographic factors to understand the epidemiology of pediatric penicillin allergy especially in the rural settings.6

Methods

This is a cross sectional retrospective demographic query of pediatric patients 0-18 years old with reported penicillin allergy in the electronic medical record from 2018-2023 in a rural tertiary health system in South Dakota.

Results

Of 350,847 patients, 10,077 (2.9%) were identified with penicillin allergy label. Of which 5,162 (51%) were male. The median age was 11(6,15). There were 8,499 (88%) Caucasians, 432 (4.5%) American Indian/Alaskan Native, 126 (1.3%) Black/African American, 49(0.5%) Asian, and 3(< 0.1%)) Pacific Island/Native Hawaiian. Amoxicillin was the most common reported allergy in 6,738 (67%) patients, penicillin in 3,163 (31%) and Augmentin in 699 (6.9%). Severe reaction was reported in 2,921 (46%) patients with rash being the most common reported reaction in 5,566 (55%). Asthma was identified in 564 (5.6%) patients. Physicians are the primary providers for 5,778 (74%) among which family medicine physicians composed the majority (5,154, 66%). Penicillin allergy labels were recorded by APP/nursing in 7,202 (71.4). Majority of patients had commercial insurance 6,485 (71%) while 2,139 (23%) had government insurance. Patients’ home addresses that could be mapped using the RUCA classification, majority of patients belonged to rural (2,901,37%) and micropolitan (2,867, 37%) areas. Area Deprivation Index median was 66.

Conclusion

Penicillin allergy is most prevalent among Caucasian pediatric patients in our rural health system with Native Americans comprising the majority of other ethnic minorities. Amoxicillin is the most common reported allergy. Heterogeneous severity and characterization of reactions have been reported for these allergies. A small percentage of patients have identified co-morbidities. Socio-demographic factors differ across pediatric patients with penicillin allergies in our cohort with overall ADI suggesting above the national median.

Disclosures

Tobias Meeissner, PhD, BioNTech: Stocks/Bonds (Public Company)|Cellworks: Grant/Research Support|GeneDX: Stocks/Bonds (Public Company)|Labcorp: Grant/Research Support|Tempus: Grant/Research Support
P-1137. Decreasing Empiric Vancomycin use for Orbital Cellulitis in Children
Authors: Downey Rachel , Parihar Nisha , Weston Natalie , Khan Soman , Bhaduri. Hauger Sarmistha , Mincher Alan Wade , Kozak Travis
Published: January 2025

Background

Orbital cellulitis in children is often caused by Staphylococcus aureus, Streptococcus viridans group, and Streptococcus pyogenes. Oral, respiratory, and skin commensals are also considered in empiric antibiotic choice. MRSA is becoming less prevalent nationally.

In 2015, our hospital implemented an evidence-based orbital cellulitis guideline to standardize care and promote antibiotic and surgical stewardship. The guidance calls for empiric clindamycin and ceftriaxone, reserving vancomycin for cases with signs of optic nerve or CNS involvement. Here we evaluate results of this guidance and summarize isolated bacteria.Fig 1.Empiric use of vancomycin pre and post guideline

Methods

Cases were pulled from the hospital chart by diagnosis code and positive computed tomography scan for orbital cellulitis for 4 years pre-guideline and (2009-2013) 7 years post-guideline (2015-2021) implementation and were manually reviewed for clinical diagnosis of orbital cellulitis. Variables collected included demographics, empiric antibiotics, presence of abscess, surgical intervention, bacterial identification by blood or surgical culture, length of stay, and related readmission. Statistic analysis included chi square, fisher's exact test and Wilcoxon ranked sum.Fig 2.Bacteria isolated from blood or surgical culture in all cases*13 cases were polymicrobial

Results

134 cases were included in the analysis (46 pre and 88 post guideline). Median age was 7 in both groups; there was incidentally a significantly higher proportion of males in the post-guideline group (54% v 75%, p=0.025). Post guideline, empiric use of vancomycin significantly decreased from 54% to 23% (p< 0.001) (fig 1). Among cases with vancomycin use post-guidance, 60% of use was concordant with the guideline. Length of stay was reduced from a median of 4 days to 3 days (p=0.001). Rate of abscesses and surgical intervention were nearly identical in pre and post populations (63% with abscess, and 24% with surgery in both groups). Overall, bacterial cultures from blood or abscess were positive in 26% of cases (10 (22%) pre, 25 (28%) post guideline); 13 (37%) were polymicrobial. All 3 MRSA cases were susceptible to clindamycin.

Conclusion

Implementation of a hospital-wide guideline can result in more judicious use of broad spectrum antibiotics. Reduction in vancomycin occurred without increased length of stay, need for surgical intervention, or readmission.

Disclosures

All Authors: No reported disclosures
P-1139. Surveying Antibiotic Treatment for Pediatric Patients with Suspected Urinary Tract Infections at Madigan Army Medical Center
Authors: Lonergan Samantha , Sainato Rebecca , Cirks Blake
Published: January 2025

Background

Urinary tract infections (UTIs) are one of the most common bacterial infections in pediatric patients presenting to the Emergency Department (ED). However, the gold standard for diagnosis is a urine culture which takes 24-48 hours to result leading to antibiotics started empirically while results are pending. This study was implemented with the primary aim of evaluating the antibiotic management of pediatric patients who were seen at a single medical center ED with suspected UTI.

Methods

Using the electronic medical record we identified pediatric cases (ages 2 months-18 years) where UTI was diagnosed in the ED during 2023 using the ICD-10 code. Data collected on each case included demographics, laboratory work-up, prescribed medications, and follow-up. Outcomes were categorized as confirmed, unknown, or negated. A confirmed UTI required an abnormal urinalysis and single species growth exceeding 50,000 cfu/mL; UTI was negated when growth was < 10,000 cfu/mL. Descriptive statistics and comparison tests were used as appropriate.

Results

There were 80 UTI diagnoses in 70 patients. 18 (22.5%) cases were confirmed and 36 (45%) were negated (Table 1). We analyzed 54 cases with confirmed or negated UTIs: 15 (27.8%) had follow-up with primary care (PCM) within 96 hours of their ED visit. When UTI was negated, 4 cases (11%) had antibiotics discontinued and all had PCM follow-up within 96 hours (p=0.043) (Table 2). Enterococcus-UTI accounted for 75% of cases where empiric treatment was inadequate. Of those without confirmed UTI, 3 returned to the ED with adverse effects from antibiotics and 2 with multiple inconclusive evaluations were referred to urology. The ED providers notified families with positive urine culture results, but no one was notified if the urine culture was negative.

Conclusion

Many pediatric patients who are treated for UTI in our ED have inconclusive or negative workups resulting in unnecessary antibiotic use, ED visits for antibiotic complications, and subspecialty referrals. Our current system does not support the discontinuation or tailoring of unnecessary or inappropriate antibiotics unless patients have close follow-up. Antibiotic stewardship requires systematic support within the ED to limit unnecessary antibiotics and the inherent complications that follow.

Disclosures

All Authors: No reported disclosures
P-1150. Prospective case-control study to examine clinical, biochemical, and serological indicators to predict Staphylococcal scalded skin syndrome
Authors: Mitra Barnali , Mitra Debdeep
Published: January 2025

Background

Staphylococcal scalded skin syndrome (SSSS) typically affects infants & children, with rare occurrences in adults. There is no rapid tool or any scoring system to diagnose SSSS, where early diagnosis is the key to successful outcome.

Methods

This study evaluates specific clinical & serological indicators to distinguish between maculopapular eruption & SSSS upon initial presentation. Additionally, we investigate the correlation between serum levels of thymus and activation-regulated chemokine (TARC) & the severity of SSSS & the extent of organ involvement.

In this observational study conducted prospectively, 25 patients diagnosed with SSSS & 25 control subjects with maculopapular rash were enrolled.

Results

The diagnostic efficacy of various factors, including TARC level ( >612.25 pg/ml), total body surface area (TBSA >30%), hsCRP ( >5mg/l), leucocytosis ( >12X 109 cells/L), & aspartate transaminase ( >90 U/L), showed statistical similarity to the diagnosis of SSSS. While baseline serum TARC levels proved to be a reliable screening tool, they did not predict the severity or outcome of SSSS. However neutrophil extracellular traps (NETs) level did correlate positively with disease severity & duration of hospital stay.

Through multivariable regression analysis, we have formulated a novel model that integrates TBSA at baseline, neutrophil percentage in leucocytosis, & hsCRP, surpassing the predictive capacity of these parameters when considered individually. The resulting equation with the highest odds for diagnosing SSSS is as follows:

Odds of SSSS (present) = Antilog [-11.26 + 0.3 x Total BSA + 0.30 x hsCRP – 0.1 x neutrophil (%)].

This composite model (incorporating TBSA at baseline, neutrophil percentage, and hsCRP) achieved a sensitivity of 96% and specificity of 100% at a cutoff point of 7.8.

Conclusion

The equation developed from our research is straightforward to apply and suitable for use in settings with limited resources. It facilitates the identification of patients who are more likely to have SSSS, enabling the early initiation of definitive treatment. Likewise, it helps in minimizing unnecessary extensive investigations for patients unlikely to have SSSS. Neutrophil extracellular traps (NET) can be definitely used as a prognostic marker in patients with severe SSSS.

Disclosures

All Authors: No reported disclosures
P-1166. Outcome of Fungemia Caused by Yeast in Children: Significance of Breakthrough Fungemia and Source Identification
Authors: Kasai Taketo , Yamada Masaki , Funaki Takanori , Ogimi Chikara
Published: January 2025

Background

Fungemia by yeast is a life-threatening infection that occurs in patients with special conditions. It is often identified by its morphology, triggering the empiric therapy. However, the management can be difficult as identification and susceptibility tests require several days, and evidence on management and outcomes in pediatric patients is limited. Thus, this study aimed to characterize pediatric fungemia by yeast and assess their outcomes to help optimize management.

Risk factor analysis for overall mortality following fungemia by yeast

Methods

This is a single-center, retrospective observational study at the largest tertiary children’s hospital in Japan. Electronic medical records of pediatric patients < 18 years who developed fungemia by yeast from April 2014 to March 2024 were reviewed. To simplify, the data on the first fungemia by yeast was collected on patients with multiple episodes, along with patient characteristics, details of identified organisms, use of antifungals, and prognosis. Breakthrough fungemia was defined when it occurred during the use of systemic antifungals for ≥ 3 days. Descriptive data, the risk for overall mortality and survival following fungemia were analyzed using chi-square test and Kaplan-Meier curve analysis with a p-value < 0.05 being considered significant.

Overall survival following fungemia by yeast according to prior use of antifungals

Results

Overall, 55 episodes of fungemia by yeast were identified in 43 patients. 28/43 (65%) patients were immunocompromised. Candida parapsilosis was the most frequently detected (20/43, 47%), followed by C. albicans (11/43, 26%). Breakthrough fungemia occurred in 17/43 (40%) cases. Mortality was significantly higher in patients with breakthrough fungemia compared to those without prior antifungals (8/17 (47%) vs. 2/26 (8%), p< 0.01). In addition, when the source of fungemia was clinically undetermined, the overall mortality rate was high (8/17, 47%, p< 0.01) (Table). Further, the survival curve after the onset of fungemia by yeast depicted the worse outcomes in patients with breakthrough fungemia (p< 0.01) (Figure).

Conclusion

In pediatric patients with fungemia by yeast, the mortality rate was higher in breakthrough fungemia and fungemia with unknown sources. Therefore, it is crucial to recognize the importance of breakthrough fungemia and identifying the source of infection to pursue appropriate source control.

Disclosures

Chikara Ogimi, MD, PhD, AstraZeneca: Honoraria|bioMerieux Japan Ltd.: Honoraria|ELSEVIER: Honoraria|KYORIN: Honoraria|Miyarisan: Honoraria|MSD: Honoraria|NOVARTIS: Honoraria|Pfizer: Honoraria
P-1170. Impact of Healthcare-associated Respiratory Virus Infections in Children
Authors: Miyashita Aki , Horikoshi Yuho , Funakoshi Hanako , Shibata Meiwa , Nakamura Keiko , Miyokawa Shigeko
Published: January 2025

Background

Respiratory viruses can spread within healthcare facilities despite stringent infection prevention measures. Although healthcare-associated respiratory virus infections (HARVI) pose a significant risk to children, pediatric HARVI are understudied. The present study aimed to evaluate the impact of HARVI on children following the SARS-CoV-2 pandemic at a tertiary children’s hospital.

Methods

This retrospective study enrolled pediatric inpatients aged ≤18 years who were hospitalized at Tokyo Metropolitan Children's Medical Center between April 2020 and March 2024. HARVI was defined as a viral infection with a new onset of respiratory symptoms past the incubation period following hospitalization. The causative virus was detected using multiplex PCR (FilmArray Respiratory Panel 2.1, BioFire). Patients with other infections were excluded. The primary outcome was the 30-day mortality rate. The secondary outcomes included PICU admission, escalation of respiratory support, and the postponement of discharge, planned surgery or chemotherapy.

Results

In total, 265 patients with HARVI were enrolled. Male patients comprised 31% of the cohort, and the median age was 31 (IQR [interquartile range]: 12-77) months. Underlying neurologic, cardiac, and congenital or genetic disorders had in 42%, 28%, and 24% of the cohort, respectively. The respiratory viruses detected were the rhinovirus/enterovirus (44%), parainfluenza virus type 3 (15%), and HKU1, NL63, 229E and OC43 coronaviruses (8%). The 30-day mortality rate was 1% in three patients with parainfluenza virus type 3, RSV, and SARS-CoV-2. The PICU admission rate was 2%. The rate of respiratory support escalation was 17%. Postponement of discharge was required in 7% of the cohort for a median period of seven (IQR: 5-8) days. Postponement of surgery was required in 3% of the cohort for a median period of 46 (IQR: 21-82) days. There was no postponement of chemotherapy.

Conclusion

Pediatric HARVI was associated with mortality and additional medical care. Therefore, strict infection prevention measures are essential.

Disclosures

Hanako Funakoshi, MD, Pfizer Japan: Husband is an employee.
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

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

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

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 < 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 < 1 year, use of non-BL SAP and administration of SAP >20 min from incision was associated with significant increase in SSI (p< 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

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

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 < 2 years old in Amman, Jordan.Figure 1.Monthly proportion of respiratory syncytial virus detections among children <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

Background

Parechovirus-A (PeV-A), especially PeV-A3, is a common cause of viral sepsis and encephalitis in neonates and young infants (age < 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 < 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

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

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>MIC: e2122, 53.1%; e2095, 40.7%) and most utilized CI dose, 24 MU/day (fT>MIC: e2122 and e2095, 100.0%) were tested. Ampicillin 2 g every 4 hours (fT>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>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>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
P-1247. Cerebrospinal Fluid Penetration of Multiple Antibiotics in Patients With Intracranial Hemorrhage: A Prospective, Observational, Clinical Study
Authors: Tseng Yu-Ju , Chen Yi-hsuan , Lan Yi-Xuan , Wu Chien-Chih , Luh Hui-Tzung
Published: January 2025

Background

External ventricular drains (EVD) are used for acute hydrocephalus in intracranial hemorrhage(ICH), potentially causing ventriculostomy-associated cerebrospinal fluid infection (VAI). Variable meningeal inflammation in VAI can result in unpredictable antibiotic penetration in cerebrospinal fluid (CSF). This observational study aimed to assess CSF penetration of intravenous antibiotics for suspected VAI treatment in neurosurgical patients.

Time to concentrations in CSF and plasma among the patients.

The figure presented the concentrations of blood and cerebrospinal fluid (CSF) measured at different time points for each patient. REVD right-sided external ventricular drain. LEVD left-sided external ventricular drain.

Methods

Adults with EVD for ICH who were receiving antibiotics, including vancomycin, ceftazidime, cefepime and meropenem, for VAI from January 2023 to April 2024 in two north Taiwan medical centers were enrolled in this study. The primary outcome was the area under the concentration (AUC) ratio between CSF and plasma (AUCCSF/plasma). Factors influencing CSF concentration was also investigated. In addition, the probability of target attainment (PTA) of anti-Pseudomonal antibiotics were calculated.

A summary of the permeability of vancomycin into the cerebrospinal fluid in this study.

ARC augmentation renal clearance. L Left-side external ventricular drain R Right-side external ventricular drain.

a. AUC was calculated from the first observation point to the last observation point.

b. It was resistant to vancomycin.

Results

A total of 9 patients (6 male) with VAI were enrolled, and contributed 7 vancomycin, 3 ceftazidime, 2 cefepime and 2 meropenem treatment courses. One patient provided two courses. The ranges of AUCCSF/plasma for vancomycin, ceftazidime, cefepime, or meropenem were as follows 0.85-15.61%, 6.74-15.61%, 0.16-128.73%, and 0.09-13.24%, respectively. The CSF to plasma concentration ratio at the end of vancomycin infusion and at the middle of dosing interval showed good correlation with AUCCSF/plasma (Spearman's coefficient 0.8 and 0.783, p-value ≦0.01) For ceftazidime, both CSF and plasma achieved at least 98% fT >MIC=8 under 2 gram every 8 hours regimen. For meropenem, the fT >MIC=2 for CSF and plasma were 0-100 % and 95.7-99.8% under 2 gram every 8 hours regimen, respectively. For cefepime, the fT >MIC=16 for CSF and plasma were 0-100% and >97%, respectively.

Conclusion

This is the first study to report real-world data of antibiotic CSF penetration in neurosurgical population in Taiwan. Ceftazidime showed adequate penetration and achieved sufficient PTA in the CSF. Additionally, the single-point ratio of vancomycin at the end of infusion and during the mid-dosing interval may serve as a surrogate for AUCCSF/plasma.

Disclosures

All Authors: No reported disclosures
P-1249. Analysis of Drug Interaction Between Valproic acid and Carbapenems
Authors: Cho Youngmin , Moon Hyejeong , Park Jaemin , Kim Chang , Han Ji Yeon , Kim Hun Min , Choi Yunsang , Choi Seong Jin , Moon Song Mi , Song Kyoung-Ho , Kim Eu Suk , Kim Hong Bin , Lee Woo-Jin , Yun Chang-Ho , Yoon Seonghae , Chung Jae-Yong , Lee Joon Hee , Park Jeong Su , Heo Eunjeong , Kim hyung-Sook , Lee Hyunju
Published: January 2025

Background

Carbapenems are broad spectrum antibiotics widely used for treatment of various infectious disease such as pneumonia, sepsis, and urinary tract infection. Carbapenems have been linked to a possible drug interaction which can lead to subtherapeutic levels of valproate and increase the risk of patients experiencing seizures. In this study, we reviewed cases of concomitant use of valproic acid and carbapenems, and investigated the impact of drug-drug interactions and effects.

Methods

The electronic medical records of patients treated with carbapenems and valproic acid at Seoul National University Bundang Hospital from 2017 to 2022 were reviewed.

Results

During the study period, a total of 183 patients were prescribed concomitantly with valproic acid and carbapenems. The average age was 64 years, 172 (94%) were >18 years of age and 11 (6%) were ≤ 18 years. The most common reason for carbapenem prescription were urinary tract infection (48.1%), pneumonia (38.3%), sepsis (24.6%), and intra-abdominal infection (5.5%). Among carbapenems, ertapenem was most common by 61.8%, followed by meropenem (39.9%), and imipenem (3.3%). Of the total cases, valproic acid monotherapy accounted for 42.6% and concomitant use with other anticonvulsants accounted for 57.4%. During concomitant use of carbapenem and valproic acid, 35.0% of patients were consulted to the infectious diseases or neurology departments about drug interactions, and 44.8% monitored the therapeutic drug concentration. During the concomitant treatment, valproic acid dosage was increased in 19.1% and other anticonvulsants were added in 12.0%. Seizure occurred in 15 cases (8.2%) of the total cases.

Conclusion

As a result of investigating drug-drug interactions between carbapenem and valproic acid, serum concentrations of valproic acid were significantly decreased, some of which actually led to convulsions. Care should be taken when administering carbapenem to patients receiving valproic acid. If concomitant administration is unavoidable, it is important to monitor serum concentrations and consider alternative anticonvulsants. Continuing education and monitoring of therapeutic drug concentrations are required for the concomitant administration of carbapenem antibiotics and valproic acid.

Disclosures

All Authors: No reported disclosures
P-1252. Individualizing Antibiotic Therapy: Pharmacokinetic Approach to Evaluate and Optimize dosing of Meropenem in Critically Ill Sepsis Patients
Authors: Dhandapani Shakthivel
Published: January 2025

Background

The optimization of antibiotic dosing poses a considerable challenge, particularly in cases of Sepsis with acute renal impairment requiring continuous renal replacement therapy (CRRT). This study centers on the widely prescribed broad-spectrum beta-lactams, specifically meropenem, recognizing its extensive use in severe and complex clinical scenarios. The primary objectives of this study is to formulate new guidelines facilitating dose individualization, thus enhancing therapeutic outcomes for this critical population.

Meropenem dosing recommendations for sepsis shock patients with acute renal impairment

Methods

Three studies were conducted based on specific hypotheses. The initial study involved a comprehensive systematic literature review aimed at critically evaluating the existing evidence regarding the dosing regimens of meropenem. Subsequently, Studies 2 and 3 were undertaken as observational, prospective, open-labeled, multicenter pharmacokinetic investigations within the Intensive Care Unit of a prominent tertiary care hospital in Coimbatore, India. The study cohort comprised thirty patients administered with meropenem experiencing septic shock with acute renal impairment requiring continuous renal replacement therapy. Population Pharmacokinetic models were meticulously developed, validated, and subjected to Monte Carlo simulations for comprehensive analysis.

Results

A comprehensive literature review exposed the limitations of current dosing recommendations, pointing to varied sickness severities, renal function levels, admission diagnostics, CRRT settings, and disparate pharmacokinetic (PK) methodologies. For meropenem, a crucial relationship between 24-hour urine output and total clearance emerged. Oligoanuric patients (< 100mL/24h) displayed a 30% decrease in total clearance compared to those with preserved diuresis ( >500mL/24h). Monte Carlo simulations supported tailored dosing recommendations, addressing bacterial susceptibility and patient diuresis status.

Conclusion

For optimal antibiotic dosing, our findings highlight the importance of considering clinical and demographic factors, including 24-hour urine output and patient weight. These insights can be implemented at the bedside to help navigate the complexities of antibiotic optimization within the Intensive Care Unit.

Disclosures

All Authors: No reported disclosures