2025 Southeastern Residency Conference

Title: Evaluation of Maintenance-and-Reliever Therapy Utilization for Pediatric Asthma 

Authors: Chiara Huber, Christina Cox, Katie Rasmussen, Kimberly Grubbs, Logan Miller, Heather Staples

Background: Asthma is the most common pediatric chronic condition, affecting over 4.5 million children. Prior to guideline updates, the standard approach to moderate to severe asthma in children included a short acting beta agonist (SABA) inhaler for relief of asthma symptoms, plus a separate inhaled corticosteroid (ICS) or ICS/long-acting beta agonist (LABA) inhaler for maintenance therapy. In 2019-2020, the Global Initiative for Asthma (GINA) and National Heart Lung and Blood Institute (NHLBI) asthma guidelines were updated to recommend the use of combination ICS-formoterol as both maintenance and reliever therapy (MART) as a preferred regimen in moderate to severe asthma in adults and children ≥ 5 years old. Despite new recommendations, a recent evaluation of MART use in adults found low adoption rates among eligible patients. Factors associated with MART adoptions included baseline maintenance use of ICS-formoterol, private insurance, younger patients and newer clinicians. Since limited information exists for pediatric patients, this study aims to describe MART implementation in pediatric asthma patients and identify the factors associated with MART recommendations.   

Methods: This retrospective cohort study included patients aged 5-18 with asthma who were admitted to Prisma Health Children’s Hospital-Midlands for an asthma exacerbation between January 1, 2022, and July 1, 2023. The primary outcome was the proportion of patients who qualified for MART and received a MART recommendation. For the purposes of this study, patients qualified for MART if they were utilizing an ICS or ICS/LABA inhaler at time of admission and had received at least one course of non-inhaled corticosteroids in the last year. Secondary outcomes included asthma readmissions within one year and an evaluation of factors that may be associated with MART recommendations. Statistical analysis will involve descriptive statistics and a multivariate regression analysis to assess the relationship between demographic data and MART therapy. 

Results: 598 patients were screened for enrollment and 246 were included in the primary analysis. The median patient age was 8 years, 69.5% of patients were Black, and 63.5% of patients were on Medicaid. 102 patients qualified for MART based on study criteria, however only 4 patients (3.9%)  were discharged with MART recommendations. 36 patients were readmitted for asthma within one year. Compared to those who did not qualify, patients who qualified for MART were more likely to be readmitted for asthma (21.6% vs 9.7%) and have a high risk disease state (14.7% vs 9.7%).

Conclusions: MART utilization remained very long among qualifying patients. Patients who qualified for MART had high rates of asthma readmissions and more frequently had disease states associated with higher exacerbation risk. 

Objective: 
Investigate the incidence of culture-proven infection in pre-term and VLBW and low birth weight (LBW) neonates in the NICU at USACWH
 
Self-Assessment Question: 
What probiotic had the greatest incidence of positive cultures? A. Culturelle B. UP4 C. Ultimate Flora Baby


Background: 
Pre-term neonates have an immature gut barrier and alterations in the microbiota increase their risk for morbidity and mortality. Probiotics are used to colonize the gastrointestinal tract with beneficial microorganisms to prevent complications such as necrotizing enterocolitis (NEC) and colonization of Clostridium difficile. Currently, the American Gastroenterological Association (AGA) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines recommend probiotics in pre-term and low-birth weight neonates to prevent NEC in the hospitalized setting. A risk factor of probiotics in this patient population is the translocation of a probiotic species across their permeable barrier and out of the digestive tract.  The University of South Alabama Children’s and Women’s Hospital (USACWH) used probiotics liberally in the neonatal intensive care unit (NICU) until the fall of 2023. Probiotic use ceased after the U.S Food and Drug Administration (FDA) issued a healthcare warning on probiotic use in hospitalized pre-term or very low birth weight (VLBW) infants due to the potential risk of invasive and potentially fatal disease from live bacteria or yeast.   This study aims to investigate the incidence of culture-proven infection in pre-term and VLBW and low birth weight (LBW) neonates in the NICU at USACWH.
 
Methods: 
This is a single-site, retrospective review of neonates admitted to a level III NICU between 2017 and 2024.  The primary outcome was the incidence of positive cultures matching a probiotic species in preterm or VLBW and LBW infants. Pre-term neonates between 21 weeks to 38 weeks gestational age or LBW defined as < 2,500 grams, received > 72 hours of probiotics, and a positive culture matching the probiotic species were included. Patients were excluded if they were > 38 weeks gestational age, weighed > 2,500 grams, or received < 72 hours of probiotics. The key secondary data points include past medical history, type of probiotic, day of admission probiotics were initiated, duration of probiotic, type of culture, culture speciation, ICD-10 code for NEC, and cause of death.   Statistical tests used were means and standard deviations for descriptive statistics, Naranjo criteria, means and standard deviations.
 
Results:  
A total of 871 patients received probiotics. There was a total of 6 neonates with positive cultures matching the probiotic species. This correlates with an incidence rate of 0.69 new positive culture for every 100 patients.  All 6 neonates with positive cultures received Ultimate Flora Baby (UFB), containing Bifidobacterium spp (B. infantis, B. breve, B. longum, B. rhamnoses, B. acidophilus) and Lactobacillus spp (L. rhamnoses, L. acidophilus). Out of the 871 patients, 726 (83%) patients received UFB, 133 (15%) patients received UP4, and 12 (2%) patients received Culturelle.  A Naranjo score of 6 suggests the positive blood cultures were a probable adverse event from the probiotic. However, other factors might have contributed to the positive cultures. The results of the possible factors that may have contributed to the positive cultures are still pending.  
 
Conclusion: 
Among preterm, VLBW, and LBW infants receiving probiotics in the NICU at USACWH there was a low incidence rate of positive blood cultures.  Factors that could have contributed to the positive cultures is still in progress.  

Title: Evaluating The Incidence of Adverse Effects Associated with High-Dose Intrapartum Vancomycin Administration for Group B Strep Prophylaxis


Authors: Jesse Klus, Kendall Heetdirks, Tanya Makhlouf


Objective: Evaluate the incidence of acute kidney injury and other pertinent adverse reactions in pregnant patients receiving high-dose vancomycin for intrapartum Group B Strep prophylaxis 


Self Assessment Question: MJ is a 29 YOF G1P0 at 39w5d who presents in active labor. She has had an uncomplicated pregnancy course thus far. She was found to be GBS positive and does have a high-risk allergy to penicillin. Clindamycin susceptibilities are unknown Her Scr is 0.89 and she weighs 70 kg. Which of the following would be the best regimen for GBS prophylaxis? 
A.Vancomycin 1000 mg IV Q12h
B.Clindamycin 900 mg IV Q8h
C.Cefazolin 2000 mg IV Q8h
D.Vancomycin 20 mg/kg IV Q8h


Background/Purpose: Prior to the implementation of intrapartum Group B Strep (GBS) prophylaxis, GBS was the most common cause of neonatal sepsis. Approximately 50% of women who are colonized with GBS will transmit the bacteria to their newborn either during the intrapartum period or after rupture of membranes. Without the use of prophylactic antibiotics in the intrapartum period, about 1-2% of newborns exposed to GBS develop early onset infections. The American College of Obstetricians and Gynecologists (ACOG) recommends administering GBS prophylaxis to women who have either known or unknown GBS colonization to decrease the rate of transmission to the neonate. Penicillin G is the preferred agent for GBS prophylaxis; however, cefazolin can be utilized in patients who have a low-risk penicillin allergy and vancomycin is preferred in patients who have a high-risk penicillin allergy and either known or unknown resistance to clindamycin. In June 2019, the recommended vancomycin dose was increased from 1000 mg IV every 12 hours to 20 mg/kg/dose (max 2000 mg) IV every 8 hours based on studies evaluating maternal and neonatal vancomycin levels. The purpose of this study was to evaluate the incidence of adverse effects associated with high-dose vancomycin for GBS prophylaxis during labor. 
 
Methodology: This was a multi-center, prospective, IRB approved, cohort study conducted at the Moses Cone Women’s and Children’s Center and Alamance Regional Medical Center in Greensboro, NC. On October 4, 2023, both centers adopted the vancomycin 20 mg/kg/dose every 8 hours dosing regimen for GBS prophylaxis in the intrapartum period. Patients were included in if their gestational age was at least 23 weeks and received at least one dose of vancomycin for GBS prophylaxis from October 1, 2022, to November 1, 2024. Patients were excluded if they received antibiotics for another indication, received an antibiotic for GBS prophylaxis other than vancomycin, had known intrauterine fetal demise, or were dialysis dependent. The primary objective was the incidence of acute kidney injury (AKI) following vancomycin dosing, as defined by an increase in serum creatinine of at least 0.3 mg/dL within 48 hours. Secondary objectives further evaluated the safety of high-dose vancomycin. Results were evaluated utilizing Fisher’s Exact and two sample T-tests.  
 
Results: A total of 93 patients were included in the analysis. There were 2 incidences of AKI in the post-group compared to none in the pre-group (p = 0.19). There was no statistically significant difference seen in the rates of GBS infection of the newborn and vancomycin flushing reactions between groups. More doses of vancomycin were given in the post-group (2.0 vs 1.7, p = 0.14) and the dose of vancomycin was higher in the post-group (1625 mg vs 1000 mg, p < 0.001). There were no trough levels obtained in the pre-group and five trough levels obtained in the post-group. The majority of trough levels drawn in the post-group were supratherapeutic.
 
Conclusions: High-dose vancomycin was not associated with a significant increase in AKI.   The difference seen in trough levels obtained between groups can be attributed to both increased dosing frequency in the high-dose group and overall short labor durations, making obtaining trough levels less feasible. While most of the trough levels obtained in the high-dose group were supratherapeutic, there was no indication that this resulted in increased adverse events. Additionally, the new dosing regimen provided adequate protection against GBS in newborns, as indicated by low infection rates. This evaluation demonstrates that high-dose vancomycin is a safe regimen for GBS prophylaxis in the intrapartum period. Larger evaluations are necessary to confirm the findings of this study.  

Title:  Optimal Enoxaparin Dosing in Children with Congenital Heart Disease Less than 1 Year of Age 


Authors: Katelyn Price, Hania Zaki, Haseena Hussain, Jennifer Sterner Allison, Helen Giannopoulos, Gary Woods, Josh Branstetter 


Objective: Evaluate enoxaparin dosing regimens in children with congenital heart disease in patients less than 1 year of age. 


Self Assessment Question: 
Which of the following enoxaparin dosing strategies would be best to use to acheive initial therapeutic levels quicker based on the results of this study?
A. 0.75 mg/kg q12h
B. 1 mg/kg q12h 
C. 1.5 mg/kg q12h
D. 1 mg/kg q24h 


Background: Venous thromboembolism (VTE) prevalence amongst pediatric patients with congenital heart disease has increased over the years. Enoxaparin’s pharmacokinetic properties and less intensive monitoring parameters make it a desirable treatment option. Currently, reported enoxaparin dosing strategies and their correlation to therapeutic anti-Xa levels are variable for infants aged 2 to 12 months.  


Methods: This was a single center, retrospective, quasi-experimental study conducted between January 2008 and June 2023 in patients receiving therapeutic enoxaparin. Patients were divided into pre (January 2008 to December 2014) and post (June 2020 to June 2023) intervention groups, with the pre-intervention group receiving an enoxaparin dosing regimen of 1 mg/kg every 12 hours (standard dose) and post-intervention group receiving an enoxaparin dosing regimen of 1.5 mg/kg every 12 hours (high dose). Patients were included if they were between the ages of 2 to 12 months of age, admitted to the heart center, and had at least one heparin assay drawn 4-6 hours after a dose. Patients were excluded if they had thrombocytopenia defined as platelets at baseline less than 100,000 plts/µL, poor renal function defined as a creatinine clearance less than 30 ml/min, or an anti-xa goal other than 0.5 - 1 unit/ml. The primary objective was to evaluate the percent of patients who achieved initial target anti-xa levels. Secondary objectives included time to target anti-Xa level, number of dose changes needed to obtain goal anti-xa levels, and bleeding.


Results: A total of 85 patients were included in this study, 33 in the standard dose group and 52 in the high dose group. The median age was 3.73 months (IQR 3.01 to 6.53) in the standard group and 4.18 months (IQR 3.08 to 5.76) in the high dose group. There were similar demographics between both groups with the exception of more Black or African American (29 (56%) vs 8 (24%); p = 0.003) patients in the high dose group. More patients in the high dose group achieved initial therapeutic levels of enoxaparin (36 (69%) vs 5 (15%); p < 0.001).  The time between initial dose of enoxaparin and first therapeutic anti-Xa level was longer in the standard dose group compared to the high dose group, respectively (87 hrs (IQR 41 to 112) vs 24 hrs (IQR 16 to 40; p< 0.001)).  There was no difference in the incidence of minor bleeding (6 (18%) vs 5 (6%); p = 0.084) or major bleeding (1 (3%) vs 7 (13%); p = 0.14) between the standard and high dose groups, respectively. 


Conclusion: High dose enoxaparin in infants with congenital heart disease resulted in a higher percentage of initial anti-Xa target attainment and a decreased time to target anti-Xa level. There was no difference in minor or major bleeding between the standard and high dose strategies. Based on our findings, it is safe and effective to dose enoxaparin higher in infants with congenital heart disease.  

Title: Evaluating the Safety and Efficacy of an Automatic 24-hour Stop Date for Antibiotics in the Treatment of Early-Onset Sepsis in the Neonatal Intensive Care Unit


Authors: Tyler Tolbert, Corinne Murphy, McKenzie Hodges, Darryl Wanton Jr.


Background: Early-Onset Sepsis (EOS) remains a significant concern in the neonatal intensive care unit (NICU), necessitating the use of empiric antibiotic therapies. However, prolonged antibiotic exposure is associated with adverse neonatal outcomes including disruption of normal flora, increased incidence of antibiotic resistance, and increased risk for necrotizing enterocolitis. Previous practice included 72 hours of empiric antibiotics for EOS which caused an increase in duration of therapy even though typical pathogens can be identified within 24 hours. Our institution previously had an automatic stop date of 36 hours for EOS antibiotics, but we recently transitioned to an automatic stop date of 24 hours for EOS antibiotics in order to reduce unnecessary drug exposure. This study evaluated the safety and efficacy of implementing a 24-hour automatic stop date for empiric antibiotics in neonates suspected of EOS compared to the previous 36-hour protocol. 

Methods: This study was a single-center, retrospective, pre/post-implementation chart review. Neonates receiving antibiotics for EOS were categorized into two groups based on treatment periods: pre-implementation (36-hour protocol) and post-implementation (24-hour protocol). The primary outcome was treatment failure, defined as the resumption of antibiotics within 72 hours of discontinuation. Secondary outcomes included the incidence of necrotizing enterocolitis, mortality, and length of hospital stay. Data on neonatal demographics, antibiotic duration, and clinical outcomes were collected and analyzed. Comparative analyses using chi-squared and t-tests were used to assess statistical significance between the two groups.
 
Results: For our primary outcome of treatment failure there was no statistical difference in the incidence of treatment failure between a 24 hour automatic stop date and a 36 hour automatic stop date for empiric antibiotics. For our secondary outcomes, late onset sepsis was not observed in either study group during the study period. There was also no statistical difference between the groups when analyzing the incidence of death which occurred in 9% of patients on 24-hour protocol and 10.5% of patients on the 36-hour protocol, or the incidence of necrotizing enterocolitis which occurred in 3% and 5.3% of patients respectively. The average length of stay was also not statistically significant between the groups, but there was a longer average length of stay during the 36 hour protocol time frame.

Conclusion: This study assessed the impact of implementing a 24-hour empiric antibiotic stop date for early-onset sepsis in the Neonatal Intensive Care Unit. The results showed that reducing the duration of empiric antibiotics from 36 to 24 hours was not associated with an increased rate of treatment failure. This is a significant finding because it suggests that a shorter antibiotic duration may be just as effective in ruling out early-onset sepsis while also reducing unnecessary antibiotic exposure.
 
Contact: tyler.tolbert@piedmont.org

Title: Dose-Dependent QTc Prolongation of Methadone in Pediatric Patients


Authors: Kaitlyn Currie, Justin K. Chen, Janae Townsend, Jillian Mantione


Objective: Determine thedose relationshipfor methadone and QTc prolongation in the pediatric population.


Background: Methadone is a synthetic opioid commonly used to wean patients off continuous opioid infusions to prevent withdrawal. Methadone is associated with prolongation of the QTc intervalon electrocardiogram (EKG). In pediatric patients, the dose-dependent relationship of methadone to QTc prolongation has not been established. The primary aim of this study was to investigate the risk of QTc prolongation in pediatric patients maintained on methadone at Children’s Healthcare of Atlanta. 


Methods: A retrospective chart review of patients less than 18 years old initiated on methadone between January 1, 2023 and April 30, 2024, in the intensive care setting. Patients were excluded if they received methadone for <24 hours, did not have EKG results while on methadone, had a history of long QT syndrome, or if they were on methadone for the following indications: chronic pain, palliative care, and/or addiction.

Results: A total of 79 patients met criteria for inclusion, comprised of 266 EKGs. The median age was 0.91 years (IQR 0.36-5.49) with 40 (50.9%) of patients being male. The median baseline QTc was 424 ms (IQR 408-441) for those who had an EKG prior to methadone initiation. There was no correlation between methadone weight-based dose and length of QTc (r=0.07, p=0.23). An analysis comparing low (<0.25 mg/kg/day), moderate (0.25-0.5 mg/kg/day), and high (>0.5 mg/kg/day) dosing of methadone did not show a difference in QTc among the three groups (p=0.71). A secondary analysis comparing patients with a baseline QTc and their QTc on methadone showed no difference (424 ms versus 430 ms, p=0.24).  

Conclusion: This retrospective analysis could not determine a relationship between weight-based methadone dosing and QTc. Patients did not experience a statistically significant difference between their baseline QTc and their QTc on methadone. 

TITLE: Utility of Clonidine Conversion to Prevent Dexmedetomidine Withdrawal Syndrome in Pediatric Patients
 
AUTHORS: Emily Hardy, Andrea Gerwin, Renee Hughes, Paige Klingborg 
 
BACKGROUND: In 2022, the Society of Critical Care Medicine (SCCM) issued a guideline recommending alpha-2 receptor agonists as the preferred class for sedation in critically ill pediatric patients. Amidst emerging concern regarding potential dexmedetomidine withdrawal in this population, recent evidence has supported the use of clonidine, another alpha-2 agonist, as a bridging agent to mitigate or prevent withdrawal. While some institutions may have implemented the use of clonidine in dexmedetomidine weaning, there is no consensus or validated protocol. This study aimed to examine the relationship between cumulative dexmedetomidine exposure and clonidine requirements and will expand upon a previous analysis at the study site that focused on a period prior to the SCCM guideline update.  

METHODS: This IRB-approved, single center, retrospective observational study focused on patients admitted to the PICU from January 2018 to May 2024. Inclusion criteria included receipt of a continuous dexmedetomidine infusion > 24 hours and enteral clonidine for treatment or prevention of dexmedetomidine withdrawal. Patients were excluded if they used clonidine prior to admission or if clonidine was initiated for an alternate indication. Included patients were divided into two groups – a non-escalation and an escalation group – based on whether the patient received an increase in their clonidine dose (at provider discretion). The primary outcome assessed the relationship between cumulative dexmedetomidine exposure and maximum required clonidine dose. Secondary outcomes included dexmedetomidine withdrawal assessment, rate of clonidine failure following initial clonidine dose, hospital and ICU length of stay, ventilator days, central line days, and incidence of tracheostomy placement.
 
RESULTS: Compared to the non-escalation group, the escalation group had a statistically significant increase in duration of dexmedetomidine (346.4 vs 284.3, p-value=0.0114) and increased cumulative dexmedetomidine dose (341.2 vs 230.8, p-value=0.0128). The difference in initial clonidine dose was not significant (5.7 vs 4.9, p-value=0.7928). The escalation group had a statistically significant increase in hospital LOS (36 vs 27.5, p-value=0.0355) and ICU LOS (27 vs 20.5, p-value=0.0426). There was no statistically significant difference in ventilator days, CVL days, or incidence of tracheostomy.  
 
CONCLUSION: Higher cumulative dexmedetomidine exposure is associated with higher clonidine dose requirements. Both hospital and ICU LOS were significantly decreased in patients who did not require an increase in their clonidine dose. Utilizing cumulative dexmedetomidine exposure to determine initial clonidine dose may be beneficial.