The nitroimidazole antibiotic, metronidazole, is frequently prescribed to infants with serious intra-abdominal infections, and multiple dosing recommendations exist. We sought to evaluate the extent to which metronidazole doses and associated exposures achieved desired efficacy and safety in infants enrolled in the Antibiotic Safety in Infants with Complicated Intra-abdominal Infections (SCAMP) trial (NCT01994993). SCAMP participants received intravenous metronidazole as part of multimodal antimicrobial therapy.

Methadone is used in hospitalized children to treat pain and iatrogenic opiate withdrawal. Optimal pediatric dosing for both enteral and intravenous methadone is unknown. We conducted two prospective, multi-center, open-label studies to characterize the pharmacokinetics of methadone in the pediatric population.

Oxcarbazepine (OXZ) is an antiepileptic drug whose pharmacological effect is primarily mediated by its active metabolite, 10-monohydroxy derivative (MHD). OXZ is approved for use in adults and children older than 2 years with an age- and body weight-tiered dosing recommendation, but dosing guidance for children with obesity is lacking. This work aimed to assess the dosing requirements of OXZ in children with obesity to support label extension.

Oxcarbazepine (OXC) is a second-generation antiseizure medication, effective through its active metabolite, 10-mono-hydroxy derivative (MHD). OXC is used as adjunctive therapy for focal-onset and primary generalized tonic-clonic seizures, with recommended dosing based on age and body weight. This study uses physiologically based pharmacokinetic (PBPK) modeling and leverages pharmacokinetic (PK) data acquired from children enrolled in pragmatic trials to understand dosing and subsequent exposure requirements in children with obesity.

Midazolam has been used as a sedative for hospitalized children on- and off-label; however, factors affecting interindividual variability (IIV) in observed clearance for this population are not fully understood and can result in extreme under- or overexposure. Obesity has been described as a significant influence on midazolam in adolescents, which could potentially alter drug exposure. The goal of this study was to use two modeling strategies to evaluate dose-exposure of midazolam in children with and without obesity.

Diazepam is a benzodiazepine approved for use in adults and children. The label incorporates recommended dosing for status epilepticus in children. Published population pharmacokinetic (PK) modeling recommends an intravenous bolus dose of 0.2 mg/kg capped at 8 mg to reach the suggested target exposure of 200-600 ng/mL at 10 min post dose in children up to 17 years of age. This model was developed for children generally without obesity based on IV data, and it is unclear how increased body weight may affect exposure or target attainment given capped dosing.

The objective of this study was to evaluate the safety of furosemide in preterm infants at the risk of developing bronchopulmonary dysplasia (BPD). This multicenter, randomized, dose-escalating, placebo-controlled trial enrolled infants born <29 weeks gestational age at 7-28 days postnatal age and at risk for BPD. In preterm infants, furosemide did not increase the overall incidence of AEs, hearing loss, or nephrocalcinosis, but did increase the incidence of electrolyte abnormalities. Furosemide given for 28 consecutive days was not associated with a difference in moderate-to-severe BPD or death at 36 weeks postmenstrual age.

Risks associated with clinical trial participation are a foremost consideration during protocol development whereas trial-associated burdens receive less focus despite their measurable impact on enrollment and retention. Of late, the U.S. Food and Drug Administration (FDA) has elevated discussions on barriers to research participation resulting from overly burdensome trials. Given the agency's role in shaping clinical protocol design, this study examined the perceived burden associated with FDA-proposed study changes in the context of pediatric, off-patent, labeling studies.

This study conducted an opportunistic pharmacokinetic study to evaluate the population pharmacokinetics of meropenem, an antimicrobial commonly used to treat Gram-negative infections in adults of different ages, including older adults, and determined optimal dosing regimens. Meropenem dosing should be based on renal function rather than age. For patients without renal impairment, extended infusion may increase the probability of target attainment.

The objective of this study was to determine current prescribing practice of acid-suppressive therapy in preterm infants admitted to the neonatal intensive care unit (NICU). A cohort study of infants 22 to 27 weeks gestation were discharged from Pediatrix Medical Group NICUs between 2015 and 2020. The study showed that acid-suppressive therapies are used commonly in preterm infants and receipt is higher in infants with lower BWs. Use has significantly decreased over time and appears to be targeted, with many infants treated for one-week courses and without a diagnosis of GERD.

Increases in adult stimulant prescribing pose a potential risk due to the higher prevalence of contraindicated conditions among this population. This study sought to identify patient, provider, and visit characteristics predictive of potentially inappropriate adult stimulant prescriptions. The proportion of potentially inappropriate adult stimulant prescriptions increased over time and with patient age. Visits to primary care providers were predictive of potentially inappropriate prescribing, and a history of substance abuse was predictive of new stimulant prescriptions; therefore, quality improvement interventions regarding safe stimulant prescribing practices may be warranted.

New drugs to target different pathways in pulmonary hypertension have resulted in increased combination therapy, but details of this use in infants are not well described. This large multicenter database study describes the pharmacoepidemiology of combination pulmonary vasodilator therapy in critically ill infants. The study revealed an increased use of combination pulmonary vasodilator therapy, favouring inhaled nitric oxide and sildenafil, yet with considerable practice variation. Further research is needed to determine the optimal combination, sequence, dosing, and disease-specific indications for combination therapy.

This study aimed to analyze trends in gabapentin use in neonatal intensive care units (NICUs) and examine demographic characteristics, diagnoses, and concomitant medications associated with its use. Gabapentin use was rare but increased over time despite limited research on its safety and efficacy in infants, illuminating the need for further studies.

Dexamethasone is a synthetic glucocorticoid approved for treating disorders of various organ systems in both adult and pediatric populations. Currently, approved pediatric dosing recommendations are weight-based, but it is unknown whether differences in dexamethasone drug disposition and exposure exist for children with obesity. This study aimed to develop a population pharmacokinetic (PopPK) model for dexamethasone with data collected from children with obesity.

Pantoprazole is a proton pump inhibitor indicated for the treatment of gastroesophageal reflux disease, a condition that disproportionately affects children with obesity. Appropriately dosing pantoprazole in children with obesity requires understanding the body size metric that best guides dosing, but pharmacokinetic (PK) trials using traditional techniques are limited by the need for larger sample sizes and frequent blood sampling. This study explored the effect of obesity on pantoprazole PK and evaluated label-suggested dosing in this population.

Dexmedetomidine is a sedative used in both adults and off-label in children with considerable reported pharmacokinetic (PK) interindividual variability affecting drug exposure across populations. Several published models describe the population PKs of dexmedetomidine in neonates, infants, children, and adolescents, though very few have been externally evaluated. A prospective PK dataset of dexmedetomidine plasma concentrations in children and young adults aged 0.01-19.9 years was collected as part of a multicenter opportunistic PK study.

This study examined pathogen distribution, antibiotic resistance patterns, and hospital outcomes of infants with bacterial meningitis in neonatal intensive care units (NICUs) in the US from 2013-2018.

Acyclovir is the first-line therapy for neonatal herpes simplex virus infections. Therapy can mitigate morbidity and mortality but carries a risk for toxicity. This study aimed to compare acyclovir dosing in neonatal intensive care units to published recommendations based on population pharmacokinetic (PopPK) analysis.

In the neonatal intensive care unit, infants are at risk for late-onset sepsis. When blood cultures are negative, antibiotic stewardship efforts encourage stopping antibiotics, yet the duration of therapeutic exposure after the last dose is unknown. Piperacillin and cefepime exposures remained therapeutic long after the expected 8- to 12-hour dosing interval. PDAE is an important consideration for antibiotic stewardship among hospitalized infants, particularly premature infants and those within 1 month postbirth.

Levetiracetam is an antiseizure medication used for several seizure types in adults and children aged 1 month and older; however, due to a lack of data, pharmacokinetic (PK) variability of levetiracetam is not adequately characterized in certain populations, particularly neonates, children younger than 2 years of age, and children older than 2 years of age with obesity. PBPK modeling simulations revealed that the current US FDA-labeled pediatric dosing regimen listed in the prescribing information can produce the required exposure of levetiracetam in these target populations with dose adjustments for children with obesity aged 4 years to younger than 16 years.

This study characterized the incidence, associated clinical factors, timing of infection, microbiology, and incidence of concordant blood culture of urinary tract infections (UTIs) in very low birth weight (VLBW <1,500g) infants. UTI is a common cause of infection in VLBW infants, especially among the smallest, most premature, male infants, and those with a longer duration of hospitalization. Neonatal clinicians should consider obtaining urine culture in the setting of late-onset sepsis evaluations in VLBW infants.

Pharmacokinetic models rarely undergo external validation in vulnerable populations such as critically ill infants, thereby limiting the accuracy, efficacy, and safety of model-informed dosing in real-world settings. Here, we describe an opportunistic approach using dried blood spots (DBS) to evaluate a population pharmacokinetic model of metronidazole in critically ill preterm infants of gestational age (GA) ≤31 weeks from the Metronidazole Pharmacokinetics in Premature Infants study.

At-home COVID-19 testing resulted in significant data gaps; K-12 data could have supplemented community data. In future public health emergencies, reporting of school data could minimize data gaps, but requires additional resources including funding to track infections and standardized data reporting methods.

This study sought to describe the epidemiology, risk factors, and timing of spontaneous intestinal perforation (SIP) among infants born at 22-24 weeks' gestational age (GA). Antenatal magnesium exposure, antenatal indomethacin exposure, postnatal hydrocortisone exposure, postnatal indomethacin exposure, and weight loss ≥15% were associated with SIP.

A unique feature of the Duke Summer Training in Academic Research (STAR) program is its focus on mentorship. STAR is an opportunity for junior faculty members and fellows to learn how to be mentors, and for undergraduate and high school students to learn how to be mentored. These are important and fundamental points; mentorship, from the perspective of mentor or mentee, should be a deliberate and skilled activity that can result from adequate training.

This study examined the association between hypoglycemia and the occurrence of early onset sepsis (EOS) in premature infants admitted to the neonatal intensive care unit (NICU). Hypoglycemia may be an early marker of EOS, particularly in episodes caused by Gram-negative organisms and when using a stricter definition of hypoglycemia.

Little is known about late-onset sepsis (LOS) evaluations in extremely low gestational age newborns (ELGANs). This study describes frequencies of LOS evaluation in ELGANs, infant characteristics, and empiric therapy choices during evaluations.

The DCRI Pediatrics group designed a summer internship program that had a wide reach and reflects its purpose and mission to conduct research to help children everywhere. This led to the creation of the Duke STAR (Summer Training in Academic Research) Program, a program that provides ~20 high school or college students per summer the opportunity to be exposed to clinical research and to work closely with researchers and practicing clinicians. Recruiting efforts prioritized participants from historically marginalized communities in North Carolina, with a goal to include at least several students each year who were “hidden talent.”

This study evaluated the diagnostic and predictive utility of cerebrospinal fluid (CSF) white blood cell (WBC) components in the diagnosis of bacterial meningitis in infants discharged from the neonatal intensive care unit (NICU). No single clinical prediction rule had the optimal discriminatory power for predicting culture-proven bacterial meningitis, and clinicians should be cautious when interpreting CSF WBC parameters in infants with suspected meningitis.

Widespread school closures and health care avoidance during the COVID-19 pandemic led to disruptions in access to pediatric mental health care. This study conducted a retrospective analysis of emergency and inpatient administrative claims from privately insured children aged 6-20 years in North Carolina between January 2019 and December 2020.