Acyclovir Dosing Practices Across a Multicenter Cohort of Neonatal Intensive Care Units

The Pediatric Infectious Disease Journal • June 2024

Foote HP, Thomassy H, Baquero L, Cayli M, Jacobs E, Paladugu A, Roy A, Heyward E, Clark RH, Hornik CP, Benjamin DK, Benjamin DK Jr, Greenberg RG

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.

Postdiscontinuation Antibiotic Exposure in Hospitalized Infants at Risk for Late-onset Sepsis in the Neonatal Intensive Care Unit

The Pediatric Infectious Disease Journal • June 2024

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Wade KC, Greenberg RG, Benjamin DK Jr., Chen L, Vo B, Ang BL, Boutzoukas A, Zimmerman KO, Clark RH, Cohen-Wolkowiez M, Le J on behalf of the Administrative Core Committee of the Best Pharmaceuticals for Children Act – Pediatric Trials Network

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.

Application of Physiologically Based Pharmacokinetic Modeling to Characterize the Effects of Age and Obesity on the Disposition of Levetiracetam in the Pediatric Population

Clinical Pharmacokinetics • June 2024

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Maglalang PD, Sinha J, Zimmerman K, McCann S, Edginton A, Hornik CP, Hornik CD, Muller WJ, Al-Uzri A, Meyer M, Chen L, Anand R, Perrin E, Gonzalez D., Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee

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.

Urinary Tract Infection Epidemiology in NICUs in the United States

American Journal of Perinatology • May 2024

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Kilpatrick R, Boutzoukas AE, Chan E, Girgis V, Kinduelo V, Kwabia SA, Yan J, Clark RH, Zimmerman KO, Greenberg RG

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.

Opportunistic dried blood spot sampling validates and optimizes a pediatric population pharmacokinetic model of metronidazole

Antimicrobial Agents and Chemotherapy • April 2024

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Randell RL, Balevic SJ, Greenberg RG, Cohen-Wolkowiez M, Thompson EJ, Venkatachalam S, Smith MJ, Bendel C, Bliss JM, Chaaban H, Chhabra R, Dammann CEL, Downey LC, Hornik C, Hussain N, Laughon MM, Lavery A, Moya F, Saxonhouse M, Sokol GM, Trembath A, Weitk

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.

Leveraging School Infection Data to Address Community COVID-19 Data Gaps

Journal of the Pediatric Infectious Diseases Society • December 2023

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Moreda E, Al-Dhalimy H, Ha M, Nwanaji-Enwerem E, Nguyen A, Pieters K, Brookhart MA, Hickerson J, Benjamin, Jr DK, Zimmerman KO, Boutzoukas AE

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.

Risk factors and epidemiology of spontaneous intestinal perforation among infants born at 22-24 weeks’ gestational age

Journal of Perinatology • January 2024

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Thakkar PV, Sutton KF, Detwiler CAB, Henegar JG, Narayan JR, Perez-Romero M, Strausser CM, Clark RH, Benjamin DK Jr, Zimmerman KO, Goldberg RN, Younge N, Tanaka D, Smith PB, Greenberg RG, Kilpatrick R

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.

Mentorship

Journal of the Pediatric Infectious Diseases Society • December 2023

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Zimmerman KO

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.

Association Between Hypoglycemia and the Occurrence of Early Onset Sepsis in Premature Infants

Journal of the Pediatric Infectious Diseases Society • December 2023

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Kumar KR, Shah SJ, Fayyad RM, Turla TM, O’Sullivan LM, Wallace B, Clark RH, Benjamin Jr DK, Greenberg RG, Hornik CP

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.

Late-Onset Sepsis Evaluation and Empiric Therapy in Extremely Low Gestational Age Newborns

Journal of the Pediatric Infectious Diseases Society • December 2023

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Speier RL, Cotton CM, Lewis K, Benajmin DK Jr, Keeler K, Kidimbu G, Roberts W, Clark RH, Zimmerman KO, Stark A, Greenberg RG

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.