Study Population

Antibiotic Safety and Effectiveness in Premature Infants With Complicated Intraabdominal Infections

Posted on by Kayla Korzekwinski

The Pediatric Infectious Disease Journal • June 2021

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Smith MJ, Boutzoukas A, Autmizguine J, Hudak M, Zinkhan E, Bloom BT, Heresi G, Lavery A, Courtney S, Sokol GR, Cotton CM, Bliss J, Mendley S, Bendel C, Dammann C, Weitkamp JH, Saxonhouse MA, Mundakel GT, Debski J, Lewandowski A, Erinjeri J, Gao J, Benjamin DK, Hornik C, Smith PB, Cohen-Wolkowiez M, on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network
In premature infants, complicated intraabdominal infections (cIAIs) are a leading cause of morbidity and mortality. Although universally prescribed, the safety and effectiveness of commonly used antibiotic regimens have not been established in this population. One hundred eighty infants ≤33 weeks gestational age and <121 days postnatal age with cIAI were randomized to ≤10 days of ampicillin, gentamicin, and metronidazole (group 1); ampicillin, gentamicin, and clindamycin (group 2); or piperacillin-tazobactam and gentamicin (group 3). There were no differences in safety outcomes between antibiotic regimens. Each of the antibiotic regimens are safe in premature infants with cIAI.

The use of supplemental hydrocortisone in the management of persistent pulmonary hypertension of the newborn

Posted on by Kayla Korzekwinski

Journal Perinatology • April 2021

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Aleem S, Robbins C, Murphy B, Elliott S, Akinyemi C, Paredes N, Tolia VN, Zimmerman KO, Goldberg RN, Benjamin DK, Greenberg RG

This study aimed to characterize the association between hydrocortisone receipt and hospital outcomes of infants with persistent pulmonary hypertension of the newborn (PPHN). There was no association between hydrocortisone receipt and death, CLD, or oxygen at discharge in our cohort. Prospective studies are needed to evaluate the effectiveness of hydrocortisone in infants with PPHN.

Use of Electronic Health Records to Identify Exposure-Response Relationships in Critically Ill Children: An Example of Midazolam and Delirium

Posted on by Kayla Korzekwinski

Journal of Pediatric Intensive Care • March 2021

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Zimmerman KO, Spears T, Cobbaert M, Boakye-Agyeman F, Wu H, Cohen-Wolkowiez M, Watt KM, Benjamin DK, Becker ML, Traube C, Smith PB

Adverse drug events are common in critically ill children and often result from systemic or target organ drug exposure. Methods of drug dosing and titration that consider pharmacokinetic alterations may improve our ability to optimally dose critically ill patients and reduce the risk for drug-related adverse events. To demonstrate this possibility, this study explored the exposure-response relationship between midazolam and delirium in critically ill children.

Impact of COVID-19-related School Closures on the Drivers of Child Health

Posted on by Kayla Korzekwinski

North Carolina Medical Journal • February 2021

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Boutzoukas AE, Akinboyo IC, Wong CA, Benjamin DK, Zimmerman KO

The COVID-19 pandemic resulted in large-scale school closures in an effort to reduce the spread of disease. This article reviews the potential impact of COVID-19-related school closures on the health of children in North Carolina, with particular attention to the impact of school closures on drivers of child health.

Comparative safety profile of chloral hydrate versus other sedatives for procedural sedation in hospitalized infants

Posted on by Kayla Korzekwinski

Journal of Neonatal-Perinatal Medicine • June 2020

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Dallefeld SH, Smith PB, Crenshaw EG, Daniel KR, Gilleskie ML, Smith DS, Balevic S, Greenberg RG, Chu V, Clark R, Kumar KR, Zimmerman KO

Given the limited available evidence on chloral hydrate safety in neonatal populations and the discrepancy in chloral hydrate acceptance between the US and other countries, we sought to clarify the safety profile of chloral hydrate compared to other sedatives in hospitalized infants.

Safety, Effectiveness, and Exposure-Response of Micafungin in Infants: Application of an Established Pharmacokinetics Model to Electronic Health Records

Posted on by Kayla Korzekwinski

The Pediatric Infectious Disease Journal • February 2020

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Rivera-Chaparro ND, Ericson J, Wu H, Smith BP, Clark RH, Benjamin DK, Cohen-Wolkowiez M, Greenberg RG
Micafungin is used off-label in the United States to treat invasive candidiasis in neonates. This study used an established pharmacokinetic model to determine micafungin exposures for 46 courses in 39 hospitalized infants. In this small cohort of infants, micafungin exposure was not associated with laboratory markers of liver toxicity, death, or failure of microbiological clearance.

Dexmedetomidine Pharmacokinetics and a New Dosing Paradigm in Infants Supported With Cardiopulmonary Bypass

Posted on by Kayla Korzekwinski

Anesthesia & Analgesia • December 2019

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Zimmerman KO, Wu H, Laughon M, Greenberg RG, Walczack R, Schulman SR, Smith PB, Hornik CP, Cohen-Wolkowiez M, Watt KM

Dexmedetomidine is increasingly used off-label in infants and children with cardiac disease during cardiopulmonary bypass (CPB) and in the postoperative period. Despite its frequent use, optimal dosing of dexmedetomidine in the setting of CPB has not been identified but is expected to differ from dosing in those not supported with CPB. This study had the following aims: (1) characterize the effect of CPB on dexmedetomidine clearance (CL) and volume of distribution (V) in infants and young children; (2) characterize tolerance and sedation in patients receiving dexmedetomidine; and (3) identify preliminary dosing recommendations for infants and children undergoing CPB.

Innovative Study Designs Optimizing Clinical Pharmacology Research in Infants and Children

Posted on by Kayla Korzekwinski

The Journal of Clinical Pharmacology • October 2019

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Balevic SJ, Cohen-Wolkowiez M

Almost half of recent pediatric trials failed to achieve labeling indications, due in large part to inadequate study design. Therefore, innovative study methods are crucial to optimize trial design while also reducing the potential harms inherent with drug investigation. New and innovative study designs are imperative to address current clinical pharmacology gaps and to ensure future therapeutics are safe and effective for children.

Rifampin Pharmacokinetics and Safety in Preterm and Term Infants

Posted on by Kayla Korzekwinski

Antimicrobial Agents and Chemotherapy • May 2019

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Smith PB, Cotten CM, Hudak ML, Sullivan JE, Poindexter BB, Cohen-Wolkowiez M, Boakye-Agyeman F, Lewandowski A, Anand R, Benjamin DK Jr, Laughon MM; Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee.

Rifampin is active against methicillin-resistant staphylococcal species and tuberculosis (TB). We performed a multicenter, prospective pharmacokinetic (PK) and safety study of intravenous rifampin in infants of <121 days postnatal age (PNA). We enrolled 27 infants; the median (range) gestational age was 26 weeks (23 to 41 weeks), and the median PNA was 10 days (0 to 84 days). We collected 102 plasma PK samples from 22 of the infants and analyzed safety data from all 27 infants. We analyzed the data using a population PK approach.

Surfactant Administration in Preterm Infants: Drug Development Opportunities

Posted on by Kayla Korzekwinski

The Journal of Pediatrics • May 2019

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Taylor G, Jackson W, Hornik CP, Koss A, Mantena S, Homsley K, Gattis B, Kudumu-Clavell M, Clark R, Smith PB, Laughon MM

This study evaluated how frequently surfactant is used off-label in preterm infants. The majority of surfactant given to preterm infants is administered off-label. The uptrend in administration via INSURE coincides with increased supporting evidence. The gap between FDA labeling and current clinic practice exemplifies an opportunity for label expansion, which may require additional prospective or retrospective safety and/or effectiveness data for infants of older GA and higher birth weight.