Infants

Metronidazole exposure-response and safety in infants

Posted on by Jeannine Sato

Antimicrobial Agents and Chemotherapy, November 2025

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Randell RL, Balevic SJ, Greenberg RG, Cohen-Wolkowiez M, Smith MJ, Benjamin DK Jr, Bendel C, Bliss JM, Chaaban H, Chhabra R, Dammann CEL, Downey LC, Hornik CD, Hussain N, Laughon MM, Lavery A, Moya F, Saxonhouse M, Sokol GM, Trembath A, Weitkamp J-H, Hornik CP; Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee.

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.

Population Pharmacokinetics to Support Intravenous and Enteral Methadone Dosing in Children

Posted on by Jeannine Sato

Journal of Clinical Pharmacology, January 2026

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Watt KM, Thompson EJ, Lam L, Zimmerman K, Hornik CP, Atz AM, Fernandez A, Hupp SR, Bhatt-Mehta V, Benjamin DK Jr, Anand R, Cohen-Wolkowiez M, Gonzalez D, Smith PB, Capparelli EV; Best Pharmaceuticals for Children Act — Pediatric Trials Network Steering Committee.

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. 

Furosemide Safety in Preterm Infants at Risk for Bronchopulmonary Dysplasia: A Randomized Clinical Trial

Posted on by Jeannine Sato

The Journal of Pediatrics • April 2025

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Greenberg RG, Lang J, Smith PB, Shekhawat P, Courtney SE, Hudak ML, Moya F, Iyengar A, Eldemerdash A, Bloom B, Go M, Hanna M, Rhein L, Aliaga S, Lewis T, Febre A, Kiefer AS, Bhatt-Mehta V, Khoury JA, Selewski D, Anand R, Martz K, Payne EH, Zimmerman KO, Benjamin DK Jr, Laughon M; Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee.

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.

Pharmacoepidemiology of combination pulmonary vasodilator therapy in critically ill infants

Posted on by Kayla Korzekwinski

Cardiology in the Young • January 2025

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Kumar KR, Ciociola EC, Skinner KR, Dixit GM, Alvarez S, Benjamin EK, Faulkner JC, Greenberg RG, Clark RH, Benjamin Jr DK, Hornik CP and Jan Hau Lee

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.

Trends in Gabapentin Use in Neonatal Intensive Care Units from 2005 to 2020

Posted on by Kayla Korzekwinski

American Journal of Perinatology • November 2024

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Roberts AG, Kilpatrick R, Diaz LD, Benjamin S, Espinoza Santiago AJ, Jallow B, Monteith MF, Rumsey S, Clark RH, Zimmerman K, Benjamin DK Jr, Greenberg RG

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.

Using Real-World Data to Externally Evaluate Population Pharmacokinetic Models of Dexmedetomidine in Children and Infants

Posted on by Kayla Korzekwinski

The Journal of Clinical Pharmacology • August 2024

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McCann S, Helfer VE, Balevic SJ, Hornik CH, Goldstein SL, Autmizguine J, Meyer M, Al-Uzri A, Anderson SG, Payne EH, Turdalieva S, Gonzalez D., Best Pharmaceuticals for Children Act – Pediatric Trials Network

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.

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

Posted on by Kayla Korzekwinski

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

Posted on by Kayla Korzekwinski

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.

Urinary Tract Infection Epidemiology in NICUs in the United States

Posted on by Kayla Korzekwinski

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

Posted on by Kayla Korzekwinski

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.