Neonates

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

Posted on by Kayla Korzekwinski

Journal of the Pediatric Infectious Diseases Society • December 2023

Access article on PubMed.

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

Posted on by Kayla Korzekwinski

Journal of the Pediatric Infectious Diseases Society • December 2023

Access article on PubMed.

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.

Safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia: Rationale and methods of a phase II randomized trial

Posted on by Kayla Korzekwinski

Contemporary Clinical Trials Communications • December 2022

Access article on PubMed.

Lang JE, Hornik CD, Martz K, Jacangelo J, Anand R, Greenberg R, Hornik C, Zimmerman K, Smith PB, Benjamin DK, Laughon M
Bronchopulmonary dysplasia (BPD) is a disease of chronic respiratory insufficiency stemming from premature birth and iatrogenic lung injury leading to many complications. BPD is the most common pulmonary sequela of prematurity and is often fatal; however, there remains no FDA-approved therapies to treat or prevent BPD. Sildenafil is increasingly used off-label in premature infants despite scant safety and efficacy data. We developed the phase II SIL02 trial to describe the safety, pharmacokinetics and preliminary effectiveness of intravenous and enteral sildenafil in premature infants at risk for BPD.

Exposure-safety relationship for acyclovir in the treatment of neonatal herpes simplex virus disease

Posted on by Kayla Korzekwinski

Early Human Development • July 2022

Access article on PubMed.

Ericson J, Benjamin DK Jr., Boakye-Agyeman F, Balevic SJ, Cotten MC, Adler-Shohet F, Laughon M, Poindexter B, Harper B, Payne EH, Kaneshige K, Smith PB; Best Pharmaceuticals for Children Act – Pediatric Trials Network
Neonatal herpes simplex virus (HSV) disease has been treated with high-dose (20 mg/kg/dose) acyclovir since 1991. This study aimed to determine the safety of acyclovir in infants with neonatal HSV treated with high-dose acyclovir and examine the association between acyclovir dose and exposure with adverse events (AEs). The odds of experiencing any clinical or laboratory AE did not differ by predicted acyclovir exposure. Although AEs were common with high-dose acyclovir exposure, severe AEs were rare. Acyclovir exposure was not associated with AEs.

Ampicillin dosing in premature infants for early-onset sepsis: exposure-driven efficacy, safety, and stewardship

Posted on by Kayla Korzekwinski

Journal of Perinatology • July 2022

Access article on PubMed.

Le J, Greenberg RG, Yoo Y, Clark RH, Benjamin DK Jr., Zimmerman KO, Cohen-Wolkowiez M, Wade K
This study simulated ampicillin concentrations in newborns to define optimal ampicillin dosing for empiric early-onset sepsis (EOS) therapy in preterm neonates. For EOS in preterm infants, two ampicillin doses (50 mg/kg) provided optimal bactericidal exposures, while minimizing potential toxicity.

Safety of sildenafil in extremely premature infants: a phase I trial

Posted on by Kayla Korzekwinski

Journal of Perinatology • January 2022

Access article on PubMed.

Jackson W, Gonzalez D, Smith PB, Ambalavanan N, Atz A, Sokol GM, Hornik CD, Stewart D, Mundakel G, Poindexter BB, Ahlfeld SK, Mills M, Cohen-Wolkowiez M, Martz K, Hornik CP, Laughon MM; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
This study sought to characterize the safety of sildenafil in premature infants. Safety was evaluated based on adverse events (AEs), transaminase levels, and mean arterial pressure monitoring. There was one serious AE related to the study drug involving hypotension associated with a faster infusion rate than specified by the protocol. There were no AEs related to elevated transaminases. Sildenafil was well tolerated by the study population. Drug administration times and flush rates require careful attention to prevent infusion-related hypotension associated with faster infusions of IV sildenafil in premature infants.

Prolonged Post-Discontinuation Antibiotic Exposure in Very Low Birth Weight Neonates at Risk for Early-Onset Sepsis

Posted on by Kayla Korzekwinski

Journal of the Pediatric Infectious Diseases Society • May 2021

Access article on PubMed.

Le J, Greenberg RG, Benjamin DK Jr, Yoo Y, Zimmerman KO, Cohen-Wolkowiez M, Wade KC; on behalf of the Administrative Core Committee of the Best Pharmaceuticals for Children Act – Pediatric Trials Network
Premature, very low birth weight neonates are at risk for early-onset sepsis and receive ampicillin and gentamicin post-birth. Antimicrobial stewardship supports short-course antibiotics, but how long antibiotic concentrations remain therapeutic post-last dose is unknown. This study used simulations to examine antibiotic exposures in 34,689 neonates. Therapeutic exposure for ampicillin and gentamicin was evaluated relative to the minimum inhibitory concentration for common pathogens. Ampicillin exposure remains therapeutic long after the last dose. Short-course ampicillin provided therapeutic exposures throughout the typical blood culture incubation period.

Early-onset sepsis in term infants admitted to neonatal intensive care units (2011-2016)

Posted on by Kayla Korzekwinski

Journal of Perinatology • January 2021

Access article on PubMed.

Bech Polcwiartek L, Smith PB, Benjamin DK, Zimmerman KO, Love A, Tiu L, Murray S, Kang P, Ebbesen F, Hagstrøm S, Clark RH, Greenberg RG
This study investigated characteristics of term infants culture-evaluated for early-onset sepsis (EOS) in neonatal intensive care units (NICUs), frequencies of organisms causing EOS, and factors associated with EOS. EOS was most commonly caused by group B Streptococcus. Lower EOS risk was associated with low Apgar score, Cesarean delivery, small for gestational age, prenatal antibiotic exposure, and positive or unknown maternal GBS screening result. Increased risk was associated with prolonged rupture of membranes, maternal age <19 years, vasopressor treatment, and ventilator support.

Exchange transfusion safety and outcomes in neonatal hyperbilirubinemia

Posted on by Kayla Korzekwinski

Pediatric Emergency Care • October 2020

Access article on PubMed.

Wolf MF, Childers J, Gray KD, Chivily C, Glenn M, Jones L, Kpa M, McMannen T, Reyes I, Zimmerman KO, Clark RH, Greenberg RG

This study aimed to characterize the prevalence of exchange transfusion (ET), clinical characteristics of infants receiving ET, and ET-associated morbidity and mortality. It was a multicenter cohort study of infants ≥23 weeks of gestational age (GA) with hyperbilirubinemia who underwent ET within 30 days of birth from 1997 to 2016. Infants ≤ 29 weeks of GA had greater odds of death following ET compared with term infants. These data will support clinicians in evaluating risks and prognosis for infants who require ET.

Safety of Metronidazole in Late Preterm and Term Infants With Complicated Intraabdominal Infections

Posted on by Kayla Korzekwinski

Pediatric Infectious Disease Journal • September 2020

Access article on PubMed.

Commander SJ, Gao J, Zinkhan EK, Heresi G, Courtney SE, Lavery AP, Delmore P, Sokol GM, Moya F, Benjamin DK Jr, Bumpass TG, Debski J, Erinjeri J, Sharma G, Tracy ET, Cohen-Wolkowiez M, Hornik CP; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee

Metronidazole is frequently used off-label in infants with complicated intra-abdominal infections (cIAI) to provide coverage against anaerobic organisms, but its safety and efficacy in this indication are unknown. Metronidazole safety was evaluated by reporting of adverse events (AEs) and safety events of special interest. In a cohort of late pre-term and term infants with cIAIs, combination antibiotic therapy that included metronidazole was safe, and therapeutic success was high.