Study Population

Intestinal Fatty-Acid Binding Protein and Metronidazole Response in Premature Infants

Posted on by Kayla Korzekwinski

Journal of Neonatal and Perinatal Medicine • November 2014

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Sampson MR, Bloom BT, Arrieta A, Capparelli E, Benjamin DK Jr, Smith PB, Kearns GL, van den Anker J, Cohen-Wolkowiez M.

In premature infants with suspected intra-abdominal infection, biomarkers for treatment response to antimicrobial therapy are lacking. Intestinal fatty acid-binding protein (I-FABP) is specific to the enterocyte and is released in response to intestinal mucosal injury. I-FABP has not been evaluated as a surrogate marker of disease response to antimicrobial therapy. We examined the relationship between metronidazole exposure and urinary I-FABP concentrations in premature infants with suspected intra-abdominal infection.

Medication use in the neonatal intensive care unit

Posted on by Kayla Korzekwinski

American Journal of Perinatology • October 2014

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Hsieh EM, Hornik CP, Clark RH, Laughon MM, Benjamin DK Jr, Smith PB; Best Pharmaceuticals for Children Act—Pediatric Trials Network.

The aim of the article is to provide an update on medication use in infants admitted to the neonatal intensive care unit (NICU) in the United States and examine how use has changed over time. We performed a retrospective review (2005-2010) of a large prospectively collected administrative database.

Use of opportunistic clinical data and a population pharmacokinetic model to support dosing of clindamycin for premature infants to adolescents

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Clinical Pharmacology and Therapeutics • September 2014

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Gonzalez D, Melloni C, Yogev R, Poindexter BB, Mendley SR, Delmore P, Sullivan JE, Autmizguine J, Lewandowski A, Harper B, Watt KM, Lewis KC, Capparelli EV, Benjamin DK Jr, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act – Pediatric Trials Network Administrative Core Committee.

Clindamycin is commonly prescribed to treat children with skin and skin-structure infections (including those caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA)), yet little is known about its pharmacokinetics (PK) across pediatric age groups. A population PK analysis was performed in NONMEM using samples collected in an opportunistic study from children receiving i.v. clindamycin per standard of care.

Characterization of the population pharmacokinetics of ampicillin in neonates using an opportunistic study design

Posted on by Kayla Korzekwinski

Antimicrobial Agents and Chemotherapy • June 2014

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Tremoulet A, Le J, Poindexter B, Sullivan JE, Laughon M, Delmore P, Salgado A, Ian-U Chong S, Melloni C, Gao J, Benjamin DK Jr, Capparelli EV, Cohen-Wolkowiez M; Administrative Core Committee of the Best Pharmaceuticals for Children Act-Pediatric Trials Network.

Although ampicillin is the most commonly used drug in neonates, developmental pharmacokinetic (PK) data to guide dosing are lacking. Ampicillin is primarily renally eliminated, and developmental changes are expected to influence PK. We conducted an open-label, multicenter, opportunistic, prospective PK study of ampicillin in neonates stratified by gestational age (GA) (≤ 34 or >34 weeks) and postnatal age (PNA) (≤ 7 or >7 days).

Pharmacokinetics of Antimicrobials in Obese Children

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GaBI Journal • June 2014

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Sampson M, Cohen-Wolkowiez M, Benjamin D Jr, Capparelli E, Watt K.

Childhood obesity is common and results in substantial morbidity. The most commonly prescribed drugs in obese children are antibiotics. However, physiological changes associated with childhood obesity can alter antibiotic pharmacokinetics and optimal body size measures to guide dosing in this population are ill defined. This combination can result in therapeutic failures or drug-related toxicities. This review summarizes pharmacokinetic information for antibiotics in obese children and implications for dosing.

Effect of fluconazole prophylaxis on candidiasis and mortality in premature infants: a randomized clinical trial

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JAMA • June 2014

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Benjamin DK Jr, Hudak ML, Duara S, Randolph DA, Bidegain M, Mundakel GT, Natarajan G, Burchfield DJ, White RD, Shattuck KE, Neu N, Bendel CM, Kim MR, Finer NN, Stewart DL, Arrieta AC, Wade KC, Kaufman DA, Manzoni P, Prather KO, Testoni D, Berezny KY, Smith PB; Fluconazole Prophylaxis Study Team.

Invasive candidiasis in premature infants causes death and neurodevelopmental impairment. Fluconazole prophylaxis reduces candidiasis, but its effect on mortality and the safety of fluconazole are unknown. This study was a randomized, blinded, placebo-controlled trial of fluconazole in premature infants. Infants weighing less than 750 g at birth (N = 361) from 32 neonatal intensive care units (NICUs) in the United States were randomly assigned to receive either fluconazole or placebo twice weekly for 42 days.

Changes in the Incidence of Candidiasis in Neonatal Intensive Care Units

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Pediatrics • February 2014

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Aliaga S, Clark RH, Laughon M, Walsh TJ, Hope W, Benjamin DK, Kaufman D, Arrieta A, Benjamin DK Jr, Smith PB
Neonatal invasive candidiasis is associated with significant morbidity and mortality. We describe the association between invasive candidiasis and changes in use of antifungal prophylaxis, empirical antifungal therapy, and broad-spectrum antibacterial antibiotics over time. We examined data from 709,325 infants at 322 NICUs managed by the Pediatrix Medical Group from 1997 to 2010. We determined the cumulative incidence of invasive candidiasis and use of antifungal prophylaxis, broad-spectrum antibacterial antibiotics, and empirical antifungal therapy by year.

Triazole use in the nursery: fluconazole, voriconazole, posaconazole, and ravuconazole

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Current Drug Metabolism • February 2014

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Cohen-Wolkowiez M, Poindexter B, Bidegain M, Weitkamp JH, Schelonka RL, Randolph DA, Ward RM, Wade K, Valencia G, Burchfield D, Arrieta A, Mehta V, Walsh M, Kantak A, Rasmussen M, Sullivan JE, Finer N, Rich W, Brozanski BS, van den Anker J, Blumer J, Laug

The management of invasive fungal infections has progressed greatly over the last two decades with the azole antifungals playing a significant role. Related to this class, future research is needed in order to better assess dosing, safety, schedules and areas of use of these agents in infants admitted to the neonatal intensive care unit.

Population pharmacokinetics of intravenous acyclovir in preterm and term infants

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The Pediatric Infectious Disease Journal • December 2013

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Sampson MR, Bloom BT, Lenfestey RW, Harper B, Kashuba AD, Anand R, Benjamin DK Jr, Capparelli E, Cohen-Wolkowiez M, Smith PB; Best Pharmaceuticals for Children Act–Pediatric Trials Network.

Acyclovir is used to treat herpes infections in preterm and term infants; however, the influence of maturation on drug disposition and dosing requirements is poorly characterized in this population. We administered intravenous acyclovir to preterm and term infants <31 days postnatal age and collected plasma samples. We performed a population pharmacokinetic analysis.

Evaluation of the Mercy TAPE: performance against the standard for pediatric weight estimation

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Annals of Emergency Medicine • October 2013

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Abdel-Rahman SM, Paul IM, James LP, Lewandowski A; Best Pharmaceuticals for Children Act-Pediatric Trials Network.

We assessed the performance of 2 new devices (2D- and 3D-Mercy TAPE) to implement the Mercy Method for pediatric weight estimation and contrasted their accuracy with the Broselow method. We enrolled children aged 2 months through 16 years in this prospective, multicenter, observational study.