Infections

Impact of the COVID-19 Pandemic on Pediatric Preventive Health Care Among North Carolina Children Enrolled in Medicaid

Posted on by Kayla Korzekwinski

Journal of the Pediatric Infectious Diseases Society • December 2023

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Thakkar PV, Scott Z, Hoffman M, Delarosa J, Hickerson J, Boutzoukas AE, Benjamin DK Jr., Brookhart MA, Zimmerman KO, Moorthy GS

This study used an administrative claims database from North Carolina Medicaid to evaluate the rates of well-child visits and immunization administration for children ≤14 months of age, and used a quasi-Poisson regression model to estimate the rate ratio of each outcome during the pandemic period (3/15/2020 through 3/15/2021) compared with the pre-pandemic period (3/15/2019 through 3/14/2020). The rates of well-child visits and immunization administrations among North Carolina children enrolled in public insurance substantially decreased during the first year of the COVID-19 pandemic.

Population Pharmacokinetics of Piperacillin/Tazobactam Across the Adult Lifespan

Posted on by Kayla Korzekwinski

Clinical Pharmacokinetics • January 2023

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Hemmersbach-Miller M, Balevic SJ, Winokur PL, Landersdorfer C, Gu K, Chan AW, Cohen-Wolkowiez M, Conrad T, An G, Kirkpatrick C, Swamy GK, Walter EB, Schmader KE

Piperacillin/tazobactam is one of the most frequently used antimicrobials in older adults. Using an opportunistic study design, we evaluated the pharmacokinetics of piperacillin/tazobactam as a probe drug to evaluate changes in antibacterial drug exposure and dosing requirements, including in older adults.

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

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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.

Development and Evaluation of a Virtual Population of Children with Obesity for Physiologically Based Pharmacokinetic Modeling

Posted on by Kayla Korzekwinski

Clinical Pharmacokinetics • February 2022

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Gerhart JG, Carreno FO, Edginton AN, Sinha J, Perrin E, Kumar KR, Rikhi A, Hornik CP, Harris V, Ganguly S, Cohen-Wolkowiez M, Gonzalez D; on behalf of the Best Pharmaceuticals for Children Act — Pediatric Trials Network Steering Committee
A virtual population of children with obesity was developed using national survey, electronic health record, and clinical trial data, as well as data extracted from the literature. The objective of this study was to develop a virtual population of children with obesity to enable physiologically based pharmacokinetic modeling, then use the novel virtual population in conjunction with previously developed models of clindamycin and trimethoprim/sulfamethoxazole to better understand dosing of these drugs in children with obesity. Model simulations supported current recommended weight-based dosing in children with obesity for clindamycin and trimethoprim/sulfamethoxazole, as they met target exposure despite these changes in clearance and volume of distribution.

External Evaluation of Two Pediatric Population Pharmacokinetics Models of Oral Trimethoprim and Sulfamethoxazole

Posted on by Kayla Korzekwinski

Antimicrobial Agents and Chemotherapy • June 2021

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Wu YSS, Cohen-Wolkowiez M, Hornik CP, Gerhart JG, Autmizguine J, Cobbaert M, Gonzalez D
This study tested the pediatric pharmacokinetics (PK) of the antibiotic combination trimethoprim (TMP)-sulfamethoxazole (SMX) that is used to treat a variety of infections. Both models used supported TMP-SMX dose increases in infants and young children for resistant pathogens with a MIC of 1 mg/liter, although the required dose increase based on the external model was lower.

Physiologically-Based Pharmacokinetic Modeling Characterizes the CYP3A-Mediated Drug-Drug Interaction Between Fluconazole and Sildenafil in Infants

Posted on by Kayla Korzekwinski

Clinical Pharmacology & Therapeutics • January 2021

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Salerno SN, Edginton A, Gerhart JG, Laughon MM, Ambalavanan N, Sokol GM, Hornik CD, Stewart D, Mills M, Martz K, Gonzalez D; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
Infants being treated for pulmonary hypertension and prevention or treatment of invasive candidiasis may be given sildenafil with fluconazole concurrently. Physiologically-based pharmacokinetic (PBPK) modeling can potentially predict pediatric drug-drug interactions (DDIs) when clinical DDI data are limited. This study highlights the feasibility of PBPK modeling to predict DDIs in infants and the need to include CYP3A7 parameters.

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

Posted on by Kayla Korzekwinski

Journal of Perinatology • January 2021

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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.

Hospital-acquired Pneumonia and Ventilator-associated Pneumonia in Children: A Prospective Natural History and Case-Control Study

Posted on by Kayla Korzekwinski

Pediatric Infectious Disease Journal • August 2020

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Ericson JE, McGuire J, Michaels MG, Schwarz A, Frenck R, Deville JG, Agarwal S, Bressler AM, Gao J, Spears T, Benjamin DK, Smith PB, Bradley, JS

We examined laboratory and clinical features that might improve pediatric hospital-acquired and ventilator-associated bacterial pneumonias (HABP/VABP) trial efficiency by identifying risk factors predisposing children to HABP/VABP and describing the epidemiology of pediatric HABP/VABP. Food and Drug Administration-defined HABP/VABP occurred in 10%-12% of pediatric patients admitted to ICUs. Risk factors vary by age group.

Probiotic Use and Safety in the Neonatal Intensive Care Unit: A Matched Cohort Study

Posted on by Kayla Korzekwinski

Journal of Pediatrics • July 2020

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Gray KD, Messina JA, Cortina C, Owens T, Fowler M, Foster M, Gbadegesin S, Clark RH, Benjamin DK, Zimmerman KO, Greenberg RG

This study sought to determine the prevalence of probiotic administration in infants born preterm over time, as well as the association between probiotic administration and select adverse outcomes. Probiotic use increased over the study period and varied among neonatal intensive care units. Probiotic administration was associated with a decrease in NEC and death, and an increase in Candida infection, but no increase in bloodstream infection or meningitis.

Population Pharmacokinetics of Doxycycline in Children

Posted on by Kayla Korzekwinski

Antimicrobial Agents and Chemotherapy • September 2019

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Thompson EJ, Wu H, Melloni C, Balevic S, Sullivan JE, Laughon M, Clark KM, Kalra R, Mendley S, Payne E, Erinjeri J, Gelber C, Harper B, Cohen-Wolkoweiz M, Hornik CP

Doxycycline is a tetracycline-class antimicrobial labeled by the United States (U.S.) Food and Drug Administration for children >8 years of age for many common childhood infections. Doxycycline is not labeled for children ≤8 years of age, due to the association between tetracycline class antibiotics and tooth staining. We leveraged opportunistically-collected plasma samples after intravenous (IV) and oral doxycycline doses received per standard of care to characterize the pharmacokinetics (PK) of doxycycline in children of different ages between 0 and 18 years.