Antibacterials

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.

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

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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

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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.

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

Posted on by Kayla Korzekwinski

Pediatric Infectious Disease Journal • September 2020

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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.

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.

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.

Medication Use in the Neonatal Intensive Care Unit and Changes from 2010 to 2018

Posted on by Kayla Korzekwinski

The Journal of Pediatrics • January 2022

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Stark A, Smith PB, Hornik CP, Zimmerman KO, Hornik CD, Pradeep S, Clark RH, Benjamin DK, Laughon M, Greenberg RG.

The goal of this study was to provide up-to-date medication prescribing patterns in US neonatal intensive care units (NICUs) and to examine trends in prescribing patterns over time. The most frequently prescribed medications included ampicillin, gentamicin, caffeine citrate, poractant alfa, morphine, vancomycin, furosemide, fentanyl, midazolam, and acetaminophen. Of the top 50 medications used in infants with extremely low birth weight, only 20 (40%) are FDA-labeled for use in infants. Trends of medication use in the NICU change substantially over time. It is imperative to identify changes in medication use in the NICU to better inform further prospective studies.

Pharmacokinetics of Ceftazidime in Children and Adolescents with Obesity

Posted on by Kayla Korzekwinski

Paediatric Drugs • September 2021

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Maharaj AR, Wu H, Zimmerman KO, Muller WJ, Sullivan JE, Sherwin CMT, Autmizguine J, Rathore MH, Hornik CD, Al-Uzri A, Payne EH, Hornik CP, on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee

The aim of this study was to evaluate ceftazidime pharmacokinetics (PK) in a cohort that includes a predominate number of children and adolescents with obesity and assess the efficacy of competing dosing strategies.

Physiologically Based Pharmacokinetic (PBPK) Modeling of Meropenem in Preterm and Term Infants

Posted on by Kayla Korzekwinski

Clinical Pharmacokinetics • June 2021

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Ganguly S, Edginton A, Gerhart JG, Cohen-Wolkowiez M, Greenberg RG, Gonzalez D; on behalf of the Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee
This study applied physiologically based pharmacokinetic (PBPK) modeling to characterize the disposition of the antibiotic meropenem in preterm and term infants. Meropenem is approved by the US Food and Drug Administration for use in pediatric patients, including treating complicated intra-abdominal infections in infants < 3 months of age. The PBPK model-based simulations were performed to evaluate meropenem dosing in the product label for infants < 3 months of age treated for complicated intra-abdominal infections. The PBPK model used supports the meropenem dosing regimens recommended in the product label for infants <3 months of age.

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.