Infections

Use of Population Pharmacokinetics and Electronic Health Records to Assess Piperacillin-Tazobactam Safety in Infants

Posted on by Kayla Korzekwinski

The Pediatric Infectious Disease Journal • September 2017

Access article on PubMed.

Salerno S, Hornik CP, Cohen-Wolkowiez M, Smith PB, Ku LC, Kelly MS, Clark R, Gonzalez D; Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee.

Piperacillin, in combination with tazobactam, is frequently used in infants for treating nosocomial infections, although safety data in this population are limited. Electronic health record (EHR) data can be used to evaluate drug safety in infants, but measures of drug exposure are lacking. To relate simulated piperacillin exposure with adverse events (AEs) in infants using EHR data, we identified infants discharged from 333 neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2012.

Late-onset Sepsis in Extremely Premature Infants: 2000-2011

Posted on by Kayla Korzekwinski

The Pediatric Infectious Disease Journal • August 2017

Access article on PubMed.

Greenberg RG, Kandefer S, Do BT, Smith PB, Stoll BJ, Walsh MC, Bell EF, Carlo WA, Laptook AR, Sánchez PJ, Shankaran S, Van Meurs KP, Ball MB, Hale EC, Newman NS, Das A, Higgins RD, Cotton CM, for the Eunice Kennedy Shriver National Institute of Child Health

Late-onset sepsis (LOS) is an important cause of death and neurodevelopmental impairment in premature infants. The purpose of this study was to assess overall incidence of LOS, distribution of LOS-causative organisms and center variation in incidence of LOS for extremely premature infants over time.

Timing of Multiorgan Dysfunction among Hospitalized Infants with Fatal Fulminant Sepsis

Posted on by Kayla Korzekwinski

American Journal of Perinatology • June 2017

Access article on PubMed.

Wynn JL, Kelly MS, Benjamin DK, Clark RH, Greenberg R, Benjamin DK Jr, Smith PB

This study sought to identify the progression of specific signs of multiorgan dysfunction among infants with fatal sepsis. Hospitalized infants with fatal LOS manifest respiratory, cardiovascular, renal, immune, and hematologic dysfunction. Knowledge of these factors and their timing may be important for the development and testing of novel therapeutics to reduce sepsis mortality.

Pharmacokinetics of Clindamycin in Obese and Nonobese Children

Posted on by Kayla Korzekwinski

Antimicrobial Agents and Chemotherapy • March 2017

Access article on PubMed.

Smith MJ, Gonzalez D, Goldman JL, Yogev R, Sullivan JE, Reed MD, Anand R, Martz K, Berezny K, Benjamin DK Jr, Smith PB, Cohen-Wolkowiez M, Watt K; Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee.

Although obesity is prevalent among children in the United States, pharmacokinetic (PK) data for obese children are limited. Clindamycin is a commonly used antibiotic that may require dose adjustment in obese children due to its lipophilic properties. We performed a clindamycin population PK analysis using data from three separate trials. A total of 420 samples from 220 children, 76 of whom had a body mass index greater than or equal to the 95th percentile for age, were included in the analysis. Compared to other metrics, total body weight (TBW) was the most robust measure of body size.

Risk factors for group B streptococcal disease in neonates of mothers with negative antenatal testing

Posted on by Kayla Korzekwinski

Journal of Perinatology • February 2017

Access article on PubMed.

Parente V, Clark RH, Ku L, Fennell C, Johnson M, Morris E, Romaine A, Benjamin DK, Smith PB, Greenberg R

The aim of this study was to identify risk factors for early-onset group B Streptococcus (EOGBS) disease in neonates of mothers with negative antenatal screening. Maternal age <18 years and black race were the strongest predictors of EOGBS. Further research investigating contributors to the discordance between screening results and neonatal outcomes in these populations is needed.

Metronidazole Metabolism in Neonates and the Interplay Between Ontogeny and Genetic Variation

Posted on by Kayla Korzekwinski

The Journal of Clinical Pharmacology • February 2017

Access article on PubMed.

Wang LA, Gonzalez D, Leeder JS, Tyndale RF, Pearce RE, Benjamin DK Jr, Kearns GL, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee.

Metronidazole is commonly used to treat intra-abdominal infections in neonates. The parent drug is converted to 5 metabolites, with 2-hydroxy-metronidazole being the most clinically significant, as it possesses 30–65% of the antimicrobial activity of the parent compound. In vitro studies have demonstrated that cytochrome P450 2A6 (CYP2A6) is the primary catalyst responsible for metronidazole hydroxylation. This enzyme is initially expressed at low levels at birth, with expression increasing over the course of the first year of life to reach adult levels. CYP2A6 is known to be a highly polymorphic gene with more than 45 variant alleles that result in inactive to ultra-rapid metabolizer phenotypes. Additionally, certain allelic variants such as CYP2A6*17 have amino acid changes that alter metabolism for some but not other substrates, resulting in different metabolizing phenotypes for the same genotype. The role of genetic variation on variable metronidazole metabolism in neonates has not been previously described, nor has the effect of CYP2A6*17 on metronidazole been characterized. As such, the objective of this study was to evaluate the effect of CYP2A6 genetic variation on the pharmacokinetics of metronidazole in a small cohort of preterm neonates.

Burden of Invasive Staphylococcus aureus Infections in Hospitalized Infants

Posted on by Kayla Korzekwinski

JAMA Pediatrics • December 2016

Access article on PubMed.

Ericson JE, Popoola VO, Smith PB, Benjamin DK, Benjamin DK Jr, Clark RH, Milstone AM
Staphylococcus aureus is a frequent cause of infection in hospitalized infants. These infections are associated with increased mortality and morbidity, and longer hospital stays, but data on the burden of S. aureus disease in hospitalized infants are limited. This study compared demographics and mortality of infants with invasive methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA), determined the annual proportion of S. aureus infections that were MRSA, and compared the risk of death following an invasive MRSA infection to the risk following an invasive MSSA infection.

Exposure Matching of Pediatric Anti-infective Drugs: Review of Drugs Submitted to the Food and Drug Administration for Pediatric Approval

Posted on by Kayla Korzekwinski

Clinical Therapeutics • September 2016

Access article on PubMed.

Zimmerman K, Putera M, Hornik CP, Smith PB, Benjamin DK Jr, Mulugeta Y, Burckart GJ, Cohen-Wolkowiez M, Gonzalez D

We sought to determine the extent of exposure matching, defined by a comparison of area under the concentration-time curve, between children and adults, for anti-infective drug products submitted to the FDA for approval.

Electronic Health Records and Pharmacokinetic Modeling to Assess the Relationship between Ampicillin Exposure and Seizure Risk in Neonates

Posted on by Kayla Korzekwinski

Journal of Pediatrics • August 2016

Access article on PubMed.

Hornik CP, Benjamin DK Jr, Smith PB, Pencina MJ, Tremoulet AH, Capparelli EV, Ericson JE, Clark RH, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act—Pediatric Trials Network.

This was a retrospective observational cohort study of electronic health record (EHR) data combined with pharmacokinetic model derived drug exposure predictions. We used the EHR from 348 Pediatrix Medical Group neonatal intensive care units from 1997 to 2012. We included all infants 24-41 weeks gestational age, 500-5400 g birth weight, first exposed to ampicillin prior to 25 days postnatal age. In this cohort of hospitalized infants, higher ampicillin exposure was associated with seizures as documented in the EHR.

Adverse Events After Routine Immunization of Extremely Low Birth Weight Infants

Posted on by Kayla Korzekwinski

JAMA Pediatrics • August 2016

Access article on PubMed.

DeMeo SD, Raman SR, Hornik CP, Wilson CC, Clark R, Smith PB
Immunization of extremely low birth weight (ELBW) infants in the neonatal intensive care unit (NICU) is associated with adverse events including fever and apnea/bradycardia in the immediate post-immunization period. This presents a diagnostic dilemma for clinicians, leading to the potential for immunization delay and sepsis evaluations. The goal of this study is to compare the incidence of sepsis evaluations, need for increased respiratory support, intubation, seizures, and death among immunized ELBW infants in the 3 days pre- and post-immunization.