Antibacterials

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

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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.

Clindamycin Pharmacokinetics and Safety in Preterm and Term Infants

Posted on by Kayla Korzekwinski

Antimicrobial Agents and Chemotherapy • April 2016

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Gonzalez D, Delmore P, Bloom BT, Cotten CM, Poindexter BB, McGowan E, Shattuck K, Bradford KK, Smith PB, Cohen-Wolkowiez M, Morris M, Yin W, Benjamin DK Jr, Laughon MM.

Clindamycin may be active against methicillin-resistant Staphylococcus aureus, a common pathogen causing sepsis in infants, but optimal dosing in this population is unknown. We performed a multicenter, prospective pharmacokinetic (PK) and safety study of clindamycin in infants. We analyzed the data using a population PK analysis approach and included samples from two additional pediatric trials.

Dosing in neonates: Special considerations in physiology and trial design

Posted on by Kayla Korzekwinski

Pediatric Research • January 2016

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Ku LC, Smith PB
Determining the right dose for drugs used to treat neonates is critically important. Neonates have significant differences in physiology affecting drug absorption, distribution, metabolism, and elimination that makes extrapolating dosages from adults and older children inappropriate. Fortunately, specialized analytical techniques, such as the use of dried blood spots, scavenged sampling, population pharmacokinetics analyses, and sparse sampling, have helped investigators better define doses that maximize efficacy and safety. Through the use of these methods, successful clinical trials have resulted in recent changes to drug dosing in this population.

Vancomycin Cerebrospinal Fluid Pharmacokinetics in Children with Cerebral Ventricular Shunt Infections

Posted on by Kayla Korzekwinski

The Pediatric Infectious Disease Journal • October 2015

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Autmizguine J, Moran C, Gonzalez D, Capparelli EV, Smith PB, Grant GA, Benjamin DK Jr, Cohen-Wolkowiez M, Watt KM.
This study described the cerebrospinal fluid (CSF) exposure of vancomycin in 8 children prescribed intravenous vancomycin therapy for cerebral ventricular shunt infection.

Cefepime and Ceftazidime Safety in Hospitalized Infants

Posted on by Kayla Korzekwinski

The Pediatric Infectious Disease Journal • August 2015

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Arnold CJ, Ericson J, Cho N, Tian J, Wilson S, Chu VH, Hornik CP, Clark RH, Benjamin DK Jr, Smith PB; Best Pharmaceuticals for Children Act–Pediatric Trials Network Administrative Core Committee.

Cefepime and ceftazidime are cephalosporins used for the treatment of serious Gram-negative infections. These cephalosporins are used off-label in the setting of minimal safety data for young infants. We identified all infants discharged from 348 neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2012 who were exposed to either cefepime or ceftazidime in the first 120 days of life. We reported clinical and laboratory adverse events occurring in infants exposed to cefepime or ceftazidime and used multivariable logistic regression to compare the odds of seizures and death between the 2 groups.

Use and Safety of Erythromycin and Metoclopramide in Hospitalized Infants

Posted on by Kayla Korzekwinski

Journal of Pediatric Gastroenterology and Nutrition • August 2015

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Ericson JE, Arnold C, Cheeseman J, Cho J, Kaneko S, Wilson E, Clark RH, Benjamin DK Jr, Chu V, Smith PB, Hornik CP; Best Pharmaceuticals for Children Act–Pediatric Trials Network Administrative Core Committee.

Prokinetic medications are used in premature infants to promote motility and decrease time to full enteral feeding. Erythromycin and metoclopramide are the most commonly used prokinetic medications in the neonatal intensive care unit (NICU), but their safety profile is not well defined.

Rifampin use and safety in hospitalized infants

Posted on by Kayla Korzekwinski

American Journal of Perinatology • May 2015

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Arnold CJ, Ericson J, Kohman J, Corey KL, Oh M, Onabanjo J, Hornik CP, Clark RH, Benjamin DK Jr, Smith PB, Chu VH; Best Pharmaceuticals for Children Act–Pediatric Trials Network Administrative Core Committee.

This study aims to examine the use and safety of rifampin in hospitalized infants. Observational study of clinical and laboratory adverse events among infants exposed to rifampin from 348 neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2012.

Pharmacokinetics and safety of recently approved drugs used to treat methicillin-resistant Staphylococcus aureus infections in infants, children and adults

Posted on by Kayla Korzekwinski

Expert Review of Clinical Pharmacology • May 2015

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Gostelow M, Gonzalez D, Smith PB, Cohen-Wolkowiez M
Methicillin-resistant Staphylococcus aureus (MRSA) remains a significant cause of morbidity in hospitalized infants. Over the past 15 years, several drugs have been approved for the treatment of S. aureus infections in adults. The use of there majority of these drugs has extended into the treatment of MRSA infections in infants, frequently with minimal safety or dosing information. Here, we review current pharmacokinetic, safety, and efficacy data of these drugs with a specific focus in infants.

Simultaneous determination of trimethoprim and sulfamethoxazole in dried plasma and urine spots

Posted on by Kayla Korzekwinski

Bioanalysis • May 2015

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Gonzalez D, Melloni C, Poindexter BB, Yogev R, Atz AM, Sullivan JE, Mendley SR, Delmore P, Delinsky A, Zimmerman K, Lewandowski A, Harper B, Lewis KC, Benjamin DK Jr, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act–Pediatric Trials Network Administrative Core Committee.

Trimethoprim-sulfamethoxazole (TMP-SMX) is an antimicrobial drug combination commonly prescribed in children and adults. The study objectives were to validate and apply an HPLC-MS/MS method to quantify TMP-SMX in dried plasma spots (DPS) and dried urine spots (DUS), and perform a comparability analysis with liquid matrices.

Anaerobic antimicrobial therapy after necrotizing enterocolitis in VLBW infants

Posted on by Kayla Korzekwinski

Pediatrics • January 2015

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Autmizguine J, Hornik CP, Benjamin DK Jr, Laughon MM, Clark RH, Cotten CM, Cohen-Wolkowiez M, Benjamin DK, Smith PB; Best Pharmaceuticals for Children Act—Pediatric Trials Network Administrative Core Committee.

To evaluate the effect of anaerobic antimicrobial therapy for necrotizing enterocolitis (NEC) on clinical outcomes in very low birth weight (≤1500 g) infants. We identified very low birth weight infants with NEC from 348 US NICUs from 1997 to 2012. Anaerobic antimicrobial therapy was defined by antibiotic exposure on the first day of NEC. We matched (1:1) infants exposed to anaerobic antimicrobial therapy with infants who were not exposed by using a propensity score stratified by NEC severity (medical and surgical).