Clindamycin Pharmacokinetics and Safety in Preterm and Term Infants

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.

Effect of Catheter Dwell Time on Risk of Central Line–Associated Bloodstream Infection in Infants

Pediatrics December 2015

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Greenberg RG, Cochran KM, Smith PB, Edson BS, Schulman J, Lee HC, Govindaswami B, Pantoja A, Hardy D, Curran J, Lin D, Kuo S, Noguchi A, Itmann P, Duncan S, Gupta M, Piccarillo A, Karna P, Cohen M, Giuliano M, Carroll S, Page B, Guzman-Cottrill J, Walker

Central venous catheters in the NICU are associated with significant morbidity and mortality because of the risk of central line–associated bloodstream infections (CLABSIs). The purpose of this study was to determine the effect of catheter dwell time on risk of CLABSI. Increased dwell time was not associated with increased risk of CLABSI for PICCs. For tunneled catheters, infection incidence was significantly higher in weeks 7 and 9 compared with week 1.

Vancomycin Cerebrospinal Fluid Pharmacokinetics in Children with Cerebral Ventricular Shunt Infections

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

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.

Fluconazole population pharmacokinetics and dosing for prevention and treatment of invasive Candidiasis in children supported with extracorporeal membrane oxygenation

Antimicrobial Agents and Chemotherapy • June 2015

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Watt KM, Gonzalez D, Benjamin DK Jr, Brouwer KL, Wade KC, Capparelli E, Barrett J, Cohen-Wolkowiez M.

Candida infections are a leading cause of infectious disease-related death in children supported by extracorporeal membrane oxygenation (ECMO). The ECMO circuit can alter drug pharmacokinetics (PK); thus, standard fluconazole dosing may result in suboptimal drug exposures. The objective of our study was to determine the PK of fluconazole in children on ECMO. Forty children with 367 PK samples were included in the analysis.

Rifampin use and safety in hospitalized infants

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

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

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.

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

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.

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

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.