Rifampin Pharmacokinetics and Safety in Preterm and Term Infants

Antimicrobial Agents and Chemotherapy • May 2019

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Smith PB, Cotten CM, Hudak ML, Sullivan JE, Poindexter BB, Cohen-Wolkowiez M, Boakye-Agyeman F, Lewandowski A, Anand R, Benjamin DK Jr, Laughon MM; Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee.

Rifampin is active against methicillin-resistant staphylococcal species and tuberculosis (TB). We performed a multicenter, prospective pharmacokinetic (PK) and safety study of intravenous rifampin in infants of <121 days postnatal age (PNA). We enrolled 27 infants; the median (range) gestational age was 26 weeks (23 to 41 weeks), and the median PNA was 10 days (0 to 84 days). We collected 102 plasma PK samples from 22 of the infants and analyzed safety data from all 27 infants. We analyzed the data using a population PK approach.

Pharmacokinetics of ticarcillin-clavulanate in premature infants

British Journal of Clinical Pharmacology  May 2019

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Watt KM, Hornik CP, Balevic SJ, Mundakel G, Cotten CM, Harper B, Benjamin DK, Anand R, Laughon M, Smith PB, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act Pediatric Trials Network Steering Committee

Ticarcillin-clavulanate covers a broad spectrum of pathogens that are common in premature infants. In infants <30 weeks gestational age, pharmacokinetic data to guide ticarcillin-clavulanate dosing are lacking. This study enrolled premature infants <30 weeks gestational age, determined pharmacokinetic parameters, and performed dosing simulations to determine optimal dosing for ticarcillin-clavulanate.

Population Pharmacokinetics of Trimethoprim-Sulfamethoxazole in Infants and Children

Antimicrobial Agents and Chemotherapy • December 2017

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Autmizguine J, Melloni C, Hornik CP, Dallefeld S, Harper B, Yogev R, Sullivan JE, Atz AM, Al-Uzri A, Mendley S, Poindexter B, Mitchell J, Lewandowski A, Delmore P, Cohen-Wolkowiez M, Gonzalez D; the Pediatric Trials Network Steering Committee.

Trimethoprim (TMP)-sulfamethoxazole (SMX) is used to treat various types of infections, including community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and Pneumocystis jirovecii infections in children. Pharmacokinetic (PK) data for infants and children are limited, and the optimal dosing is not known. We performed a multicenter, prospective PK study of TMP-SMX in infants and children.

Burden of Invasive Staphylococcus aureus Infections in Hospitalized Infants

JAMA Pediatrics December 2016

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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.

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.

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.

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.