Multidrug resistant (MDR) bacteria, namely methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, have become an increasing therapeutic challenge. Vancomycin and carbapenems are the primary treatment strategy for serious infections caused by these MDR bacteria. In the recent two decades, cases of reduced susceptibility to these antibiotics have emerged, and the frequency of these reports continues to increase worldwide, in both the hospital and outpatient settings. Despite significant advances in screening and detection, treatment approaches for MDR infections in pediatric patients are specifically challenged due to suboptimal dosing information for marketed antibiotics and the unavailability of new antibiotics. Analyzing the pediatric pharmacokinetic- pharmacodynamics (PK-PD) profile of antibiotics useful in MDR infections will optimize dosing, thereby maximizing therapeutic effects and minimizing toxicities. The purpose of this Mentored Patient-Oriented Research Career Development (K-23) proposal is to develop the knowledge and aptitude necessary for the candidate to become an independent researcher in clinical translational pharmacotherapy (CTP), a term encompassing the candidate's interest in conducting basic life sciences research that has the potential to improve health outcomes of pediatric patients with serious infections caused by MDR bacteria. The candidate is a pharmacist faculty member at the University of California, San Diego (UCSD) Skaggs School of Pharmacy and Pharmaceutical Sciences and in-residence at Miller Children's Hospital &Long Beach Memorial Medical Center. Under the robust mentorship of Dr. Victor Nizet (Professor of Pediatrics and Chief of the Division of Pediatric Pharmacology &Drug Discovery at UCSD) for support in overall career planning, and Dr. Edmund Capparelli (Clinical Professor of Pharmacy and Director of the NICHD Pediatric Pharmacology Research Unit at UCSD) for training in PK-PD modeling, the candidate will conduct PK-PD analyses using previously and prospectively collected samples within collaborating children's hospitals. The strength of this 5-year career development plan is that it incorporates didactic and laboratory training, responsible conduct of research, mentored research and professional networking. She will obtain a Masters of Advanced Studies in Clinical Research. Her long-term career goal is to promote safe and appropriate use of antimicrobial medications among patients with MDR infections, and through research, to enhance our understanding of, and management strategies for, MDR infections. The worldwide emerging resistance among multidrug resistant (MDR) bacteria has become an increasing therapeutic challenge. Coupled to this challenge is the minute pharmacologic data that exist in children and limited availability of new antimicrobial agents with novel mechanisms of action. This project's objectives are to examine the pediatric pharmacokinetic-pharmacodynamic profiles of antibiotics useful in MDR infections in order to optimize dosing, and to disseminate these clinically applicable data since it may lead to new dosing recommendations in children.

Public Health Relevance

The worldwide emerging resistance among multidrug resistant (MDR) bacteria have become an increasing therapeutic challenge. Coupled to this challenge is the minute pharmacologic data that exist in children and limited availability of new antimicrobial agents with novel mechanisms of action. This project's objectives are to examine the pediatric pharmacokinetic-pharmacodynamic profiles of antibiotics useful in MDR infections in order to optimize dosing, and to disseminate these clinically applicable data since it may lead to new dosing recommendations in children.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AI089978-03
Application #
8259846
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Xu, Zuoyu
Project Start
2010-05-15
Project End
2015-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
3
Fiscal Year
2012
Total Cost
$128,250
Indirect Cost
$9,500
Name
University of California San Diego
Department
None
Type
Schools of Pharmacy
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Le, Jennifer; Vaida, Florin; Nguyen, Emily et al. (2014) Population-Based Pharmacokinetic Modeling of Vancomycin in Children with Renal Insufficiency. J Pharmacol Clin Toxicol 2:1017-1026
Le, Jennifer; Ngu, Becky; Bradley, John S et al. (2014) Vancomycin monitoring in children using bayesian estimation. Ther Drug Monit 36:510-8
Le, Jennifer; Bradley, John S; Murray, William et al. (2013) Improved vancomycin dosing in children using area under the curve exposure. Pediatr Infect Dis J 32:e155-63