The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

 

Johns Hopkins School of Public Health

Research Grants 2005-2006

Development of a mathematical model to predict bacterial response to antimicrobial agents

Vincent Tam, PharmD
University of Houston College of Pharmacy

The emergence of bacterial resistance to antimicrobial agents is rising at an alarming rate. New agents must be developed rapidly and continuously to combat infections caused by these resistant pathogens. In pre-clinical development off new antimicrobial agents, a large number of laboratory animals are routinely used to explore the appropriate dosing regimens (dose and dosing frequency) to be investigated in clinical trials. However, the choice of these dosing regimens to be tested is often empiric. This trial-and-error approach is grossly inefficient and the use of laboratory animals is not always necessary in many of the conventional development phases. Our goal is to understand how mathematical modeling and simulation can be optimally incorporated in pre-clinical investigation of antimicrobial agents to streamline the development process. We propose to develop a methodology combining mathematical modeling and computer simulations to predict bacterial response to antimicrobial agents. The effect associated with an antimicrobial agent (given as different dosing regimens) could be evaluated efficiently using computer simulations. By guiding the choice of dosing regimens to be investigated, the proposed modeling system approach would enhance the efficiency of the antimicrobial development process and likely result in a significant reduction of the number of laboratory animals required for pre-clinical testing. Animals will unlikely be used at all in testing of agents predicted to have minimal antimicrobial activity, thus avoiding unnecessary use of the animals. For agents predicted to have antimicrobial activity, animal investigators could focus on only a few dosing regimens with high probabilities of success.