Leon I. Goldberg Early Investigator Award Lecture

Moving from Point-Based Analysis to Systems-Based Modeling: Integration of Knowledge to Address Antimicrobial Resistance

Antibacterial response to antibiotics is influenced by a range of factors, including exposure at the site of infection, immune response of the host, and resistance profile of the infecting pathogen. To guide antibacterial drug development and optimization, it is essential to understand the relationship between pharmacokinetic (PK) exposure and the resulting antibacterial pharmacodynamic (PD) effect. While summary PK/PD indices, such as drug exposure normalized by the minimum inhibitory concentration (MIC), continue to play an important role, it is important to recognize the limitations associated with this approach. Model-based approaches can link the time course of antibiotic exposure with the antibacterial response, incorporating the impact of dynamic changes in exposure and knowledge about the system that influences treatment outcome in patients. This approach can help inform dosing of antibiotics to limit the emergence of resistance and preserve the activity of the drug.

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