Mechanisms and clinical effects of antibiotic interactions

Antibiotic therapy increasingly relies on the use of combinations of antibiotics, especially for serious and difficult-to-treat cases.

Even though combinations have been used for over 70-years, there exists is a lack of understanding of the molecular mechanisms that underpin how these combinations work.

This project will fill this knowledge gap, and we will in detail study how antibiotics interact to produce combination effects that are either stronger (synergistic) or weaker (antagonistic), than expected from additivity.Furthermore, since antagonistic drug interactions could reduce the treatment effect, and, conversely, synergistic activities could provide an advantage, optimal use of combination therapy in clinical settings depends upon our ability to quantify the interaction profile of antibiotic combinations for the patient’s specific isolate and refine the combination accordingly, something which is currently not done.We will address three general questions:1.

Why do different antibiotic combinations vary in their effect.

I.e. which mechanisms underlie the fact that certain combinations of antibiotics are synergistic and others are antagonistic or additive?2.

Why do different isolates of the same species show differences in their interaction profile for the same antibiotic combination?3.

Can refined combination therapy based on the antibiotic interaction profile of each unique patient isolate improve treatment outcome?