Antibiotic resistance [1-3] is a significant public health concern [4-5] that threatens to reduce or even eliminate the effectiveness of some of our most important treatment options for bacterial infections. The marked increase in lifespan and overall health enjoyed by modern society is credited in no small part to drugs like penicillin and its more recent derivatives. However, we are at risk of losing our advantage over bacterial infections due to the overuse and misuse of antibiotics.  As the number of resistant strains increases, the burden on the US health care system, in terms of human lives and dollars spent, only grows. The purpose of the proposed research is to increase our understanding of the specific conditions that lead to the development of antibiotic resistance. In particular, we will focus on periodic doses of antibiotics, which more closely mimic the concentration profile of the drug over time inside the body. By using experimental conditions that control the type, concentration, and period of application of antibiotic, we can map in unprecedented detail the situations that are most likely to cause antibiotic resistance. Results from this study have direct implications for the most effective way to schedule the administration of antibiotics that optimizes patient outcomes and minimizes the risk of inadvertently creating resistant bacteria.