Antimicrobial resistance is identified as a top public health threat in critical need of innovation. Our translational research focuses on the pharmacodynamics of antimicrobials in the treatment of complex bacterial infections. We identify novel ways to employ antibiotics in patients to combat antimicrobial resistance development and treatment failure. This is done using a laboratory bench-to-bedside approach that encompasses multidisciplinary research collaborations in the basic science, medicine, and pharmacy disciplines. We focus primarily on antimicrobial dosing and combinations to treat multi-drug resistance Gram-positive infections, such as methicillin-resistant Staphylococcus aureus. We focus on three major themes related to this topic in both the laboratory and clinic: (1) novel combination approaches to improve antibacterial activity (2) anti-virulence strategies to reduce bacterial pathogenicity, and (3) host-pathogen immunologic response in the presence of antibiotics. Our goal is to identify a precision approach, in terms of both the patient and bacteria, to better utilize antibiotics, minimize resistance development, and optimize patient outcomes.