In this episode, we dive into the evolving strategies for treating Pseudomonas aeruginosa infections with piperacillin-tazobactam (PTZ). Challenging the conventional high-dose approach of 4.5g IV every six hours, recent evidence and Monte Carlo simulations suggest that more isn’t always better. For most strains with MICs ≤8 mg/L, the standard 3.375g IV Q6H is usually sufficient, while higher MIC infections (≥16 mg/L) often require extended infusions to maximize the time the drug remains above the MIC (fT>MIC). We break down why time above MIC...not just total dose, is the key to improving clinical outcomes and how this insight is reshaping how we think about optimal PTZ therapy.