Over the past 20 years, the study of antimicrobial resistance mechanisms has evolved from a largely descriptive discipline into a predictive science. The SENTRY Antimicrobial Surveillance Program—which collects and characterizes approximately 30,000 clinical isolates annually from around the world—has helped define the modern understanding of resistance epidemiology and directly supported the development and positioning of many antibacterial agents approved in the last 15 years.

A major inflection occurred around 2010, when the development of β-lactam/β-lactamase inhibitor combinations began to require precise differentiation of activity against specific resistance mechanisms. This shift transformed the field, driving a move from retrospective observation to systematic, prospective surveillance integrated with advanced molecular characterization.

In this presentation I will discuss how the genetic characterization studies performed using the SENTRY Program platform aided the differentiation of antimicrobial agents and provided support for clinical decisions. Ultimately, these insights underscore a fundamental shift in antimicrobial therapy—from choosing drugs based on organisms to selecting them based on resistance mechanisms.