Discovery and Clinical Translation era
In the Discovery and Clinical Translation era (1928–1964), the emergence of natural‑product antibiotics transformed medicine, centering on penicillin and the later‑discovered aminoglycosides. Alexander Fleming first identified penicillin's antibacterial effect in 1928, opening a new paradigm for microbial control. Howard Florey and Ernst Boris Chain then purified penicillin, demonstrated scalable production, and guided early clinical trials that established dosing, safety, and therapeutic adoption. Selman Waksman and colleagues isolated streptomycin in the 1940s, launching the aminoglycoside era and propelling systematic screening of soil microbes to broaden the antibiotic arsenal.
Standardization and Surveillance era
During 1965–2004, antimicrobial susceptibility testing moved from ad hoc methods to standardized dilution techniques, breakpoints, and quality-control programs that enabled comparable data across laboratories. The Kirby-Bauer disk diffusion method, codified by William Kirby and collaborators including J. C. Sherris and M. J. Turck, became a foundational standard for routine susceptibility testing. Prominent figures such as William A. Pfaller advanced the integration of surveillance networks (notably SENTRY) with standardized testing protocols and interpretive breakpoints through NCCLS/CLSI guidelines. The era also acknowledged horizontal gene transfer and plasmid-mediated enzymes, prompting integration of molecular diagnostics with epidemiological surveillance within the standardized framework.