The lingering legacy of one letter in antimicrobial susceptibility testing.

For decades, the 'Intermediate' (I) category in antimicrobial susceptibility testing was frequently misinterpreted as indicative of therapeutic failure, rather than an opportunity for dose optimization. This misunderstanding shaped prescribing behaviour, antimicrobial trial design and guideline development. The 2019 European Committee on Antimicrobial Susceptibility Testing redefinition of the 'I' category as 'Susceptible, Increased Exposure' (SIE) highlighted the potential for treatment efficacy through dose adjustment, challenging entrenched prescribing behaviours and exposing limitations in historical trials, guidelines and surveillance practices. Antimicrobial stewardship that employs SIE-based strategies can preserve narrower-spectrum agents. However, the misapplication of 'I' can promote unnecessary broad-spectrum antimicrobial prescribing. Surveillance systems, clinical decision support and antimicrobial stewardship should be continuously updated to reflect current pharmacological principles and thereby enhance patient care outcomes.