The site of infection is the most critical factor in selecting antimicrobial therapy because it determines the likely pathogens involved and the drug’s ability to reach effective concentrations at the infection site. Different tissues have variable blood supply and barriers (e.g., blood-brain barrier) affecting drug penetration. Choosing an antimicrobial without considering this can lead to therapeutic failure despite appropriate antimicrobial spectrum. Thus, tailoring therapy to the infection site ensures optimal efficacy and patient outcomes.

Reference: Principles and Practice of Infectious Diseases, Mandell GL et al., 9th Edition.