INTRODUCTION – PRINCIPLES OF ANTIMICROBIAL USE

Pharmacokinetics and Pharmacodynamics

Many factors affect the choice of an antimicrobial agent in the acute care setting. Selection of an agent with in vitro activity against the infecting pathogen is necessary but not sufficient. Pharmacokinetic (distribution of the drug in the body) and pharmacodynamic (effect of the drug on its target) factors must also be taken into account. The most important pharmacokinetic consideration is the concentration of the drug at the site of infection. The physicochemical properties of antimicrobials determine their distribution throughout the body, and these properties may be unfavorable for the penetration of certain tissue compartments.

Sites of particular concern for the adequate penetration of antimicrobials include bone, compartments of the eye, and the central nervous system. Additionally, abscess cavities are poorly penetrated and should be drained regardless of whether systemic antimicrobial therapy is to be used. Even treatment of pulmonary and urinary tract infections depends on site-specific penetration, and recommendations for standard therapies reflect this. Thus, clinicians should rely on standard therapy or use alternative drugs that are documented to achieve effective concentrations at the site of interest. Unfortunately, data as to the relative penetration of different drugs may be lacking, although predictions based on physicochemical characteristics (e.g., protein binding) can be made.

An important pharmacodynamic distinction is whether a drug's activity is bactericidal or bacteriostatic.