The rationale for aerosolized antibiotics.

In order for an antimicrobial agent to be effective, it must fulfill two requirements. First, the agent must reach the site of infection and remain in the vicinity for an adequate length of time. Second, it must bind to a target site and remain bound for a length of time sufficient to disrupt the life cycle of the cell. Once these requirements are met, the drug is able to exert its antimicrobial activity against the cell. In an effort to better understand and predict the killing activity of antibiotics, we have attempted to develop parameters that describe the accumulation and diffusion of drug to and from body sites (pharmacokinetics) and quantify how much of a compound is needed at the site of infection to yield the desired effect (minimum inhibitory concentration). Furthermore, integration of these parameters allows us to evaluate host, drug, and microbial factors and formulate criteria to assess and predict drug activity in patients (pharmacodynamics). Knowledge and application of pharmacodynamic principles can assist clinicians in optimizing antimicrobial therapy by allowing them to maximize the antimicrobial activity of an agent while minimizing patient exposure and thus reducing the likelihood of toxicity.