Tissue penetration of antibacterial agents: how should this be incorporated into pharmacodynamic analyses?

Despite the accepted knowledge that the activity of antibiotics depends on the unbound concentration at the site of infection, current pharmacodynamic analysis mostly relies on published total blood concentrations. Such concentrations do not necessarily correlate with concentrations at the site of infection. Methodological problems and separation of bound and unbound fractions, however, limit the applicability of most measured 'tissue concentrations' as adequate pharmacokinetic input into pharmacodynamic analyses. Recently, research on using free blood concentrations as surrogate concentrations has received more attention and may be useful for infection sites such as soft tissue infections. Although our understanding of antibiotic pharmacodynamics in tissues has become much more advanced, we are still lacking appropriate and accurate pharmacokinetic data derived from the site of infection.