"Difficult to treat infections" pharmacokinetic and pharmacodynamic factors--a review.

"Difficult to cure infections" are characterized by poor penetration of antibiotics into infected vegetations, altered metabolic state of bacteria within the vegetation, absence of adequate host defense/cellular response. These infections typically include endocarditis, urinary tract infections (infected urinary tract stones), abscesses, infected fibrin clots (septic thromboemboli, haematomas, catheter-related infections) and foreign body infections. Four main aspects are discussed for the influence on human therapy: 1. the kinetics of antibiotic diffusion into vegetations 2. the specificity of some pharmacodynamic aspects and pharmacokinetic regimes 3. fibrin as one of the main constituents associated with infectious processes and 4. synergistical activities of antibiotic combinations on bacterial vegetations.