Tissue penetration of antibiotics.

To be effective, antibiotics must be active against the offending pathogen(s) and must reach sufficient concentrations at the site of infection where microorganisms have induced severe inflammation. Such inflammation may, depending on the infected tissue, increase or decrease antibiotic penetration. Once it has reached the infected site an antibiotic may be inactivated locally. In this work, we have reviewed: 1. Factors modulating the penetration of antibiotics in tissues of normal and infected humans and animals; 2. The relationship between concentrations and efficacy of antimicrobials in experimental and human infections; 3. The mechanisms by which high tissue levels of antibiotics may be toxic; 4. New antibiotic targetting delivery systems which may increase tissue concentrations of antibiotics. To better understand the interaction between antimicrobial agents, pathogens in specific infected sites and the host, more experimentation dealing simultaneously with tissue penetration and antibiotic efficacy in acute and chronic infection is required. Innovative approaches to the therapy of human infections are needed.