Use of fluoroquinolones for intracellular pathogens

Current microbiologic techniques (determinations of minimal inhibitory and/or microbicidal concentrations) are unable to delineate the true role of anti-infectious drugs in the treatment of human infections due to intracellular pathogens. The prediction and evaluation of the efficacy of quinolones against intracellular pathogens requires information on four different steps. (1) Quinolones should be able to penetrate phagocytes; intramacrophagic concentration is highly dependent on serum pharmacokinetics; finally, the best quinolone should have the longest serum half-life and reach highest maximum serum concentrations. (2) The evaluation of antibacterial activity requires an adequate cellular model (e.g., multiplication of Legionella pneumophila within human monocyte-derived macrophages). (3) The prediction of drug efficacy requires an experimental animal model. (4) Clinical trials in human disease are necessary. This stage is difficult when the evaluation concerns severe infectious diseases because the rarity of these diseases makes random clinical trials difficult. In this paper we describe methodologies for assessing the efficacy of quinolones against intracellular bacterial pathogens with a particular focus on Legionella pneumophila.