Treatment of Intracellular Infections

The intracellular location of some bacteria remains a critical point to explain failures of antibiotic treatment from infected hosts. Parasites that multiply only within eukaryotic cells are obligate intracellular pathogens, whereas facultative intracellular pathogens may multiply in cell-free models. Bacteria can reside in phagocytic cells including neutrophils, macrophages, and monocytes or in nonphagocytic cells such as endothelial cells or in erythrocytes. Activity of antibiotics against intracellular bacteria depends on several factors, including pharmacodynamic and pharmacokinetic properties of drugs. Fluoroquinolone compounds in cells may be located both in the cytosol and lysosomes, whereas weak base antibiotics such as the aminoglycosides and the macrolides are concentrated within lysosomes. Although antibiotic susceptibility of facultative intracellular bacteria can be assessed in cell-free systems using classic MIC determination methods, the antibiotic susceptibility of obligate intracellular bacteria should be determined only in infected cell models. Animal models have been used to assess antibiotic therapeutic efficacy against intracellular pathogens. Many studies have compared the efficacy of quinolones in vitro and in vivo against intracellular pathogens. Antibiotic susceptibility of obligate intracellular bacteria, as determined using in vitro cell models is discussed in this chapter. Antibiotic treatment recommendations for intracellular pathogens are provided.