Tissue-Directed Antibiotics and Intracellular Parasites: Complex Interaction of

Antibiotics with significant tissue penetration and intracellular accumulation may have an important role in the treatment of intracellular infections. However, clinically relevant evalua-tion of these antibiotics in vitro remains a challenge. Measurement ofserum drug concentrations or serum bactericidal levels may not be relevant. Measurement of intracellular drug concentra-tions may be simplistic, given the complex interaction of drug, microbe, and phagocyte. The effect of an antibiotic on an intracellular organism depends on the drug's penetration into the cell, its intracellular location, its metabolism within the cell, and its antimicrobial activity within the organism's specific intracellular microenvironment. Legionella micdadei, an intracellular parasite that grows within monocytes, has been used for the evaluation of drugs like azithromy-cin that are concentrated intracellularly. The development ofantibiotics with significant tissue pen-etration and intracellular accumulation has rekindled the de-bate as to the relation between the results of in vitro assays and in vivo drug efficacy [I, 2]. Historically, it has not been possible to measure antibiotic concentrations at the mos