TISSUE-DIRECTED ANTIBIOTICS AND INTRACELLULAR PARASITES - COMPLEX INTERACTION OF PHAGOCYTES, PATHOGENS, AND DRUGS

Antibiotics with significant tissue penetration and intracellular accumulation may have an important role in the treatment of intracellular infections. However, clinically relevant evaluation of these antibiotics in vitro remains a challenge. Measurement of serum drug concentrations or serum bactericidal levels may not be relevant. Measurement of intracellular drug concentrations 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 azithromycin that are concentrated intracellularly.