Macrolides and the immune system

Macrolides achieve much greater in vivo and clinical efficacy than might be expected from standard in vitro testing. There is accumulating evidence to suggest that macrolides act synergistically with the host immune system. In contrast to β-lactams, macrolides have increased activity in serum. Phagocytes are a key component of the host immune system against intracellular pathogens. Antibiotics can alter bacterial susceptibility to both uptake and intracellular phagocytic killing. Macrolides appear to enhance phagocyte killing of bacteria whereas β-lactams have a limited or negative effect. Both macrolides and quinolones achieve high intraphagocytic concentrations that are associated with intracellular antibacterial activity. Azithromycin, which is chemically related to the macrolides, achieves particularly high intracellular levels within phagocytes which may be associated with enhanced synergistic activity.