Cellular uptake and intraphagocytic activity of the new fluoroquinolone AF3013 against Klebsiella pneumoniae

The entry of an antibiotic into phagocytes is a prerequisite for its intrac ellular bioactivity against susceptible facultative or obligatory intracell ular microorganisms. AF 3013 is a new fluoroquinolone, and its uptake into and elimination from mouse peritoneal macrophages, together with its effect s on phagocytic and antimicrobial mechanisms against Kiebsiella pneumoniae, were investigated. AF 3013 efficiently penetrated into phagocytic cells at all concentrations tested. The uptake proceeded rapidly and was energy ind ependent, since it was not affected by cell viability, environmental temper ature or the addition of a metabolic inhibitor Therefore, a possible passiv e transmembrane diffusion mechanism might be proposed. The elution of AF 30 13 from macrophages occurred relatively slowly; in fact, 60 min after the r emoval of extracellular AF 3013, nearly 40% of the drug still remained in t he phagocytes. Exposure to I MIC of AF 3013 significantly enhanced macropha ges phagocytosis and increased intracellular bactericidal activity against K, pneumoniae, Following preexposure of macrophages to 1 MIC of AF 3013, th ere was a significant increase in both phagocytosis and killing compared wi th the controls, indicating the ability of AF 3013 to interact with biologi cal membranes and remain active within phagocytes. Preexposure of Klebsiell a to AF 3013 made the bacteria more susceptible to the bactericidal mechani sms of macrophages than untreated organisms.