V. Tullio et al., Cellular uptake and intraphagocytic activity of the new fluoroquinolone AF3013 against Klebsiella pneumoniae, DRUG EXP CL, 25(1), 1999, pp. 1-11
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.