Effect of pefloxacin on microorganism: host cell interaction.
Recent evidence indicates that certain antibiotics affect bacterial adherence and phagocyte-micro-organism interactions. These interactions are important in the early stages of bacterial pathogenesis, that is, attachment to mucosal surfaces and invasion. Among the antibiotics of interest in this field are the fluoroquinolones. Sub-MICs of pefloxacin can alter the ability of Gram-positive cocci (Staphylococcus aureus, Enterococcus faecalis) and Gram-negative bacilli (Escherichia coli) to adhere to different eukaryotic cells (uroepithelial and buccal cells) and to fibrin-platelet matrices. The mechanism by which pefloxacin reduces adhesion is not completely understood. However in the case of Esch. coli, the inhibition of haemagglutination and adherence corresponds to: (1) a decrease in production of fimbriae; (2) changes in the composition of outer membrane proteins; and (3) an effect on partition coefficient (carried out with the PEG/dextran system) which can be attributed to changes in electric and/or hydrophobic properties of the Esch. coli surface. The first step of phagocytosis is represented by adherence of opsonized bacteria to the membrane receptors of phagocytes. Consequently, the action of pefloxacin on phagocytosis is also of importance. Pretreatment of bacteria (Staph. aureus, Ent. faecalis, Esch. coli and Legionella pneumophila) with 1/4 the MIC of pefloxacin leads to an increase in uptake of the different strains by phagocytes (polymorphonuclear leucocytes and macrophages). Exposure of the phagocytes to 10 mg/l of pefloxacin enhances phagocytosis of strains that have not been pretreated. Finally, entry of antibiotics into phagocytic cells is a prerequisite for activity against intracellular organisms. The concentration of pefloxacin by polymorphs and macrophages is high (intracellular concentration/extracellular concentration = 5-10). Such findings correlate well with the intracellular activity of pefloxacin, demonstrated with guinea pig macrophages and different bacteria (Staph. aureus, L. pneumophila).
Desnottes
J F
JF
Rhône-Poulenc Santé, Centre de Recherches de Vitry-Alfortville, Vitry-sur-Seine, France.
Diallo
N
N
Loubeyre
C
C
Moreau
N
N
D001422:Bacterial Adhesion / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D015366:Pefloxacin / Q000378:metabolism / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D015366:Pefloxacin