The inhibitory and postantibacterial activities of pefloxacin, ciprofloxacin, and ofloxacin against virulent Legionella pneumophila serogroup 1 were evaluated in cell-free and cellular models. In the absence of macrophages (with the tissue culture medium alone), bacterial numbers remained unchanged at 24 h in the presence of 0.1 ,ug of pefioxacin, ciprofloxacin, or ofloxacin per ml and 1.0 ,ug of pefloxacin per ml, whereas they were reduced in the presence of 1.0 ,ug of ciprofloxacin or ofioxacin per ml. Experiments to evaluate the postantibacterial effects of these drugs were therefore performed with concentrations of 0.1 ,ug/ml. In the cell-free model, brief exposure (1 h) of bacteria to each antimicrobial agent resulted in a transient decrease in numbers followed by logarithmic growth. In the cellular model, all three drugs (at 0.1 and 1.0 ,ug/ml) inhibited the intracellular multiplication of L. pneumophila. The intracellular postantibacterial effects of 0.1 ,ug of pefloxacin, ciprofloxacin, and ofloxacin per ml, which were left in contact with L. pneumophila-infected human macrophages for 24 h, were evaluated at various times after removal of the drugs. Pefloxacin was found to exhibit a significant inhibitory effect at 72 h, whereas following the removal of ciprofloxacin and ofloxacin, rapid bacterial multiplication occurred, leading to the destruction of the macrophage monolayer within 48 h.Thus, while pefloxacin, ciprofloxacin, and ofloxacin all inhibited the multiplication of L. pneumophila in human monocyte-derived macrophages, only pefloxacin exhibited a prolonged postantibacterial effect.Three new fluoroquinolones, pefloxacin (6, 37), ciprofloxacin (17-19), and ofloxacin (35, 36), have been shown to be more active than erythromycin (6, 37) and josamycin (36) against Legionella pneumophila in cellular and experimental animal infection models. Other new difluorinated and trifluorinated quinolone agents have also been found to be active against L. pneumophila (7, 13, 16, 26, 31). We have previously demonstrated that pefloxacin shows a potent postantibacterial effect (PAE) against virulent L. pneumophila serogroup 1 in guinea pig infection and human monocyte-derived macrophage models (6, 37). Recently, Edelstein and Edelstein (12) have shown that contrary to ciprofloxacin, WIN 57273, a new quinolone antimicrobial agent, inhibits the growth of L. pneumophila grown in guinea pig alveolar macrophages in an irreversible manner.The objective of this study was to evaluate and compare the intracellular PAEs of three quinolones, pefloxacin, ciprofloxacin, and ofloxacin, against L. pneumophila. The drug concentration that would inhibit but not kill the Legionella strain that was used, thus allowing the determination of intracellular PAE, was assessed first in a macrophage-free model. We then compared the intracellular inhibitory activities and PAEs of the three antimicrobial agents in a macrophage model. MATERIALS AND METHODSBacteria. L. pneumophila serogroup 1 (strain Paris CB 81-13) was used in all experiments. T...