The interaction between four fluoroquinolones (ciprofloxacin, norfloxacin, pefloxacin, and ofloxacin) and biofilms of Pseudomonas aeruginosa in wells of microtiter plates and on segments of vascular catheters was studied in an in vitro model of vascular catheter colonization. Subinhibitory concentrations (one-half, onefourth, and one-eighth of the MIC) of the fluoroquinolones reduced the adherence of P. aeruginosa to 30 to 33, 44 to 47, and 61 to 67% of that of controls, respectively. The addition of high concentrations of the fluoroquinolones (12.5 and 400 g/ml) to preformed biofilms (grown for 48 h at 37؇C) decreased the adherence of P. aeruginosa to 69 to 77 and 39 to 60% of that of controls, respectively. In an in vitro model of vascular catheter colonization, subinhibitory concentrations (one-half, one-fourth, and one-eighth of the MIC) of fluoroquinolones reduced the number of adherent bacteria to 21 to 23, 40 to 46, and 55 to 70% of that of the controls, respectively. Scanning electron microscopy demonstrated a significant reduction in glycocalyx formation and adherent bacteria in the presence of pefloxacin at one-half to one-eighth of the MIC. Vascular catheter segments precolonized with P. aeruginosa for 24 h and exposed to the fluoroquinolones at 4 to 25 times the MIC (50 g/ml) for 2 h showed <5% growth of adherent cells compared with controls. No adherent organisms were cultured in the presence of 8 to 50 times the MIC (100 g/ml). Scanning electron microscopy studies of preformed biofilms exposed to pefloxacin verified the results obtained by culture. These data show that subinhibitory concentrations of ciprofloxacin, norfloxacin, pefloxacin, and ofloxacin inhibit the adherence of P. aeruginosa to plastic surfaces and vascular catheters. Clinically achievable concentrations of fluoroquinolones (50 to 100 g/ml) were able to eradicate preformed biofilms on vascular catheters.The use of various medical devices such as indwelling vascular catheters, cardiac pacemakers, prosthetic heart valves, chronic ambulatory peritoneal dialysis catheters, and prosthetic joints has greatly facilitated the medical and surgical management of serious illnesses. Bacterial infections following colonization and biofilm formation on these devices are a major cause of morbidity in patients receiving prosthetic devices (5). Biofilms have also been demonstrated on tissues in chronic bacterial diseases that are characterized by resistance to antimicrobial chemotherapy (27). Extracellular slime or glycocalyx production is an important factor in the adherence of bacteria and their protection from host defense mechanisms. Extensive glycocalyx production has been demonstrated on cultures of Staphylococcus epidermidis (14), S. aureus (4), Pseudomonas aeruginosa (15), Escherichia coli (3), and Bacteroides species (16).Different approaches (including the use of various antimicrobial agents) to the eradication of biofilm bacteria have been studied. The combination of tobramycin and piperacillin (1), the combination of tosufloxacin and er...