The MICs and MBCs of CI-934, ciprofloxacin, difloxacin (A-56619), A-56620, norfloxacin, enoxacin, amifloxacin, and coumermycin were determined for 43 clinical isolates of Enterococcus faecalis known to be resistant to penicillin-aminoglycoside synergy. Results were compared with those obtained for 37 synergysusceptible E. faecalis and 22 Enterococcus faecium strains. Although no substantial differences in quinolone activities were observed between synergy-resistant and -susceptible E. faecalis strains, CI-934 and ciprofloxacin were the drugs that demonstrated the greatest bactericidal activity against both types of E. faecalis. The MBCs of the other quinolones were generally within a single twofold dilution of the MICs, but their antienterococcal activity did not approach that of CI-934 or ciprofloxacin. The MBCs for 90% of the isolates of CI-934 for synergy-resistant and -susceptible E. faecalis strains were 1 and <0.5 ,ug/ml, respectively. The ciprofloxacin MBC for 90% of the E. faecalis strains tested was 1 ,ug/ml. For E. faecium isolates the CI-934 and ciprofloxacin MBCs for 90% of the isolates were 8 and 4 ,ug/ml, respectively. Time-kill assays performed with synergysusceptible enterococcal strains showed that the bactericidal activities of both CI-934 and ciprofloxacin were less than those of the penicillin-aminoglycoside combinations tested. However, against synergy-resistant isolates the activities of these two quinolones were comparable with and sometimes greater than those of penicillinaminoglycoside combinations.Aminoglycoside and penicillin (or ampicillin) combinations have been the most effective treatment for serious enterococcal infections (13,17,22). The synergistic bactericidal activity that these drugs demonstrate is particularly important for their use in the treatment of enterococcal endocarditis. However, by acquiring plasmids that encode for various aminoglycoside-modifying enzymes, Enterococcus faecalis isolates can exhibit high-level aminoglycoside resistance (MIC, -2,000 Fig/ml) and be refractory to antibiotic synergy (6,12,19). Infections caused by these resistant strains present serious therapeutic dilemmas (10), and their incidence at one medical center has been reported as high as 55% of all clinical enterococcal isolates (37). In addition, the therapeutic problems posed by the emergence of high-level aminoglycoside resistance have been complicated by the discovery of ,-lactamase-producing strains of E. faecalis (25). The resistance emerging among E. faecalis isolates as well as Enterococcus faecium resistance to antibiotics, which has been known for some time (20,23), indicates that the choice of antibiotics that may be selected for use against enterococci is extremely limited.Several of the recently developed fluoroquinolone antibiotics have demonstrated a broad spectrum and a high level of antibacterial activity (3,18,30,34), and certain of these drugs have shown good activity against some E. faecalis isolates (15, 18). However, thorough evaluations of fluoroquinolone activity aga...