In Vitro Activities of Fluoroquinolones against the Spirochete Borrelia burgdorferi

Little is known to date about the in vitro activity of fluoroquinolones against Borrelia species. Our study aimed at determining the in vitro activities of 15 quinolones against nine isolates of the Borrelia burgdorferi sensu lato complex in addition to one Borrelia valaisiana and one Borrelia bissettii tick isolate. For the determination of MICs, a standardized colorimetric microdilution method was applied. Determination of minimal borreliacidal concentrations providing 100% killing of the final inoculum (MBCs) after 72 h and time-kill experiments were performed by conventional culture in Barbour-Stoenner-Kelly medium in combination with dark-field microscopy. The rank order of potency on a microgram-per-milliliter basis for the substances with in vitro activity against B. burgdorferi was gemifloxacin (MIC at which 90% of the isolates tested are inhibited [MIC(90)], 0.12 μg/ml) > sitafloxacin (MIC(90), 0.5 μg/ml), grepafloxacin (MIC(90), 0.5 μg/ml) > gatifloxacin (MIC(90), 1 μg/ml), sparfloxacin (MIC(90), 1 μg/ml), trovafloxacin (MIC(90), 1 μg/ml) > moxifloxacin (MIC(90), 2 μg/ml), ciprofloxacin (MIC(90), 2 μg/ml) > levofloxacin (MIC(90), 4 μg/ml) > ofloxacin (MIC(90), 8 μg/ml), norfloxacin (MIC(90), 8 μg/ml) > fleroxacin (MIC(90), >16 μg/ml), and pefloxacin (MIC(90), 32 μg/ml) > nalidixic acid (MIC(90), 256 μg/ml). After 72 h of exposure, gemifloxacin was borreliacidal (100% killing) against the isolates investigated at a median MBC of 4 μg/ml. In the other compounds tested, median MBCs were higher (≥8 μg/ml). Results of electron microscopy and time-kill studies clearly support an in vitro activity of some fluoroquinolones against borreliae. Our study demonstrates for the first time the enhanced in vitro effectiveness of some of the recently introduced 4-quinolones against B. burgdorferi.