Impact of 4th Generation Fluoroquinolones on Growth Rate and Detection Time of Fungal Pathogens

Abstract

Abstract: : Purpose: The fluoroquinolones can bind to both eucaryotic and procaryotic topoisomerases and may have some antifungal activity. We investigated the in vitro and in vivo activity of moxifloxacin and gatifloxacin to reduce or inhibit the recovery of ocular fungal pathogens in a laboratory model and in culture positive patients with prior exposure. Methods: For the laboratory evaluation, isolates 10⁵ colonies/ml of Fusarium oxysporum and Candida albicans were exposed to commercial preparations of moxifloxacin (Vigamox®), gatifloxacin (Zymar®), natamycin and buffer and sampled at 0, 1, 4 and 24 hours. Impact of the in vivo exposure was measured using detection time, colony counts, and smear positivity for 116 cultures from patients with documented fungal infections. Results:Gatifloxacin and natamycin reduced the colony counts by 99.9% at 1, 4, and 24 hours for both F. oxysporum and C. albicans. Counts were lower but did not reach 99.9% inhibition for C. albicans with the moxifloxacin exposure at any of the time periods. No organisms were recovered at 4 and 24 hours with moxifloxacin and F. oxypsorum. Growth control was positive (10⁵ colonies/ml) or higher for both isolates at all time periods. Fungal isolates constituted 10.6% (116/1098) of the nonviral pathogens recovered during the study period. The most frequent pathogens were Fusarium sp. (49, 42%), Candida sp. (21, 18%) and Curvularia sp. (13, 11%). Seventy–three percent of the isolates were recovered within 3 days. For gatifloxacin and moxifloxacin, the 3 day rate was 44% (4/9) and 82% (9/11). No significant difference was observed for patients identified as pretreated [72.5% (50/69)] vs those who were not [73.6% (14/19)]. Colony counts averaged 3 per set of 4 plates for pretreated vs 10 for nontreated. The average for gatifloxacin was 5 and for moxifloxacin 7. Smear positivity was less than 60 % for treated and nontreated patients and ranged from 40% (gatifloxacin) to 57% for nontreated patients. Conclusions: Both in vitro and in vivo data documented an inhibition of fungal growth by gatifloxacin and to moxifloxacin. This could have significance in the recovery and detection of fungal pathogens for patients in whom these fluoroquinolones have been used.

Keywords: fungal disease • antibiotics/antifungals/antiparasitics • drug toxicity/drug effects