[The effect of propyl gallate on the activity of various antifungal drugs against filamentous fungi in vitro].
OBJECTIVE
The influence of an antioxidant, propyl gallate (PG), on the activity of amphotericin B (AMB), terbinafine (TBF), butenafine (BTF) and ketoconazole (KCZ) against ocular pathogenic filamentous fungi in vitro was investigated to determine whether PG could increase the antifungal activity.


METHODS
Susceptibility tests were performed against 6 isolates of ocular pathogenic filamentous fungi (Fusarium solanae, Fusarium moniliforme, Fusarium poae, Fusarium oxysporum, Aspergillus fumigatus and Aspergillus flavus) and 2 quality control strains (Candida krusei ATCC 6258 and Cadida parapsilosis ATCC 22019) by the NCCLS M38-P broth microdilution method (MIC). PG was added to the incubation media at a final concentration of 400 microg/ml. Antifungal agents were serially two-fold diluted and final dilutions were made in 1640 and PG-1640 culture media to a concentration ranging from 0.0313 to 16 microg/ml for AMB, TBF, BTF and KCZ. One hundred microl of the corresponding diluted inoculum suspension was added to each well of the microdilution tray. The MIC end-point of AMB was determined as 100% growth reduction and the MIC end-point of TBF, BTF, KCZ and PG was determined as 75% growth reduction as compared with the turbidity produced by the control well.


RESULTS
At a concentration of 400 microg/ml, PG did not show any antifungal activity under these experimental conditions. The combination of PG (400 microg/ml) with amphotericin B revealed a remarkably increased activity against all of the isolates of ocular pathogenic filamentous fungi and quality control strains. In the combination of PG with terbinafine, a remarkably increased activity was observed against Fusarium solanae, Fusarium poae, Fusarium oxysporum, Aspergillus fumigatu and Aspergillus flavus. The combination of PG with butenafine had remarkably synergistic effect against Fusarium solanae, but did not synergistic or even showed antagonistic effect for other isolates. The combination of PG with ketaconazole was synergistic against Fusarium solanae, but was antagonistic against all other isolates.


CONCLUSIONS
Combination of PG and amphotericin has remarkably synergistic effect against all tested ocular pathogenic filamentous fungi isolates. Combination of PG and terbinafine has remarkably synergistic effect against some isolates. The PG-amphotericin combination and the PG-terbinafine combination may have a role in future studies of antifungal eye drops.
Xu
Yan
Y
Henan Institute of Ophthalmology, Zhengzhou 450003, China. xuyan990301@yahoo.com.cn
Pang
Guang-ren
GR
Lü
Xue-fang
XF
Chen
Zu-ji
ZJ
Sun
Sheng-tao
ST
Song
Jie-zhen
JZ
D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001231:Aspergillus flavus / Q000187:drug effects; D001232:Aspergillus fumigatus / Q000187:drug effects; D001596:Benzylamines / Q000494:pharmacology; D004357:Drug Synergism; D005658:Fungi / Q000187:drug effects*; D005670:Fusarium / Q000187:drug effects; D066298:In Vitro Techniques; D007654:Ketoconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009281:Naphthalenes / Q000494:pharmacology*; D011435:Propyl Gallate / Q000494:pharmacology*; D000077291:Terbinafine
D000935:Antifungal Agents; D000975:Antioxidants; D001596:Benzylamines; D009281:Naphthalenes; D000666:Amphotericin B; D011435:Propyl Gallate; C067594:butenafine; D000077291:Terbinafine; D007654:Ketoconazole