The synergy of honokiol and fluconazole against clinical isolates of azole-resistant Candida albicans.
OBJECTIVE
To evaluate the interaction of fluconazole (FLC) and honokiol (HNK) in vitro and vivo against azole-resistant (azole-R) clinical isolates of Candida albicans.


RESULTS
A checkerboard microdilution method was used to study the in vitro interaction of FLC and HNK in 24 azole-R clinical isolates of C. albicans. In vivo antifungal activity was performed to further analyse the interaction between FLC and HNK. In the in vitro study, synergism was observed in all 24 FLC-resistant strains tested as determined by fractional inhibitory concentration index (FICI), and in 22 strains by Delta E models. No antagonistic activity was observed in any of the strains tested. These positive interactions were also confirmed by using the time-killing test for the selected strain C. albicans YL371, which shows strong susceptible to the combination of HNK and FLC. In the in vivo study, the mice with candidiasis were treated successfully by a combination therapy of HNK with FLC, the results showed a decrease of the colony forming unit in infected and treated animals compared to the controls, at the conditions of the treatment used in this study.


CONCLUSIONS
Synergistic activity of HNK and FLC against clinical isolates of FLC-resistant C. albicans was observed in vitro and in vivo.


CONCLUSIONS
This report might provide a potential therapeutic method to overcome the problem of drug-resistance in C. albicans.
Jin
J
J
Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China.
Guo
N
N
Zhang
J
J
Ding
Y
Y
Tang
X
X
Liang
J
J
Li
L
L
Deng
X
X
Yu
L
L
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D002176:Candida albicans / Q000187:drug effects* / Q000302:isolation & purification; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D015169:Colony Count, Microbial; D025141:Drug Resistance, Fungal; D004357:Drug Synergism; D015725:Fluconazole / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D016896:Treatment Outcome; D000498:Allyl Compounds; D010636:Phenols
D000935:Antifungal Agents; D001713:Biphenyl Compounds; D015725:Fluconazole; D017705:Lignans; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols