In vitro antidermatophytic synergism of double and triple combination of clioquinol with ciclopirox and terbinafine.
Antifungal Agents
/ pharmacology
Arthrodermataceae
/ drug effects
Cell Survival
/ drug effects
Ciclopirox
/ pharmacology
Clioquinol
/ pharmacology
Drug Combinations
Drug Synergism
Fungi
/ classification
Humans
Leukocytes
/ drug effects
Microbial Sensitivity Tests
Terbinafine
/ pharmacology
Tinea
/ drug therapy
ciclopirox
clioquinol
dermatophytes
synergism
terbinafine
Journal
Mycoses
ISSN: 1439-0507
Titre abrégé: Mycoses
Pays: Germany
ID NLM: 8805008
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
24
03
2020
revised:
07
05
2020
accepted:
30
05
2020
pubmed:
9
6
2020
medline:
13
7
2021
entrez:
8
6
2020
Statut:
ppublish
Résumé
Dermatophytoses are the most frequent fungal infections worldwide and there have been described clinical resistance to the commonly used antifungals. Clioquinol is an antimicrobial that had the oral formulations withdrawn from the market in the 70s due to the report of neurotoxicity and recently has been considered as an effective alternative for the treatment of dermatophytosis. To evaluate the effect of the double and triple association between clioquinol with terbinafine and ciclopirox on clinical isolates of dermatophytes. The cytotoxicity of these associations on human leukocytes was also verified. Checkerboard method was used to evaluate the interaction between antifungal agents. Time-kill assay was used to verify fungicidal action and evaluate the combination with greater effect for TRU47 isolate. Cell viability was assessed by loss of integrity of the leukocyte membrane in order to verify the toxicity. Synergistic interaction was observed in 42% of isolates when terbinafine was associated with clioquinol and in 50% of isolates when ciclopirox was associated with clioquinol. The triple association resulted in synergistic interaction for 75% of the isolates. Clioquinol + terbinafine and triple combination were more effective for TRU47 isolate, and the combinations exhibited a time-dependent fungicidal effect. Furthermore, the results of cell viability demonstrated that clioquinol and terbinafine combination is not cytotoxic to human leukocytes. Clioquinol in combination with antifungals in the treatment of dermatophytosis can be a therapeutic strategy to overcome problems related to resistance, action spectrum and toxicity of the antifungal drugs used in the clinic.
Sections du résumé
BACKGROUND
BACKGROUND
Dermatophytoses are the most frequent fungal infections worldwide and there have been described clinical resistance to the commonly used antifungals. Clioquinol is an antimicrobial that had the oral formulations withdrawn from the market in the 70s due to the report of neurotoxicity and recently has been considered as an effective alternative for the treatment of dermatophytosis.
OBJECTIVES
OBJECTIVE
To evaluate the effect of the double and triple association between clioquinol with terbinafine and ciclopirox on clinical isolates of dermatophytes. The cytotoxicity of these associations on human leukocytes was also verified.
METHODS
METHODS
Checkerboard method was used to evaluate the interaction between antifungal agents. Time-kill assay was used to verify fungicidal action and evaluate the combination with greater effect for TRU47 isolate. Cell viability was assessed by loss of integrity of the leukocyte membrane in order to verify the toxicity.
RESULTS
RESULTS
Synergistic interaction was observed in 42% of isolates when terbinafine was associated with clioquinol and in 50% of isolates when ciclopirox was associated with clioquinol. The triple association resulted in synergistic interaction for 75% of the isolates. Clioquinol + terbinafine and triple combination were more effective for TRU47 isolate, and the combinations exhibited a time-dependent fungicidal effect. Furthermore, the results of cell viability demonstrated that clioquinol and terbinafine combination is not cytotoxic to human leukocytes.
CONCLUSIONS
CONCLUSIONS
Clioquinol in combination with antifungals in the treatment of dermatophytosis can be a therapeutic strategy to overcome problems related to resistance, action spectrum and toxicity of the antifungal drugs used in the clinic.
Substances chimiques
Antifungal Agents
0
Drug Combinations
0
Ciclopirox
19W019ZDRJ
Clioquinol
7BHQ856EJ5
Terbinafine
G7RIW8S0XP
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
993-1001Informations de copyright
© 2020 Blackwell Verlag GmbH.
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