Abstract:
:The microbiologic and clinical resistance of dermatophytes is seldom reported, and the mechanisms associated with resistance are not well known. This study investigated the effect of efflux pump modulators (EPMs) (i.e., haloperidol HAL and promethazine PTZ) and their inhibiting activity on the minimum inhibitory concentrations of itraconazole (ITZ) and fluconazole (FLZ) against selected M. canis strains. M. canis strains with low (≤ 1 μg/ml itraconazole and < 64 μg/ml fluconazole) and high (> 1 μg/ml itraconazole and ≥ 64 μg/ml fluconazole) azole MIC values were tested using Checkerboard microdilution assay. The disk diffusion assay, the minimum fungicidal concentration and the time-kill assay were also performed in order to confirm the results of checkerboard microdilution assay. The MIC values of ITZ and FLZ of M. canis decreased in the presence of subinhibitory concentrations of HAL and PTZ, the latter being more effective with a greater increased susceptibility. Synergism was observed in all strains with high azole MICs (FICI < 0.5) and no synergism in the strains with low azole MICs. A fungicidal activity was observed after 48 h of incubation when ITZ and FLZ were tested in combination with HAL or PTZ. These results suggest that the drug efflux pumps are involved in the defense mechanisms to azole drugs in M. canis strains. The synergism might be related to an increased expression of efflux pump genes, eventually resulting in azole resistance phenomena. Complementary studies on M. canis resistance are advocated in order to investigate the molecular mechanisms of this phenomenon.
journal_name
Mycopathologiajournal_title
Mycopathologiaauthors
Aneke CI,Rhimi W,Otranto D,Cafarchia Cdoi
10.1007/s11046-019-00419-7subject
Has Abstractpub_date
2020-04-01 00:00:00pages
279-288issue
2eissn
0301-486Xissn
1573-0832pii
10.1007/s11046-019-00419-7journal_volume
185pub_type
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