title: The role of drug efflux pumps in Malassezia pachydermatis and Malassezia furfur defence against azoles.
abstract: This study aims to evaluate the effect of efflux pump modulators (EPMs) on the minimal inhibitory concentration (MIC) of fluconazole (FLZ) and voriconazole (VOR) in Malassezia furfur and Malassezia pachydermatis. The in vitro efficacy of azoles, in combination with EPMs (ie haloperidol-HAL, promethazine-PTZ and cyclosporine A-CYS), against 21 M. furfur from bloodstream infection patients and 14 M. pachydermatis from the skin of dogs with dermatitis, was assessed using a broth microdilution chequerboard analysis. Data were analysed using the model-fractional inhibitory concentration index (FICI) method. The MIC of FLZ and VOR of Malassezia spp. decreased in the presence of sub-inhibitory concentrations of HAL and/or PTZ. The synergic effect was observed only in strains with FLZ MIC≥128 μg/mL for M. furfur, FLZ MIC≥64 μg/mL for M. pachydermatis and VOR MIC≥4 μg/mL in both Malassezia spp. These results suggest that the drug efflux pumps are involved as defence mechanisms to azole drugs in Malassezia yeast. The synergism might be related to an increased expression of efflux pump genes, eventually resulting in azole resistance phenomena. Finally, the above FLZ and VOR MIC values might be considered the cut-off to discriminate susceptible and resistant strains.
authors: Dipartimento di Medicina Veterinaria, Università degli Studi di Bari "Aldo Moro", Bari, Italy.
authors: Roberta
authors: R
authors: Iatta
authors: Dipartimento di Medicina Veterinaria, Università degli Studi di Bari "Aldo Moro", Bari, Italy.
authors: Maria Rita
authors: MR
authors: Puttilli
authors: Dipartimento di Medicina Veterinaria, Università degli Studi di Bari "Aldo Moro", Bari, Italy.
authors: Davide
authors: D
authors: Immediato
authors: Dipartimento di Medicina Veterinaria, Università degli Studi di Bari "Aldo Moro", Bari, Italy.
authors: Domenico
authors: D
authors: Otranto
authors: Dipartimento di Medicina Veterinaria, Università degli Studi di Bari "Aldo Moro", Bari, Italy.
authors: Claudia
authors: C
authors: Cafarchia
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology*; D003872:Dermatitis / Q000382:microbiology; D003881:Dermatomycoses / Q000097:blood / Q000382:microbiology; D004285:Dogs; D025141:Drug Resistance, Fungal; D004357:Drug Synergism; D015725:Fluconazole / Q000494:pharmacology; D019450:Genes, MDR; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D008290:Malassezia / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D011398:Promethazine / Q000494:pharmacology*; D012867:Skin / Q000382:microbiology; D065819:Voriconazole / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D016572:Cyclosporine; D015725:Fluconazole; D011398:Promethazine; D006220:Haloperidol; D065819:Voriconazole
keywords: 
  Malassezia furfur
  ; 
  Malassezia pachydermatis
  ; azoles; efflux pump inhibitors; haloperidol; promethazine