title: In vitro interactions of calcineurin inhibitors with conventional antifungal agents against the yeast form of Penicillium marneffei.
abstract: Penicillium marneffei can cause a life-threatening disseminated mycosis in immunocompromised hosts. However, therapeutic strategies for the treatment of this infectious disease are limited. Reports of other fungi suggest that calcineurin inhibitors interact with antifungal agents to improve the treatment outcomes. Here, we evaluated the in vitro interaction of the calcineurin inhibitors cyclosporine A and tacrolimus (FK506) combined with conventional antifungal agents against the pathogenic yeast form of P. marneffei. We demonstrate that the combination of cyclosporine A with amphotericin B, itraconazole, or fluconazole was synergistic for 85, 65, and 30 % of P. marneffei strains, respectively. In contrast, no synergism was observed in all the combinations containing tacrolimus. Furthermore, antagonism was not observed for any combination. In conclusion, the therapeutic potential of a combinatory approach using the calcineurin inhibitor cyclosporine A with conventional antifungal drugs may lead to improved treatment regimens for P. marneffei infections. We propose that mechanism of action studies with cyclosporine A and antifungal agents is needed.
authors: Department of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.
authors: Dongdong
authors: D
authors: Mo
authors: Xin
authors: X
authors: Li
authors: Lili
authors: L
authors: Wei
authors: Chenghang
authors: C
authors: Sun
authors: Hao
authors: H
authors: Liang
authors: Cunwei
authors: C
authors: Cao
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D065095:Calcineurin Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D015725:Fluconazole / Q000494:pharmacology / Q000627:therapeutic use; D017964:Itraconazole / Q000494:pharmacology / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D010407:Penicillium / Q000187:drug effects*; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use; D015003:Yeasts / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D065095:Calcineurin Inhibitors; D017964:Itraconazole; D016572:Cyclosporine; D015725:Fluconazole; D016559:Tacrolimus