In Vitro Antifungal Activity of Sertraline and Synergistic Effects in Combination with Antifungal Drugs against Planktonic Forms and Biofilms of Clinical Trichosporon asahii Isolates.

Kirsten Nielsen,Lin Cong,Yong Liao,Rongya Yang,Suteng Yang

doi:10.1371/journal.pone.0167903

Kirsten Nielsen, Lin Cong + Show 3 more

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https://doi.org/10.1371/journal.pone.0167903

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Abstract

Trichosporon asahii (T. asahii) is the major pathogen of invasive trichosporonosis which occurred mostly in immunocompromised patients. The biofilms formation ability of T. asahii may account for resistance to antifungal drugs and results a high mortality rate. Sertraline, a commonly prescribed antidepressant, has been demonstrated to show in vitro and in vivo antifungal activities against many kinds of pathogenic fungi, especially Cryptococcus species. In the present study, the in vitro activities of sertraline alone or combined with fluconazole, voriconazole, itraconazole, caspofungin and amphotericin B against planktonic forms and biofilms of 21 clinical T. asahii isolates were evaluated using broth microdilution checkerboard method and XTT reduction assay, respectively. The fractional inhibitory concentration index (FICI) was used to interpret drug interactions. Sertraline alone exhibited antifungal activities against both T. asahii planktonic cells (MICs, 4–8 μg/ml) and T. asahii biofilms (SMICs, 16–32 μg/ml). Furthermore, SRT exhibited synergistic effects against T. asahii planktonic cells in combination with amphotericin B, caspofungin or fluconazole (FICI≤0.5) and exhibited synergistic effects against T. asahii biofilms in combination with amphotericin B (FICI≤0.5). SRT exhibited mostly indifferent interactions against T. asahii biofilms in combination with three azoles in this study. Sertraline-amphotericin B combination showed the highest percentage of synergistic effects against both T. asahii planktonic cells (90.5%) and T. asahii biofilms (81.0%). No antagonistic interaction was observed. Our study suggests the therapeutic potential of sertraline against invasive T. asahii infection, especially catheter-related T. asahii infection. Further in vivo studies are needed to validate our findings.

Highlights

Trichosporon asahii (T. asahii) is an opportunistic pathogen which belongs to the member of basidiomycete yeast-like fungi and can cause invasive trichosporonosis in immunocompromised patients [1].PLOS ONE | DOI:10.1371/journal.pone.0167903 December 8, 2016In Vitro Activities of Sertraline and Antifungal Drugs Against T. asahii
sessile MICs (SMICs), the sessile minimum inhibitory concentrations capable of decreasing 50% in absorbance compared to the growth control wells; FICI, fractional inhibitory concentration index; FICI 0.5, synergy; FICI > 0.5–4, indifference; FICI > 4, antagonism; GM, the geometric means of MIC and FICI values; Syn, a combination indicating synergistic interaction; Ind, a combination indicating indifferent interaction; Ant, a combination indicating antagonistic interaction; FLC, fluconazole; ITC, itraconazole; VRC, voriconazole; CAS, caspofungin; AMB, amphotericin B; SRT, sertraline doi:10.1371/journal.pone.0167903.t004
For the antifungal combinations susceptibility testing against T. asahii biofilms, the SRT/ AMB combination showed the highest percentage of synergistic effects (81.0%; FICI, 0.094–0.563) and the SMICs obviously decreased from 16–32 μg/ml to 4–16 μg/ml for SRT and from 128–1024 μg/ml to 8–64 μg/ml for AMB

Summary

Introduction

Trichosporon asahii (T. asahii) is an opportunistic pathogen which belongs to the member of basidiomycete yeast-like fungi and can cause invasive trichosporonosis in immunocompromised patients [1]. Echinocandins are not recommended for treating invasive trichosporonosis since Trichosporon spp. is intrinsic resistant to this antifungal drug class [1,6]. The newer triazoles (such as voriconazole) are considered to be the most effective drugs class for invasive trichosporonosis treatment because they exhibit good in vitro and in vivo activity against Trichosporon spp. and result good clinical outcome [1,6]. The ability of T. asahii to form biofilms on medical implanted devices may account for the clinical resistance to antifungal drugs and results a high mortality rate. SRT has been demonstrated to show in vitro synergistic effects in combination with antifungal drugs against Aspergillus spp. and Cryptococcus neoformans (C. neoformans) [19,20,21]. T. asahii may be helpful to evaluate the possible application of SRT in treating T. asahii infections

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