Infectious Diseases Unit, 3rd Department Pediatrics, Basic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessalonikigrid.4793.9 and Hippokration General Hospital, Thessaloniki, Greece.
Department of Microbiology, AHEPA University Hospitalgrid.411222.6, Thessaloniki, Greece.
Antimicrob Agents Chemother. 2021 Oct 18;65(11):e0063821. doi: 10.1128/AAC.00638-21. Epub 2021 Aug 9.
and Fusarium species are emerging opportunistic pathogens, causing invasive fungal diseases in humans, particularly in immunocompromised patients. Biofilm-related infections are associated with increased morbidity and mortality. Here, we assessed the ability of Scedosporium apiospermum and Fusarium solani species complex (FSSC) isolates to form biofilms and evaluated the efficacy of deoxycholate amphotericin B (D-AMB), liposomal amphotericin B (L-AMB), and voriconazole (VRC), alone or in combination, against mature biofilms. Biofilm formation was assessed by safranin staining and spectrophotometric measurement of optical density. Planktonic and biofilm damage was assessed by XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt] reduction assay. Planktonic cell and biofilm MICs were determined as the minimum concentrations that caused ≥50% fungal damage compared to untreated controls. The combined activity of L-AMB (0.5 to 32 mg/liter) and VRC (0.125 to 64 mg/liter) against biofilms was determined by the checkerboard microdilution method and analyzed by the Bliss independence model. Biofilm MICs of D-AMB and L-AMB against S. apiospermum isolates were 1 and 2 mg/liter and against FSSC isolates were 0.5 and 1 mg/liter, respectively. Biofilm MICs of VRC against S. apiospermum and FSSC were 32 mg/liter and >256 mg/liter, respectively. Synergistic effects were observed at 2 to 4 mg/liter of L-AMB combined with 4 to 16 mg/liter of VRC against S. apiospermum biofilms (mean Δ ± standard error, 17% ± 3.7%). Antagonistic interactions were found at 0.5 to 4 mg/liter of L-AMB combined with 0.125 to 16 mg/liter of VRC against FSSC isolates, at -28% ± 2%. D-AMB and L-AMB were more efficacious against S. apiospermum and FSSC biofilms than VRC.
并且，镰孢菌属和尖端赛多孢菌属物种正在成为机会性致病真菌，导致人类侵袭性真菌感染，尤其是免疫功能低下的患者。生物膜相关感染与发病率和死亡率的增加有关。在这里，我们评估了尖端赛多孢菌和尖孢镰刀菌属复合种（FSSC）分离株形成生物膜的能力，并评估了脱氧胆酸盐两性霉素 B（D-AMB）、脂质体两性霉素 B（L-AMB）和伏立康唑（VRC）单独或联合应用对成熟生物膜的疗效。通过吖啶橙染色和分光光度法测量光密度来评估生物膜的形成。通过 XTT [2,3-双（2-甲氧基-4-硝基-5-磺苯基）-2H-四唑-5-羧基苯胺盐]还原测定法评估浮游生物和生物膜的损伤。浮游细胞和生物膜 MIC 被确定为与未处理对照相比导致≥50%真菌损伤的最小浓度。通过棋盘微量稀释法确定 L-AMB（0.5 至 32mg/L）和 VRC（0.125 至 64mg/L）对生物膜的联合活性，并通过 Bliss 独立性模型进行分析。D-AMB 和 L-AMB 对尖端赛多孢菌分离株的生物膜 MIC 分别为 1 和 2mg/L，对 FSSC 分离株的 MIC 分别为 0.5 和 1mg/L。VRC 对尖端赛多孢菌和 FSSC 的生物膜 MIC 分别为 32mg/L 和>256mg/L。在 2 至 4mg/L 的 L-AMB 与 4 至 16mg/L 的 VRC 联合作用下，观察到尖端赛多孢菌生物膜的协同作用（平均Δ±标准误差，17%±3.7%）。在 0.5 至 4mg/L 的 L-AMB 与 0.125 至 16mg/L 的 VRC 联合作用下，对 FSSC 分离株发现拮抗相互作用，为-28%±2%。D-AMB 和 L-AMB 对尖端赛多孢菌和 FSSC 生物膜的疗效优于 VRC。
