The in vitro activity of ibuprofen, a nonsteroidal anti-inflammatory drug, was evaluated against Sporothrix brasiliensis and S. schenckii, either alone or in combination with amphotericin B, itraconazole, or terbinafine. The inhibitory activity of ibuprofen as a single agent was determined according to minimum inhibitory concentration (MIC) values, while the effect of ibuprofen combined with amphotericin B, itraconazole, or terbinafine was estimated by microdilution checkerboard methodology. The ultrastructural alterations of S. schenckii after exposure to the combination of ibuprofen and amphotericin B were evaluated by scanning electron microscopy (SEM) and flow cytometry analysis. As a single agent, ibuprofen inhibited Sporothrix growth with a MIC median of 256 μg/mL, while the MIC medians of ibuprofen in combination with antifungals were 16 μg/mL and 128 μg/mL. The MIC values of amphotericin B, itraconazole, and terbinafine were reduced when isolates were co-incubated with ibuprofen, mainly the polyene. The major alteration after treatment with the ibuprofen/amphotericin B combination was the increase in the presence of filamentous forms and high membrane damage with loss of plasma membrane integrity. In summary, we demonstrated that ibuprofen increases the in vitro activity of antifungals, mainly amphotericin B, against S. brasiliensis and S. schenckii. Future in vivo studies exploring combination therapy with ibuprofen and antifungals in animal models are needed to confirm its efficacy.

中文翻译：

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布洛芬联合抗真菌药的抗孢子丝菌活性

单独或与两性霉素 B、伊曲康唑或特比萘芬联合使用，评估了布洛芬（一种非甾体抗炎药）对巴西孢子丝菌和申克链球菌的体外活性。布洛芬作为单药的抑制活性根据最低抑菌浓度 (MIC) 值确定，而布洛芬与两性霉素 B、伊曲康唑或特比萘芬联合使用的效果则通过微量稀释棋盘法来评估。通过扫描电子显微镜 (SEM) 和流式细胞术分析评估了布洛芬和两性霉素 B 组合暴露后申克链球菌的超微结构变化。作为单一药剂，布洛芬抑制孢子丝菌的生长，MIC 中值为 256 μg/mL，而布洛芬与抗真菌药组合的 MIC 中位数分别为 16 μg/mL 和 128 μg/mL。当分离物与布洛芬（主要是多烯）共同孵育时，两性霉素 B、伊曲康唑和特比萘芬的 MIC 值会降低。用布洛芬/两性霉素 B 组合治疗后的主要变化是丝状形式和高度膜损伤的增加以及质膜完整性的丧失。总之，我们证明布洛芬增加了抗真菌剂（主要是两性霉素 B）对巴西链球菌和申克链球菌的体外活性。未来需要在动物模型中探索布洛芬和抗真菌药联合治疗的体内研究，以确认其疗效。当分离物与布洛芬（主要是多烯）共同培养时，特比萘芬和特比萘芬减少。用布洛芬/两性霉素 B 组合治疗后的主要变化是丝状形式和高度膜损伤的增加以及质膜完整性的丧失。总之，我们证明布洛芬增加了抗真菌剂（主要是两性霉素 B）对巴西链球菌和申克链球菌的体外活性。未来需要在动物模型中探索布洛芬和抗真菌药物联合治疗的体内研究以确认其疗效。当分离物与布洛芬（主要是多烯）共同培养时，特比萘芬和特比萘芬减少。用布洛芬/两性霉素 B 组合治疗后的主要变化是丝状形式和高度膜损伤的增加以及质膜完整性的丧失。总之，我们证明布洛芬增加了抗真菌剂（主要是两性霉素 B）对巴西链球菌和申克链球菌的体外活性。未来需要在动物模型中探索布洛芬和抗真菌药联合治疗的体内研究，以确认其疗效。我们证明布洛芬增加了抗真菌剂（主要是两性霉素 B）对巴西链球菌和申克链球菌的体外活性。未来需要在动物模型中探索布洛芬和抗真菌药联合治疗的体内研究，以确认其疗效。我们证明布洛芬增加了抗真菌剂（主要是两性霉素 B）对巴西链球菌和申克链球菌的体外活性。未来需要在动物模型中探索布洛芬和抗真菌药联合治疗的体内研究，以确认其疗效。