Background

The emergence of resistant isolates has brought challenges to the treatment of sporotrichosis, prompting the search for new therapeutic strategies. Previous studies reported that nonsteroidal anti-inflammatory drugs (NSAIDs) show in vitro activity against several pathogenic fungi, including species of Candida, Cryptococcus, and Trichosporon.

Aims

This study aimed to investigate the in vitro efficacy of three NSAIDs (acetylsalicylic acid, diclofenac sodium, and ibuprofen), alone and in combination with itraconazole, against eleven clinical isolates of Sporothrix brasiliensis and Sporothrix schenckii.

Methods

Minimal inhibitory concentrations were determined by the broth microdilution method. Drug interactions and the fractional inhibitory concentration index of NSAIDs and itraconazole were assessed by the checkerboard method.

Results

When used alone, ibuprofen was the most active NSAID, followed by acetylsalicylic acid. Combinations of NSAIDs with itraconazole showed synergistic antifungal activity against nine isolates. It was also found that itraconazole combined with acetylsalicylic acid, diclofenac sodium, or ibuprofen, led to resistance reversal in two, three, and five of the six drug-resistant isolates, respectively.

Conclusions

The results indicate that the combination of itraconazole and the evaluated NSAIDs are a promising strategy for the treatment of sporotrichosis.

中文翻译：

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非甾体类抗炎药逆转巴西孢子丝菌和申克孢子丝菌对伊曲康唑的耐药性

背景

耐药菌株的出现给孢子丝菌病的治疗带来了挑战，促使人们寻找新的治疗策略。先前的研究报告说，非甾体类抗炎药 (NSAID) 在体外对几种致病真菌具有活性，包括念珠菌属、隐球菌属和毛孢菌属。

宗旨

本研究旨在研究三种非甾体抗炎药（乙酰水杨酸、双氯芬酸钠和布洛芬）单独使用和与伊曲康唑联合使用对 11 种巴西孢子丝菌和申克孢子丝菌临床分离株的体外疗效。

方法

最小抑菌浓度通过肉汤微量稀释法测定。通过棋盘法评估药物相互作用以及 NSAIDs 和伊曲康唑的部分抑菌浓度指数。

结果

单独使用时，布洛芬是最活跃的 NSAID，其次是乙酰水杨酸。NSAIDs 与伊曲康唑的组合显示出对九种分离物的协同抗真菌活性。还发现伊曲康唑与乙酰水杨酸、双氯芬酸钠或布洛芬联合使用，分别导致六种耐药菌株中的两种、三种和五种耐药性逆转。

结论

结果表明，伊曲康唑和评估的 NSAIDs 的组合是治疗孢子丝菌病的有前途的策略。