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ALA-PDT 联合伊曲康唑治疗皮肤原念珠菌病的疗效观察。

Combinatory effect of ALA-PDT and itraconazole in the treatment of cutaneous protothecosis.

机构信息

Department of Dermatology and Venereology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, #107 Yanjiang West Rd., Guangzhou, Guangdong 510120, China.

Department of Dermatology and Venereology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, #107 Yanjiang West Rd., Guangzhou, Guangdong 510120, China; Shenzhen Qianhai Taikang Hospital, No. 3099, Menghai Avenue, Nanshan District, Shenzhen, Guangdong 518000, China.

出版信息

Photodiagnosis Photodyn Ther. 2024 Oct;49:104332. doi: 10.1016/j.pdpdt.2024.104332. Epub 2024 Sep 13.

DOI:10.1016/j.pdpdt.2024.104332
PMID:39278300
Abstract

BACKGROUND

As a rare subcutaneous infection, protothecosis is easily misdiagnosed. Similar to other subcutaneous infection, there is no unified standard for treatment, for cases not suitable for surgery, clinicians often use antifungal drugs based on their experience, and the course of treatment varies from several months to several years. Based on the fact that there are few relevant materials and researches on photodynamic therapy (PDT), we conducted a study based on a clinical case that used oral itraconazole combined with 5-aminolevylinic acid photodynamic therapy (ALA-PDT) to treat a patient with cutaneous protothecosis caused by Prototheca wicherhamii.

METHODS

Different concentrations of ALA and different light doses were used to investigate the effects of ALA-PDT on the growth inhibition of P. wickerhamii in vitro with Colony-counting Methods. And we used transmission electron microscopy (TEM) to visualize the structural changes and the effects of ALA-PDT treating on cellular structures of the P. wickerhamii. Futher, we performed the susceptibility test of P. wickerhamii to itraconazole before and after ALA-PDT in vitro.

RESULTS

We have successfully treated a patient with cutaneous protothecosis caused by P. wickerhamii by using combination therapy in a total of 9-week course of treatment. In vitro, ALA-PDT can inhibit the growth of P. wickerhamii when the ALA concentration was 5 mg/mL (P < 0.01), and this effect became stronger as the concentration of ALA or light dose is increased. Using TEM, we confirmed that ALA-PDT can disrupt the cell wall structure and partition structure of P. wickerhamii, which may contribute to its inhibitory effect. Further studies showed that the MIC of itraconazole for P. wickerhamii was decreased after ALA-PDT.

CONCLUSIONS

ALA-PDT combined with oral itraconazole can be used to treat cutaneous protothecosis. Accordingly, ALA-PDT can destroy the cell wall and partition structure of P. wickerhamii leading to an inhibitory effect on it in vitro, and the effect is enhanced with the increase of ALA concentration and light dose. Also, the sensitivity of P. wickerhamii to itraconazole is observed increased after ALA-PDT. So our study provides a theoretical basis for the promising treatment against cutaneus protothecosis.

摘要

背景

作为一种罕见的皮下感染,原植体病很容易被误诊。与其他皮下感染一样,目前尚无统一的治疗标准。对于不适合手术的病例,临床医生通常根据经验使用抗真菌药物,治疗过程从数月到数年不等。鉴于光动力疗法(PDT)的相关资料和研究较少,我们基于临床病例进行了一项研究,该病例使用口服伊曲康唑联合 5-氨基酮戊酸光动力疗法(ALA-PDT)治疗由粘质沙雷氏菌引起的皮肤原植体病。

方法

采用集落计数法,用不同浓度的 ALA 和不同的光剂量研究 ALA-PDT 对体外粘质沙雷氏菌生长抑制的影响。并用透射电子显微镜(TEM)观察 ALA-PDT 对粘质沙雷氏菌细胞结构的影响。此外,我们还在体外进行了粘质沙雷氏菌对伊曲康唑的药敏试验前后的 ALA-PDT 实验。

结果

我们成功地用联合治疗方案治疗了一名患有粘质沙雷氏菌引起的皮肤原植体病患者,治疗总疗程为 9 周。在体外,当 ALA 浓度为 5mg/ml 时,ALA-PDT 能抑制粘质沙雷氏菌的生长(P < 0.01),且随着 ALA 浓度或光剂量的增加,这种效果变得更强。使用 TEM,我们证实 ALA-PDT 可以破坏粘质沙雷氏菌的细胞壁结构和分隔结构,这可能是其抑制作用的原因。进一步的研究表明,ALA-PDT 后粘质沙雷氏菌对伊曲康唑的 MIC 值降低。

结论

ALA-PDT 联合口服伊曲康唑可用于治疗皮肤原植体病。因此,ALA-PDT 可以破坏粘质沙雷氏菌的细胞壁和分隔结构,从而在体外对其产生抑制作用,且随着 ALA 浓度和光剂量的增加,其效果增强。此外,ALA-PDT 后粘质沙雷氏菌对伊曲康唑的敏感性增加。因此,我们的研究为治疗皮肤原植体病提供了一种有前途的治疗方法。

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