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脂质体两性霉素 B 和阿尼芬净联合使用抗真菌锁技术(ALT)治疗实验模型中导管相关的白色念珠菌和光滑念珠菌感染的疗效。

Efficacy of liposomal amphotericin B and anidulafungin using an antifungal lock technique (ALT) for catheter-related Candida albicans and Candida glabrata infections in an experimental model.

机构信息

Antibiotic Resistance Laboratory, Infectious Diseases Department, Vall d'Hebron Research Institute (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, Spain.

出版信息

PLoS One. 2019 Feb 19;14(2):e0212426. doi: 10.1371/journal.pone.0212426. eCollection 2019.

Abstract

OBJECTIVE

The aims of this study were as follows. First, we sought to compare the in vitro susceptibility of liposomal amphotericin B (LAmB) and anidulafungin on Candida albicans and Candida glabrata biofilms growing on silicone discs. Second, we sought to compare the activity of LAmB versus anidulafungin for the treatment of experimental catheter-related C. albicans and C. glabrata infections with the antifungal lock technique in a rabbit model.

METHODS

Two C. albicans and two C. glabrata clinical strains were used. The minimum biofilm eradication concentration for 90% eradication (MBEC90) values were determined after 48h of treatment with LAmB and anidulafungin. Confocal microscopy was used to visualize the morphology and viability of yeasts growing in biofilms. Central venous catheters were inserted into New Zealand rabbits, which were inoculated of each strain of C. albicans and C. glabrata. Then, catheters were treated for 48h with saline or with antifungal lock technique using either LAmB (5mg/mL) or anidulafungin (3.33mg/mL).

RESULTS

In vitro: anidulafungin showed greater activity than LAmB against C. albicans and C. glabrata strains. For C. albicans: MBEC90 of anidulafungin versus LAmB: CA176, 0.03 vs. 128 mg/L; CA180, 0.5 vs. 64 mg/L. For C. glabrata: MBEC90 of anidulafungin versus LAmB: CG171, 0.5 vs. 64 mg/L; CG334, 2 vs. 32 mg/L. In vivo: for C. albicans species, LAmB and anidulafungin achieved significant reductions relative to growth control of log10 cfu recovered from the catheter tips (CA176: 3.6±0.3 log10 CFU, p≤0.0001; CA180: 3.8±0.1 log10 CFU, p≤0.01). For C. glabrata, anidulafungin lock therapy achieved significant reductions relative to the other treatments (CG171: 4.8 log10 CFU, p≤0.0001; CG334: 5.1 log10 CFU, p≤0.0001).

CONCLUSIONS

For the C. albicans strains, both LAmB and anidulafungin may be promising antifungal lock technique for long-term catheter-related infections; however, anidulafungin showed significantly higher activity than LAmB against the C. glabrata strains.

摘要

目的

本研究的目的如下。首先,我们试图比较两性霉素 B 脂质体(LAmB)和安尼拉fungin 在硅胶盘上生长的白色念珠菌和光滑念珠菌生物膜上的体外药敏性。其次,我们试图比较 LAmB 与安尼拉fungin 治疗实验性导管相关白色念珠菌和光滑念珠菌感染的活性,使用抗真菌锁定技术在兔模型中。

方法

使用两种白色念珠菌和两种光滑念珠菌临床株。在治疗 48 小时后,用 LAmB 和安尼拉fungin 测定最小生物膜清除浓度 90%(MBEC90)值。共焦显微镜用于观察生物膜中酵母的形态和活力。将中央静脉导管插入新西兰兔体内,用每种白色念珠菌和光滑念珠菌菌株接种。然后,用生理盐水或用含有两性霉素 B(5mg/mL)或安尼拉fungin(3.33mg/mL)的抗真菌锁定技术处理导管 48 小时。

结果

体外:安尼拉fungin 对白色念珠菌和光滑念珠菌菌株的活性大于 LAmB。对于白色念珠菌:安尼拉fungin 与 LAmB 的 MBEC90:CA176,0.03 对 128mg/L;CA180,0.5 对 64mg/L。对于光滑念珠菌:安尼拉fungin 与 LAmB 的 MBEC90:CG171,0.5 对 64mg/L;CG334,2 对 32mg/L。体内:对于白色念珠菌种,LAmB 和安尼拉fungin 与生长对照相比,从导管尖端回收的 log10 cfu 显著减少(CA176:3.6±0.3 log10 CFU,p≤0.0001;CA180:3.8±0.1 log10 CFU,p≤0.01)。对于光滑念珠菌,安尼拉fungin 锁疗与其他治疗方法相比,log10 CFU 显著减少(CG171:4.8 log10 CFU,p≤0.0001;CG334:5.1 log10 CFU,p≤0.0001)。

结论

对于白色念珠菌株,两性霉素 B 脂质体和安尼拉fungin 都可能是治疗长期导管相关感染的有前途的抗真菌锁定技术;然而,安尼拉fungin 对光滑念珠菌株的活性明显高于两性霉素 B。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9eea/6380555/e5279f5a8409/pone.0212426.g001.jpg

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