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单独使用卡泊芬净或与多粘菌素B联合使用对烟曲霉和耐碳青霉烯铜绿假单胞菌的混合生物膜有效。

Caspofungin alone or combined with polymyxin B are effective against mixed biofilm of Aspergillus fumigatus and carbapenem-resistant Pseudomonas aeruginosa.

作者信息

Fortes Bruna Nakanishi, Scheunemann Gaby, de Azevedo Melo Analy Salles, Ishida Kelly

机构信息

Institute of Biomedical Sciences, University of São Paulo, Prof. Lineu Prestes Avenue, 1374 - 05508-000, São Paulo/SP, Brazil.

Department of Medicine, Federal University of São Paulo, Botucatu Street, 720 - 04039-032, São Paulo/SP, Brazil.

出版信息

Res Microbiol. 2023 Jan-Feb;174(1-2):103993. doi: 10.1016/j.resmic.2022.103993. Epub 2022 Sep 30.

Abstract

Aspergillus fumigatus and Pseudomonas aeruginosa biofilms are associated to the recalcitrant and persistent infections due to resistance to antimicrobials. Here, we evaluated the effect of antimicrobials on single and mixed biofilms of A. fumigatus and P. aeruginosa (carbapenem-resistant and susceptible strains) determining total biomass by crystal violet, cell viability by colony forming unit count, and microscopy. Polymyxin B (PMB) had the best action on P. aeruginosa biofilms inhibiting the biomass (2-4 μg/mL) and it was efficient reducing the viable bacterial cells. Amphotericin B (AMB) and caspofungin (CAS) were the best antifungal at inhibiting A. fumigatus biofilms and reducing fungal viability at concentration ≥1 and ≥ 16 μg/mL, respectively. In addition, CAS was able to significantly reduce P. aeruginosa viability in mixed biofilms. CAS combined with PMB also significantly reduced the mixed biofilm biomass and fungal and bacterial viability mainly against carbapenem-resistant bacterium. The light and fluorescence microscopy showed alterations on hyphae morphology and confirmed the increase of fungal and bacterial death cells after combined therapy of mixed biofilms. Taken together, our work showed that CAS alone and its combination with PMB showed better potential in reducing mixed biofilm biomass and fungal and bacterial viability, even for the carbapenem-resistant P. aeruginosa strain.

摘要

烟曲霉和铜绿假单胞菌生物膜与因对抗菌药物耐药而导致的顽固性和持续性感染有关。在此,我们通过结晶紫测定总生物量、通过菌落形成单位计数测定细胞活力以及借助显微镜,评估了抗菌药物对烟曲霉和铜绿假单胞菌(耐碳青霉烯和敏感菌株)单一及混合生物膜的影响。多粘菌素B(PMB)对铜绿假单胞菌生物膜的作用最佳,可抑制生物量(2 - 4μg/mL),并能有效减少活菌细胞。两性霉素B(AMB)和卡泊芬净(CAS)分别在浓度≥1μg/mL和≥16μg/mL时,是抑制烟曲霉生物膜和降低真菌活力的最佳抗真菌药物。此外,CAS能够显著降低混合生物膜中铜绿假单胞菌的活力。CAS与PMB联合使用还能显著降低混合生物膜的生物量以及真菌和细菌的活力,主要针对耐碳青霉烯细菌。光学显微镜和荧光显微镜显示菌丝形态发生改变,并证实了混合生物膜联合治疗后真菌和细菌死亡细胞增加。综上所述,我们的研究表明,单独使用CAS及其与PMB联合使用在降低混合生物膜生物量以及真菌和细菌活力方面具有更好的潜力,即使对于耐碳青霉烯的铜绿假单胞菌菌株也是如此。

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