Fraunhofer Institute for Toxicology and Experimental Medicine (Fraunhofer ITEM), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Centre for Lung Research (DZL), Member of the REBIRTH Cluster of Excellence, Nikolai-Fuchs-Straße 1, Hannover, Germany.
Helmholtz Institute for Pharmaceutical Research (HIPS), Helmholtz Centre for Infection Research, Universitätscampus E8.1, Saarbrücken, Germany.
J Antimicrob Chemother. 2018 Oct 1;73(10):2762-2769. doi: 10.1093/jac/dky241.
In the context of cystic fibrosis, Pseudomonas aeruginosa biofilms often develop in the vicinity of airway mucus, which acts as a protective physical barrier to inhaled matter. However, mucus can also adsorb small drug molecules administered as aerosols, including antibiotics, thereby reducing their bioavailability. The efficacy of antibiotics is typically assessed by determining the MIC using in vitro assays. This widespread technique, however, does not consider either bacterial biofilm formation or the influence of mucus, both of which may act as diffusion barriers, potentially limiting antibiotic efficacy.
We grew P. aeruginosa biofilms in the presence or absence of human tracheal mucus and tested their susceptibility to tobramycin and colistin.
A significant reduction of tobramycin efficacy was observed when P. aeruginosa biofilms were grown in the presence of mucus compared with those grown in the absence of mucus. Diffusion of tobramycin through mucus was reduced; however, this reduction was more pronounced in biofilm/mucus mixtures, suggesting that biofilms in the presence of mucus respond differently to antibiotic treatment. In contrast, the influence of mucus on colistin efficacy was almost negligible and no differences in mucus permeability were observed.
These findings underline the important role of mucus in the efficacy of anti-infective drugs.
在囊性纤维化的背景下，铜绿假单胞菌生物膜通常在气道黏液附近形成，黏液作为吸入物质的保护性物理屏障。然而，黏液也可以吸附作为气溶胶给药的小分子药物，包括抗生素，从而降低其生物利用度。抗生素的疗效通常通过体外测定 MIC 来评估。然而，这种广泛使用的技术既不考虑细菌生物膜的形成，也不考虑黏液的影响，这两者都可能作为扩散屏障，潜在地限制抗生素的疗效。
我们在存在或不存在人气管黏液的情况下培养铜绿假单胞菌生物膜，并测试它们对妥布霉素和多粘菌素的敏感性。
与在不存在黏液的情况下相比，当铜绿假单胞菌生物膜在黏液存在的情况下生长时，妥布霉素的疗效显著降低。妥布霉素通过黏液的扩散减少；然而，在生物膜/黏液混合物中，这种减少更为明显，这表明存在黏液的生物膜对抗生素治疗的反应不同。相比之下，黏液对多粘菌素疗效的影响几乎可以忽略不计，并且没有观察到黏液通透性的差异。
这些发现强调了黏液在抗感染药物疗效中的重要作用。
