Laura Müller1, Xabier Murgia2,3, Lorenz Siebenbürger4, Carsten Börger4, Konrad Schwarzkopf5, Katherina Sewald1, Susanne Häussler6,7, Armin Braun1, Claus-Michael Lehr2,4,8, Marius Hittinger4, Sabine Wronski1. 1. 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. 2. Helmholtz Institute for Pharmaceutical Research (HIPS), Helmholtz Centre for Infection Research, Universitätscampus E8.1, Saarbrücken, Germany. 3. Korea Institute of Science and Technology, KIST Europe, Campus E7.1, Saarbrücken, Germany. 4. PharmBioTec GmbH, Science Park 1, Saarbrücken, Germany. 5. Department of Anaesthesia and Intensive Care, Klinikum Saarbrücken, Winterberg 1, Saarbrücken, Germany. 6. Helmholtz Institute for Infection Research, Inhoffenstraße 7, Braunschweig, Germany. 7. TWINCORE, Centre for Experimental and Clinical Infection Research, Feodor-Lynen-Straße 7, Hannover, Germany. 8. Department of Pharmacy, Saarland University, Campus, Saarbrücken, Germany.
Abstract
Objectives: 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. Methods: We grew P. aeruginosa biofilms in the presence or absence of human tracheal mucus and tested their susceptibility to tobramycin and colistin. Results: 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. Conclusions: These findings underline the important role of mucus in the efficacy of anti-infective drugs.
Objectives: 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. Methods: We grew P. aeruginosa biofilms in the presence or absence of human tracheal mucus and tested their susceptibility to tobramycin and colistin. Results: 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. Conclusions: These findings underline the important role of mucus in the efficacy of anti-infective drugs.
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