Human airway mucus alters susceptibility of Pseudomonas aeruginosa biofilms to tobramycin, but not colistin.

Autor:	Müller L; 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., Murgia X; Helmholtz Institute for Pharmaceutical Research (HIPS), Helmholtz Centre for Infection Research, Universitätscampus E8.1, Saarbrücken, Germany.; Korea Institute of Science and Technology, KIST Europe, Campus E7.1, Saarbrücken, Germany., Siebenbürger L; PharmBioTec GmbH, Science Park 1, Saarbrücken, Germany., Börger C; PharmBioTec GmbH, Science Park 1, Saarbrücken, Germany., Schwarzkopf K; Department of Anaesthesia and Intensive Care, Klinikum Saarbrücken, Winterberg 1, Saarbrücken, Germany., Sewald K; 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., Häussler S; Helmholtz Institute for Infection Research, Inhoffenstraße 7, Braunschweig, Germany.; TWINCORE, Centre for Experimental and Clinical Infection Research, Feodor-Lynen-Straße 7, Hannover, Germany., Braun A; 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., Lehr CM; Helmholtz Institute for Pharmaceutical Research (HIPS), Helmholtz Centre for Infection Research, Universitätscampus E8.1, Saarbrücken, Germany.; PharmBioTec GmbH, Science Park 1, Saarbrücken, Germany.; Department of Pharmacy, Saarland University, Campus, Saarbrücken, Germany., Hittinger M; PharmBioTec GmbH, Science Park 1, Saarbrücken, Germany., Wronski S; 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.
Jazyk:	angličtina
Zdroj:	The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2018 Oct 01; Vol. 73 (10), pp. 2762-2769.
DOI:	10.1093/jac/dky241
Abstrakt:	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.
Databáze:	MEDLINE
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