دورية أكاديمية
أعرض في EDS

In vivo demonstration of Pseudomonas aeruginosa biofilms as independent pharmacological microcompartments.

التفاصيل البيبلوغرافية
العنوان: In vivo demonstration of Pseudomonas aeruginosa biofilms as independent pharmacological microcompartments.
المؤلفون: Christophersen L; Department of Clinical Microbiology, Rigshospitalet, Copenhagen University Hospital. Henrik Harpestrengsvej 4A 2100-DK, Copenhagen, Denmark., Schwartz FA; Department of Clinical Microbiology, Rigshospitalet, Copenhagen University Hospital. Henrik Harpestrengsvej 4A 2100-DK, Copenhagen, Denmark., Lerche CJ; Department of Clinical Microbiology, Rigshospitalet, Copenhagen University Hospital. Henrik Harpestrengsvej 4A 2100-DK, Copenhagen, Denmark., Svanekjær T; Department of Health Technology, Technical University of Denmark. Ørsteds Plads 349 2800-DK, Kgs. Lyngby, Denmark., Kragh KN; Institute for Immunology and Microbiology and the Costerton Biofilm Center, Faculty of Health and Medical Sciences, University of Copenhagen, Panum Institute, Blegdamsvej 3B 2200-DK, Copenhagen, Denmark., Laulund AS; Department of Clinical Microbiology, Rigshospitalet, Copenhagen University Hospital. Henrik Harpestrengsvej 4A 2100-DK, Copenhagen, Denmark., Thomsen K; Department of Clinical Microbiology, Rigshospitalet, Copenhagen University Hospital. Henrik Harpestrengsvej 4A 2100-DK, Copenhagen, Denmark., Henneberg KÅ; Department of Health Technology, Technical University of Denmark. Ørsteds Plads 349 2800-DK, Kgs. Lyngby, Denmark., Sams T; Department of Health Technology, Technical University of Denmark. Ørsteds Plads 349 2800-DK, Kgs. Lyngby, Denmark., Høiby N; Department of Clinical Microbiology, Rigshospitalet, Copenhagen University Hospital. Henrik Harpestrengsvej 4A 2100-DK, Copenhagen, Denmark; Institute for Immunology and Microbiology and the Costerton Biofilm Center, Faculty of Health and Medical Sciences, University of Copenhagen, Panum Institute, Blegdamsvej 3B 2200-DK, Copenhagen, Denmark., Moser C; Department of Clinical Microbiology, Rigshospitalet, Copenhagen University Hospital. Henrik Harpestrengsvej 4A 2100-DK, Copenhagen, Denmark. Electronic address: moser@dadlnet.dk.
المصدر: Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society [J Cyst Fibros] 2020 Nov; Vol. 19 (6), pp. 996-1003. Date of Electronic Publication: 2020 Feb 15.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101128966 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-5010 (Electronic) Linking ISSN: 15691993 NLM ISO Abbreviation: J Cyst Fibros Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam ; New York : Elsevier, c2002-
مواضيع طبية MeSH: Biofilms/*drug effects , Cystic Fibrosis/*drug therapy , Cystic Fibrosis/*microbiology , Pseudomonas aeruginosa/*drug effects , Tobramycin/*pharmacokinetics, Alginates/pharmacology ; Animals ; Disease Models, Animal ; Female ; Mice ; Mice, Inbred BALB C
مستخلص: Background: Pseudomonas aeruginosa is difficult to eradicate from the lungs of cystic fibrosis (CF) patients due to biofilm formation. Organs and blood are independent pharmacokinetic (PK) compartments. Previously, we showed in vitro biofilms behave as independent compartments impacting the pharmacodynamics. The present study investigated this phenomenon in vivo.
Methods: Seaweed alginate beads with P. aeruginosa resembling biofilms, either freshly produced (D0) or incubated for 5 days (D5) were installed s.c in BALB/c mice. Mice (n = 64) received tobramycin 40 mg/kg s.c. and were sacrificed at 0.5, 3, 6, 8, 16 or 24 h after treatment. Untreated controls (n = 14) were sacrificed, correspondingly. Tobramycin concentrations were determined in serum, muscle tissue, lung tissue and beads. Quantitative bacteriology was determined.
Results: The tobramycin peak concentrations in serum was 58.3 (±9.2) mg/L, in lungs 7.1 mg/L (±2.3), muscle tissue 2.8 mg/L (±0.5) all after 0.5 h and in D0 beads 19.8 mg/L (±3.5) and in D5 beads 24.8 mg/L (±4.1) (both 3 h). A 1-log killing of P. aeruginosa in beads was obtained at 8h, after which the bacterial level remained stable at 16 h and even increased in D0 beads at 24 h. Using the established diffusion retardation model the free tobramycin concentration inside the beads showed a delayed buildup of 3 h but remained lower than the MIC throughout the 24 h.
Conclusions: The present in vivo study based on tobramycin exposure supports that biofilms behave as independent pharmacological microcompartments. The study indicates, reducing the biofilm matrix would increase free tobramycin concentrations and improve therapeutic effects.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.
(Copyright © 2020. Published by Elsevier B.V.)
فهرسة مساهمة: Keywords: Alginate beads; Biofilm model; Chronic infection; Independent pharmacological compartment; Pharmacodynamics; Pharmacokinetics
المشرفين على المادة: 0 (Alginates)
VZ8RRZ51VK (Tobramycin)
تواريخ الأحداث: Date Created: 20200219 Date Completed: 20211018 Latest Revision: 20211018
رمز التحديث: 20240628
DOI: 10.1016/j.jcf.2020.01.009
PMID: 32067957
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-5010
DOI:10.1016/j.jcf.2020.01.009