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J Cyst Fibros. 2019 Jan 30. pii: S1569-1993(19)30011-6. doi: 10.1016/j.jcf.2019.01.005. [Epub ahead of print]

Hyperbaric oxygen treatment increases killing of aggregating Pseudomonas aeruginosa isolates from cystic fibrosis patients.

Author information

1
Department of Clinical Microbiology, Rigshospitalet, 2100 Copenhagen, Denmark; Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health Sciences University of Copenhagen, 2200 Copenhagen, Denmark.
2
Department of Clinical Microbiology, Rigshospitalet, 2100 Copenhagen, Denmark; Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health Sciences University of Copenhagen, 2200 Copenhagen, Denmark; Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark. Electronic address: pojensen@sund.ku.dk.
3
Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health Sciences University of Copenhagen, 2200 Copenhagen, Denmark.
4
Department of Clinical Microbiology, Rigshospitalet, 2100 Copenhagen, Denmark; Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health Sciences University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: mette.kolpen@regionh.dk.

Abstract

BACKGROUND:

Pseudomonas aeruginosa is a major pathogen of the chronic lung infections in cystic fibrosis (CF) patients. These persistent bacterial infections are characterized by bacterial aggregates with biofilm-like properties and are treated with nebulized or intravenous tobramycin in combination with other antibiotics. However, the chronic infections are close to impossible to eradicate due to reasons that are far from fully understood. Recent work has shown that re‑oxygenation of hypoxic aggregates by hyperbaric oxygen (O2) treatment (HBOT: 100% O2 at 2.8 bar) will increase killing of aggregating bacteria by antibiotics. This is relevant for treatment of infected CF patients where bacterial aggregates are found in the endobronchial secretions that are depleted of O2 by the metabolism of polymorphonuclear leukocytes (PMNs). The main objective of this study was to investigate the effect of HBOT as an adjuvant to tobramycin treatment of aggregates formed by P. aeruginosa isolates from CF patients.

METHODS:

The effect was tested using a model with bacterial aggregates embedded in agarose. O2 profiling was used to confirm re‑oxygenation of aggregates.

RESULTS:

We found that HBOT was able to significantly enhance the effect of tobramycin against aggregates of all the P. aeruginosa isolates in vitro. The effect was attributed to increased O2 levels leading to increased growth and thus increased uptake of and killing by tobramycin.

CONCLUSIONS:

Re‑oxygenation may in the future be a clinical possibility as adjuvant to enhance killing by antibiotics in cystic fibrosis lung infections.

KEYWORDS:

Antibiotic tolerance; Cystic fibrosis; Hyperbaric oxygen; Lung infections; Pseudomonas aeruginosa

PMID:
30711384
DOI:
10.1016/j.jcf.2019.01.005

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