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

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@article{b8c47d4ef9da4d14b75e627cd1bdcc8b,
title = "Hyperbaric oxygen treatment increases killing of aggregating Pseudomonas aeruginosa isolates from cystic fibrosis patients",
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.",
author = "M{\o}ller, {Signe Agnete} and Jensen, {Peter {\O}strup} and Niels H{\o}iby and Oana Ciofu and Kragh, {Kasper N{\o}rskov} and Thomas Bjarnsholt and Mette Kolpen",
note = "Copyright {\circledC} 2019. Published by Elsevier B.V.",
year = "2019",
month = "9",
doi = "10.1016/j.jcf.2019.01.005",
language = "English",
volume = "18",
pages = "657--664",
journal = "Journal of Cystic Fibrosis",
issn = "1569-1993",
publisher = "Elsevier BV",
number = "5",

}

RIS

TY - JOUR

T1 - Hyperbaric oxygen treatment increases killing of aggregating Pseudomonas aeruginosa isolates from cystic fibrosis patients

AU - Møller, Signe Agnete

AU - Jensen, Peter Østrup

AU - Høiby, Niels

AU - Ciofu, Oana

AU - Kragh, Kasper Nørskov

AU - Bjarnsholt, Thomas

AU - Kolpen, Mette

N1 - Copyright © 2019. Published by Elsevier B.V.

PY - 2019/9

Y1 - 2019/9

N2 - 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.

AB - 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.

U2 - 10.1016/j.jcf.2019.01.005

DO - 10.1016/j.jcf.2019.01.005

M3 - Journal article

VL - 18

SP - 657

EP - 664

JO - Journal of Cystic Fibrosis

JF - Journal of Cystic Fibrosis

SN - 1569-1993

IS - 5

ER -

ID: 58995108