title: Reinforcement of the bactericidal effect of ciprofloxacin on Pseudomonas aeruginosa biofilm by hyperbaric oxygen treatment.
abstract: Chronic Pseudomonas aeruginosa lung infection is the most severe complication in cystic fibrosis patients. It is characterised by antibiotic-tolerant biofilms in the endobronchial mucus with zones of oxygen (O2) depletion mainly due to polymorphonuclear leucocyte activity. Whilst the exact mechanisms affecting antibiotic effectiveness on biofilms remain unclear, accumulating evidence suggests that the efficacy of several bactericidal antibiotics such as ciprofloxacin is enhanced by stimulation of the aerobic respiration of pathogens, and that lack of O2 increases their tolerance. Reoxygenation of O2-depleted biofilms may thus improve susceptibility to ciprofloxacin possibly by restoring aerobic respiration. We tested such a strategy using reoxygenation of O2-depleted P. aeruginosa strain PAO1 agarose-embedded biofilms by hyperbaric oxygen treatment (HBOT) (100% O2, 2.8bar), enhancing the diffusive supply for aerobic respiration during ciprofloxacin treatment. This proof-of-principle study demonstrates that biofilm reoxygenation by HBOT can significantly enhance the bactericidal activity of ciprofloxacin on P. aeruginosa. Combining ciprofloxacin treatment with HBOT thus clearly has potential to improve the treatment of P. aeruginosa biofilm infections.
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, Juliane Mariesvej 22, 2100 Copenhagen, Denmark; Department of International Health, Immunology and Microbiology, UC-CARE, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Kolpen
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, Juliane Mariesvej 22, 2100 Copenhagen, Denmark.
authors.forename: Nabi
authors.initials: N
authors.lastname: Mousavi
authors.affiliation: Biomedical Engineering, Department of Electrical Engineering, Technical University of Denmark, 2800 Lyngby, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sams
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, Juliane Mariesvej 22, 2100 Copenhagen, Denmark; Department of International Health, Immunology and Microbiology, UC-CARE, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bjarnsholt
authors.affiliation: Department of International Health, Immunology and Microbiology, UC-CARE, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Oana
authors.initials: O
authors.lastname: Ciofu
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, Juliane Mariesvej 22, 2100 Copenhagen, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Moser
authors.affiliation: Marine Biological Section, Department of Biology, University of Copenhagen, 3000 Helsingør, Denmark; Plant Functional Biology and Climate Change Cluster, University of Technology Sydney, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Kühl
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, Juliane Mariesvej 22, 2100 Copenhagen, Denmark; Department of International Health, Immunology and Microbiology, UC-CARE, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Høiby
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, Juliane Mariesvej 22, 2100 Copenhagen, Denmark. Electronic address: peter.oestrup.jensen@regionh.dk.
authors.forename: Peter Østrup
authors.initials: PØ
authors.lastname: Jensen
mesh_terms: D000332:Aerobiosis; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002939:Ciprofloxacin / Q000494:pharmacology*; D006874:Hydrostatic Pressure; D050296:Microbial Viability / Q000187:drug effects*; D010100:Oxygen / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin; D010100:Oxygen
keywords: Biofilm; Ciprofloxacin; Cystic fibrosis; Hyperbaric oxygen treatment; Pseudomonas aeruginosa