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Antimicrob Agents Chemother. 2018 Feb 23;62(3). pii: e01953-17. doi: 10.1128/AAC.01953-17. Print 2018 Mar.

Hyperbaric Oxygen Reduces Aspergillus fumigatus Proliferation In Vitro and Influences In Vivo Disease Outcomes.

Author information

1
Geisel School of Medicine at Dartmouth, Department of Microbiology and Immunology, Hanover, New Hampshire, USA.
2
Geisel School of Medicine at Dartmouth, Department of Medicine, Lebanon, New Hampshire, USA.
3
Geisel School of Medicine at Dartmouth, Department of Microbiology and Immunology, Hanover, New Hampshire, USA robert.a.cramer.jr@dartmouth.edu.

Abstract

Recent estimates suggest that more than 3 million people have chronic or invasive fungal infections, causing more than 600,000 deaths every year. Aspergillus fumigatus causes invasive pulmonary aspergillosis (IPA) in patients with compromised immune systems and is a primary contributor to increases in human fungal infections. Thus, the development of new clinical modalities as stand-alone or adjunctive therapy for improving IPA patient outcomes is critically needed. Here we tested the in vitro and in vivo impacts of hyperbaric oxygen (HBO) (100% oxygen, >1 atmosphere absolute [ATA]) on A. fumigatus proliferation and murine IPA outcomes. Our findings indicate that HBO reduces established fungal biofilm proliferation in vitro by over 50%. The effect of HBO under the treatment conditions was transient and fungistatic, with A. fumigatus metabolic activity rebounding within 6 h of HBO treatment being removed. In vivo, daily HBO provides a dose-dependent but modest improvement in murine IPA disease outcomes as measured by survival analysis. Intriguingly, no synergy was observed between subtherapeutic voriconazole or amphotericin B and HBO in vitro or in vivo with daily HBO dosing, though the loss of fungal superoxide dismutase genes enhanced HBO antifungal activity. Further studies are needed to optimize the HBO treatment regimen and better understand the effects of HBO on both the host and the pathogen during a pulmonary invasive fungal infection.

KEYWORDS:

Aspergillus fumigatus; fungal biofilm; fungal growth; hyperbaric oxygen; invasive aspergillosis; oxygen radicals

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