Hyperbaric Oxygen Reduces Aspergillus fumigatus Proliferation and Influences Disease Outcomes.

Recent estimates suggest that more than 3 million people have chronic or invasive fungal infections, causing more than 600,000 deaths every year. 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 and impacts of hyperbaric oxygen (HBO) (100% oxygen, >1 atmosphere absolute [ATA]) on proliferation and murine IPA outcomes. Our findings indicate that HBO reduces established fungal biofilm proliferation by over 50%. The effect of HBO under the treatment conditions was transient and fungistatic, with metabolic activity rebounding within 6 h of HBO treatment being removed. , 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 or 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.