Hyperbaric Oxygen Treatment in Humans With Gram Positive Cocci Endocarditis

Overview

Infectious endocarditis (IE) is defined as an infection anywhere on the endocardium, most often localised to the cardiac valves. It is an infection with an increasing incidence and in Denmark with 6-700 new cases annually. Approximately 45% of the patients must undergo cardiac surgery with replacement of infected cardiac valves by prosthetic valves. Recently, the formation of biofilms infections has drawn attention with respect to the effects of hyperbaric re-oxygenation of stricken tissues as anaerobic bacterial metabolism with low levels of activity within the biofilm environment, may be responsible for the development of antimicrobial resistance. Polymorphonuclear leukocytes (PMNs) consume available oxygen in the conversion of oxygen to ROS and in the formation of reactive nitrogen species (RNS) by inducible nitric oxide (iNOS) as PMN's are activated by bacteria. In pre-clinical context the effect of hyperbaric oxygen treatment (HBOT) in re-oxygenating biofilm related infections have been demonstrated in infected lungs with Pseudomonas aeruginosa and staphylococcus aureus endocarditis. Adjunctive HBOT has never been offered to patients with IE. However, HBOT may be associated with reduced compliance and side effects, such as equalisation problems of ears and sinuses and confinement anxiety, and the treatment is organizational challenging. On this basis the investigators suggest an initial feasibility study as the basis for a later and larger scaled randomized controlled trial of HBOT in patients with IE.

During antibiotic treatments with the indicated antibiotics the susceptible bacteria are subjected to metabolic changes of the Krebs cycles leading to intrabacterial accumulation of toxic hydroxyl oxygen radicals. The intrabacterial toxic reactive oxygen species (ROS) can subsequently react with DNA, lipids or proteins resulting in damages of those bacterial components adding to the killing of the bacteria. A consequence is that bactericidal antibiotics have reduced activity in infectious foci with poor oxygen supply like in abscesses or in biofilm infections as in IE and/or rapid consumption of oxygen due to PMN influx. The bacterial damages may, if killing is not obtained, result in mutations and selection of antibiotic resistant mutants. However, these discoveries also provide a possibility for improving the antibacterial effect by increasing the oxygen pressure in the infectious focus. This can be obtained by increasing oxygen tension in the tissues by treating the patients with HBOT - and have been shown in vitro and in vivo pre-clinical experiments. Exposing Pseudomonas aeruginosa biofilm models in vitro to HBOT has proved effective by significantly increasing the bactericidal effect of ciprofloxacin. More important, in an animal (rats) model of left-sided S. aureus IE on the aortic valves, tobramycin killing effect was significantly improved by adding HBOT as adjunctive therapy. Moreover, the rats revealed a reduced inflammatory response and improved clinical scores. No side effects were recorded during that study. In addition, the HBOT is also believed to improve the antibacterial effect of the PMNs, and thereby add to an enhanced elimination of infectious focus. This is being estimated by measurements of the respiratory burst of the PMNs, as well as their phagocytic capacity right before and right after the HBOT.