Model of Ciprofloxacin Killing Enhanced by Hyperbaric Oxygen Treatment in Pseudomonas aeruginosa Biofilms

In chronic Pseudomonas aeruginosa (PA) biofilm lung infections the bacteria are protected from the immune system of the host and from antibiotic treatment. It has been demonstrated that the susceptibility of the bacteria to antibiotic treatment can be enhanced by hyperbaric oxygen treatment. Here we present a reaction-diffusion model that describes the combined effect of ciprofloxacin diffusion, oxygen diffusion and depletion, bacterial growth and killing, and adaptation of the bacteria to ciprofloxacin. In the model, the oxygen diffusion and depletion use a set of parameters derived from experiments. The description of ciprofloxacin killing uses parameter values from the literature in combination with our estimates. The complete oxygen model comprises a reaction-diffusion equation describing the oxygen consumption by using a Michaelis-Menten reaction term. The oxygen model performed well in predicting oxygen concentrations in both time and depth into the biofilm. At 2.8 bar pure oxygen pressure, HBOT increases the penetration depth of oxygen into the biofilm by a of factor 4 and we see that hyperbaric oxygen treatment significantly increases the killing by ciprofloxacin in a PAO1 biofilm in alignment with the experimental results