TY - JOUR

T1 - Hyperbaric oxygen therapy counteracts Pseudomonas aeruginosa biofilm micro-compartment phenomenon in murine thermal wounds

AU - Laulund, Anne Sofie

AU - Schwartz, Franziska Angelika

AU - Høiby, Niels

AU - Thomsen, Kim

AU - Moser, Claus

N1 - Publisher Copyright: © 2023 The Authors

PY - 2023

Y1 - 2023

N2 - Background: Biofilm antibiotic tolerance is partly explained by the behavior of a biofilm as an independent pharmacokinetic micro-compartment. Hyperbaric oxygen therapy has been shown to potentiate antibiotic effects in biofilms. The present study investigates the effect of hyperbaric oxygen therapy (HBOT) on the biofilm micro-pharmacokinetic/pharmacodynamic behavior of tobramycin in an animal biofilm model. Methods: Full-thickness necroses were created mid-scapular on mice by means of a thermal lesion. After four days, three 16 h seaweed alginate biofilm beads containing Pseudomonas aeruginosa PAO1 were inserted under the necrosis, and three beads were inserted under the adjacent non-affected skin. The mice were randomized to three groups I) HBOT for 1.5 h at 2.8 atm and 0.8 mg tobramycin/mouse subcutaneously; II) Tobramycin as monotherapy, same dose; III) Saline control group. Half the number of mice from group 1 and 2 were sacrificed, and beads were recovered in toto after 3 h and the other half and the placebo mice were sacrificed and beads collected after 4.5 h. Results: Lower CFUs were seen in the burned group receiving HBOT at 3 and 4.5 h compared to beads in the atmospheric environment (p = 0.043 and p = 0.0089). At 3 h, no CFU difference was observed in the non-burned skin (HBOT vs atmospheric). At 4.5 h, CFU in the non-burned skin had lower CFUs in the group receiving HBOT compared to the corresponding atmospheric group (p = 0.02). CFU was higher in the burned skin than in the non-burned skin at 3 h when HBOT was applied (p = 0.04), effect faded out at 4.5 h. At both time points, the tobramycin content in the beads under burned skin were higher in the HBOT group than in the atmospheric groups (p = 0.031 and p = 0.0078). Only at 4.5 h a higher tobramycin content was seen in the beads under the HBOT-treated burned skin than the beads under the corresponding non-burned skin (p = 0.006). Conclusion: HBOT, as an anti-biofilm adjuvant treatment of chronic wounds, counteracts biofilm pharmacokinetic micro-compartmentalization through increased available tobramycin and augmented bacterial killing.

AB - Background: Biofilm antibiotic tolerance is partly explained by the behavior of a biofilm as an independent pharmacokinetic micro-compartment. Hyperbaric oxygen therapy has been shown to potentiate antibiotic effects in biofilms. The present study investigates the effect of hyperbaric oxygen therapy (HBOT) on the biofilm micro-pharmacokinetic/pharmacodynamic behavior of tobramycin in an animal biofilm model. Methods: Full-thickness necroses were created mid-scapular on mice by means of a thermal lesion. After four days, three 16 h seaweed alginate biofilm beads containing Pseudomonas aeruginosa PAO1 were inserted under the necrosis, and three beads were inserted under the adjacent non-affected skin. The mice were randomized to three groups I) HBOT for 1.5 h at 2.8 atm and 0.8 mg tobramycin/mouse subcutaneously; II) Tobramycin as monotherapy, same dose; III) Saline control group. Half the number of mice from group 1 and 2 were sacrificed, and beads were recovered in toto after 3 h and the other half and the placebo mice were sacrificed and beads collected after 4.5 h. Results: Lower CFUs were seen in the burned group receiving HBOT at 3 and 4.5 h compared to beads in the atmospheric environment (p = 0.043 and p = 0.0089). At 3 h, no CFU difference was observed in the non-burned skin (HBOT vs atmospheric). At 4.5 h, CFU in the non-burned skin had lower CFUs in the group receiving HBOT compared to the corresponding atmospheric group (p = 0.02). CFU was higher in the burned skin than in the non-burned skin at 3 h when HBOT was applied (p = 0.04), effect faded out at 4.5 h. At both time points, the tobramycin content in the beads under burned skin were higher in the HBOT group than in the atmospheric groups (p = 0.031 and p = 0.0078). Only at 4.5 h a higher tobramycin content was seen in the beads under the HBOT-treated burned skin than the beads under the corresponding non-burned skin (p = 0.006). Conclusion: HBOT, as an anti-biofilm adjuvant treatment of chronic wounds, counteracts biofilm pharmacokinetic micro-compartmentalization through increased available tobramycin and augmented bacterial killing.

U2 - 10.1016/j.bioflm.2023.100159

DO - 10.1016/j.bioflm.2023.100159

M3 - Journal article

C2 - 37928621

AN - SCOPUS:85172915379

VL - 6

JO - Biofilm

JF - Biofilm

SN - 2590-2075

M1 - 100159

ER -