Atividade da prometazina, deferiprona e mel de Manuka contra biofilmes de Staphylococcus aureus e Pseudomonas aeruginosa em modelo ex vivo de feridas

Abstract

Infection is the most common factor that leads to wound chronicity and complication, especially when microorganisms are in the form of biofilm. Thus, this study aimed to evaluate the antibiofilm activity of promethazine, deferiprone and Manuka honey against Staphylococcus aureus and Pseudomonas aeruginosa in vitro and ex vivo in a wound model on porcine skin. For this, the Minimum Inhibitory Concentrations (MICs) for promethazine, deferiprone and Manuka honey were determined against eight isolates of each bacterial species. Then, the effect of these compounds on mature biofilms was evaluated to define the Minimum Biofilm Eradication Concentration (MBEC) and quantify the biomass of the biofilms. Finally, biofilms were formed on porcine skin and the effect of the compounds was evaluated by counting Colony-Forming Units (CFUs) and analyzing the architecture of biofilms by confocal microscopy. Promethazine, deferiprone and Manuka honey MICs ranged from 97.66 to 781.25 μg/mL, 512 to >1024 μg/mL and 10 to 40%, respectively, against both bacterial species. The minimum biofilm eradication concentrations (MBEC) values for promethazine, deferiprone and Manuka honey were 195.31-1562.5 μg/mL, ≥1024 μg/mL and from 20->40%, respectively, for the two species. As for the quantification of mature biofilm biomass, promethazine caused a significant reduction in concentrations of 781.25 and 195.31 μg/mL for S. aureus and 97.66 - 1562.5 μg/mL for P. aeruginosa. Deferiprone significantly reduced biomass at 512 and 1024 μg/mL concentrations for both species. While Manuka honey reduced the biomass only of S. aureus, at concentrations of 20 and 40%. Concerning biofilms grown on ex vivo model, the three tested compounds significantly reduced CFU counts for both bacterial species, altering the biofilm architecture. Promethazine was the most effective compound, reducing the CFU counts by about 4 log, in the MBEC concentration. Promethazine, deferiprone and Manuka honey have different in vitro antimicrobial properties, but were effective against biofilms grown on ex vivo wound model, showing their potential use in the management of biofilm-associated wounds.