Usnic acid chitosan-coated liposomes synergistic activity with polymyxin B against multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii clinical in vitro.

BACKGROUND

The rise of multidrug-resistant (MDR) Gram-negative bacterial infections, particularly those caused by Pseudomonas aeruginosa and Acinetobacter baumannii, necessitates innovative treatment strategies. Usnic acid (UA), a natural compound with antimicrobial properties, has limited clinical use due to poor solubility and toxicity. This study evaluated the antibacterial, antibiofilm, and hemocompatibility profiles of UA encapsulated in chitosan-coated liposomes (Lipo-UA-Chi), alone and in combination with polymyxin B (PMB).

METHODS

UA, PMB, Lipo-UA-Chi, and their combinations were tested in vitro against MDR clinical strains of P. aeruginosa and A. baumannii. Antibacterial activity was assessed via broth microdilution and checkerboard assays. Antibiofilm inhibition and eradication were evaluated using the crystal violet method. Hemolytic activity was measured to assess cytotoxicity.

RESULTS

The Lipo-UA-Chi + PMB combination demonstrated additive or synergistic interactions in all tested strains, with MIC reductions of up to 128-fold for PMB and 4-fold for Lipo-UA-Chi. This combination also achieved superior biofilm inhibition, reaching up to 100% in specific P. aeruginosa strains, and eradication of up to 81.3%.

CONCLUSION

These findings highlight Lipo-UA-Chi combined with PMB as a promising and biocompatible strategy to improve antimicrobial efficacy and biofilm control in MDR infections. Although limited to in vitro evaluation, these findings support the potential of this formulation as a promising alternative to current polymyxin-based regimens.