Effect of 3,3′-Diindolylmethane on the Antibacterial Activity of Fluoroquinolones as Constituents of Potential Drug Products for Topical Application

The aim of the study was to overcome the resistance to fluoroquinolones of Gram-positive and Gram-negative, largely drug-resistant bacteria that infect combat-related traumatic injuries to the skin and adjacent tissues. For this purpose, 0.1% ofloxacin, levofloxacin, or moxifloxacin in combination with 0.1%, 0.5%, or 1.0% of 3,3'-diindolylmethane (DIM) were incorporated into a water-soluble ointment base. The experimental results showed that the ointment base promoted the release of ofloxacin while it absorbed a significant amount of water. In vitro experiments using the agar diffusion method demonstrated that the components of the ointment base and DIM in increasing concentrations enhanced the susceptibility of 6 clinical bacterial strains to fluoroquinolones. A colloidal nonionic surfactant solution containing 0.1% ofloxacin and 1.0% DIM effectively prevented biofilm formation of both clinical strains and a standard strain of <i>Pseudomonas aeruginosa</i>. Confocal laser scanning microscopy revealed that the impact of the colloidal solution on biofilm formation by <i>P. aeruginosa</i> 4791 resulted in a remarkable destruction of the biofilm integrity, accompanied by a significant reduction in biofilm thickness. This research highlights the potential of the combined use of fluoroquinolones and DIM in water-soluble ointments for the local treatment of purulent wounds infected with resistant bacterial strains in the inflammatory phase.