New strategies for the management of biofilms formed by Gram-negative bacteria

The global rise of multidrug-resistant (MDR) Gram-negative bacteria (GNB) has intensified the threat of chronic and hard-to-treat infections, many of which are associated with biofilm formation. These biofilms confer enhanced resistance to antimicrobials and immune responses, posing a major clinical challenge.

This review summarizes the biological mechanisms of biofilm formation in GNB and explores both traditional and novel strategies for their prevention and eradication. The literature search covered peer-reviewed articles from major databases, focusing on therapeutic approaches such as quorum sensing inhibitors, EPS matrix disruptors, phage therapy, nanotechnology, and synergistic drug combinations. The novelty of this review lies in its effort to understand biofilm biology to identify key intervention points and organize therapeutic strategies according to their biological, chemical or physical nature. Emphasis is also placed on combined approaches that simultaneously target multiple components of the biofilm structure.

Despite significant in vitro progress, most antibiofilm strategies remain experimental. Translating these findings into clinical applications requires standardization, in vivo validation, and regulatory alignment. A multidisciplinary approach integrating different agents and targeted drug delivery systems holds promise for improving patient outcomes.