Biocides as drivers of antibiotic resistance: A critical review of environmental implications and public health risks

Biocides constitute a cornerstone of microbial control strategies in healthcare, food processing, water treatment, and industrial environments. Their broad-spectrum antimicrobial properties, rapid action, and operational flexibility make them indispensable for preventing and/or controlling microbial contamination. Despite their utility, the efficacy of biocides is significantly constrained when confronting microbial biofilms - structured, surface-associated communities encased in an extracellular polymeric matrix. The biofilm phenotype impedes biocide diffusion, fosters physicochemical gradients that induce differential metabolic states, and promotes the survival of tolerant or persister subpopulations. These factors collectively lead to incomplete inactivation, repeated contamination events, and an increased risk of chronic system colonization. Concurrently, the extensive and sometimes sub-optimal use of biocides has raised concerns regarding their role in shaping the environmental resistome. Sublethal biocide exposure, frequently encountered at biofilm interfaces or through improper dosing, can exert selective pressure for adaptive mechanisms, including efflux pump upregulation, alterations in membrane composition, enzymatic detoxification, and activation of the global stress response. Importantly, several of these pathways confer decreased susceptibility not only to biocides but also to structurally or functionally unrelated antibiotics, thereby promoting cross-resistance. Additionally, biocides may co-select antimicrobial resistance genes co-located with biocide tolerance determinants on plasmids, transposons, or integrons, facilitating their persistence and dissemination within microbial communities and across environmental compartments. Evidence of increased tolerance to key clinical antimicrobials following exposure to disinfectants such as quaternary ammonium compounds and chlorhexidine underscores the relevance of these processes for public health. This seminar critically examines the dualistic nature of biocides, as both essential agents for microbial control and potential drivers of resistance evolution. By integrating current knowledge on biofilm tolerance mechanisms, resistome dynamics, and cross-resistance phenomena, it aims to inform risk-benefit assessments and support the development of evidence-based biocide stewardship strategies.