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

Abstract

The widespread and indiscriminate use of biocides poses significant threats to global health, socioeconomic development, and environmental sustainability by accelerating antibiotic resistance. Bacterial resistance development is highly complex and influenced significantly by environmental factors. Increased biocide usage in households, agriculture, livestock farming, industrial settings, and hospitals produces persistent chemical residues that pollute soil and aquatic environments. Such contaminants contribute to the selection and proliferation of resistant bacteria and antimicrobial resistance genes (ARGs), facilitating their dissemination among humans, animals, and ecosystems. In this review, we conduct a critical assessment of four significant issues pertaining to this topic. Specifically, (i) the role of biocides in exerting selective pressure within the environmental resistome, thereby promoting the proliferation of resistant microbial populations and contributing to the global spread of antimicrobial resistance genes (ARGs); (ii) the role of biocides in triggering transient phenotypic adaptations in bacteria, including efflux pump overexpression, membrane alterations, and reduced porin expression, which often result in cross-resistance to multiple antibiotics; (iii) the capacity of biocides to disrupt bacteria and make the genetic content accessible, releasing DNA into the environment that remains intact under certain conditions, facilitating horizontal gene transfer and the spread of resistance determinants; (iv) the capacity of biocides to disrupt bacterial cells, releasing intact DNA into the environment and enhancing horizontal gene transfer of resistance determinants; and (iv) the selective interactions between biocides and bacterial biofilms in the environment, strengthening biofilm cohesion, inducing resistance mechanisms, and creating reservoirs for resistant microorganisms and ARG dissemination. Collectively, this review highlights the critical environmental and public health implications of biocide use, emphasizing an urgent need for strategic interventions to mitigate their role in antibiotic resistance proliferation.

Keywords: Adaptive resistance; Antibiotic resistance; Biocides; Biofilms; Cross-resistance.

Graphical abstract

Fig. 1

World distribution of biocides and antibiotics (in ng L⁻¹) in rivers, basins, seas or lakes, and wastewater treatment plants (influent). The investigated biocides and antibiotics were selected due to their high relevance, prevalence, and use worldwide. AMP: Ampicillin; ATMAC: Alkyltrimethylammonium compounds; AZM: Azithromycin; BZK: Benzylalkyldimethylammonium compounds; CHX: Chlorhexidine; CIP: Ciprofloxacin; CLM: Clarithromycin; CTAB: Cetyltrimethylammonium bromide; DADMAC: Dialkyldimethylammonium compounds; ERY: Erythromycin; NOR: Norfloxacin; PhP: Ortho-phenylphenol; ROX: Roxithromycin; SMZ: Sulfamethoxazole; STZ: Sulfathiazole; TCC: Triclocarban; TCS: Triclosan; TET: Tetracycline; TMP: Trimethoprim.

Fig. 2

Compilation of the mechanisms by which biocides promote antibiotic resistance addressed in this study [15,84,126,127].

Fig. 3

Ascending order of resistance to biocides and antibiotics (based on McDonnell and Russell [68]).

Fig. 4

Non-specific structural and functional alterations in the bacterial outer layers following biocide exposure, leading to resistance to a broad spectrum of antimicrobials, evolving the over-expression of efflux pumps, the over-expression of multigene and protein systems, altered exopolysaccharide production, alterations in surface charge and in lipid content, and reduced expression of porins (based on Lorusso, Carrara [130], Huang, Wu [159], De Gaetano, Lentini [163], Chetri [164]).