Information about biocide-specific resistance/tolerance and the co-selection of resistance to other antimicrobials following biocide use remains limited. This literature review aimed to investigate the development of bacterial resistance/tolerance to PT3 (veterinary hygiene) and PT4 (food and feed production) biocides, with a focus on zoonotic pathogens, foodborne bacteria, and indicator organisms. The review also explored the co-selection of resistance to antimicrobials and/or other biocides.

The specific objectives of this work were to:

• 1. Identify biocidal products associated with resistance/tolerance development.
• 2. Determine the target microorganisms linked to resistance/tolerance.
• 3. Examine methodologies used to evaluate biocide resistance/tolerance.
• 4. Assess substances (e.g., antimicrobials or other biocides) for which resistance may emerge after biocide use.

Comprehensive literature searches spanning 1950 to 2023 were conducted using PubMed and Scopus electronic databases. The review followed a registered protocol (PROSPERO) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. A total of 182 studies from 30 countries were included, encompassing a variety of biocidal products and bacterial species originating from diverse sources.

The majority of studies were experimental, employing diverse methodologies, with Minimum Inhibitory Concentration (MIC) analysis emerging as the most frequently utilized method. Biocidal products were categorized based on their mode of action and commercial formulations, revealing substantial variability in bacterial resistance/tolerance depending on the species and isolate origins. Biofilms and spores presented unique challenges, with biofilm survival influenced by biocide concentration, type, and exposure time.

Among studies reporting resistance/tolerance, Quaternary Ammonium Compounds (QACs), particularly benzalkonium chloride, were the most studied. These compounds were shown to induce resistance/tolerance in various pathogenic foodborne, zoonotic, and indicator bacteria. However, most studies did not detect bacterial resistance/tolerance to PT3 and PT4 biocides.

Notably, the studies varied widely in design and lacked consistent criteria to distinguish resistant/tolerant bacteria from non-resistant/tolerant ones, complicating the ability to draw definitive conclusions. Evidence of genotypic resistance/tolerance to biocides and co-selection with other antimicrobials/biocides, especially involving benzalkonium chloride, was identified in some studies.

Despite its comprehensiveness, this review highlights several limitations and underscores the urgent need for standardization in future studies. Recommendations include developing guidelines, such as epidemiological cut-off values (ECOFFs), to determine and interpret bacterial susceptibility to biocides. Such efforts should involve not only health agencies but also commercial producers of biocidal products. The findings provide valuable insights into the complex dynamics of bacterial resistance to biocidal products, emphasizing the necessity for continued research and the establishment of standardized evaluation frameworks.