Does Environmental Exposure to Pharmaceutical and Personal Care Product Residues Result in the Selection of Antimicrobial‐Resistant Microorganisms, and is this Important in Terms of Human Health Outcomes?

Abstract

The environment plays a critical role in the development, dissemination, and transmission of antimicrobial resistance (AMR). Pharmaceuticals and personal care products (PPCPs) enter the environment through direct application to the environment and through anthropogenic pollution. Although there is a growing body of evidence defining minimal selective concentrations (MSCs) of antibiotics and the role antibiotics play in horizontal gene transfer (HGT), there is limited evidence on the role of non-antibiotic PPCPs. Existing data show associations with the development of resistance or effects on bacterial growth rather than calculating selective endpoints. Research has focused on laboratory-based systems rather than in situ experiments, although PPCP concentrations found throughout wastewater, natural water, and soil environments are often within the range of laboratory-derived MSCs and at concentrations shown to promote HGT. Increased selection and HGT of AMR by PPCPs will result in an increase in total AMR abundance in the environment, increasing the risk of exposure and potential transmission of environmental AMR to humans. There is some evidence to suggest that humans can acquire resistance from environmental settings, with water environments being the most frequently studied. However, because this is currently limited, we recommend that more evidence be gathered to understand the risk the environment plays in regard to human health. In addition, we recommend that future research efforts focus on MSC-based experiments for non-antibiotic PPCPS, particularly in situ, and investigate the effect of PPCP mixtures on AMR. Environ Toxicol Chem 2022;00:1-14.

Pharmaceuticals and Personal Care Products in the Environment: What Progress Has Been Made in Addressing the Big Research Questions?

“…We now have a much improved understanding of the mechanisms of selection and drivers of AMR in the environment (Manaia et al, 2024). The last decade has seen an increase in the volume of laboratory‐derived data on minimal selective concentrations, concentrations shown to promote horizontal gene transfer, and the development of new methodologies to derive predicted‐no‐effect concentrations (PNECs) for resistance (Manaia et al, 2024; Stanton et al, 2024). The evidence that environmental exposure to PPCPs is contributing to the AMR crisis is now much stronger, with comparisons of monitoring data with PNECs indicating risks of selection in some regions, associations being found between the occurrence of PPCPs in the environment and resistance selection and human acquisition of resistance being demonstrated from some environmental settings (Stanton et al, 2024).…”

“…Work needs to continue to understand the role the environment plays in the risk of AMR to human health (Manaia et al, 2024). We also need to widen the work to consider the impacts of a range of non‐antibiotic contaminants on levels of resistance in the environment and start to consider potential mixture interactions and risks from an AMR perspective (Manaia et al, 2024; Stanton et al, 2024).…”

Environmental Risks of Pharmaceutical Mixtures in Aquatic Ecosystems: Reflections on a Decade of Research

“…However, their relevance to real‐world scenarios is limited because most studies have been done using binary mixtures and green algae (Sharma et al, 2021), and few have examined species, like cyanobacteria, that are more sensitive to antibiotics (Välitalo et al, 2017) or environmentally relevant mixtures. In addition, we are unaware of studies to date that assess the role of mixtures of antibiotics and other antimicrobial substances (e.g., metals, quaternary ammonium compounds) on the development of antimicrobial resistance (AMR; see also Manaia et al, 2024; Stanton et al, 2024). Endocrine‐active compounds have been assessed in a variety of in vitro and in vivo tests to understand mixture toxicity.…”

Exposure to environmental stress decreases the resistance of river microbial communities towards invasion by antimicrobial resistant bacteria

“…pathogenic and commensal bacteria from the human gut microbiome) which are regularly enriched in antibiotic resistant genes (ARGs) [12][13][14]. In addition, abiotic pollutants, such as pesticides [15,16], pharmaceutical products [17,18], personal care products [19,20] and metal trace elements [7,9,19] are regularly co-introduced with the bacterial contaminants. These are known to exert selection pressures on ARB and furthermore lead to increased horizontal gene transfer rates which result in the amplification of ARGs once they entered the river microbiome [12,[20][21][22][23], hence making rivers a reservoir and breeding ground for AMR [5,24,25].…”

“…In addition, abiotic pollutants, such as pesticides [15,16], pharmaceutical products [17,18], personal care products [19,20] and metal trace elements [7,9,19] are regularly co-introduced with the bacterial contaminants. These are known to exert selection pressures on ARB and furthermore lead to increased horizontal gene transfer rates which result in the amplification of ARGs once they entered the river microbiome [12,[20][21][22][23], hence making rivers a reservoir and breeding ground for AMR [5,24,25]. However, there is no clear understanding whether the co-introduction of stressors through, e.g., wastewater effluents, also affects the invasion success of the constantly incoming resistant bacteria into the river microbiomes.…”