Biocide-tolerance and antibiotic-resistance in community environments and risk of direct transfers to humans: Unintended consequences of community-wide surface disinfecting during COVID-19?

Abstract

During the current pandemic, chemical disinfectants are ubiquitously and routinely used in community environments, especially on common touch surfaces in public settings, as a means of controlling the virus spread. An underappreciated risk in current regulatory guidelines and scholarly discussions, however, is that the persisting input of chemical disinfectants can exacerbate the growth of biocide-tolerant and antibiotic-resistant bacteria on those surfaces and allow their direct transfers to humans. For COVID-19, the most commonly used disinfecting agents are quaternary ammonium compounds, hydrogen peroxide, sodium hypochlorite, and ethanol, which account for two-thirds of the active ingredients in current EPA-approved disinfectant products for the novel coronavirus. Tolerance to each of these compounds, which can be either intrinsic or acquired, has been observed on various bacterial pathogens. Of those, mutations and horizontal gene transfer, upregulation of efflux pumps, membrane alteration, and biofilm formation are the common mechanisms conferring biocide tolerance in bacteria. Further, the linkage between disinfectant use and antibiotic resistance was suggested in laboratory and real-life settings. Evidence showed that substantial bacterial transfers to hands could effectuate from short contacts with surrounding surfaces and further from fingers to lips. While current literature on disinfectant-induced antimicrobial resistance predominantly focuses on municipal wastes and the natural environments, in reality the community and public settings are most severely impacted by intensive and regular chemical disinfecting during COVID-19 and, due to their proximity to humans, biocide-tolerant and antibiotic-resistant bacteria emerged in these environments may pose risks of direct transfers to humans, particularly in densely populated urban communities. Here we highlight these risk factors by reviewing the most pertinent and up-to-date evidence, and provide several feasible strategies to mitigate these risks in the scenario of a prolonging pandemic.

Keywords: Antimicrobial; Contact surface; Coronavirus; Drug resistance; Infection Control; SARS-CoV-2.

Graphical abstract

Fig. 1

Active ingredients in EPA-approved disinfectants for COVID-19. As of March 3, 2021, a total of 535 products are listed, with 34 biocidal active compounds contained within. Quaternary ammonium compounds (QACs) were found in 247 products, hydrogen peroxide in 82 products, sodium hypochlorite in 74 products, and ethyl alcohol in 35 products. Other common active ingredients include peroxyacetic acid (30), phenolic (29), isopropanol (21), and hypochlorous acid (21). Most of these approved products contain only one active ingredient (n = 431), and some products contain two (n = 90) or more (n = 14). A QAC product may contain one or several benzalkyl dimethyl ammonium compounds (BACs) and dialkyl dimethyl ammonium compounds (DADMACs), or a combination of both. Specifically, among the 247 QACs products approved, 117 contained only BACs, 19 contained only DADMACs, and 111 products contained both BACs and DADMACs. There are also 49 products containing QACs and other non-QAC biocidal active compound such as ethanol or isopropanol. All products are intended for use on surfaces (not humans). EPA expects them to kill the novel coronavirus (SARS-CoV-2) when used in accordance with their label directions. This list is regularly updated by the EPA (available at: https://cfpub.epa.gov/giwiz/disinfectants/index.cfm).

Fig. 2

Classification of microorganisms based on their tolerance of biocidal agents. Groups containing bacteria are highlighted in bold. Adapted with permission of Elsevier from Russell (1999).

Fig. 3

Intra-cellular and inter-cellular mobility of mobile genetic elements containing resistance genes. Thin black arrow and thick green arrow represent intra-cellular processes and inter-cellular horizontal gene transfer, respectively. (A) A composite transposon bearing a resistance gene could transpose from the chromosome to a plasmid. (B) Transfer of unit transposon between plasmids within the cell. (C) A gene cassette can excise from or insert into an integron via a circular intermediate. (D) Excision of ICE from chromosome in donor cell (reversibly) to form a circular structure, which is capable of conjugative transfer to recipient cell and integrates into recipient chromosome by site-specific recombination. (E) Intercellular transfer of plasmid was mediated by conjugation or mobilization. In addition, it can be mediated by transformation or bacteriophage transduction. Reprint with permission of American Society for Microbiology from Partridge et al. (2018). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4

Schematic of representatives of the five known efflux pump families. The MATE, MFS, SMR and RND families are powered by electrochemical energy (transmembrane ion gradients, i.e., H⁺ or Na⁺). The ABC superfamily directly utilizes ATP as energy source to pump out disinfectant molecule from the cell. Reprint with permission of American Society for Microbiology from Piddock (2006).

Fig. 5

The dense extracellular matrix of biofilms can degrade biocides and hamper their penetration, protecting the sensitive bacteria inside. In actual environments, some bacteria are exposed to subinhibitory concentrations of biocides. This kind of selective pressure can further increase the propensity to give rise to tolerant cells. Reprint with permission of the Royal College of Paediatrics and Child Health and BMJ from Bock (2019).

Fig. 6

A schematic illustration on the potential growth of disinfectant-tolerant and antibiotic-resistant bacteria on contact surfaces in community and public settings, posing risks of direct transfers to humans. With a highly non-diverse spectrum of biocidal agents in disinfectant products approved for COVID-19, these unintended consequences may arise from the regular and intensive surface disinfecting during COVID-19 and perhaps extended to the post-pandemic area.