Quaternary ammonium disinfectants and antiseptics: tolerance, resistance and potential impact on antibiotic resistance

Abstract

Background Due to the substantial increase in the use of disinfectants containing quaternary ammonion compounds (QACs) in healthcare and community settings during the COVID-19 pandemic, there is increased concern that heavy use might cause bacteria to develop resistance to QACs or contribute to antibiotic resistance. The purpose of this review is to briefly discuss the mechanisms of QAC tolerance and resistance, laboratory-based evidence of tolerance and resistance, their occurrence in healthcare and other real-world settings, and the possible impact of QAC use on antibiotic resistance. Methods A literature search was conducted using the PubMed database. The search was limited to English language articles dealing with tolerance or resistance to QACs present in disinfectants or antiseptics, and potential impact on antibiotic resistance. The review covered the period from 2000 to mid-Jan 2023. Results Mechanisms of QAC tolerance or resistance include innate bacterial cell wall structure, changes in cell membrane structure and function, efflux pumps, biofilm formation, and QAC degradation. In vitro studies have helped elucidate how bacteria can develop tolerance or resistance to QACs and antibiotics. While relatively uncommon, multiple episodes of contaminated in-use disinfectants and antiseptics, which are often due to inappropriate use of products, have caused outbreaks of healthcare-associated infections. Several studies have identified a correlation between benzalkonium chloride (BAC) tolerance and clinically-defined antibiotic resistance. The occurrence of mobile genetic determinants carrying multiple genes that encode for QAC or antibiotic tolerance raises the concern that widespread QAC use might facilitate the emergence of antibiotic resistance. Despite some evidence from laboratory-based studies, there is insufficient evidence in real-world settings to conclude that frequent use of QAC disinfectants and antiseptics has promoted widespread emergence of antibiotic resistance. Conclusions Laboratory studies have identified multiple mechanisms by which bacteria can develop tolerance or resistance to QACs and antibiotics. De novo development of tolerance or resistance in real-world settings is uncommon. Increased attention to proper use of disinfectants is needed to prevent contamination of QAC disinfectants. Additional research is needed to answer many questions and concerns related to use of QAC disinfectants and their potential impact on antibiotic resistance.

Antimicrobial Tolerance in Salmonella: Contributions to Survival and Persistence in Processing Environments

“…QACs can bind to the phospholipid layer of the cell membrane as well as membranous proteins [11,24,59]. Cell surface permeability is greatly affected by the actions of QACs because once the compound binds to the cell membrane, it becomes easily absorbed by the cell [23,60].…”

“…Antimicrobial 'tolerance' and 'resistance' are often used interchangeably, and as expressed by Maillard in 2022 [10], there is a lack of agreement among the scientific community and many studies about the term used to accurately describe bacterial reduced susceptibility to antimicrobials. Therefore, as used by Boyce in 2023 [11], 'antimicrobial tolerance' in this review means bacteria has shown reduced susceptibility to an antimicrobial agent.…”

Efficacy of Novel Quaternary Ammonium and Phosphonium Salts Differing in Cation Type and Alkyl Chain Length against Antibiotic-Resistant Staphylococcus aureus

“…Quaternary heteronium salts (QHSs), such as quaternary ammonium and phosphonium compounds, present a promising avenue for discovering new antibiotics to counter antibacterial resistance [ 6 , 12 , 13 , 14 , 15 ]. Since the 1930s, quaternary ammonium salts (QASs) have been integral components of various antiseptics and disinfectants [ 6 , 16 , 17 , 18 , 19 ], finding applications in household, agriculture, medicine, and industry [ 16 , 17 , 19 ]. The structure of QASs comprises a positively charged nitrogen atom (head) linked through four bonds to alkyl or aryl chains (tails) with varying numbers of carbon atoms [ 16 , 17 , 18 ].…”

“…Since the 1930s, quaternary ammonium salts (QASs) have been integral components of various antiseptics and disinfectants [ 6 , 16 , 17 , 18 , 19 ], finding applications in household, agriculture, medicine, and industry [ 16 , 17 , 19 ]. The structure of QASs comprises a positively charged nitrogen atom (head) linked through four bonds to alkyl or aryl chains (tails) with varying numbers of carbon atoms [ 16 , 17 , 18 ]. Depending on their structure, they exhibit antimicrobial activity against Gram-positive bacteria, fungi, and enveloped viruses [ 16 ].…”

Synthesis, characterization and cell selectivity of poly(quaternary ammonium chlorides): effect of the degree of quaternization and copolymer composition

“…[39][40][41][42][43][44][45][46] To the best of our knowledge, there is no report detailing the facile preparation of poly(vinyl quaternary ammonium chloride)s with varying quaternary ammonium species starting from 4-vinyl benzyl chloride, except for two reports that contain specific derivatives such as poly(vinyl benzyl trimethylammonium chloride) and 4-vinyl benzyl dimethylhexadecylammonium chloride. [47][48][49] Considering that benzalkyl ammonium chlorides are widely used 50 as disinfectants, ophthalmic preservatives and antiseptics, quaternary ammonium polymers obtained by the quaternization of homo-and copoly(4-vinyl benzyl chloride) can be potentially used as antimicrobial agents. Thus, in spite of the usefulness of this approach for preparing a diverse range of homo-and copoly(vinyl quaternary ammonium and imidazolium chloride)s, a facile route for preparing these polymers conveniently from readily available starting materials has not been reported.…”