benzethonium chloride
Regulatory sources consulted
Approved indications
- First aid to help prevent infection and temporarily relieve pain in minor cuts, scrapes, and burns.
Clinical warnings
- Major warning · For external use only and flammable. Do not use in the eyes, on large areas, or for more than 1 week unless directed. Seek advice first for deep or puncture wounds, bites, or serious burns; stop if the condition worsens, persists, recurs, or infection develops. — DailyMed/openFDA, SPL set ID 036fd504-0cda-60ab-e063-6394a90a2f18
Pregnancy and lactation
No specific recommendation is established during pregnancy or breastfeeding.
Recent literature (PubMed)
This review examined 3655 articles on benzalkonium chloride (BKC), benzethonium chloride (BZT) and chloroxylenol (CHO) aiming to understand their impact on antimicrobial resistance. Following the application of inclusion/exclusion criteria, only 230 articles were retained for analysis; 212 concerned BKC, with only 18 for CHO and BZT. Seventy-eight percent of studies used MIC to measure BKC efficacy. Very few studies defined the term 'resistance' and 85% of studies defined 'resistance' as <10-fold increase (40% as low as 2-fold) in MIC. Only a few in vitro studies reported on formulated products and when they did, products performed better. In vitro studies looking at the impact of BKC exposure on bacterial resistance used either a stepwise training protocol or exposure to constant BKC concentrations. In these, BKC exposure resulted in elevated MIC or/and MBC, often associated with efflux, and at time, a change in antibiotic susceptibility profile. The clinical relevance of these findings was, however, neither reported nor addressed. Of note, several studies reported that bacterial strains with an elevated MIC or MBC remained susceptible to the in-use BKC concentration. BKC exposure was shown to reduce bacterial diversity in complex microbial microcosms, although the clinical significance of such a change has not been established. The impact of BKC exposure on the dissemination of resistant genes (notably efflux) remains speculative, although it manifests that clinical, veterinary and food isolates with elevated BKC MIC carried multiple efflux pump genes. The correlation between BKC usage and gene carriage, maintenance and dissemination has also not been established. The lack of clinical interpretation and significance in these studies does not allow to establish with certainty the role of BKC on AMR in practice. The limited literature and BZT and CHO do not allow to conclude that these will impact negatively on emerging bacterial resistance in practice.
Benzethonium chloride (BZT) is an excipient used in numerous products including (R,S)-ketamine (ketamine) drug formulations for human and veterinary use. Emerging evidence indicates BZT is pharmacologically active. BZT may therefore contribute to some of the clinical or preclinical effects observed with ketamine. In the present study, we evaluated: (i) the affinity of BZT for neurotransmitter receptors and transporters, (ii) the effects of BZT on hippocampal synaptic transmission in vitro, and (iii) plasma and brain concentrations of BZT following its intraperitoneal administration to male CD1 mice. Radioligand binding assays determined the affinity of BZT for neurotransmitter targets. Effects of BZT on field excitatory postsynaptic potentials (fEPSPs) were established via electrophysiological recordings from slices collected from male C57BL/6J mice. The binding assays revealed that BZT binds to numerous receptors (e.g., σ2 Ki = 7 nM) and transporters (e.g., dopamine transporter Ki = 545 nM). Bath application of BZT potentiated hippocampal fEPSPs in mouse hippocampal slices with an EC50 of 2.03 nM. Following intraperitoneal administration, BZT was detected in the plasma, but not in the brain of mice. These data highlight that studies measuring peripheral endpoints or directly exposing systems, in vitro, intracerebroventricularly, or intracortically, to BZT-containing formulations should account for the direct effects of BZT. Our findings also suggest that earlier data attributing pharmacological effects to ketamine may be confounded by BZT and that additional investigation into the functional impact of BZT is warranted. This article is part of the Special Issue on 'Ketamine and its Metabolites'.
The recent global pandemic has resulted in increased use of quaternary ammonium compounds (QACs). Currently, QACs are active ingredients in 292 disinfectants recommended by the US EPA for use against SARS-CoV-2. Among QACs, benzalkonium chloride (BAK), cetrimonium bromide (CTAB), cetrimonium chloride (CTAC), didecyldimethylammonium chloride (DDAC), cetrimide, quaternium-15, cetylpyridinium chloride (CPC), and benzethonium chloride (BEC) were all identified as potential culprits of skin sensitivity. Given their widespread utilization, additional research is needed to better classify their dermal effects and identify other cross-reactors. In this review, we aimed to expand our knowledge about these QACs to further dissect its potential allergic and irritant dermal effects on healthcare workers during COVID-19.
Background: The unprecedented outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has dramatically changed the global approach to public health, emphasizing the importance of measures to control and prevent infections. In response to the COVID-19 crisis, stringent hygiene practices and surface disinfection have become the norm, with an unprecedented surge in the use of disinfectants and antiseptics (DAs). Main Text: While these measures have been crucial in curbing the spread of the virus, an emerging concern has taken center stage: the potential impact of the prolonged and widespread use of antimicrobial compounds in these products on the development of antibiotic resistance. Antimicrobial resistance (AMR) has long been recognized as one of the most pressing global health threats. Quaternary ammonium compounds (QAC) such as benzalkonium chloride, benzethonium chloride, and cetylpyridinium chloride, which are extensively used in DAs formulations, have gained less attention in the context of AMR. Conclusion: A high abundance of QACs was detected in wastewater, and certain bacteria such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterococcus species developed resistance to these compounds over time. We analyzed the available evidence from the scientific literature, examining the presence and concentrations of QACs in different water sources, and their resistance mechanisms. This review aimed to shed light on the multifaceted challenges that arise from the dual battle against the COVID-19 pandemic and the ongoing global fight against AMR.