Cetrimide 0.2% / Benzalkonium chloride 0.01% cream

Biocidal agents used for disinfection are usually not suspected to enhance cross-resistance to antibiotics. The aim of this review was therefore to evaluate the effect of 13 biocidal agents at sublethal concentrations on antibiotic resistance in Gram-negative species. A medline search was performed for each biocidal agent on antibiotic tolerance, antibiotic resistance, horizontal gene transfer, and efflux pump. In cells adapted to benzalkonium chloride a new resistance was most frequently found to ampicillin (eight species), cefotaxime (six species), and sulfamethoxazole (three species), some of them with relevance for healthcare-associated infections such as Enterobacter cloacae or Escherichia coli. With chlorhexidine a new resistance was often found to ceftazidime, sulfamethoxazole and imipenem (eight species each) as well as cefotaxime and tetracycline (seven species each). Cross-resistance to antibiotics was also found with triclosan, octenidine, sodium hypochlorite, and didecyldimethylammonium chloride. No cross-resistance to antibiotics has been described after low level exposure to ethanol, propanol, peracetic acid, polyhexanide, povidone iodine, glutaraldehyde, and hydrogen peroxide. Taking into account that some biocidal agents used in disinfectants have no health benefit (e.g., in alcohol-based hand rubs) but may cause antibiotic resistance it is obvious to prefer products without them.

Abstract licence: CC BY

BackgroundDue 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.MethodsA 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.ResultsMechanisms 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.ConclusionsLaboratory 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.

Abstract licence: CC BY

PurposeTo provide an overview of artificial tears marketed in the following Nordic countries: Denmark, Finland, Norway, Iceland and Sweden. Furthermore, this review aimed to highlight the different preservatives and other constituents found in artificial tears in the Nordic market, focussing on adverse effects.MethodsArtificial tears appearing in online pharmacies in Denmark, Norway, Sweden, Finland and Iceland were included, and tables listing their components were created. Based on the preservatives and other constituents found in the artificial tears on the Nordic market, a literature search was conducted to investigate differences and potential adverse effects. This was achieved using PubMed with MeSH and free text search terms. Included articles were (i) studies performed on humans in vivo or in vitro human models, (ii) published between 2000 and 2023 and (iii) focussing on adverse effects, preservatives, toxicity, other constituents and preservative-free artificial tears.ResultsA total of 88 artificial tears were found on the Nordic market. Approximately 32% (28 out of 88) of the artificial tears contain preservatives. Eleven of these are preserved with benzalkonium chloride (BAK) or cetrimide. After a thorough literature search, evidence has been found for the toxic effects of BAK and cetrimide. There is no evidence of toxic effects of lubricants, osmoprotectants and lipids.ConclusionsThe findings of this review highlight the paradoxical fact that many treatments for ocular surface diseases contain toxic preservatives that may lead to worsening of the condition. In particular, long-time toxic effects of BAK may contribute to disease progression.

Abstract licence: CC BY-NC-ND