User talk:Youngeun92

Introduction

Benzalkonium chloride (BAC) is a major non-alcohol-based active ingredient used for clinical, food line, and domestic household biocides (16,19). A biocide is a general term for a chemical agent, that may be applied topically in/on living tissue (antiseptic) or on inanimate objects (disinfectant), in order to inhibit growth of (“-static”) or kill (“-cidal”) microorganisms (20). In communities where people are in constant contact with one another and surfaces covered with microorganisms, hand hygiene is important for infection control (16,26,30,31). Studies found the use of antiseptic hand sanitizers subdued the prevalence of the common cold, acute respiratory syndromes, gastroenteritis, viral influenza, and more (1,14,17,24,26,27,31). Similarly, this practice is important in limiting hospital-acquired, or nosocomial, infections between patients and clinical staff by limiting spread of opportunists like Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSAs), and vancomycin-resistant Enterococcus (VREs) (4,8,12,16,18,29). For such preventative measures, there are a variety of hand sanitizers available with alcohol and alcohol-free antiseptic agents including ethanol, triclosan and benzalkonium chloride (16,20). Recently alcohol-free hand sanitizers with triclosan or benzalkonium chloride have been gaining ground due to concerns that ethanol is dries out the skin, is too toxic, and there are frequent cases of intentional ingestion (9,13,16) Additional concerns involve the extensive use of antiseptics risking the selective survival of antiseptic resistant pathogens, which may be simultaneously selecting for antibiotic resistance (10,21,25,29). This theory of simultaneous or “cross-selection” suggests that selection of either antiseptic or antibiotic resistance will also select for the other, ultimately resulting in weaker antibacterial therapy and pressure for careful use of both biocides (1,7,25,28). Despite speculations of evolving resistance mechanisms, BACs are extensively used biocides especially efficacious against enveloped microorganisms (16,19,20).

General Mode of Antiseptic Activity

Since the discovery of penicillin, research of antibiotic mechanisms garnered much attention with widespread studies dissecting details of resistance against vancomycin , β-lactams, and other antibiotics (12,15,32). In contrast, studies on the mechanistic details of particular antiseptics remains largely inconclusive aside from the generality that antiseptics have less specific activities at multiple targets compared to antibiotics (18, 20). This broad level of activity is well summarized by McDonnell and Russell (1999), as the antiseptic first interacting with the cell surface, then penetrating into the cell, and finally acting at intracellular target sites. Sheldon (2005) further suggests that the details behind each antiseptic depend on the biocide’s chemical nature, the pathogen, and the test conditions (including but not limited to antiseptic concentration, pH, time of exposure, and temperature). In this way, antiseptic mechanisms lack mechanistic details, but the general activity is still well agreed upon.

Quaternary Ammonium Compounds (QACs):

BACs are classified as Quaternary Ammonium Compounds, which are positively charged derivatives of ammonium compounds with the chemical formula NR4+, where R can be different carbon-hydrogen containing groups (23). QACs are commonly used as antiseptic agents because of their cationic amphiphilic property, having a distinct hydrophobic and hydrophilic region, resulting from nucleophilic substitution of alkyldimethylamine and benzyl chloride (10). BAC’s hydrophilic cationic region destabilizes the pathogen’s surface by forming electrostatic interactions with negatively charged components (10,20,32). These interactions effectively outcompete the divalent cations, which normally stabilizes surface structures by linking adjacent negatively-charged components (10,20,32). Once close contact is accomplished by the hydrophilic region, the BAC’s hydrophobic region proceeds to penetrate the hydrophobic bilayer to cause cell leakage and lysis (10,19,20). The ultimate effect of BACs is to damage the pathogen’s membrane, thus for bacteria, disrupting essential cell processes like ATP synthesis or solute uptake (20). Therefore BAC’s amphiphilicity is critical in interacting with and perturbing target membranes for efficacious antimicrobial action.

Susceptible Microorganisms

The key component of BAC’s antimicrobial activity is membrane destruction, which is most effective against Gram-positive bacteria, some Gram-negative bacteria, some enveloped viruses, fungi, yeasts and protozoa (10). a)Non-sporulating Gram-positive bacteria: Staphylococcus aureus is a Gram-positive bacterium that can survive on antiseptic-free hands for at least 150 minutes, which is enough time for it to spread and persist as a leading cause of nosocomial infections (16). However, S. aureus is readily killed with BACs because their cell walls are chiefly composed of slightly-negatively-charged peptidoglycan and techoic acids (10,20). These surface structures also lack effective permeability properties and allow uptake of more BACs and other antimicrobial substances (10,20).

b)Enveloped viruses: Some viruses require a lipid envelope, which serves a dual function: first, as a protective barrier from harsh environmental conditions of pH or desiccation, and secondly as an undesirable target for BAC-based antiseptics (20). Therefore, enveloped viruses like HIV, HBV, influenza, measles, vaccinia, meningopneumonitis, semliki forest virus, canine distemper, rabies, fowl laryngotracheitis, and feline pneumonitis are all susceptible to BACs (2,20,24).