Biocides are a products that contain one or more active substances and preparations that are anticipated to exterminate, control and remove harmful microorganism to human, animals and manufacture products (1). Each services in hospital depends on the effectiveness of disinfectants, without disinfectants hospitals may not undergo their day to day activities. Biocides used in health facilities for disinfecting any surfaces and materials that potentially contain pathogens. Additionally biocides used as an antiseptics to remove pathogens from mucous membrane and damaged patient skin and also used for health professional’s skin (2) (3).
Furthermore biocides are widely used for different purpose other than hospitals such as; – In consumer products; soaps, detergents, wipers, toothpastes and cosmetics. In food industry; mainly used as preservative in production, storage and transportation process. In animal husbandry; direct application of disinfectants on the skins during milk production and disinfecting animal’s facilities, vehicles and materials mainly between the bathes and during infection outbreak. In water treatment; disinfectants used for elimination and prevention of pathogens and molds in drinking water, waste water and cooling towers (3).
The efficacy, spectrum and mechanism of action are some of the determining factor of biocides classification, these factors are also the bases for biocides selection. The spectrum of biocides can be bacteriostatic; only prevent bacterial growth and multiplication, after the disinfectants removal the bacteria begin to regenerate and grow. Disinfectants can be bactericidal; a chemicals that eliminate all form of bacteria except spores. Disinfectants can also be Sporicidal; are disinfectants that are potent enough to eliminate spores (2).There are different kind of biocides based on their functional group includes;- derivatives of imidazole, phenols, alcohols, organic acids and esters, Aromatic diamidines, aldehydes, amines, quarternary ammonium compounds (QATs), Antimicrobial dyes, Bromine, halogen compounds, ionic silver and nanosilver, oxidizing agents, isothiazolones, and biguanides.
All these groups of biocides are also used in hospital and non-hospital related areas (4).The complete biocides target and mechanism of action is complicated and not well-understand but cell wall, cell membrane, cellular proteins, cytoplasmic constitute (nucleic acids, ribosomes different), specific groups( thiol, amino and sulphydryl group) are the targets of biocides in general (4) (5) (6).Biocides Products Targets Mechanism Alcohol Ethanol2-Propanol2-Phenoxyethanol Cytoplasmic Membrane Protein Increase permeabilityProtein denaturationAldehydes GlutaraldehydeFormaldehydeGlyoxal Cell wallCytoplasmic constituentsProtein denaturation Cross-linkingGeneral coagulationProtein denaturationAmines DiethylamineGlucoprotamin Cell wallCytoplasmic membrane Cross-linkingIncreased permeabilityHalogen compounds(oxidizing) Sodium hypochloriteChlorine dioxideCalcium hypochlorite Nucleic acidsOuter membrane Specific groups IntercalationIncrease permeabilityThiol, Sulphydryl groupsQuarternary ammonium compounds (QATs) Benzalkonium chlorideDidecyldimethylammoniumchlorid Cell wall Cytoplasmic “membraneProtein Cross-linkingIncrease permeabilityMembrane potential and- electron transport chainEnzyme inhibitionBiguanides ChlorhexidinePolyhexamethylenbiguanid (PHMBAlexidine Outer membrane Cytoplasmic membraneCytoplasmic constituents Increase permeabilityIncrease permeabilityGeneral coagulationEnzyme inhibitionPhenolics Triclosan Outer membraneCytoplasmic membraneCytoplasmic constitute Increase permeabilityIncrease permeability General coagulationEnzyme inhibitionOxidizing agents Hydrogen peroxideSodium persulfate Nucleic acidsBiocides induce autocidal activitiesRibosomesSpecific groups Intercalating Accumulation of free radicleGeneral coagulationThiol, Sulphydryl groupsOrganic acids and esters Parabens Benzoic acidPropionic acid Salicylic acidFormic acid Nucleic acidsCytoplasmic membrane IntercalatingIncrease permeabilityTransport inhibitionIsothiazolinones ChlormethylisothiazolinoneIsothiazolinone (CMIT/MIT) EnzymesSpecific groups InhibitionThiol, Sulphydryl groupsIodine and iodophors Iodine and iodophors Specific groups Thiol groupsHexachlorophine Hexachlorophine Cytoplasmic membraneCytoplasmic constitute Increase permeability Transport inhibitionGeneral coagulationHeavy metal derivative MercurySilverCopper Outer Cell membraneproteinNucleic acids Increase permeability InhibitionIntrinsic defensive factors of bacteriaInsusceptibility is the phenomena used to indicate resistance due natural factors, whereas the word tolerance and resistance are used to indicate the existence of strains that have high minimum inhibition concentration (MIC) compared with other sensitive strain. To be more precise, tolerance is used to indicate the adaptation to MIC whereas resistance used to expresses the adaptation of minimum biocidal concentration (MBC) (6). Microorganisms are not totally defenseless to the environmental stress. Variations in susceptibility pattern towards biocides resulted from varation in microbial intrinsic factors such as Phenotypic change; – Microorganisms could be found in physical environments such as biofilms, endospores and intracellularlly which potentially decrease the efficiency of biocides from getting access to microorganisms. The study shows significant reduction of susceptibility of E.coli towards hydrogen peroxide or chlorine dioxide and quaternary ammonium compounds in the presence of biofilms (6) (7). More ever the combination of biofilms from different bacteria species have higher resistance effect towards biocides of single bacteria species (8) (9). Spore is a complex structure which enable bacteria to survive through different environmental stress including disinfectants. Spore known to provide high level of protection by creating physical barrier of bacterial internal and surface structure from stress in the environment. Most disinfectants that are bactericidal are not sporocidal. Some disinfectants has to be in higher in concentration to be sporocidal (10) (11). Intrinsic reduced permeability barrier in mycobacteria emanated from mycobacteria cell wall structure. Which is found in mycobacterial cell wall, this waxy cell wall prevent the entrance of disinfectants and antiseptics into the cell. Low number of prion on the mycobacterial cell surface resulted in reduced bacteria permeability to hydrophilic agents and also due to the mycobacterial thick lipid bilayer structure the permeability of lipophilic agents is slower (12) (13). Gram negative bacteria are less sensitive against biocides than Gram positive bacteria’s these is due to the presence of outer membrane and outer membrane proteins (6). The difference in cell surface structure makes gram negative bacteria less susceptibility and less permeable than gram positive bacteria towards sodium dodecyl sulphate, hydrogen peroxide, sodium hypochlorite, phenol, ethylene diaminetetra acetic acid, chlorohexidine gluconate, and povidine iodine (14). Likewise, as a result of reduced permeability and uptake in gram negative bacteria they are relatively less sensitive to hydrocarbon biocides than gram positive bacteria (15) (16). Could bacteria resist or tolerate biocides? Biocidal mechanism of action is quite complex likewise the development of tolerance is not evidently understood. But after some microbes exposed to sub-lethal concentration of biocides for different generation they show higher minimum inhibition concentration than their parent generation. But it is not proven if all microbial are able to develop resistance or tolerance to all type of biocides. However, some studies are able to show the existence of resistance or tolerance towards some biocidesd (17) (18) (19) (20) (21) (22).Benzalkonium chloride have showed adaptation after being exposed to sub-minimum inhibition concentration of benzalkonium chloride(BK) for 7 to 30 days. The minimum inhibition concentration increase for more than 1.5-20 fold. Even without the presence of BK in the growing media the tolerance of benzalkonium chlorids were stable in subsequent generations. The minimum inhibition of E. coli ATCC 11775 increase from 25g/ml to 150g/ml. In adopted strain different tolerance mechanism has been identified such as active efflux pump, membrane impermeability, and horizontal gene transfer.
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