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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.
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.
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.
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.
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.
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.
Insusceptibility 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.
Microorganisms are not totally defenseless to environmental stress. Variations in susceptibility pattern towards biocides resulted from varation in microbial intrinsic factors such as
Phenotypic change; Microorganisms could be naturally found in physically protective environment 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. More ever the combination of biofilms from different bacteria species have higher resistance effect towards biocides of single bacteria species.
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.
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 .
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. 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, chlorhexidine gluconate, and povidine iodine. 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.
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. Additionally, some isolated has higher minimum inhibition concentration than the wild type strains 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 biocides.
Benzalkonium chloride in twelve studies have showed adaptation after being exposed to sub-minimum inhibition concentration for 7 to 30 days in some strains. The minimum inhibition concentration increase for more than 1.5-100 fold. Even without the presence of BK in the growing media the tolerance of benzalkonium chlorids were stable in subsequent generations. In one paper the minimum inhibition concentration 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.
Chlorhexidine is the common kind of disinfectant used in the hospitals. It is obtained in freebase and in stable salt form such as chlorhexidine diacetate (CHA), chlorhexidine dihydrochloride, chlorhexidine digluconate, chlorhexidine gluconate (CHG) and chlorhexidine phosphanilate. Ten studies have showed the evolvement of chlohexidine tolerant strains after they exposed to sub-inhibitory concentration of chlorhexidine. Hospital isolated methicillin-resistant S. aureus (HA-MRSA), intermediate resistance to vancomycin (VISA), methicillin-susceptible S. aureus (MSSA) have displayed higher minimum inhibition concentration to chlorhexidine compared with environmental isolate strain. In this particular paper isolate with qac genes connected with higher MIC. The mechanism of action for the development of tolerance is the cumulative factors of reduced permeability, efflux pump, and horizontal gene transfer.
Triclosan is the type of biocides obtained mostly in consumer products. The name triclosan mostly named after biocidal tolerance. Nine papers has proven that the existence of triclosan adaptation by microbes. One study has indicated that 0.0004% exposure of triclosan can induce resistance. Reduced membrane permeability and efflux pump plays a significant role in the development of tolerance by different bacteria besides that horizontal gene transfer plays a role in the circulation the resistance gene between different bacteria. We can't conclude that triclosan exposure to certain bacteria's can leads to tolerance, for example, no tolerance of triclosan noticed after 1 and 4 ?g/ml of triclosan exposure to eight L. monocytogenes straines.
Others biocides such as dicamba (Kamba), 2,4-dichlorophenoxyacetic acid, glyphosate, eugenol were perceived when different strains of E.coli increase their tolerance after they being exposed to different concentration of those biocides for different days. Three studies has been mentioned different E.coli strain tolerated didecyl dimethyl ammonium chloride (DDAC) as a result of sub-minimum inhibitory concentration exposure for extended period. Additionally, three studies investigated on Thymol, demonstrated that sub-lethal exposure E.coli could induce tolerance.
However, this not true all the time some other bacteria show no change on the minimum inhibition concentration when we compare it with their parent generation.
Additionally, some isolated has higher minimum inhibition concentration than the wild type of strains. This isolate are mostly identified around the hospital environment than in the community setting
Tolerance induced by one type of biocides could incudes other biocidal tolerance, this has been demonstrated in different studies. Adaptation to quaternary ammonium compound could induced tolerance towards biocides such as acriflavine and triclosan. Furthermore, benzalkonium chloride-resistant enterica serovar Virchow co-resistant to biocide chlorhexidine, the partent strain were not resistant to chlorhexidine. But in the same study didn't demonstrate the converse, chlorhexidine resistance were not co-resistance to benzalkonium chlorides.
Suggesting specific resistance mechanism rather than generic mechanisms. But In another study, chlorhexidine resistance Pseudomonas stutzeri were co-resistant to different biocides in different level including benzalkonium chloride such as cetylpyridinium chloride and triclosan. After Escherichia coli and Listeria monocytogenes strains exposure to didecyl dimethyl ammonium chloride (DDAC) for seven days resulted in the increasing of the minimum inhibition concentration by three fold. DDAC resistant strains demonstrated higher co-resistance to benzalkonium chloride and Galox Horizon containing DDAC and glutaraldehyde.
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