Chemical Antimicrobial Agents.pdf

Chemical Antimicrobial Agents Disinfection - Antimicrobial agents that are applied to the surface of non-living objects to destroy microorganisms - To clean surfaces in the dental surgery and agents used for cleaning instruments. - Reduction of the microbial population to acc...

Chemical Antimicrobial Agents Disinfection - Antimicrobial agents that are applied to the surface of non-living objects to destroy microorganisms - To clean surfaces in the dental surgery and agents used for cleaning instruments. - Reduction of the microbial population to acceptable lower levels for a defined purpose. o Low level: kills most vegetative bacteria, fungi and viruses, but does not include some of the more resistant micro-organisms o Intermediate level: kills all vegetative bacteria and most fungi and viruses o High level: kills all micro-organisms but not necessarily bacterial spores Antisepsis - Destruction or inhibition of microorganisms on living tissues - Adequate antimicrobial activity but not be toxic or irritating for tissue - Used before surgery or on a wound to help prevent spread of infections - Mouthwashes, root canal treatment medicaments, hand hygiene (e.g., isopropyl alcohol wipe). Preservation - Added in pharmaceutical preparations to prevent microbial growth and spoilage - In non-sterile products, micro-organisms may be introduced during manufacturing - Minimising the risk of contamination in sterile product due to administration - Commonly used preservatives in topical and transdermal products Comparison with other antimicrobials - Chemical antimicrobial agents (disinfectants, antiseptics, preservatives) are NOT selective to a certain type of micro-organism - DiNerent from anti- bacterial / fungal / viral / protozoal / parasitic agents, which are selective - Antibiotics is the subset of antibacterial agents that are natural biological structures. Antibacterial agents also include semi- or fully synthetic - Choice of antimicrobial agents - Chemical and physical properties of antimicrobial agents. o Corrosive, inflammable, viscosity, solubility in water, pH, etc. - Microbiological challenge. o Types of micro-organisms o Level of contamination (bioburden) - Intended application o Where the antimicrobial agent is used. o Whether for disinfection, antisepsis, or preservation. o Whether the agent aNects the pharmaceutical products. (prac 2) - Environmental factors: organic matters (e.g. blood, body fluid, saliva, etc) can alter the eNectiveness of antimicrobial agents. - Toxicity of the agent: whether the antimicrobial agent is safe to use. Antimicrobial agent mechanism Factors influencing antimicrobial agents - Concentration of antimicrobial agent o Higher the concentration, more eNective (Prac 2) - Temperature o Bactericidal activity is increased at higher temperature o Increasing the temperature is not always applicable o Degradation of antimicrobial agents o Other ingredients might be heat-sensitive - Acidity o For the antimicrobial molecule, changing pH may change the degree of ionisation o For the cells, changing pH may change the negative charges of bacterial cell wall Factors influencing antimicrobial agents - Interfering substances o Organic matter, such as serum, blood, pus, earth, food residues, milk, skin fats, may decrease the eNect o Surfactant, such as soap detergent § May increase the eNect by increasing bacterial cell permeability § May decrease the eNect by interacting with the antimicrobial agents - Micro-organism o Formation of biofilms o Natural resistance of micro-organisms o Microbial resistance due to density / growth conditions Natural resistance of micro-organisms - Proteinaceous infectious (prion) particles: made only of protein (lack of DNA) - WHO recommends the combined use of NaOH and autoclaving at 134°C - Recall Prac 2 Determination of MICs (s. epidermidis. vs e. coli) DiDerent phases of bacteria - Spores have a low water content - Spores are covered with tough materials - Some spores can resist boiling water and ethanol. - E.g., bacillus stearothermophilus, grow within a temperature range of 30 –75 °C. Its spores are used as biological indicators for sterilization. Growth of the spores after sterilization process indicates that the sterilization failed. DiDerent types of bacteria - Mycobacteria o Smallest bacteria o Low cellular permeability o Have a very thin cell wall (peptidoglycan layer is thin) and the cell wall consist of 60% of a hydrophobic waxy lipid. - Gram positive and negative o Gram+ bacteria have a thicker peptidoglycan cell wall. o Gram – bacteria have a thinner peptidoglycan and an additional lipopolysaccharide layer. Lipopolysaccharide provides additional protection. So, Gram- bacteria are more resistant to antimicrobial agents Microbial resistance due to density & growth condition. - The larger the number of micro-organisms (greater bioburden), the longer it takes to kill them. - Bacteria in logarithmic phase are more susceptible to antimicrobial agents than bacteria in stationary phase. - Antimicrobials target bacteria cell walls or the protein synthesis processes of DNA transcription and RNA translation. - In stationary phase, cells switch to a survival mode. Biofilms - A community of micro-organisms attached to a surface. - May consist of multiple bacterial species. - Biofilm causes severe medical problems. o Infection of implantable and indwelling (몸 안에 남는) medical devices, bio-corrosion of materials, tooth caries. o Bacteria as biofilms are several hundred times more resistant to microbial agents than free cells. o In nature most bacteria aggregate as biofilms Formation of biofilms - Conditioning layer: deposition of organic molecules (proteins) - Bacteria will strike and adsorb to the surface for some time, and then desorb - Attached bacteria excrete extracellular matrices (sticky polymers) - The biofilms are permeated at all levels by a network of channels - Biofilm spreads by releasing new “pioneer bacteria” to colonise downstream section Families of chemical antimicrobial agents - Alcohols - Aldehydes - Biguanides - Phenolic compounds - Halogens - Organic and inorganic acids - Heavy metal derivatives - Peroxygens - Surfactants Alcohol - Examples: ethanol and isopropanol - Usage: disinfectant, antiseptic, preservative (e.g. benzyl alcohol) - Mechanism: act on cell membrane, resulting in leakage of cell constituents - Application: 70% (below 50% ethanol is not eDective) - Advantage: Fast acting / compatibility / acts & evaporates / topical application - Disadvantage: Flammable/ poor penetration in organic matters Aldehydes - Example: formaldehyde (CH2O) - Usage: disinfection and sterilisation - Mechanism of action o Act on cell wall: covalently binding to cell wall o Act on cytoplasm: denature and coagulate proteins - Advantages o Rapid rate of kill o Highly eNective disinfectant o Organic matters have little eNect. - Disadvantages o Causes irritation o Toxic and carcinogenic. Biguanides - Example: Chlorohexidine - Usage: topical antiseptic: contact-lens solution, bladder irrigation, oral antiseptic in dental application - Advantages: Non-toxic to mucous membrane and skin - Disadvantages: Low solubility in water, low antimicrobial eNect - Recall chlorhexidine as a preservative for Cetomacrogol lotion (Prac 2) Phenolic compounds - Example: thymol and chlorocresol - Usage: disinfectants, preservatives, antiseptics - Mechanism of action: act on cell membrane - Advantages o Persistent o Good bacterial activity - Disadvantages o Poor aqueous solubility o Caustic eNect on skin and tissue. o Not to be used where they can contaminate the food/ o Activity is reduced in the presence of organic matters. Bisphenols: composed of two phenolic groups - Example: triclosan - Application: can be used as an antiseptics and preservative in soap, toothpaste, shower foams, deodorants and fabrics - Lower toxicity and irritancy than monophenolic compounds - Like mono-phenolic compound has low water solubility - In 2017, FDA rules: Companies will NOT be able to use triclosan or 23 other active ingredients in these products without premarket review due to insuNicient data regarding their safety and eNectiveness. Halogens - Chlorine compounds (e.g., sodium hypochlorite (NaClO) in Milton solutions) - Mechanism of action o Act on cell membrane: halogenation of amino acids in proteins. o In cell cytoplasm: inhibition of DNA synthesis. - Usage: o Disinfection of water supplies, surfaces, equipment. o Preservation of food. Iodine compounds - In comparison to chlorine compounds o Iodine has lower solubility and less irritant o Iodine is less susceptible to inactivation by organics o Iodine can stain skin and less eNective against spores - Povidone-iodine is designed using a similar approach to that of making polymerized quaternary ammonium compounds. - Organic and inorganic acids - Example: acetic acid (vinegar), benzoic acid(occurs naturally in many plants), salicylic acid (cosmetics), lactic acid (an ingredient in sweat) - Usage: widely used for preservation of food and pharmaceutical products; antifungal topical treatment; anti-acne - Mechanism of action: o On cell membrane: inhibition of energy processes in cell - Advantages o Low bactericidal activity o More toxic at lower pH value o Inactivated at higher pH value - Disadvantages o Low bactericidal activity o More toxic at lower pH value o Inactivated at higher pH value. Heavy metal derivatives - Example: silver, mercury, copper - Usage: o Mercury: prevent mould in painting o Copper: kill green algae in water reservoirs o Silver: antiseptics and preservatives in pharmaceutical products - Dental amalgam (silver -filling) is a mixture of mercury, silver, copper, tin and zinc used to fill cavities in teeth, being gradually replaced by resin -based composites - Advantages: Biocidal at low concentrations - Disadvantages: Corrosive / toxic to living cell Peroxygens - Example: hydrogen peroxide (H2O2 ) - Usage o Disinfectant of soft contact lenses o General disinfectant and antiseptic - Mechanism of action o Oxidise thiol groups in enzymes and proteins o Generate free hydroxyl radical (OH-) to damage DNA - Advantages o High level bactericidal activity o Environmentally friendly (biodegradable) o At high concentration / temperature kill bacterial spores - Disadvantages o Corrosive, irritant at high concentrations o Unstable, so benzoic acid is added as stabilizer Surfactants - Structure: have a hydrophobic group and a hydrophilic group - Mechanism of action o Breaks the oily film into tiny droplet oil o Microbes are removed mechanically by scrubbing and washed out by water - Two main types surfactants o Cationic: hydrophilic group ionise to cation o Anionic: hydrophilic group ionise to anion - Quaternary ammonium compounds (QACs) - Example: benzethonium chloride - Usage: food processing industry, antiseptic (skin, mucous membranes, throat infection), preservative (eye drops) - Mechanism of action: on cell cytoplasmic membrane: change the cell’s permeability and cause the leakage of cytoplasmic constituents - Advantages o Surface active – cleaning property o Non-toxic, stable at storage, no odour - Disadvantages o Low antimicrobial activity o Inactivated chemical agents. Preservation of medicine and cosmetics - Non-sterile product: to prevent the spoilage and degradation of product due to metabolic activity of micro-organisms - The rate of deterioration depends on o Type and quantity of micro-organisms o Physicochemical properties of environment o Molecular structure of chemicals in the product - Sterile products: to prevent microbial contamination during usage. - The rate of in-use contamination depends on o Type of the container o Operator – introduced contamination. DiDerent techniques of preservation