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chemical non medicinal antimicrobials

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  2. 2. <ul><li>Terminology of Chemical Antimicrobial Agents: </li></ul><ul><li>Sterilant: Sterilization – Sterilant – Sterile. </li></ul><ul><li>Disinfectant: kills the vegetative forms – does not kill their spores. – used on inanimate objects. </li></ul><ul><li>Germicide: kills vegetative form but not their spores. </li></ul><ul><li>Antiseptic: applied to the surface of the body – prevent multiplication, (either by killing Mos or by inhibiting their growth and metabolic activities. (Often used on cuts or abrasions to prevent infection). </li></ul><ul><li>Sanitizer: microbial populations could not exceed specific numbers. Agent that kills 99.9% of microorganisms contaminating an area. – commonly applied to inanimate objects. </li></ul>
  3. 3. Characteristics of an Ideal chemical agent. <ul><li>An Ideal antimicrobial chemical agent would have characteristics that make it effecctive under all conditions. </li></ul><ul><li>The specifications for an ideal chemical agent can be : </li></ul><ul><li>Antimicrobial activity: inhibit or kill microbes. (Broad and Narrow) </li></ul><ul><li>Solubility: Soluble in water or other suitable solvents </li></ul><ul><li>Stability: Storage of the substance for reasonable periods should not result in significant loss of antimicrobial action. </li></ul><ul><li>Lack of toxicity: It should not harm humans or animals. </li></ul><ul><li>Homogeneity: Preparation should be uniform in composition so that active ingredients are present in each application. </li></ul>
  4. 4. <ul><li>6. Minimum inactivation by extraneous material: when combine with proteins or other organic materials found in the substance being treated, this decreases the amount of the chemical available for action against microorganism. </li></ul><ul><li>7. Activity at ordinary temperatures: It should not be necessary to raise the temperature beyond that normally found in the environment were the agent is to be used. </li></ul><ul><li>8. Ability to penetrate: Unless the chemical can penetrate the surface, its antimicrobial action is limited to the site of application. </li></ul><ul><li>9. Material safety: The compound should not rest or other wise disfigure metals, nor should it stain or damage fabrics. </li></ul><ul><li>10. Deodorizing ability: The agent should either be oderless or have a pleasant smell. </li></ul><ul><li>11. Detergent ability: Should has cleansing properties </li></ul><ul><li>12. Availability and low cost: The product should be readily available and inexpensive. </li></ul>
  5. 5. <ul><li>EFFECTIVENESS OF ANTIMICROBIAL AGENT ACTIVITY: </li></ul><ul><li>The efficiency of an antimicrobial agent is affected by at least six factors. </li></ul><ul><li>Population size: Larger population requires a longer time to die. </li></ul><ul><li>Population composition: Effectiveness of an agent varies greatly with the nature of the organisms being treated. </li></ul><ul><li>Concentration/Intensity of an antimicrobial Agent: More concentrated a chemical agent or intense a physical agent, the more rapidly microorganisms are destroyed. </li></ul><ul><li>Exposure time: Longer exposure , the more organisms are killed. </li></ul><ul><li>Temperature: Lower concentration of disinfectant or sterilizing agent can be used at a higher temperature. </li></ul><ul><li>Local Environment: The population to be controlled is not isolated but surrounded by environmental factors that may either offer protection or aid in its destruction. </li></ul>
  6. 6. DISINFECTANTS <ul><li>Applied to non living objects to destroy microorganisms, the process of which is known as disinfection. </li></ul><ul><li>Antibiotics – that destroy microorganisms within the body. </li></ul><ul><li>Sanitizers - substances that reduce the number of microorganisms to a safe level. </li></ul><ul><li>sanitizers must be capable of killing 99.999%, known as a 5 log reduction, of a specific bacterial test population, and to do so within 30 seconds. </li></ul>
  7. 7. <ul><li>Properties: </li></ul><ul><li>Disinfectant must be effective against a wide variety of infectious agents (gram +ve and gram –ve bacteria, acid fast bacteria, bacterial endospores, fungi and viruses) at high dilutions and in the presence of organic matter. </li></ul><ul><li>The disinfectant must have the following properties: </li></ul><ul><ul><li>The chemical must be toxic for infectious agent. </li></ul></ul><ul><ul><li>Should not be toxic to people </li></ul></ul><ul><ul><li>Should be stable upon storage. </li></ul></ul><ul><ul><li>Should be oderless or with a pleasant odor. </li></ul></ul><ul><ul><li>Should be soluble in water and lipids for penetration into microorganisms. </li></ul></ul><ul><ul><li>Should have a low surface tension </li></ul></ul><ul><ul><li>Should be relatively inexpensive. </li></ul></ul>
  8. 8. <ul><li>Classification of Chemical disinfectants: </li></ul><ul><li>Strong Disinfectants: for articles eg; formalin solution </li></ul><ul><li>Mild Disinfectants (Antiseptics): can be appled to soft tissue and skin. eg; ethyl alcohol, iodine, soap etc. </li></ul><ul><li>Mechanism of Action of Disinfectants: act by denaturing or altering proteins or lipids or interfere with energy yielding systems or inhibit some steps of the metabolic pathways. </li></ul><ul><li>Concentration of the disinfectant: some disinfectant had to be diluted once or twice to be used. Care must be taken not to over dilute the disinfectant. </li></ul>
  9. 9. <ul><li>Advantages of Disinfectants: </li></ul><ul><li>Decontamination of objects before disposal or reuse: Phenols and hypochlorite solutions. </li></ul><ul><li>Reduction of microbes in the environment: Phenol, formaldehyde gas, hypochlorite solution, 70% alcohol or methylated spirit. </li></ul><ul><li>Disinfection of the skin of hands and operation site on the patient: an aqueous solution of cholorhexidine, 1% iodine or 70% alcohol. </li></ul>
  10. 10. <ul><li>TYPES OF DISINFECTANTS: </li></ul><ul><li>Alcohols: </li></ul><ul><li>Ethanol or isopropanol – skin (wide microbiocidal activity, non corrosive but can be a fire hazard. </li></ul><ul><li>More effective combined with purified water – 70% isopropyl alcohol or 62% ethyl alcohol is more effective than 95% alcohol. </li></ul><ul><li>Not effective against fungal or bacterial spores. </li></ul>
  11. 11. <ul><li>Aldehydes: </li></ul><ul><li>Glutaraldehyde have a wide microbiocidal activity and are sporocidal and fungicidal. </li></ul><ul><li>Partly inactivated by organic matter. </li></ul>
  12. 12. <ul><li>Halogens: </li></ul><ul><li>Chloramine – used in drinking water treatment. </li></ul><ul><li>- Chlorine – used to disinfect swimming pools and small amount to reduce waterborne diseases in drinking water. </li></ul>
  13. 13. <ul><li>Halogens: </li></ul><ul><li>Hypochlorites (Sodium hypochlorite) – common household bleach to disinfect drains and toilets. </li></ul><ul><ul><ul><li>Calcium hypochlorite – swimming pool additive. </li></ul></ul></ul><ul><ul><ul><li>Hypochlorous acid – is true disinfectant. </li></ul></ul></ul><ul><ul><ul><li>Hypobromite solution also sometime used. </li></ul></ul></ul><ul><li>Iodine – dissoved in an organic solvent or as Lugol’s iodine solution. – poultry industry. Added to birds drinking water. </li></ul><ul><ul><ul><li>Tincture of iodine has also been used as an antiseptic for skin cuts and scrapes. </li></ul></ul></ul><ul><li>Chloramine-T is antibacterial </li></ul>
  14. 14. <ul><li>Oxidizing agents: </li></ul><ul><li>Act by oxidising the cell membranes. </li></ul><ul><li>Chlorine dioxide – advanced disinfectant for drinking water. Sodium chlorite, sodium chlorate and potassium chlorate are used as precursors for generating chlorine dioxide. </li></ul><ul><li>Hydrogen peroxide – in hospitals to disinfect surface, also in food packaging industry. 3% used as antiseptic. </li></ul><ul><li>Ozone is a gas that can be added to water for sanitation. </li></ul><ul><li>Acidic Electrolyzed water - strong oxidising solution. Anolyte has a typical PH 3.5 to 8.5 and an Oxidation – Reduction Potential (ORP) of +600 to +1200mV. </li></ul><ul><li>Peracetic Acid – Hydrogen peroxide + acetic acid. – Broadly effective </li></ul><ul><li>Potassium permagnanate – red crystalline powder – disinfect aquariums, swimming pools, mouth before pulling out teeth., and wounds. </li></ul><ul><li>Potassium peroxymonosulfate – wide spectrum disinfectant for labs. Virkon kills bacteria, viruses and fungi. It is used as a 1% solution in water, keeps for one week once it is made up. </li></ul>
  15. 15. <ul><li>Phenolics: </li></ul><ul><li>Active ingredients in some household disinfectants. </li></ul><ul><li>Phenol – (carbolic acid) – rather corrosive and sometime toxic to sensitive people. </li></ul><ul><li>O-phenylphenol – less corrosive </li></ul>
  16. 16. <ul><li>Chloroxylenol – Dettol – household disinfectant and antiseptic. </li></ul><ul><li>Hexachlorophene – phenolic – germicidal additive. </li></ul><ul><li>Thymol – Herb thyme – 100% botanical disinfectant with an EPA registration (#74771-1). </li></ul>
  17. 17. <ul><li>Quaternary ammonium compounds: </li></ul><ul><li>Quats – benzalkonium chloride. </li></ul><ul><li>Biocides - also kill algae. </li></ul><ul><li>Use in Large scale industrial water system. </li></ul><ul><li>Also against enveloped viruses. </li></ul>
  18. 18. <ul><li>Other: </li></ul><ul><li>Biguanide Polymer polyaminopropyl biguanide </li></ul><ul><li>High intensity shortwave ultraviolet light </li></ul>
  19. 19. SELECTIVE TOXICITY <ul><li>The principle of selective toxicity is to have a negative effect on an organism with minimum effect on thehost. </li></ul><ul><li>This can be brought about by drugs which exploit differences between the invading organism and the host. </li></ul><ul><li>1. By inhibiting cell wall synthesis </li></ul><ul><li> e.g. Penicillins, cephalosporins </li></ul><ul><li> Human cells do not have a cell wall, so these drugs are specific only for bacteria. They will kill or stop replication of the bacteria without damaging the host. </li></ul><ul><li>2. Altering cell wall permeability </li></ul><ul><li>3. Inhibition of protein synthesis </li></ul><ul><li> e.g. Tetracyclins, aminoglycosides, chloramphenicol, erythromycin </li></ul><ul><li>Selective toxicity relies on the fact that the bacterial ribosome differs in size to the human ribosome </li></ul><ul><li>4. Inhibition of nucleic acid synthesis </li></ul><ul><li>Affect microbial specific enzymes, e.g. DNA dependent RNA polymerase </li></ul><ul><li>5. Antimetabolites </li></ul><ul><li>Affect the metabolism of the organism by having a negative effect on some vital </li></ul><ul><li>metabolite. Humans are unable to synthesise folate and so must get it from the food, </li></ul><ul><li>whereas bacteria must make their own. Hence, inhibition of folate metabolism can hinder bacterial growth. </li></ul><ul><li>e.g. Trimethoprim </li></ul>
  20. 20. <ul><li>Chemotherapy of bacterial infections </li></ul><ul><li>Antibiotics were initially isolated from one species of organism and were found to inhibit the growth of another. </li></ul><ul><li>There are a number of very important criteria which need to be considered when trying to optimise treatment for a bacterial infection: </li></ul><ul><li>1. Spectrum of activity of the drug/any resistance </li></ul><ul><li>Use a drug which is effective against the infecting organism. Hence, cultures should be taken to try and identify the organism first before initiating antimicrobial therapy. </li></ul><ul><li>Also, cultures of the organism can be tested to see whether or not they are resistant to any antibiotic. Once we have this sensitivity data? it is possible to modify the therapy by choosing agents to which the organism is not resistant. </li></ul><ul><li>Narrowest spectrum antibiotics are specific for certain bacteria and hence limit the spread of resistance. Broad spectrum antibiotics not only affect the bacteria in question, but many others which are present . </li></ul><ul><li>Also the dose and duration needs to be considered. Subtherapeutic doses often lead to resistance. </li></ul>
  21. 21. <ul><li>2. Toxicity profile and patient factors </li></ul><ul><li>Sometimes an alternative drug needs to be used if a person has an allergic reaction to the drug being used (common in penicillin). </li></ul><ul><li>Patient factors such as age and any underlying disease needs to be considered – often the dose needs to be altered to prevent toxicity. e.g. A lot of’ drugs are excreted by the kidney and kidney function in the elderly is often decreased. Chloramphenicol in the young can be toxic since its metabolism is dependent on the liver. which is immature (may lack certain metabolic enzymes) in the neonate. </li></ul>
  22. 22. <ul><li>3. Combination of agents </li></ul><ul><li>Sometimes a combination of drugs may be useful (e.g. amoxycillin with clavulanic acid), while other combinations may not be. </li></ul><ul><li>4. Bacteristatic vs. bactericidal </li></ul><ul><li>In an immunocompetent host, a bacteristatic agent may be sufficient to limit the infection but may not be appropriate in an immuno compromised host. In these cases, a bactericidal agent is better. </li></ul><ul><li>Often there is pressure from patients to prescribe a certain antibiotic. e.g. Treatment of a streptococcal throat infection is often with prescription of penicillin. However, if no antibioitic treatment were given then the person would recover in about the same time - hence there is no benefit in using an antibiotic (more likelihood of side effects and development of resistance), However. if the doctor does not prescribe penicillin and the patient is expecting it, then problems may arise with the doctor patient relationship. </li></ul>
  23. 23. <ul><li>Agents affecting cell wall synthesis (antibacterial) </li></ul><ul><li>Beta lactams are the commonest of these agents </li></ul><ul><li>Beta lactams include: </li></ul><ul><ul><li>Penicillins </li></ul></ul><ul><ul><li>Cephalosporins </li></ul></ul><ul><ul><li>Carbapenems </li></ul></ul><ul><ul><li>Monobactams </li></ul></ul><ul><ul><li>Beta lactamase inhibitors </li></ul></ul><ul><li>Other agents which inhibit cell wall synthesis and are non beta lactams are: </li></ul><ul><ul><li>Bacitracin </li></ul></ul><ul><ul><li>Vancomycin </li></ul></ul><ul><ul><li>Cycloserine </li></ul></ul>