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13/11/2012 Gabor Pozsgai MD. Faculty of Medicine University of Pécs 2012 • Inhibition of pathogen cell division • Elimination of pathogens 1 13/11/2012 • Antimicrobial drugs – chemoterapeutics – may be given systemically • Disinfectants and antiseptics – cannot be used systemically • Urinary antiseptics are given systemically, but exert their action locally in the urinary tract • Antiseptics – applied topically to mucous membranes or skin • Disinfectants – toxic, only for non sterilizable instruments and objects 2 13/11/2012 • Phenol coefficient – effect of compounds is compared to that of 5% phenol • The more concentrated the solution the less time is needed for it to exert its effect • • • • • Bacteriostatic/bactericidal Sporocidal Virucidal Fungicidal Parasiticidal 3 13/11/2012 • • • • • • • • • Alcohols and glycols Aldehydes Phenols and derivatives Acid derivatives Halogens and halogen containing compounds Oxidizing agents Metals Surface active detergents Other compounds • Aliphatic alcohols – ethanol, isopropanol – antimicrobial activity increases with number of carbon atoms – 70% solution is the most active 4 13/11/2012 • Aliphatic alcohols – do not kill parasites and bacterial spores – solutions have to be filtered through 0.22 μm pores – hydrogen peroxyde shlould be added – may be used to the skin – aerosol can be used to clean ventilators – mostly in combinations • Glycols – triethylene glycol – fumes are used to sterilize air 5 13/11/2012 • Widest spectrum – bactericidal, sporocidal, virucidal, fungicidal • React with amino moieties of proteins – proteins are precipitated – damage tissues – mostly applied to objects • Formaldehyde – gaseous – formalin • saturated solution containing 34-38% – 10% solution may be used to mucous membranes – explosive when mixed with sodium hypochlorite – often combined with anionic detergents 6 13/11/2012 • Formaldehyde – the gas is used to sterilize rooms – solid polymer is used – releases formaldehyde if treated with steam – may be explosive if too concentrated • Methenamine – urinary antiseptic – releases formaldehyde in acidic urine – often combined with mandelic acid 7 13/11/2012 • Glutaraldehyde – used to sterilize instruments – 24.5% glutaraldehyde in 70% isopropanol at pH7.5-8.5 – very toxic to tissues • have to be cleaned from instruments • sodium bisulfite or sterile water – can be combined with anionic detergents • Phenol – now obsolete – at least 1-2% solution is needed – 5% is toxic and precipitates proteins – gets into the CNS and damages plasma membranes – excitatory symptoms, hypothermia, fainting – only used for objects and discharges 8 13/11/2012 • Cresol – poorly soluble in water – mixed with anionic detergents – bactericidal, parasiticidal – more active at high temperatures • • • • Amylmetacresol Chlorcresol Thymol Hexylresorcinol – urinary antiseptic 9 13/11/2012 • Hexachlorophene – bacteriostatic and fungistatic – surgical hand antiseptic – were used for newborns – may be absorbed and damages the CNS – carbanilide and salicylanilide derivatives are used instead – these cause rashes and photosensitivity • Chlorhexidine – not effective against Pseudomonas and Serratia – used to the skin throat and wounds – 4% chlorhexidine gluconate 10 13/11/2012 • Boric acid – 5% solution or powder – binds to pyridoxine – sodium tetraborate in glycerol is used for oral thrush of infants – boric acid in vaseline – may be used for vaginal irrigation – very toxic in children if absorbed • Benzoic acid – preservative in food and drugs – esters of paraoxybenzoic acid are more suitable – methyl, ethyl, propyl or benzyl esters 11 13/11/2012 • Salicylic acid – used in dermatology – fungicidal and keratolytic – relieves itch and sweating – dissolved in alcohol, as dermal patch, ointment and paste • Mandelic acid – urinary antiseptic – decreases pH of urine to 5.0 12 13/11/2012 • Iodine – bactericidal, sporocidal, virucidal, fungicidal – low tissue toxicity • Tincture of iodine – alcoholic solution containing 5% iodine and 4% potassium iodide – potassium iodide inhibits formation of toxic hypoiodides – degraded when exposed to light – the solution gets lighter • Lugol's iodine – 5% iodine dissolved in potassium iodide – antithyroid effect 13 13/11/2012 • Povidone-iodine – water soluble iodine complex of polyvinylpyrrolidone – surgical antiseptic – also used for wounds and vaginal irrigation • Povidone-iodine – causes local reddening and burning sensation in the skin – liberates histamine from mast cells – alcoholic solutions may irritate mucous membranes – iodine may cause allergy and anaphylaxis 14 13/11/2012 • Chlorine – gaseous – used to sterilize water – hypochlorous acid is formed and disintegrates to hydrochloric acid and oxygen – more active at higher temperatures – damages metals, plastics, rubber and textiles – precipitates on surface of large dirt crumbs • Hypochlorites – damage bacterial membranes – form chloramines with amino groups of proteins – bactericidal, sporocidal, virucidal • Bleaching powder – calcium hypochlirote – badly damages tissues – used for walls, lavatories, pools, water 15 13/11/2012 • Sodium hypochlorite – used for wounds with boric acid – explosive if mixed with formalin • Chloramine B – benzene derivative – more stable, less toxic – chlorogen, halazone • Sodium dichloroisocyanuric acid – pH should be set to 6.2-6.8 – release corrosive chlorine gas at lower pH • Bactericidal, virucidal, fungicidal • Large quantities of organic material compromises effectivity • Corrosive • Hydrogen peroxide – catalase releases nascent oxygen – short lasting effect – inactivated by trace heavy metals – corrosive for metals 16 13/11/2012 • Hydrogen peroxide – 0.3-3% for contact lenses, throat, ears, eyes and wounds – if used in body cavities, resulting gases have to be drained – 10% solution is coagulant – 30% is astringent – crystals formed with urea are sold in tablets for solution – stabilized and combined with detergents is used for instruments • Peroxyacetic acid – instable – corrodes brass, iron and zinc • Potassium permanganate – 0.1-0.5% solution – colours tissues – used for wounds 17 13/11/2012 • Mercury – reacts with thiol groups of proteins – inactivates enzymes and precipitates proteins • Inorganic compounds are obsolete – damage host proteins, too – – – – – mercuric chloride (corrosive sublimate) mercuric oxide mercuric cyanide mercuric amidochloride mercuric sulfide • Organic mercury compounds – less toxic – antifungal – spermicide – active against Trichomonas – toxic effects may be treated with glutathione or cysteine 18 13/11/2012 • Phenylmercuric borate – 0.02% for skin and mucous membranes • Thiomersal – ethylmercuric thiosalicylilate sodium • Merbromin – dibromhydroxymercuric fluorescein sodium • Silver – silver ions damage tissues and precipitate proteins – protein bound and colloidal silver is less toxic • Silver nitrate – astringent and wound treatment • Silver acetate – 1% eyedrop for newborns against gonorrhoea – now obsolete 19 13/11/2012 • Clean surfaces and promote penetration of antiseptics • Anionic detergents – sodium or potassium salts of fatty acids – alkaline when dissolved in water – irritate skin – no antiseptic effect – used in combination – inactivate cationic detergents • Cationic detergents – antiseptic properties – bactericidal/bacteriostatic, antifungal – increase permeability of plasma membranes – most important ones contain quaternary nitrogen – inactivated by anionic detergents 20 13/11/2012 • Cationic detergents – adsorbed to fibrous, porous materials – may be removed by such substances – form film layer on the skin – microbes may thrive under the film – can be used to clean instruments and objects • Benzalkonium chloride • Cetylpyridinium bromide • Non-ionic detergents – no antiseptic activity – do not inactivate cationic detergents – used in combination • Zwitterionic detergents – also called amphoteric detergents – positive and negative charge within the same molecule – antiseptic effect – provide long lasting bacteriostatic and fungistatic effect if dried on instrumets 21 13/11/2012 • Azo dyes • Triphenylmethane dyes – strong antiseptics – organic materials inhibit their action • Crystal violet – hexamethyl pararosaniline chloride – for wounds against Gram positive bacteria – anthelmintic effect • Fuchsine – rosaniline hydrochloride • Acridine dyes • Proflavine – for gums and throat – mutagenic • Acriflavine – developed by Ehrlich against African Trypanosomiasis • Methylene blue – methylthioninium chloride – urinary antiseptic 22 13/11/2012 • Sulfur – fungicidal and parasiticidal • Fatty acids • Undecylenic acid, propionic acid – antifungal activity • Cleaning of objects from living pathogens, bacterial spores and viruses • Physical methods • Heat • Dry heat – Incineration – Hot air oven • for glassware – Pasteurization • 30 min at 65°C, then 5 min at 85°C – Boiling • textiles 23 13/11/2012 • Moist heat • Autoclave – 20 min at 121°C on 107.8 kPa or 10 min at 134°C on 205.9 kPa – saturated high pressure steam – chemical and biological indicators are used to check effectivity • Filtration – heat sensitive fluids – 0.22 μm pores • Chemical methods • Gas sterilization • Ethylene oxide – heat-sensitive instruments, plastics, optical instruments, transfusion instruments – alkilates thiol groups of proteins – flammable – mixed with carbon dioxide or fluorinated hydrocarbons – items should be wrapped prior to sterilization – traces of the substance should be removed – items are aired for days – chemical and biological indicators are used 24