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Chemicals vary greatly in their ability to kill microorganisms. A quantitative measure of this variation is expressed as the phenol coefficient, which is the ratio of the concentration of phenol to the concentration of the agent required to cause the same amount of killing under the standard conditions of the test.
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Chemical agents act primarily by one of the three mechanisms: (1) disruption of the lipid-containing cell membrane, (2) modification of proteins, or (3) modification of DNA. Each of the following chemical agents has been classified into one of the three categories, but some of the chemicals act by more than one mechanism.
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DISRUPTION OF CELL MEMBRANES
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Ethanol is widely used to clean the skin before immunization or venipuncture. It acts mainly by disorganizing the lipid structure in membranes, but it denatures proteins as well. Ethanol requires the presence of water for maximal activity (i.e., it is far more effective at 70% than at 100%). Seventy percent ethanol is often used as an antiseptic to clean the skin prior to venipuncture. However, because it is not as effective as iodine-containing compounds, the latter should be used prior to obtaining a blood culture and installing intravenous catheters. Ethanol will not kill bacterial spores and therefore cannot be used for sterilization.
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Detergents are “surface-active” agents composed of a long-chain, lipid-soluble, hydrophobic portion and a polar hydrophilic group, which can be a cation, an anion, or a nonionic group. These surfactants interact with the lipid in the cell membrane through their hydrophobic chain and with the surrounding water through their polar group and thus disrupt the membrane. Quaternary ammonium compounds (e.g., benzalkonium chloride) are cationic detergents widely used for skin antisepsis. Benzalkonium chloride is the active ingredient in Lysol, a commonly used disinfectant for floors and other surfaces.
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Phenol was the first disinfectant used in the operating room (by Lister in the 1860s), but it is rarely used as a disinfectant today because it is too caustic. Chlorhexidine is a chlorinated phenol that is widely used as a hand disinfectant prior to surgery (“surgical scrub”) and in the cleansing of wounds. Phenols not only damage membranes, but also denature proteins.
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MODIFICATION OF PROTEINS
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Chlorine is used as a disinfectant to purify the water supply and to treat swimming pools. It is also the active component of hypochlorite (bleach, Clorox), which is used as a disinfectant in the home and in hospitals. Chlorine is a powerful oxidizing agent that kills by cross-linking essential sulfhydryl groups in enzymes to form the inactive disulfide.
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Iodine is the most effective skin antiseptic used in medical practice and should be used prior to obtaining a blood culture and installing intravenous catheters because contamination with skin flora such as Staphylococcus epidermidis can be a problem. Iodine, like chlorine, is an oxidant that inactivates sulfhydryl-containing enzymes. It also binds specifically to tyrosine residues in proteins.
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Iodine is supplied in two forms:
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Tincture of iodine (2% solution of iodine and potassium iodide in ethanol) is used to prepare the skin prior to blood culture. Because tincture of iodine can be irritating to the skin, it should be removed with alcohol.
Iodophors are complexes of iodine with detergents that are frequently used to prepare the skin prior to surgery because they are less irritating than tincture of iodine. They are also used to disinfect the skin of health-care personnel. Povidone-iodine (Betadine) is an iodophor commonly used as an antiseptic.
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Mercury and silver have the greatest antibacterial activity of the heavy metals and are the most widely used in medicine. They act by binding to sulfhydryl groups, thereby blocking enzymatic activity. Thimerosal (Merthiolate) and merbromin (Mercurochrome), which contain mercury, are used as skin antiseptics. Silver nitrate drops are effective in preventing gonococcal neonatal conjunctivitis (ophthalmia neonatorum). Silver sulfadiazine is used to prevent infection of burn wounds.
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Hydrogen peroxide is used as an antiseptic to clean wounds. Its effectiveness is limited by the organism’s ability to produce catalase, an enzyme that degrades H2O2. (The bubbles produced when peroxide is used on wounds are formed by oxygen arising from the breakdown of H2O2 by tissue catalase.) Hydrogen peroxide is an oxidizing agent that attacks sulfhydryl groups, thereby inhibiting enzymatic activity.
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Formaldehyde & Glutaraldehyde
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Formaldehyde, which is available as a 37% solution in water (formalin), denatures proteins and nucleic acids. Both proteins and nucleic acids contain essential –NH2 and –OH groups, which are the main sites of alkylation by the hydroxymethyl group of formaldehyde. Glutaraldehyde, which has two reactive aldehyde groups, is 10 times more effective than formaldehyde and is less toxic. In hospitals, it is used to sterilize respiratory therapy equipment, endoscopes, and hemodialysis equipment.
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Ethylene oxide gas is used extensively in hospitals for the sterilization of heat-sensitive materials such as surgical instruments and plastics. It kills by alkylating both proteins and nucleic acids (i.e., the hydroxyethyl group attacks the reactive hydrogen atoms on essential amino and hydroxyl groups). It is classified as a mutagen and a carcinogen.
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Strong acids and alkalis kill by denaturing proteins. Although most bacteria are susceptible, it is important to note that Mycobacterium tuberculosis and other mycobacteria are relatively resistant to 2% NaOH, which is used in the clinical laboratory to liquefy sputum prior to culturing the organism. Weak acids, such as benzoic, propionic, and citric acids, are frequently used as food preservatives because they are bacteriostatic. The action of these acids is partially a function of the organic moiety (e.g., benzoate), as well as the low pH.
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MODIFICATION OF NUCLEIC ACIDS
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A variety of dyes not only stain microorganisms, but also inhibit their growth. One of these is crystal violet (gentian violet), which is an antiseptic used to treat fungal infections of the skin. Its action is based on binding of the positively charged dye molecule to the negatively charged phosphate groups of the nucleic acids. Malachite green, a triphenylamine dye like crystal violet, is a component of Löwenstein-Jensen medium, which is used to grow M. tuberculosis. The dye inhibits the growth of unwanted organisms in the sputum during the 6-week incubation period.