LO11 PC2 ANTI-INFECTIVE AGENTSTerminology Anti-infective aka antimicrobial General term referring to drugs active against pathogensAntibiotic aka antibacterial active against bacteriaChemoprophylaxis prophylactic use of a medicationPathogenicity ability of an organism to cause disease in a humanVirulence severity of disease that an organism is able to cause; a highly virulent pathogens causes disease when present in very small numbersAcquired Resistance when a microbe is no longer affected by an anti-infectiveNephrotoxicity adverse effect on the kidneysHepatotoxicity an adverse effect on the liver Ototoxicity an adverse effect on hearingSuperinfection condition caused when a microorganism grows rapidly as a result of having less competition in its environment

Common Human Pathogens Viruses Gram (+) organisms: enterococci, streptococci and staphylococci Gram (-) organisms: E.coli, Bacteroides, Klebsiella, Proteus, Pseudomonas Opportunistic Community-acquired vs. nosocomial

Common Bacterial Pathogens StaphylococciCommon in wounds , URIs and pneumonia (MRSAresistant strain) StreptococciCommon infection in URIs, ear infections & pneumonia EnterococciCommon infection in UTIs & wounds (VREresistant strain) Escherichia coliUTIs; GI infection most commonly related to contaminated ground beef KlebsiellaCauses respiratory tract infections, UTIs, bloodstream, burn wound infections PneumococciMost common cause of pneumonia in children; otitis media ProteusCause UTIs and wound infections PseudomonasCause respiratory tract infections, UTIs, wound & burn wound infections (high resistance to many antibiotics)

Definitions and Standards for Removing Microorganisms (Block and Beale, 11th edition) Antisepsis Application of an agent to living tissue for the purpose of presenting infection.Decontamination Destruction or marked reduction in the number of activities of microorganisms.Disinfection Chemical or physical treatment that destroys most vegetative microbes or viruses, but nut spores, in or on inanimate surfaces.Sanitization Reduction of microbial load on an inanimate surface to a level considered acceptable for public health purposes. Sterilization A process intended to kill or remove all types of microorganisms, including spores, and usually including viruses with an acceptably low probability of survival.Pasteurization A process that kills non-sporulating microorganisms by hot water or steam at 65-100 degrees Centigrade.Sterilants, Antiseptics and Disinfectants Sterilants, antiseptics and disinfectants are evaluated by: intrinsic resistance of the microbe, the microbial load, the mixture of the population of microorganisms present, the amount and nature of organic material present, the concentration and stability of the disinfectant or sterilant, the time and temperature of exposure, the pH, the hydration and binding of the agent to the surface.

Extensively used in hospitals and other health care settings for a variety of topical and hard-surface applications. Chemical agents present are alcohols, phenols, iodine, and chlorine.Most demonstrate broad-spectrum antimicrobial activity.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC88911/

Antiseptics Diverse class of compounds Applied to skin surfaces or mucous membranes for anti-infective effects. Bacteriocidal or bacteriostatic. Uses: cleansing of skin and wound surfaces after injury, preparation of skin surfaces prior to injections or surgical procedures, routine disinfection of the oral cavity as part of a program of oral hygiene, disinfection of inanimate objects, including instruments and furniture surfaces. For skin cleaning - benzalkonium chloride, chlorhexidine, hexachlorophine, iodine compounds, mercury compounds, alcohol and hydrogen peroxide. Chlorhexidine - oral rinses and preoperative total body washes. Benzalkonium chloride and hexachlorophine - hand scrubs or face washes. Iodine compounds like tincture of iodine and povidone iodine have the broadest spectrum compared to all topical anti-infectives, with action against bacteria, fungi, viruses, spores, protozoa, and yeasts. Hydrogen peroxide acts through the liberation of oxygen gas, which may be useful for wound cleansing through removal of tissue debris. Thimerosal (Mersol) is a mercurcontains Hg and has activity against bacteria and yeasts. Prolonged use may result in mercury toxicity.

Precautions: Hypersensitivity reactions for chlorhexidine, benzalkonium and hexachlorophine. Skin dryness and irritation for products containing alcohol. Systemic toxicity from ingestion of iodine or mercury compounds. Chlorhexidine should not be instilled into the ear. Iodine compounds should be used sparingly during pregnancy and lactation due to risk of infant absorption of iodine with alterations in thyroid function. Interactions Antiseptics should not be used together with any other topical cream, solution, or ointment.http://medical-dictionary.thefreedictionary.com/Antiseptics

Alcohols and related compounds 1 aliphatic alcohols are germicidal. Potency increases but water solubility decreases with chain length until amyl alcohol (6 carbons) is reached.Do not destroy bacterial spores. 70% Ethyl alcohol (ethanol) and 50% isopropyl alcohol (isopropanol) are the most widely used.http://www.merckmanuals.com/vet/pharmacology/antiseptics_and_disinfectants/alcohols.html Alcohol is produced by fermentation from grain and carbohydrates or by sulfuric acidcatalyzed hydration of ethylene. Denatured alcohol is ethanol that has been rendered unfit for use in intoxicating beverages by the addition of other substances. Completely denatured alcohol contains added wood alcohol (methanol) and benzene and is unsuitable for internal or external use. Specially denatured alcohol is ethanol treated with one or more substances so that its use may be permitted for a specialized purpose, eg. For preparation of tincture of iodine.Isopropanol is slightly more potent than ethanol due to its greater depression of surface tension. Rubbing alcohol is a mixture of alcohols, with isopropanol as its principal ingredient. It is used as a skin disinfectant and rubefacient. The primary medicinal use of alcohol is external, as an antiseptic, preservative, mild counter-irritant, or solvent.http://www.merckmanuals.com/vet/pharmacology/antiseptics_and_disinfectants/alcohols.html Alcohol is metabolized in the human body by a series of oxidations.Alcohol is used in the practice of pharmacy for the preparation of spirits. tinctures, and fluidextracts. Spirits are preparations containing ethanol as the sole solvent. Tinctures are hydroalcoholic mixtures.Dehydrated Ethanol, USP or absolute ethanol contains not less than 99% w/w of C2H5OH, prepared commercially by azeotropic distillation of an ethanol:benzene mixture, with efficient removal of water. This is used primarily as a chemical reagent or solvent but has been injected for the local relief of pain in carcinomas and neuralgias. Isopropyl Alcohol, USP or Isopropanol (2-propanol) is considered a substitute for ethanol in most cases but must not be ingested. Iso-PrOH is prepared commercially by the sulfuric acidcatalyzed hydration of propylene. Iso-PrOH is used primarily as a disinfectant for the skin and for surgical instruments. The alcohol is rapidly bactericidal from 50 to 95%. Azeotropic iso-PrOH USP, is used on gauze pads for sterilization of the skin prior to hypodermic injections and in pharmaceuticals and toiletries as a solvent and preservative.Ethylene oxide (EO), has been used to sterilize temperature-sensitive medical equipment and certain pharmaceuticals that cannot be heat sterilized in an autoclave. EO effectively destroys all forms of microorganisms at ambient temperatures. EO forms explosive mixtures in air at concentrations ranging from 3 to 80% by volume. The explosion hazard is eliminated when the gas is mixed with sufficient concentrations of carbon dioxide. Carboxide is a commercial sterilant containing 10% EO and 90% carbon dioxide.

The mechanism of the germicidal action of EO probably involves the alkylation of functional groups in nucleic acids and proteins by nucleophilic opening of the oxide ring. EO is a nonselective alkylating agent and as such is extremely toxic and potentially carcinogenic. Exposure to skin and mucous membranes should be avoided. and inhalation of the gas should he prevented by use of an appropriate respiratory mask during handling and sterilizalion procedures.

Aldehydes Formaldehyde Solution, USP - colorless aqueous solution containing not 8.5), glutaraldehyde polymerizes. Non-buffered solutions are acidic, possibly because of an acidic proton on the hemiacetal form. The acidic solutions are stable but had sporocidal activity.

Phenols and derivatives Phenolic compounds denature proteins and are general protoplasmic poisons.Phenol (carbolic acid) bacteriostatic at concentrations of 0.11% , bactericidal/fungicidal at 12% , 5% solution kills anthrax spores in 48 hr. Bactericidal action enhanced by EDTA and warm temperatures; decreased by alkaline medium (through ionization), lipids, soaps, and cold temperatures. Concentrations >0.5% exert local anesthetic effect, 5% solution strongly irritating and corrosive to tissues. Oral ingestion or extensive application to skin can cause systemic toxicity - CNS and cardiovascular effects; death may result.Used for disinfection of equipment or organic materials that are to be destroyed (eg, infected food and excreta). Not used much as an antiseptic except to cauterize infected areas, eg, infected umbilicus of neonates. Incorporated into cutaneous applications for pruritus, stings, bites, burns, etc, because of its local anesthetic and antibacterial properties to relieve itching and control infections.

Liquefied Phenol, USP is phenol containing 10% water. This is a convenient way of adding phenol to a variety of pharmaceutical preparations because of ease of measurement and facility of transferring.

p-Chlorophenol is used in combination with camphor in liquid petrolatum as an external antiseptic and anti-irritant. The compound has a phenol coefficient of ~4.

p-Chloro-m-xylenol (PC-MX: Metasep) is a non-irritating antiseptic agent with broad-spectrum antibacterial and antifungal properties, marketed at 2% concentration as a shampoo, and used topically for the treatment of tinea (ringworm) infections such as athlete's foot (tinea pedis and jock itch (tinea cruris). Hexachlorophene, USP (pHisoHex) is a biphenol possessing greater potency than a monophenol. Increased degree of chlorination, increases its antiseptic potency further.Hexachlorophene is easily adsorbed onto the skin and enters the sebaceous glands. Because of this, topical application elicits a prolonged antiseptic effect, even in low concentrations.Hexachlorophene is used in concentrations of 2-3% soaps. detergent creams, lotions, and shampoos for a variety of antiseptic uses. It is, in general, effective against Gram (+) bacteria, but many Gram (-) bacteria are resistant.Banned for OTC antiseptic and cosmetic preparations, but still available by prescription.

Cresol, NF is actually a mixture of three isomeric methylphenols:The mixture occurs as a yellow to brownish-yellow liquid that has a characteristic odor of creosote. Obtained from coal tar or petroleum by alkaline extraction into aqueous medium, acidification, and fractional distillation. The mixture is an inexpensive antiseptic and disinfectant possessing a phenol coefficient of 2.5. Cresol is sparingly soluble in water, although alcohols and other organic solvents will solubilize it. Drawback to its use as an antiseptic is its unpleasant odor.

Chlorocresol, NF occurs as colorless crystals. Slightly soluble in water and is useful only as a preservative.

Thymol. NF or isopropyl m-cresol is extracted from oil of Thymus vulgaris or thyme by partitioning into alkaline aqueous medium followed by acidification. The crystals obtained from the mother liquor are large and colorless, with a thyme-like odor. It is only slightly soluble in water, but extremely soluble in alcohols and other organic solvents. It has mild fungicidal properties and is used in alcohol solutions and in dusting powders for the treatment of tinea (ringworm) infections.

Eugenol, USP obtained from clove oil. Slightly soluble in water but is miscible with alcohol and other organic solvents. Possesses both local anesthetic and antiseptic activity and can used to relieve toothaches. Also used in mouthwashes because of its antiseptic property and pleasant taste. Phenol coefficient is 14.4.

Resorcinol, USP. m-Dihydroxybenzene (resorcin) is prepared synthetically. It crystallizes as white needles or as an amorphous powder that is soluble in water and alcohol. Resorcinol is light sensitive and oxidizes readily, much less stable in solution, especially at alkaline pH. Resorcinol is only a weak antiseptic (phenol coefficient 0.4), but it is used in 1 to 3% solutions and in ointments and pastes in concentrations of 10 to 20% for the treatment of skin conditions such as ringworm, eczema. Psoriasis and seborrheic dermatitis. It is also a keratolytic agent. This property causes the stratum corneum of the skin to slough, opening the barriers to penetration for antifungal agents.

Hexylresorcinol, USP 4-Hexylresorcinol, or hexylresorcinol is a white crystalline substance with a faint phenolic. When applied to the tongue it produces a sensation of numbness. Hexylresorcinol is an effective antiseptic, possessing both hactericidal and fungicidal properties. The phenol coefficient against S. aureus is 98. Possesses surfactant properties and local anesthetic activity. It is formulated into throat lozenges because of its mild anesthetic and antiseptic properties. The compound (in the concentration present in lozenges) is probably not antiseptic, but the local anesthetic property can anesthetize the larynx.

Pine tar is a viscid blackish brown liquid, used primarily for antiseptic bandaging of wounds of the hoof and horn. Pine tar has antimicrobial properties.

Chloroxylenols are broad-spectrum bactericides with more activity against gram-(+) than gram (-) bacteria. They are active in alkaline pH; however, contact with organic matter diminishes their activity. Streptococci are more susceptible than staphylococci.

Parachloro-metaxylenol (PCMX) and dichlorometaxylenol (DCMX) are most commonly used members of this group. DCMX > active than PCMX.

A 5% chloroxylenol solution (in -terpineol, soap, alcohol, and water) is diluted with water (1:4) for skin sterilization and (1:25 to 1:50) for wound cleansing and irrigation of the uterus and vagina. PCMX is also combined with hexachlorophene to enhance its antibacterial spectrum and to prevent contamination by gram-negative organisms.http://www.merckmanuals.com/vet/pharmacology/antiseptics_and_disinfectants/phenols_and_related_compounds.html

Oxidizing agents (OA) Value as germicidal agents depend on their ability to liberate oxygen in the tissues. Many are inorganic cornpounds, including H2O2, a number of metal peroxides and sodium perborate. All react in the tissues to generate oxygen and oxygen radicals. Other OA, such as KMnO4, denature proteins in microorganisms through a direct oxidation reaction. OA are effective against anaerobic bacteria and can be used in cleansing contaminated wounds. The bubbles that form during the liberation of oxygen help to dislodge debris. Effectiveness of OA is limited by their generally poor penetrability into infected tissues and organic matter. Additionally, the action of the oxidizers is typically transient.

PEROXIDESHydrous Benzoyl Peroxide, USP. Hydrous benzoyl peroxide (Oxy-5. Oxy- 10. Vanoxide) is a white granular powder. In its pure powder form it is explosive. The compound is formulated with 30% water for safe handling. Compounded at 5 and 10% concentrations. benzoyl peroxide is both keratolytic and keratogenic. It is used in the treatment of acne. Benzoyl peroxide induces proliferation of epithelial cells, leading to sloughing and repair.

Hydrogen peroxidesolution (3%) liberates oxygen when in contact with catalase present on wound surfaces and mucous membranes. The effervescent action mechanically helps remove pus and cellular debris from wounds and is valuable for cleaning and deodorizing infected tissue but of short duration and is limited to the superficial layer of the applied surface. Hydrogen peroxide is finding increased application as a disinfectant in water treatment and food processing facilities and for sterilization of dental and surgical instruments.Recently developedaccelerated hydrogen peroxide(AHP) formulations are synergistic blends of 0.52% hydrogen peroxide with anionic and non-ionic surfactants and stabilizers that possess broad-spectrum antimicrobial activity. They are effective against bacteria, spores, mycobacteria, viruses, and fungi, with short contact times. AHP formulations are non-irritating to eyes and skin and are biodegradable, decomposing to water and oxygen with no active chemical residues. They have become leading disinfectants in human hospitals and dental clinics in recent years. A disadvantage is the potential to damage soft metals, such as brass, copper, and aluminum, and carbon-tipped instruments.

Sodium perborate, used in antiseptic solutions and in mouthwashes, acts by decomposing into sodium metaborate and hydrogen peroxide, which then gradually liberates oxygen.Benzoyl peroxideslowly releases oxygen to act as an antiseptic. However, it can cause skin irritation. It also has keratolytic and antiseborrheic activity, which makes it useful in treating pyoderma in dogs.

Peracetic acidhas been recognized only recently as a useful sterilant and antiseptic, has broad antimicrobial spectrum and lack of harmful decomposition products of hydrogen peroxide with greater lipid solubility and freedom from inactivation by tissue catalase and peroxidase. It has been accepted worldwide in the food industry, including meat and poultry processing plants and dairies. It is effective against bacteria, yeasts, fungi, and viruses at conc. of 0.0010.003% and is sporicidal at 0.250.5%, 0.2% solutions applied to compresses are effective at reducing microbial populations in severely contaminated wounds.

Potassium permanganatehas broad antimicrobial properties, but staining property is a disadvantage. It is an effective algicide (0.01%) and virucide (1%) for disinfection, but concentrations >1:10,000 tend to irritate tissues. Easily degraded.

Halogen-containing compounds Iodine and chlorine are used as topical antimicrobial agents. They owe their activity to high affinity for protoplasm, where they are believed to oxidize proteins and interfere with vital metabolic reactions.

Elemental iodine is a potent germicide with a wide spectrum of activity and low toxicity to tissues. 50 ppm I2 solution kills bacteria in 1 min and spores in 15 min. It is poorly soluble inwater but readily dissolves in ethanol, which enhances its antibacterial activity.Iodine tincture contains 2% iodine and 2.4% sodium iodide (NaI) dissolved in 50% ethanol; and used as a skin disinfectant.

Strong iodine tincture contains 7% iodine and 5% potassium iodide (KI) dissolved in 95% ethanol; it is more potent but also more irritating than tincture of iodine. Iodine solution contains 2% iodine and 2.4% NaI dissolved in aqueous solution; it is used asa nonirritant antiseptic on wounds and abrasions.Strong iodine solution (Lugol's solution) contains 5% iodine and 10% KI in aqueous solution.

Iodophores (eg, Povidone-iodine) are water-soluble combinations of iodine with detergents, wetting agents that are solubilizers, and other carriers. They slowly release iodine as an antimicrobial agent and are widely used as skin disinfectants, particularly before surgery. They do not sting or stain. Iodophores are nontoxic to tissues but may be corrosive to metals. They are effective against bacteria, viruses, and fungi but less so against spores. Iodophor solutions retain good antibacterial activity at pH