METRONIDAZOLE, MUPIROCIN, POLYMYXINS, & URINARY ANTISEPTICS
METRONIDAZOLE
Metronidazole is a nitroimidazole antiprotozoal drug (see Chapter 53) that also has potent antibacterial activity against anaerobes, including bacteroides and clostridium species. It is well absorbed after oral administration, is widely distributed in tissues, and reaches serum levels of 4-6 mcg/mL after a 250-mg oral dose. Metronidazole can also be given intravenously or by rectal suppository. The drug penetrates well into the cerebrospinal fluid and brain, reaching levels similar to those in serum. Metronidazole is metabolized in the liver and may accumulate in hepatic insufficiency.
Metronidazole is indicated for treatment of anaerobic or mixed intra-abdominal infections, vaginitis (trichomonas infection, bacterial vaginosis), C difficile colitis, and brain abscess. The typical dosage is 500 mg three times daily orally or intravenously (30 mg/kg/d). Vaginitis may respond to a single 2-g dose. A vaginal gel is available for topical use.
Adverse effects include nausea, diarrhea, stomatitis, and peripheral neuropathy with prolonged use. Metronidazole has a disulfiram-like effect, and patients should be instructed to avoid alcohol. Although teratogenic in some animals, metronidazole has not been associated with this effect in humans. Other properties of metronidazole are discussed in Chapter 53.
A structurally similar agent, tinidazole, is a once-daily drug approved for treatment of trichomonas infection, giardiasis, and amebiasis. It also is active against anaerobic bacteria, but is not FDA-approved for treatment of anaerobic infections.
MUPIROCIN
Mupirocin (pseudomonic acid) is a natural product produced by Pseudomonas fluorescens. It is rapidly inactivated after absorption, and systemic levels are undetectable. It is available as an ointment for topical application.
Mupirocin is active against gram-positive cocci, including methicillin-susceptible and methicillin-resistant strains of Staphylococcus aureus. Mupirocin inhibits staphylococcal isoleucyl tRNA synthetase. Low-level resistance, defined as a minimum inhibitory concentration (MIC) of up to 100 mcg/mL, is due to point mutation in the gene of the target enzyme. Low-level resistance has been observed after prolonged use. However, local concentrations achieved with topical application are well above this MIC, and this level of resistance appears not to result in clinical failure. High-level resistance, with MICs exceeding 1000 mcg/mL, is due to the presence of a second isoleucyl tRNA synthetase gene, which is plasmid-encoded. High-level resistance results in complete loss of activity. Strains with high-level resistance have caused nosocomial (hospital) outbreaks of staphylococcal infection and colonization. Although higher rates of resistance are encountered with intensive use of mupirocin, more than 95% of staphylococcal isolates are still susceptible.
Mupirocin is indicated for topical treatment of minor skin infections, such as impetigo (see Chapter 62). Topical application over large infected areas, such as decubitus ulcers or open surgical wounds, has been identified as an important factor leading to emergence of mupirocin-resistant strains and is not recommended. Mupirocin effectively eliminates S aureus nasal carriage by patients or health care workers, but results are mixed with respect to its ability to prevent subsequent staphylococcal infection.
POLYMYXINS
The polymyxins are a group of basic peptides active against gram-negative bacteria and include polymyxin B and polymyxin E (colistin). Polymyxins act like cationic detergents. They attach to and disrupt bacterial cell membranes. They also bind and inactivate endotoxin. Gram-positive organisms, proteus, and neisseria are resistant.
Owing to their significant toxicity with systemic administration, polymyxins have been largely restricted to topical use. Ointments containing polymyxin B, 0.5 mg/g, in mixtures with bacitracin or neomycin (or both) are commonly applied to infected superficial skin lesions. Emergence of strains of Acinetobacter baumannii and Pseudomonas aeruginosa that are resistant to all other agents has led to renewed interest in polymixins, eg, colistin as a parenteral agent for salvage therapy of infections caused by these organisms.
URINARY ANTISEPTICS
INTRODUCTION
Urinary antiseptics are oral agents that exert antibacterial activity in the urine but have little or no systemic antibacterial effect. Their usefulness is limited to lower urinary tract infections. Prolonged suppression of bacteriuria by means of urinary antiseptics may be desirable in chronic urinary tract infections in which eradication of infection by short-term systemic therapy has not been possible.
1. Nitrofurantoin
Nitrofurantoin is bacteriostatic and bactericidal for many gram-positive and gram-negative bacteria but P aeruginosa and many strains of proteus are resistant. There is no cross-resistance between nitrofurantoin and other antimicrobial agents and resistance emerges slowly. As Escherichia coli resistant to trimethoprim-sulfamethoxazole and fluoroquinolones has become more common, nitrofurantoin has become an important alternative oral agent for treatment of uncomplicated urinary tract infection.
Nitrofurantoin is well absorbed after ingestion. It is metabolized and excreted so rapidly that no systemic antibacterial action is achieved. The drug is excreted into the urine by both glomerular filtration and tubular secretion. With average daily doses, concentrations of 200 mcg/mL are reached in urine. In renal failure, urine levels are insufficient for antibacterial action, but high blood levels may cause toxicity. Nitrofurantoin is contraindicated in patients with significant renal insufficiency.
The dose for urinary tract infection in adults is 100 mg orally taken four times daily. It should not be used to treat upper urinary tract infection. Oral nitrofurantoin can be given for months for the suppression of chronic urinary tract infection. It is desirable to keep urinary pH below 5.5, which greatly enhances drug activity. A single daily dose of nitrofurantoin, 100 mg, can prevent recurrent urinary tract infections in some women.
Anorexia, nausea, and vomiting are the principal side effects of nitrofurantoin. Neuropathies and hemolytic anemia occur in glucose-6-phosphate dehydrogenase deficiency. Nitrofurantoin antagonizes the action of nalidixic acid. Rashes, pulmonary infiltration and fibrosis, and other hypersensitivity reactions have been reported.
2. Methenamine Mandelate & Methenamine Hippurate
Methenamine mandelate is the salt of mandelic acid and methenamine and possesses properties of both of these urinary antiseptics. Methenamine hippurate is the salt of hippuric acid and methenamine. Below pH 5.5, methenamine releases formaldehyde, which is antibacterial. Mandelic acid or hippuric acid taken orally is excreted unchanged in the urine, in which these drugs are bactericidal for some gram-negative bacteria when pH is less than 5.5.
Methenamine mandelate, 1 g four times daily, or methenamine hippurate, 1 g twice daily by mouth (children, 50 mg/kg/d or 30 mg/kg/d, respectively), is used only as a urinary antiseptic to suppress, not treat, urinary tract infection. Acidifying agents (eg, ascorbic acid, 4-12 g/d) may be given to lower urinary pH below 5.5. Sulfonamides should not be given at the same time because they may form an insoluble compound with the formaldehyde released by methenamine. Persons taking methenamine mandelate may exhibit falsely elevated tests for catecholamine metabolites.
DISINFECTANTS, ANTISEPTICS, & STERILANTS
INTRODUCTION
Disinfectants are strong chemical agents that inhibit or kill microorganisms (Table 50-1). Antiseptics are disinfecting agents with sufficiently low toxicity for host cells that they can be used directly on skin, mucous membranes, or wounds. Sterilants kill both vegetative cells and spores when applied to materials for appropriate times and temperatures. Some of the terms used in this context are defined in Table 50-2.
Disinfection prevents infection by reducing the number of potentially infective organisms by killing, removing, or diluting them. Disinfection can be accomplished by application of chemical agents or use of physical agents such as ionizing radiation, dry or moist heat, or superheated steam (autoclave, 120°C) to kill microorganisms. Often a combination of agents is used, eg, water and moderate heat over time (pasteurization); ethylene oxide and moist heat (a sterilant); or addition of disinfectant to a detergent. Prevention of infection also can be achieved by washing, which dilutes the potentially infectious organism, or by establishing a barrier, eg, gloves, condom, or respirator, which prevents the pathogen from entry into the host.
Handwashing is the most important means of preventing transmission of infectious agents from person to person or from regions of high microbial load, eg, mouth, nose, or gut, to potential sites of infection. Soap and warm water efficiently and effectively remove bacteria. Skin disinfectants along with detergent and water are usually used preoperatively as a surgical scrub for surgeons' hands and the patient's surgical incision.
Evaluation of effectiveness of antiseptics, disinfectants, and sterilants, although seemingly simple in principle, is very complex. Factors in any evaluation include the intrinsic resistance of the microorganism, the number of microorganisms present, mixed populations of organisms, amount of organic material present (eg, blood, feces, tissue), concentration and stability of disinfectant or sterilant, time and temperature of exposure, pH, and hydration and binding of the agent to surfaces. Specific, standardized assays of activity are defined for each use. Toxicity for humans also must be evaluated. The Environmental Protection Agency (EPA) regulates disinfectants and sterilants and the Food and Drug Administration regulates antiseptics.
Users of antiseptics, disinfectants, and sterilants need to consider their short-term and long-term toxicity because they may have general biocidal activity and may accumulate in the environment or in the body of the patient or caregiver using the agent. Disinfectants and antiseptics may also become contaminated by resistant microorganisms¾eg, spores, P aeruginosa, or Serratia marcescens¾and actually transmit infection. Most topical antiseptics interfere with wound healing to some degree. Simple cleansing with soap and water is less damaging than antiseptics to wounds. Topical antibiotics with a narrow spectrum of action and low toxicity (eg, bacitracin and mupirocin) can be used for temporary control of bacterial growth and are generally preferred to antiseptics. Methenamine mandelate releases formaldehyde in a low antibacterial concentration at acid pH and can be an effective urinary antiseptic for long-term control of urinary tract infections.
Some of the chemical classes of antiseptics, disinfectants, and sterilants are described briefly in the text that follows. The reader is referred to the general references for descriptions of physical disinfection and sterilization methods.
ALCOHOLS
The two alcohols most frequently used for antisepsis and disinfection are ethanol and isopropyl alcohol (isopropanol). They are rapidly active, killing vegetative bacteria, Mycobacterium tuberculosis, and many fungi and inactivating lipophilic viruses. The optimum bactericidal concentration is 60-90% by volume in water. They probably act by denaturation of proteins. They are not used as sterilants because they are not sporicidal, do not penetrate protein-containing organic material, may not be active against hydrophilic viruses, and lack residual action because they evaporate completely. The alcohols are useful in situations in which sinks with running water are not available for washing with soap and water. Their skin-drying effect can be partially alleviated by addition of emollients to the formulation. Use of alcohol-based hand rubs has been shown to reduce transmission of nosocomial bacterial pathogens and is recommended by the Centers for Disease Control and Prevention (CDC) as the preferred method of hand decontamination. Alcohol-based hand rubs are ineffective against spores of Clostridium difficile and assiduous handwashing with a disinfectant soap and water is still required for decontamination after caring for a patient with infection from this organism.
Alcohols are flammable and must be stored in cool, well-ventilated areas. They must be allowed to evaporate before cautery, electrosurgery, or laser surgery. Alcohols may be damaging if applied directly to corneal tissue. Therefore, instruments such as tonometers that have been disinfected in alcohol should be rinsed with sterile water, or the alcohol should be allowed to evaporate before they are used.
CHLORHEXIDINE
Chlorhexidine is a cationic biguanide with very low water solubility. Water-soluble chlorhexidine digluconate is used in water-based formulations as an antiseptic. It is active against vegetative bacteria and mycobacteria and has moderate activity against fungi and viruses. It strongly adsorbs to bacterial membranes, causing leakage of small molecules and precipitation of cytoplasmic proteins. It is active at pH 5.5-7.0. Chlorhexidine gluconate is slower in its action than alcohols, but because of its persistence it has residual activity when used repeatedly, producing bactericidal action equivalent to alcohols. It is most effective against gram-positive cocci and less active against gram-positive and gram-negative rods. Spore germination is inhibited by chlorhexidine. Chlorhexidine digluconate is resistant to inhibition by blood and organic materials. However, anionic and nonionic agents in moisturizers, neutral soaps, and surfactants may neutralize its action. Chlorhexidine digluconate formulations of 4% concentration have slightly greater antibacterial activity than newer 2% formulations. Chlorhexidine 0.5% in 70% alcohol formulations are available in some countries. Chlorhexidine has a very low skin-sensitizing or irritating capacity. Oral toxicity is low because it is poorly absorbed from the alimentary tract. Chlorhexidine must not be used during surgery on the middle ear because it causes sensorineural deafness. Similar neural toxicity may be encountered during neurosurgery.
HALOGENS
1. Iodine
Iodine in a 1:20,000 solution is bactericidal in 1 minute and kills spores in 15 minutes. Tincture of iodine USP contains 2% iodine and 2.4% sodium iodide in alcohol. It is the most active antiseptic for intact skin. It is not commonly used because of serious hypersensitivity reactions that may occur and because of its staining of clothing and dressings.
2. Iodophors
Iodophors are complexes of iodine with a surface-active agent such as polyvinyl pyrrolidone (PVP; povidone-iodine). Iodophors retain the activity of iodine. They kill vegetative bacteria, mycobacteria, fungi, and lipid-containing viruses. They may be sporicidal upon prolonged exposure. Iodophors can be used as antiseptics or disinfectants, the latter containing more iodine. The amount of free iodine is low, but it is released as the solution is diluted. An iodophor solution must be diluted according to the manufacturer's directions to obtain full activity.
Iodophors are less irritating and less likely to produce skin hypersensitivity than tincture of iodine. They act as rapidly as chlorhexidine and have a broader spectrum of action, including sporicidal action, but they lack the persistent action of chlorhexidine.
3. Chlorine
Chlorine is a strong oxidizing agent and universal disinfectant that is most commonly provided as a 5.25% sodium hypochlorite solution, a typical formulation for household bleach. Because formulations may vary, the exact concentration should be verified on the label. A 1:10 dilution of household bleach provides 5000 ppm of available chlorine. The CDC recommends this concentration for disinfection of blood spills. Less than 5 ppm kills vegetative bacteria, whereas up to 5000 ppm is necessary to kill spores. A concentration of 1000-10,000 ppm is tuberculocidal. One hundred ppm kills vegetative fungal cells in 1 hour, but fungal spores require 500 ppm. Viruses are inactivated by 200-500 ppm. Dilutions of 5.25% sodium hypochlorite made up in pH 7.5-8.0 tap water retain their activity for months when kept in tightly closed, opaque containers. Frequent opening and closing of the container reduces the activity markedly.
Because chlorine is inactivated by blood, serum, feces, and protein-containing materials, surfaces should be cleaned before chlorine disinfectant is applied. Undissociated hypochlorous acid (HOCl) is the active biocidal agent. When pH is increased, the less active hypochlorite ion, OCl- is formed. When hypochlorite solutions contact formaldehyde, the carcinogen bis-chloromethyl is formed. Rapid evolution of irritating chlorine gas occurs when hypochlorite solutions are mixed with acid and urine. Solutions are corrosive to aluminum, silver, and stainless steel.
Alternative chlorine-releasing compounds include chlorine dioxide and chloramine T. These agents retain chlorine longer and have a prolonged bactericidal action.
PHENOLICS
Phenol itself (perhaps the oldest of the surgical antiseptics) is no longer used even as a disinfectant because of its corrosive effect on tissues, its toxicity when absorbed, and its carcinogenic effect. These adverse actions are diminished by forming derivatives in which a functional group replaces a hydrogen atom in the aromatic ring. The phenolic agents most commonly used are o-phenylphenol, o-benzyl-p-chlorophenol, and p-tertiary amylphenol. Mixtures of phenolic derivatives are often used. Some of these are derived from coal tar distillates, eg, cresols and xylenols. Skin absorption and skin irritation still occur with these derivatives, and appropriate care is necessary in their use. Detergents are often added to formulations to clean and remove organic material that may decrease the activity of a phenolic compound.
Phenolic compounds disrupt cell walls and membranes, precipitate proteins, and inactivate enzymes. They are bactericidal (including mycobacteria) and fungicidal and they are capable of inactivating lipophilic viruses. They are not sporicidal. Dilution and time of exposure recommendations of the manufacturer must be followed.
Phenolic disinfectants are used for hard surface decontamination in hospitals and laboratories, eg, floors, beds, and counter or bench tops. They are not recommended for use in nurseries and especially in bassinets, where their use has been associated with hyperbilirubinemia. Use of hexachlorophene as a skin disinfectant has caused cerebral edema and convulsions in premature infants and occasionally in adults.
QUATERNARY AMMONIUM COMPOUNDS
The quaternary ammonium compounds ("quats") are cationic surface-active detergents. The active cation has at least one long water-repellent hydrocarbon chain, which causes the molecules to concentrate as an oriented layer on the surface of solutions and colloidal or suspended particles. The charged nitrogen portion of the cation has high affinity for water and prevents separation out of solution. The bactericidal action of quaternary compounds has been attributed to inactivation of energy-producing enzymes, denaturation of proteins, and disruption of the cell membrane. These agents are bacteriostatic, fungistatic, and sporistatic and also inhibit algae. They are bactericidal for gram-positive bacteria and moderately active against gram-negative bacteria. Lipophilic viruses are inactivated. They are not tuberculocidal or sporicidal, and they do not inactivate hydrophilic viruses. Quaternary ammonium compounds bind to the surface of colloidal protein in blood, serum, and milk and to the fibers in cotton, mops, cloths, and paper towels used to apply them, which can cause inactivation of the agent by removing it from solution. They are inactivated by anionic detergents (soaps), by many nonionic detergents, and by calcium, magnesium, ferric, and aluminum ions.
Quaternary compounds are used for sanitation of noncritical surfaces (floors, bench tops, etc). Their low toxicity has led to their use as sanitizers in food production facilities. CDC recommends that quaternary ammonium compounds such as benzalkonium chloride not be used as antiseptics because several outbreaks of infections have occurred that were due to growth of pseudomonas and other gram-negative bacteria in quaternary ammonium antiseptic solutions.
ALDEHYDES
Formaldehyde and glutaraldehyde are used for disinfection or sterilization of instruments such as fiberoptic endoscopes, respiratory therapy equipment, hemodialyzers, and dental handpieces that cannot withstand exposure to the high temperatures of steam sterilization. They are not corrosive for metal, plastic, or rubber. These agents have a broad spectrum of activity against microorganisms and viruses. They act by alkylation of chemical groups in proteins and nucleic acids. Failures of disinfection or sterilization can occur as a result of dilution below the known effective concentration, the presence of organic material, and the failure of liquid to penetrate into small channels in the instruments. Automatic circulating baths are available that increase penetration of aldehyde solution into the instrument while decreasing exposure of the operator to irritating fumes.
Formaldehyde is available as a 40% w/v solution in water (100% formalin). An 8% formaldehyde solution in water has a broad spectrum of activity against bacteria, fungi, and viruses. Sporicidal activity may take as long as 18 hours. Its rapidity of action is increased by solution in 70% isopropanol. Formaldehyde solutions are used for high-level disinfection of hemodialyzers, preparation of vaccines, and preservation and embalming of tissues. The 4% formaldehyde (10% formalin) solutions used for fixation of tissues and embalming may not be mycobactericidal.
Glutaraldehyde is a dialdehyde (1,5-pentanedial). Solutions of 2% w/v glutaraldehyde are most commonly used. The solution must be alkalinized to pH 7.4-8.5 for activation. Activated solutions are bactericidal, sporicidal, fungicidal, and virucidal for both lipophilic and hydrophilic viruses. Glutaraldehyde has greater sporicidal activity than formaldehyde, but its tuberculocidal activity may be less. Lethal action against mycobacteria and spores may require prolonged exposure. Once activated, solutions have a shelf life of 14 days, after which polymerization reduces activity. Other means of activation and stabilization can increase the shelf life. Because glutaraldehyde solutions are frequently reused, the most common reason for loss of activity is dilution and exposure to organic material. Test strips to measure residual activity are recommended.
Formaldehyde has a characteristic pungent odor and is highly irritating to respiratory mucous membranes and eyes at concentrations of 2-5 ppm. OSHA has declared that formaldehyde is a potential carcinogen and has established an employee exposure standard that limits the 8-hour time-weighted average (TWA) exposure to 0.75 ppm. Protection of health care workers from exposure to glutaraldehyde concentrations greater than 0.2 ppm is advisable. Increased air exchange, enclosure in hoods with exhausts, tight-fitting lids on exposure devices, and use of protective personal equipment such as goggles, respirators, and gloves may be necessary to achieve these exposure limits.
Ortho-phthalaldehyde (OPA) is a phenolic dialdehyde chemical sterilant with a spectrum of activity comparable to glutaraldehyde, although it is several times more rapidly bactericidal. OPA solution typically contains 0.55% OPA. Its label claim is that high-level disinfection can be achieved at 12 minutes at room temperature compared with 45 minutes for 2.4% glutaraldehyde. Unlike glutaraldehyde, OPA requires no activation, is less irritating to mucous membranes, and does not require exposure monitoring. It has good materials compatibility and an acceptable environmental safety profile. OPA is useful for disinfection or sterilization of endoscopes, surgical instruments, and other medical devices.
SUPEROXIDIZED WATER
Electrolysis of saline yields a mixture of oxidants, primarily hypochlorous acid and chlorine, with potent disinfectant and sterilant properties. The solution generated by the process, which has been commercialized and marketed as Sterilox for disinfection of endoscopes and dental materials, is rapidly bactericidal, fungicidal, tuberculocidal, and sporicidal. High-level disinfection is achieved with a contact time of 10 minutes. The solution is nontoxic and nonirritating and requires no special disposal precautions.
PEROXYGEN COMPOUNDS
The peroxygen compounds, hydrogen peroxide and peracetic acid, have high killing activity and a broad spectrum against bacteria, spores, viruses, and fungi when used in appropriate concentration. They have the advantage that their decomposition products are not toxic and do not injure the environment. They are powerful oxidizers that are used primarily as disinfectants and sterilants.
Hydrogen peroxide is a very effective disinfectant when used for inanimate objects or materials with low organic content such as water. Organisms with the enzymes catalase and peroxidase rapidly degrade hydrogen peroxide. The innocuous degradation products are oxygen and water. Concentrated solutions containing 90% w/v H2O2 are prepared electrochemically. When diluted in high-quality deionized water to 6% and 3% and put into clean containers, they remain stable. Hydrogen peroxide has been proposed for disinfection of respirators, acrylic resin implants, plastic eating utensils, soft contact lenses, and cartons intended to contain milk or juice products. Concentrations of 10-25% hydrogen peroxide are sporicidal. Vapor phase hydrogen peroxide (VPHP) is a cold gaseous sterilant that has the potential to replace the toxic or carcinogenic gases ethylene oxide and formaldehyde. VPHP does not require a pressurized chamber and is active at temperatures as low as 4°C and concentrations as low as 4 mg/L. It is incompatible with liquids and cellulose products. It penetrates the surface of some plastics. Automated equipment using vaporized hydrogen peroxide (eg, Sterrad) or hydrogen peroxide mixed with formic acid (Endoclens) is available for sterilizing endoscopes.
Peracetic acid (CH3COOOH) is prepared commercially from 90% hydrogen peroxide, acetic acid, and sulfuric acid as a catalyst. It is explosive in the pure form. It is usually used in dilute solution and transported in containers with vented caps to prevent increased pressure as oxygen is released. Peracetic acid is more active than hydrogen peroxide as a bactericidal and sporicidal agent. Concentrations of 250-500 ppm are effective against a broad range of bacteria in 5 minutes at pH 7.0 at 20°C. Bacterial spores are inactivated by 500-30,000 ppm peracetic acid. Only slightly increased concentrations are necessary in the presence of organic matter. Viruses require variable exposures. Enteroviruses require 2000 ppm for 15-30 minutes for inactivation.
An automated machine (Steris) that uses buffered peracetic acid liquid of 0.1-0.5% concentration has been developed for sterilization of medical, surgical, and dental instruments. Peracetic acid sterilization systems have also been adopted for hemodialyzers. The food processing and beverage industries use peracetic acid extensively because the breakdown products in high dilution do not produce objectionable odor, taste, or toxicity. Because rinsing is not necessary in this use, time and money are saved.
Peracetic acid is a potent tumor promoter but a weak carcinogen. It is not mutagenic in the Ames test.
HEAVY METALS
Heavy metals, principally mercury and silver, are now rarely used as disinfectants. Mercury is an environmental hazard, and some pathogenic bacteria have developed plasmid-mediated resistance to mercurials. Hypersensitivity to thimerosal is common, possibly in up to 40% of the population. These compounds are absorbed from solution by rubber and plastic closures. Nevertheless, thimerosal 0.001-0.004% is still used as a preservative of vaccines, antitoxins, and immune sera.
Inorganic silver salts are strongly bactericidal. Silver nitrate, 1:1000, has been most commonly used, particularly as a preventive for gonococcal ophthalmitis in newborns. Antibiotic ointments have replaced silver nitrate for this indication. Silver sulfadiazine slowly releases silver and is used to suppress bacterial growth in burn wounds (see Chapter 46).
STERILANTS
For many years, pressurized steam (autoclaving) at 120°C for 30 minutes has been the basic method for sterilizing instruments and decontaminating materials. When autoclaving is not possible, as with lensed instruments and materials containing plastic and rubber, ethylene oxide¾diluted with either fluorocarbon or carbon dioxide to diminish explosive hazard¾was used at 440-1200 mg/L at 45-60°C with 30-60% relative humidity. The higher concentrations have been used to increase penetration.
Ethylene oxide is classified as a mutagen and carcinogen. The OSHA permissible exposure limit (PEL) for ethylene oxide is 1 ppm calculated as a time-weighted average. Alternative sterilants now being used increasingly include vapor phase hydrogen peroxide, peracetic acid, ozone, gas plasma, chlorine dioxide, formaldehyde, and propylene oxide. Each of these sterilants has potential advantages and problems. Automated peracetic acid systems are being used increasingly for high-level decontamination and sterilization of endoscopes and hemodialyzers because of their effectiveness, automated features, and the low toxicity of the residual products of sterilization.
PRESERVATIVES
Disinfectants are used as preservatives to prevent the overgrowth of bacteria and fungi in pharmaceutical products, laboratory sera and reagents, cosmetic products, and contact lenses. Multi-use vials of medication that may be reentered through a rubber diaphragm, and eye and nose drops, require preservatives. Preservatives should not be irritant or toxic to tissues to which they will be applied, they must be effective in preventing growth of microorganisms likely to contaminate them, and they must have sufficient solubility and stability to remain active.
Commonly used preservative agents include organic acids such as benzoic acid and salts, the parabens, (alkyl esters of p-hydroxybenzoic acid), sorbic acid and salts, phenolic compounds, quaternary ammonium compounds, alcohols, and mercurials such as thimerosal in 0.001-0.004% concentration.
PREPARATIONS AVAILABLE
MISCELLANEOUS ANTIMICROBIAL DRUGS
Colistimethate sodium (Coly-mycin M)
Parenteral: 150 mg for injection
Methenamine hippurate (Hiprex, Urex)
Oral: 1.0 g tablets
Methenamine mandelate (generic)
Oral: 0.5, 1 g tablets; 0.5 g/5 mL suspension
Metronidazole (generic, Flagyl)
Oral: 250, 500 mg tablets; 375 mg capsules; 750 mg extended-release tablets
Parenteral: 5 mg/mL; 500 mg for injection
Mupirocin (Bactroban)
Topical: 2% ointment, cream
Nitrofurantoin (generic, Macrodantin)
Oral: 25, 50, 100 mg capsules, 25 mg/5 mL suspension
Polymyxin B (Polymyxin B Sulfate)
Parenteral: 500,000 units per vial for injection
Ophthalmic: 500,000 units per vial
DISINFECTANTS, ANTISEPTICS, & STERILANTS
Benzalkonium (generic, Zephiran)
Topical: 17% concentrate; 50% solution; 1:750 solution
Benzoyl peroxide (generic)
Topical: 2.5%, 5%, 10% liquid; 5%, 5.5%, 10% lotion; 5%, 10% cream; 2.5%, 4%, 5%, 6%, 10%, 20% gel
Chlorhexidine gluconate (Hibiclens, Hibistat, others)
Topical: 2, 4% cleanser, sponge; 0.5% rinse in 70% alcohol
Oral rinse (Peridex, Periogard): 0.12%
Glutaraldehyde (Cidex)
Instruments: 2.4% solution
Hexachlorophene (pHisoHex)
Topical: 3% liquid; 0.23% foam
Iodine aqueous (generic, Lugol's Solution)
Topical: 2-5% in water with 2.4% sodium iodide or 10% potassium iodide
Iodine tincture (generic)
Topical: 2% iodine or 2.4% sodium iodide in 47% alcohol, in 15, 30, 120 mL and in larger quantities
Nitrofurazone (generic, Furacin)
Topical: 0.2% solution, ointment, and cream
Ortho-phthalaldehyde (Cidex OPA)
Instruments: 0.55% solution
Povidone-iodine (generic, Betadine)
Topical: available in many forms, including aerosol, ointment, antiseptic gauze pads, skin cleanser (liquid or foam), solution, and swabsticks
Silver nitrate (generic)
Topical: 10, 25, 50% solution
Thimerosal (generic, Mersol)
Topical: 1:1000 tincture and solution
REFERENCES
Anonymous: Tinadazole. Med Lett Drugs Ther 2004;46:70.
Bischoff WE et al: Handwashing compliance by health care workers: The impact of introducing an accessible, alcohol-based hand antiseptic. Arch Intern Med 2000;160:1017.
Chambers HF, Winston LG: Mupirocin prophylaxis misses by a nose. Ann Intern Med 2004;140:484.
Gordin FM et al: Reduction in nosocomial transmission of drug-resistant bacteria after introduction of an alcohol-based handrub. Infect Control Hosp Epidemiol 2005;26:650.
Rutala WA, Weber DJ: New disinfection and sterilization methods. Emerg Infect Dis 2001;7:348.
Widmer AF, Frei R: Decontamination, disinfection, and sterilization. In: Murray PR et al (editors). Manual of Clinical Microbiology, 7th ed. American Society for Microbiology, 1999.