Chapter 19: Chemical disinfectants, antiseptics and preservativesDisinfectants, antiseptics and preservatives-destroy or inhibit the growth of microorganism-biocideBiocidal product-encompasses active substances and preparations containing one or more active substances-intended to destroy, deter, render harmless, prevent the action of, exert a controlling effect on any harmless organism by chemical or biological meansDisinfectant and disinfectionDisinfection-process of removing microorganisms, including pathogens, from the surfaces of inanimate objectsHigh-level disinfection-indicates destruction of all microorganisms but not necessarily bacterial spores-have good sporicidal activity-liquid chemical sterilants or chemosterilants that indicate a complete kill or sterilizationIntermediate-level disinfection-indicates destruction of all vegetative bacteria including Mycobacterium tuberculosis Low-level disinfection-can destroy most vegetative bacteria, fungi and viruses-will not include spores and some of the more resistant microorganismsAntiseptic and antisepsisAntisepsis-destruction or inhibition of microorganisms on living tissues-applied to skin and mucous membranes-must not be toxic or irritating for these tissues-mostly used to reduce the microbial population on the skin before surgery or on the hands to help prevent spread of infection by this route-lower concentrations of agents used for disinfectionPreservative and preservationPreservatives-included in pharmaceutical and many other types of formulation-prevent microbial spoilage-minimize the risk to the consumer of acquiring an infection-limit proliferation of microorganisms-should kill any microbial contaminants-not toxic-employed at very low concentrations-consequently levels of antimicrobial action also tend to be of a lower order than for disinfectants or antisepticsEconomic aspects-concerns about bacterial and other pathogenic threatsFACTORS AFFECTING CHOICE OF ANTIMICROBIAL AGENT1. Properties of the chemical agentChemical reaction and rate and extent-influenced by concentration of agent, temperature, pH and formulationTissue toxicity-determine if a chemical can be used as an antiseptic or preservative-limits the range of agents for these applications-necessitates the use of lower concentrations of the agent2. Microbial challenge-types of microorganism present and levels of microbial contamination (the bioburden)*Bioburden is high-long exposure times and/or higher concentrations of antimicrobial may be required-merit attention because of resistance to disinfection or significance in cross-infection or nosocomial infectiona. Vegetative bacteria-at in-use concentrations, chemicals used for disinfection should be capable of killing bacteria and other organisms expected in that environment within a defined contact period-problems may occur when heavily soiled articles or diluted or degraded disinfectant solutions are employedb. Mycobacterium tuberculosis-resistant to many bactericides-resistance is either: Intrinsic-due to reduced cellular permeability Acquired-due to mutation or the acquisition of plasmids-the greatest risk of acquiring infection is from the undiagnosed patientc. Bacterial spores-exhibit significantly resistance to even the most active chemical disinfectant treatment-majority of disinfectants have no useful sporicidal action in a pharmaceutical context-Bacillus and Clostridium-aldehydes, halogens and peroxygen displays very good activity and used as an alternative to physical methods for sterilization of heat-sensitive equipment-Clostridium difficile is a problematic contaminant in hospital environments, resulting in high levels of morbidity and mortality. (Antibacterial activity of some disinfectants and antiseptics is summarized in Tale 19.2 on page 316 of our book)d. Fungi-vegetative fungal form is often as sensitive as vegetative bacteria to chemical antimicrobial agents-fungal spores may be resistant, but this resistance is of lesser magnitude than that exhibited by bacterial spores-ethanol (70%) is rapid and reliable against Candida species e. Viruses-susceptibility depends on whether the viruses posses a lipid envelope-non-lipid viruses are frequently more resistant to disinfectants-responsible for many nosocomial infections-Ebola and Marburg>cause haemorrhagic fevers>highly infectious>safe destruction by disinfectants is of paramount importance-Hepatitis A>enterivirus>one of the most resistant viruses-HIV>inactivated by mostchemicals at in-use concentration>disinfect: use a high-level disinfectants-Influenza A virus>susceptible to a large number of disinfectant products when they are used I hard, non-porous surfacesf. Protozoa-Acanthamoeba>can cause acanthamoeba keratitis with associated corneal scarring and loss of vision in wearers of soft contact lenses. -Chlorine-generating systems in use are generally inadequate-Hydrogen peroxide-based disinfection is considered completely reliable and consistent in producing acanthamoebicidal effectsg. Prions-most resistant-not microorganism-no cellular structure nor do they contain nucleic acids-cause spongiform encephalopathies-risk of infectivity is highest in brain, spinal cord and eye tisssues3. Intended application`-medical preparation>ingredients used may antagonize preservative activity-disinfection of instruments>chemicals used must not adversely affect the instruments4. Environmental factors-organic matter can have a drastic effect on antimicrobial capacity either by adsorption or chemical inactivation thus reducing the concentration of active agent in solution-dried organic deposits may inhibit penetration of the chemical agent(SUMMARIZED FORM OF THE EFFECTS ON ACTIVITY BY THESE FACTORS CAN BE SEEN IN TABLE 19.4 ON PAGE 319 TO 320)5. Toxicity of the agent-Toxic volatile substance should be kept in covered containers to reduce the level of exposure to irritant vapour-face protection and impermeable nitrile rubber gloves should be worn(see Table 19.5 for the HSE Recommendations for endoscopy disinfection on page 321)TYPES OF COMPOUND1. Acids and estersa. Benzoic acid>widely used>can be alone or included in a combination with other preservatives>disadvantage: development of resistance by some organismb. Sorbic acid>widely used>most effective at pH 4 or belowc. Sulphur dioxide, sulphites and metabisulphites>preservative in the food and beverage industries>preservatives and antioxidantd. Esters of p-hydroxybenzoic acid (parabens)>widely used>overcome the marked pH dependence on activity of the acids2. Alcoholsa. Alcohols used for disinfection and antisepsis-aliphatic alcohols are used for disinfection and antisepsis-poor penetration of organic matter-restricted to clean condition-cleansing action and volatility-ethanol > concentrations between 60% to 95% are bactericaidal > 70% solution is usually employed for disinfection of skin, clean instruments, or surfaces >higher concentration, ethanol is active against fungi and most lipid-containing viruses >solvent and preservative-isopropyl alcohol>slightly greater bactericidal activity than ethanol>twice as toxic>less active against viruses>used at concentrations of 60%-70%>alternative to ethanol>preservative for cosmeticsb. Alcohols as preservatives Benzyl alcohol- antibacterial and weak local anaesthetic- used at 2%- use in cosmetics is restricted Chlorbutamol-used at concentration of 0.5%-preservative in injections and eye drops Phenylethanol-in-use concentration of 0.25-0.5%-greater activity against Gram-negative organisms Phenoxyethanol-in-use concentration at 1%-more active against Ps. aeruginosa Bronopol-in-use concentration of 0.01-0.1%-exposed to light at alkaline pH and accompanied by increase in temperature, decomposition may occur resulting to a change in color from yellow to brown3. Aldehydesa. Glutaraldehyde-has a broad spectrum of antimicrobial activity and rapid rate of kill, most vegetative bacteria being killed within a minute of exposureb. Ortho-phthaldehyde-excellent mycobactericidal activity with complete kill of M. tuberculosis within 12 minutes at room temperaturec. Formaldehyde-decontamination of isolators, safety cabinets and roomsd. Formaldehyde-releasing agents-reduce the irritancy associated with formaldehyde while maintain activity4. Biguanidesa. Chlorhexidine-antiseptic-its base is not readily soluble in water, therefore its freely soluble salts, acetate, gluconate, and HCl-nontoxic when applied to skin or mucous membranes and is an important preoperative antisepticb. Polyhexamethylene biguanides-antimicrobial activity exceeds that of monomeric biguanides5. Halogensa. Chlorine-large number of antimicrobially active chlorine compounds are commercially available, one of the most important being liquid chlorineb. Hypochlorite-oldest and remain the most useful of the chlorine disinfectantsc. Organic chlorine compounds-disinfectant and antisepsis-antimicrobial of these compounds are similar to hypochlorite when acidic conditions of use are maintainedd. Chloroform-narrow spectrum of activity-marked reductions in concentration may occur through volatilization from products, resulting in the possibility of microbial growthe. Iodine-wide spectrum of antimicrobial activity-disadvantage: staining of skin an fabrics coupled with possible sensitizing of skin and mucous membranesf. Iodophors-eliminate the disadvantages of iodine while retaining its antimicrobial activity6. Heavy metals-mercury and silver have antibacterial properties and preparations of these metals were among the earliest used antiseptic7. Hydrogen peroxide and peroxygen compounds-high level disinfectants-used in disinfection of soft contact lens8. Phenols-widely used disinfectants and preservatives-good antimicrobial activity-rapidly bactericidal but not sporicidal-more active at acid pHDisadvantage: caustic effect on skin and tissues and their systemic toxicity9. Surface-active agents-surfactants-anionic, cationic, non-ionic or ampholytic-cationic compounds play the most important role in an antimicrobial context-Cationic surface-active agents >falls within the grouo known as the quaternary ammonium compounds (QAC)>QAC exhibit greatest activity against Gram-positive bacteria10. Other antimicrobialsa. Diamidines-reduced by acid pH and in presence of blood and serumb. Dyes-have static activity but are no longer applied topically for the treatment of infections because of carcinogenictiyc. Quinoline derivatives-little used nowDISINFECTION POLICIES -aim to control the use of chemicals for disinfection and antisepsis and give guidelines on their use(SEE TABLE 19.7 ON PAGE 333)