Ocular Infections: Prophylaxis and Management Namrata Sharma, Neelima Aron, Atul Kumar
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IntroductionCHAPTER 1

Nishat Hussain Ahmed,
Gita Satpathy
The theme behind operation theatre sterilization and disinfection is: ‘The first requirement of a hospital is that it should do the sick no harm’. This is a paraphrase of the favorite aphorism of Florence Nightingale— ‘primum non nocere’ (first of all do no harm).1 Principally, the suggestion in the dictum is of harm caused to the patient as a result of hospital acquired infections.
Sight is the most valued of all assets possessed by the mortals. Modern ophthalmic interventions have come a long way in managing a variety of ophthalmic conditions, which were previously considered fatal in terms of visual loss. However, like all powers, the capability to be able to venture into intricate procedures comes with the responsibility to care for the unfavorable consequences which might arise from matters and objects other than the skill of surgery. Prevention of pre-, intra- and post-procedural infection is one such responsibility; which if overlooked can twist the whole outcome of an otherwise impeccable procedure. Sterilization and disinfection of operating rooms and instruments, and carrying out the procedures as per the infection control guidelines thus have a key role in determining the ultimate success of a procedure.
 
HISTORY
Long back, around 500 BC, the hygienic standards for care of the sick existed in civilized world, particularly in India, Egypt, Palestine and Greece. These standards were mainly based on religious concepts of practicing purity for its believed intimacy with godliness. The earliest available advice on hospital construction and hygiene is contained in the Charaka-Samhita, a Sanskrit Textbook of Medicine.2
The civilizations of fifth century BC, including ancient Greeks and Jews had high standard inflexible laws for prevention of infections in their hospitals. Similar were the standards of hospitals and intervention places of ancient Romans.3,4
By the commencement of Medieval period (5th to the 15th century AD), most of the early standards of hygiene and infection prevention were forgotten.5 The pre-renaissance era saw few surgeons understanding the importance of cleanliness and asepsis in procedures, however for the most part, these concepts were looked down upon.6,7
The scientific study of hospital infections began in first half of eighteenth century. A number of physicians and surgeons came forward with insistence on hospital infection control and procedural antisepsis. Notable are the achievements of John Pringle (1740–1780), who pioneered ‘antiseptics’ and gave the concept of ‘hospital fever’; Francis Home, Thomas Young, Alexander Hamilton and Alexander Gordon, who worked on understanding the nature of and preventing puerperal fever from 1750 to 1800; and John Bell (1790–1820), who gave valuable observations on surgical sepsis.8
As the acquaintance was building up in understanding and prevention of infections, it was understood by many that use of carbolic acid in surgical wounds 2can prevent infection. This knowledge achieved its first practical expression in the work of Joseph Lister (1865–1868). He demonstrated the role of bacteria in surgical sepsis, and that sepsis could be avoided by excluding bacteria from a surgical wound. This work pioneered the way to the principles of antiseptic, and later, aseptic surgeries.9,10 At around the same time in 1860s, Louis Pasteur was able to confirm that heat kills microbes, and sterilization came of age. The later years, with advancements in every aspect of medical, surgical and diagnostic fields; saw development of more interest in taking care of hospital acquired and surgical infections. Concepts of infection control in hospitals and thorough sterilization and disinfection of patient care devices and areas were agreed upon to be all important for successful outcome of patient interventions. This led to customization and development of different sterilization and disinfection practices especially in patient intervention areas like critical care units and operation theatres. Major milestones reached in the subject matter are shown in Table 1.1.
 
CLEANING, DISINFECTION AND STERILIZATION
Cleaning, disinfection and sterilization are the key components for favorable outcomes, in terms of infective complications; of procedures taking place in operating rooms. As the interventions and thus the devices and instruments used for them are becoming more and more complex, ever increasing is the demand to treat the devices and instruments in manners which render them safe for use in such interventions. As sterilizing all the equipment and surroundings of patient intervention is unnecessary and expensive, a methodical knowledge of the various methods of sterilization, disinfection and cleaning is important to guide the correct treatment of a place or article depending on its intended use.
 
A Rational Approach
In 1968, Earle H Spaulding devised a rational approach to disinfection and sterilization of patient-care items and equipment.
Table 1.1   Major milestones in history of sterilization and disinfection for prevention of surgical infections
S. No.
Year
Milestone
1.
1683
Antonie van Leeuwenhoek (Fig. 1.1) developed the microscope and proved the existence of microorganisms
2.
1847
Ignaz Semmelweis, an Hungarian obstetrician, advocated handwashing and fingernail scrubbing for infection prevention
3.
1862
Louis Pasteur (Fig. 1.2) gave the ‘germ’ theory of infections, later he developed the pasteurization process
4.
1867
Joseph Lister (Fig. 1.3) pioneered the way to antiseptic surgeries by initially using carbolic acid on surgical wounds and hands of surgeons
5.
1876
The first steam autoclave was made and process of tyndallization was discovered
6.
1881
Boiling as a method of sterilization for surgical drapes, gowns, dressings, instruments, etc. was used
7.
1885 to 1900
Germans made many notable contributions to the principles governing steam sterilization and chemical disinfection
8.
1900
Dry heat sterilization practice was started
9.
Early 1900's
Use of ‘ozone’ for potable water treatment in Europe
10.
1929
Recognition of ethylene oxide as an antibacterial agent
11.
Early1940's
Ethylene oxide (EtO) employed as a sterilizing agent in hospitals; thereafter sterilization by irradiation developed
12.
Late 1940's
Discovery of microwave energy
13.
1963
Glutaraldehyde was introduced as a sterilizing agent for heat-sensitive instruments
14.
1968
Earle H Spaulding proposed how an object should be disinfected or sterilized depended on the object's intended use (Spaulding's classification system)
15.
1989
Ozone sterilizers introduced for healthcare applications
16.
1993
Plasma sterilizing systems were introduced
3
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Figure 1.1: Antonie van Leeuwenhoek
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Figure 1.2: Louis Pasteur
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Figure 1.3: Joseph Lister
Spaulding categorized the instruments and items of patient care as critical, semicritical, and noncritical according to the degree of risk for infection involved in use of the items. The treatment of the items was recommended to be based on the above categorization. Although more than forty decades old, the classification still retains its logic even in the modern treatment amenities of patient care articles.11 Table 1.2 shows the Spaulding's classification of patient care devices and the recommended treatments.
Critical items confer a high-risk for infection, if they are contaminated with any microorganism. These items enter sterile tissue or the vascular system, and hence must be sterile before use. This category includes surgical instruments, cardiac and urinary catheters, implants, and ultrasound probes used in sterile body cavities. Most of the critical items should be procured as sterile or be sterilized with steam, if possible. Heat-sensitive objects can be treated with EtO, hydrogen peroxide gas plasma; or if above are not suitable, by liquid chemical sterilants.12
Semicritical items contact mucous membranes or nonintact skin. They include respiratory therapy and anesthesia equipment, endoscopes, laryngoscope blades, manometry probes, cystoscopes, diaphragm fitting rings, etc. They should be free from all microorganisms before use. However, as intact mucous membranes, such as those of the lungs and the gastrointestinal tract are generally resistant to infection by common bacterial spores-small numbers of bacterial spores are permissible. Thus, semicritical items at the least require high-level disinfection using chemical disinfectants.13,14
Noncritical items come in contact with intact skin but not mucous membranes. Intact skin acts as an effective barrier to most microorganisms; therefore, the sterility of items coming in contact with intact skin is not critical. Noncritical items can be divided into noncritical patient care items, such as bedpans, blood pressure cuffs, crutches etc.; and noncritical environmental surfaces such as table tops, computers etc. Almost no risk has been documented for transmission of infectious agents to patients through noncritical items, as long as they do not contact non-intact skin and/or mucous membranes.15,16
 
Definitions12,17,18
Cleaning is the physical removal of all visible soil, dust, and other foreign material (e.g. organic and inorganic material) from objects and surfaces and normally is accomplished manually or mechanically using water with detergents or enzymatic products.
4
Table 1.2   Spaulding's classification of patient care devices
Device classification
Definition based on intended use
Examples
Risk of infections
Recommended treatment
Critical
A device that enters normally sterile tissue or the vascular system or through which blood flows
Implants, scalpels, needles, phacoemulsification machine handpiece, forceps, scissors, hooks, cannulas
High
Sterilization
Semi-critical
A device that comes into contact with intact mucous membranes and does not ordinarily penetrate sterile tissue
Laryngoscopes, endoscopes, endotracheal tubes, manometry probes
High or intermediate
Sterilization desirable, high level disinfection acceptable
Non-critical
A device that does not ordinarily touch the patient or touches only intact skin
Stethoscopes, blood pressure cuffs, tabletops
Low
Intermediate or low level disinfection
Thorough cleaning is essential before high-level disinfection and sterilization because inorganic and organic materials that remain on the surfaces of instruments interfere with the effectiveness of these processes.
Decontamination removes pathogenic microorganisms from objects so that they are safe to handle, use, or discard. Technically, it involves cleaning with detergent and/or treatment with germicides.
Disinfection is a process that eliminates many or all pathogenic microorganisms, except bacterial spores, on inanimate objects. In healthcare settings, objects usually are disinfected by liquid chemicals or wet pasteurization. Unlike sterilization, disinfection is not sporicidal. A few disinfectants will kill spores with prolonged exposure times (e.g. 2% glutaraldehyde in 3–12 hours); these are called chemical sterilants. At similar concentrations but with shorter exposure periods (e.g. 20 minutes for 2% glutaraldehyde), these same disinfectants will kill all microorganisms except large numbers of bacterial spores; they are called high-level disinfectants.
Thus, high level disinfection (HLD) is a process that kills all microorganisms except large number of bacterial spores. Thus HLD destroys enveloped and nonenveloped viruses, gram-positive and gram negative bacteria, fungi, Mycobacteria, trophozoites and cysts.
Intermediate level disinfection (ILD) is a process which destroys mycobacteria, vegetative bacteria, trophozoites, most viruses, and most fungi but not bacterial or fungal spores.
Low-level disinfection (LLD) destroys most vegetative bacteria, some fungi, and some viruses in a practical period of time (<10 minutes).
Sterilization is a process that destroys or eliminates all forms of microbial life, including most resistant spores. It is a closely monitored, validated process carried out in healthcare facilities by physical or chemical methods. Steam under pressure, dry heat, ethylene oxide (EtO) gas, hydrogen peroxide gas plasma, and liquid chemicals are the principal sterilizing agents used in healthcare facilities. When chemicals are used to destroy all forms of microbiologic life, they can be called chemical sterilants. Sterilization destroys enveloped and non-enveloped viruses, gram-positive and gram-negative bacteria including bacterial spores, fungi and their spores, Mycobacteria, trophozoites, cysts and coccidia.
 
CLEANING12,1921
 
Cleaning of Patient Care Items
Cleaning is the first and most important step before disinfection and sterilization can occur. Presoaking may be necessary to prevent soils and proteins from drying on surgical instruments/other patient care articles. Presoaking softens the organic matter and should be done immediately after using the item. Manual cleaning follows presoaking; thorough cleaning is required to remove all organic matter and other residue, which might interfere with the later steps of disinfection or sterilization as per the category of item. While cleaning, appropriate personal protective equipment such as gloves, masks, gowns, and protective eye wear must be used; and wherever suitable, cleaning of appliances and machines should be done so as to prevent potential 5exposure to microorganisms through aerosolization and splashing. The cleaning process must be carried out in a controlled environment using standard precautions. Proper ventilation, humidity control and temperature should be maintained in the cleaning area. The work flow should be unidirectional. Instructions should be visibly and clearly labelled in the cleaning area, appliances and machines, and on cleaning agents; and compliance should be strictly maintained to ensure the proper procedure for given articles. After cleaning, the items must be inspected for cleanliness and absence of defects. Items to be sterilized should also be tested for functional integrity when applicable.
At the place of using the patient care items, clean and dirty items must be kept separate at all times. Clean supplies should be maintained in a different room or area away from soiled instruments. All used supplies and equipment are considered contaminated even when contamination might not be visible to the eye. Contaminated items, should be collected into a container. The container must be covered, and the contents must be transported to decontamination area in a manner that minimizes potential contamination of staff, patients, or the environment.
 
STERILIZATION AND DISINFECTION
Sterilization and disinfection are the processes used in healthcare settings for making an article/area safe for use in patient care. These processes differ from each other in the level of freedom from micro-organisms they provide; however, the agents used to accomplish the processes and the mechanisms with which the agents destroy the microorganisms are overlapping. For example, 2% glutaraldehyde is a chemical sterilant if the exposure time is 3–6 hours; however, with shorter exposure period of 20 minutes, it is a high level disinfectant. Understandably, factors which influence the effectiveness of sterilization and disinfection processes are also the same (Table 1.3).12 The methods of sterilization (and disinfection) can be physical or chemical methods.
Table 1.3   Factors affecting the efficacy of sterilization and disinfection12
Factor
Effect
Cleaning
Failure to adequately clean instrument results in higher bioburden, protein load, and salt concentration. These will decrease sterilization efficacy
Type of pathogen
Bacterial and fungal spores, mycobacteria and non-enveloped viruses are more resistant to sterilizing agents than vegetative bacteria and fungi and enveloped viruses
Biofilm
Biofilms reduce the efficacy of sterilization by impairing exposure of the sterilant to the microbial cell
Lumen length
Increasing lumen length impairs sterilant penetration. May require forced flow through lumen to achieve sterilization
Lumen diameter
Decreasing lumen diameter impairs sterilant penetration. May require forced flow through lumen to achieve sterilization
Restricted flow
Sterilant must come into contact with microorganisms. Device designs that prevent or inhibit this contact (e.g. sharp bends, blind lumens) will decrease sterilization efficacy
Device design and construction
Materials used in construction may affect compatibility with different sterilization processes and affect sterilization efficacy. Design issues (e.g. screws, hinges) will also affect sterilization efficacy
Temperature
Activity of most disinfectants increases as the temperature increases, but some exceptions exist. Too much increase in temperature causes the disinfectant to degrade and weakens its germicidal activity and thus might produce a potential health hazard
pH
An increase in pH improves the antimicrobial activity of some disinfectants (e.g. glutaraldehyde, quaternary ammonium compounds) but decreases the antimicrobial activity of others (e.g. phenols, hypochlorites, and iodine)
Humidity
Relative humidity is an important factor influencing the activity of gaseous disinfectants/sterilants, such as EtO, chlorine dioxide, and formaldehyde
Hardness of water
Water hardness reduces the effectiveness of certain disinfectants because high concentration of divalent cations (e.g. magnesium, calcium) in the hard water interact with the disinfectant to form insoluble precipitates
6
While some of the methods, e.g. steam under pressure are used primarily as means of sterilization, and some other, e.g. alcoholic hand rubs for the most part are used as disinfectants; many methods with different standardizations (e.g. of exposure time, concentration, etc.) can be used as either. An understanding of different sterilizing agents is vital in applying them for different categories of patient care items and areas.
 
Sterilization Practices12
The quality of sterilization procedure as a service in patient care depends not only on the effectiveness of the sterilization process but also on other things including proper precleaning, disassembling and packaging of the device, loading the sterilizer, monitoring, appropriateness of the cycle for the load contents, and quality assurance of the procedures. The sterilization practices should be devised in manners so that they can be strictly adhered to by the personnel involved, there should be absolute protection of the patients from infections, there should be minimum risks to staff and the value of the items should be preserved. Ensuring consistency of sterilization practices requires a comprehensive program that ensures operator competence and proper methods of cleaning and wrapping instruments, loading the sterilizer, operating the sterilizer, and monitoring of the entire process. The details of pre-sterilization components, various methods of sterilization and their monitoring and quality assurance will be dealt with elsewhere.
 
The Methods of Disinfection
 
The Ideal Disinfectant
An ideal disinfectant does not exist. However, it is important to know the most desirable characteristics of a perfect disinfectant, against which any disinfectant needs to be weighed to know whether the specific criteria are being met or not by that particular disinfectant. This helps in understanding the potential uses; in calculating the dilutions which are least detrimental to the patient and cleaning personnel; and in deciding the points of specific precautions for that disinfectant. Table 1.4 shows the characteristics of an ideal disinfectant.12,22
Many disinfectants are used alone or in combinations in the health-care setting. These include alcohols, chlorine and chlorine compounds, formaldehyde, glutaraldehyde, ortho-phthalaldehyde, hydrogen peroxide, iodophors, peracetic acid, phenolics, and quaternary ammonium compounds.
Disinfectants are not interchangeable, and incorrect concentrations and inappropriate disinfectants can result in improper disinfection and increased costs. Cleaning personnel should take due precautions to minimize exposure to disinfectants as many of them are associated with harmful effects to the exposed persons.23,24 An understanding of the performance characteristics of various disinfectants is vital to select an appropriate disinfectant for any item and use it in the most efficient way (Table 1.5).
Table 1.4   Properties of an ideal disinfectant12,51
Spectrum
It should have a wide antimicrobial spectrum, and be effective against all microorganisms
Action
It should be fast acting to produce a rapid kill
Penetration
It should have high penetrating power
Effect of environmental factors
It should be active in the presence of organic matter (e.g. blood, sputum, feces) and compatible with soaps, detergents, and other chemicals encountered in use
Toxicity
It should be nontoxic, safe for the user and patient
Interference with healing
It should not interfere with healing
Surface compatibility
It should not corrode instruments and metallic surfaces and should not cause the deterioration of cloth, rubber, plastics, and other materials
Usage
Easy to use with clear label directions
Residual effect
It should leave an antimicrobial film on the treated surface.
Odor
It should have no odor or a pleasant odor to facilitate its routine use
Economical
It should not be expensive and should be easily available
Solubility
It should be soluble in water
Stability
It should be stable in concentrated stocks and in working dilutions
Cleaning action
It should have good cleaning properties
Environment friendly
It should not spoil the environment on disposal
7
 
Alcohols12,17,2426
Alcohols refer to two water-soluble disinfectants, ethyl alcohol and isopropyl alcohol. These alcohols are rapidly bactericidal against vegetative forms of bacteria; they also are tuberculocidal, fungicidal, and virucidal but do not destroy bacterial spores. Their optimum bactericidal concentration is 60–90% solutions in water, and the cidal activity drops sharply when diluted below 50%.
Mode of action: The most reasonable explanation for the cidal (killing) action of alcohol is denaturation of proteins. This is supported by the observation that absolute ethyl alcohol, a dehydrating agent, is less bactericidal than mixtures of alcohol and water because proteins are denatured more quickly in the presence of water.
Table 1.5   Summary of commonly used disinfectants
Disinfectant
Advantages
Disadvantages
Uses
Alcohols
  • Minimal toxicity
  • Fast acting
  • Fast drying
  • Nonstaining and nonallergic
  • Low penetration in organic matter
  • Deleterious effects on some materials such as metals, lensed instruments, rubbers, plastics
  • Inflammable
  • Causes drying of skin
  • Mainly used as ILD or LLD
  • Small surface disinfection, e.g. trolleys, etc.
  • Surface disinfection of noncritical items, e.g. stethoscopes, ambu bags, medicine vial stoppers, ultrasound probes, etc.
  • Used in hand rubs
Chlorine and chlorine compounds
  • Inexpensive
  • Fast acting
  • Relatively nontoxic
  • Noninflammable
  • Unaffected by water hardness
  • Nonstaining
  • Poor material compatibility
  • Corrosive
  • Inactivated by organic matter
  • Diluted form unstable
  • Bleaches fabrics
  • Irritant
  • Used for HLD/ILD/LLD, based on concentration of free chlorine and contact time
  • Decontamination of spills
  • Surface decontamination
  • Disinfection of water
  • Disinfection of soiled laundry
Formaldehyde
  • Active in presence of organic matter
  • Good biocide
  • Very pungent
  • Exposure related to dermatitis, asthma and other systemic effects
  • Potential carcinogen
  • Vaccine preparation
  • Embalming/tissue and specimen preservation
  • Previously used for fumigation of critical care areas
  • Decontamination of biological safety cabinets
Glutaraldehyde
  • Active in presence of organic matter
  • Good material compatibility
  • Excellent biocide
  • Moderate residual activity
  • Coagulates blood and fixes proteins to surfaces
  • Irritant to eyes, skin and airways
  • Chronic exposure related to cases of dermatitis, colitis, keratopathy
  • Relatively costly
  • Used as a chemical sterilant/HLD
  • Sterilization/HLD of endoscopes, dialysers, respiratory equipment, transducers, etc.
  • Should not be used for noncritical articles
Hydrogen peroxide
  • Low toxicity
  • Active in presence of organic matter
  • Environment friendly
  • Good material compatibility
  • Odorless, noncorrosive
  • Fast acting
  • Strong biocide
  • Cannot be used with some endoscopes
  • Irritation and colitis can occur with chronic exposure
  • Corneal damage
  • Used as a chemical sterilant/HLD
  • Used for disinfecting semicritical and critical patient care items, e.g. endoscopes, ventilators, soft contact lenses, tonometer biprisms, etc.
  • Vaporized form is used for gas plasma sterilization8
Iodophors
  • Rapid action
  • Relatively less toxic
  • Inactivated by organic matter
  • Corrosive
  • Irritants for eyes
  • Gram-negative bacteria can grow in them
  • Used as ILD/LLD
  • Used as skin antiseptics
  • Noncritical surface decontamination
  • Disinfection of thermometers, hydrotherapy tanks, etc.
Ortho-phthalaldehyde
  • Excellent biocide
  • Fast acting
  • Active in presence of organic matter
  • Good material compatibility
  • Stains proteins and skin gray
  • Irritant for the eyes
  • Expensive
  • Slow sporicidal activity
  • Used as a chemical sterilant/HLD
  • Useful for equipment at places where glutaraldehyde resistance has emerged
Peracetic acid
  • Low toxicity
  • Active in presence of organic matter
  • May enhance removal of organic matter
  • Environment friendly
  • Leaves no residues
  • Fast acting
  • Strong biocide
  • Unstable in diluted form
  • Corrosive for metals, harmful for rubber
  • Irritant for skin and eyes
  • Costly
  • Used as a chemical sterilant/HLD
  • Used for disinfection of endoscopes and dental equipment
  • In combination with hydrogen peroxide used for disinfection of hemodialyzer
Phenolics
  • Active in presence of organic matter
  • Inexpensive
  • Noncorrosive
  • Stable
  • Leave residual film on surfaces
  • Irritant to eyes and skin
  • Corrosive
  • Skin pigmentation
  • Gram-negative bacteria can grow in them
  • Used as ILD/LLD
  • To be used only on noncritical surfaces and items
Quaternary ammonium compounds
  • Nonstaining
  • Odorless
  • Noncorrosive
  • Relatively nontoxic
  • Inactivated by hard water and organic matter
  • Irritant to skin and eyes
  • Poor bactericidal
  • Narrow spectrum
  • Leave sticky residues
  • Gram-negative bacteria can grow in them
  • Used as LLD
  • Good cleansing agents
  • To be used only on noncritical surfaces and items
The bacteriostatic (keeping the metabolism at such a low level that the organism does not multiply, nor is it able to cause disease) action is believed to be caused by inhibition of the production of metabolites essential for rapid cell division.
Uses: Alcohols are not recommended for sterilizing medical and surgical materials principally because they lack sporicidal action and they cannot penetrate protein-rich materials. They have been used effectively to disinfect oral and rectal thermometers, hospital pagers, scissors, and stethoscopes. Alcohol towelettes are used for years to disinfect small surfaces such as rubber stoppers of multiple-dose medication vials or vaccine bottles.
Alcohols have some detrimental effects on equipment, they damage the shellac mountings of lensed instruments, tend to swell and harden rubber and certain plastic tubing after prolonged and repeated use, bleach rubber and plastic tiles and damage tonometer tips (by deterioration of the glue) if used 9routinely. They also evaporate rapidly, thus extended exposure time is difficult to achieve unless the items are immersed.
 
Chlorine and Chlorine Compounds12,17,2732
Hypochlorites are the most widely used of the chlorine disinfectants. They are available as liquid (e.g. sodium hypochlorite) and solid (e.g. calcium hypochlorite) preparations. They have a broad spectrum of antimicrobial activity, do not leave toxic residues, are unaffected by water hardness, are inexpensive and fast acting, remove dried or fixed organisms and biofilms from surfaces, and have a low incidence of serious toxicity. Unfavorable effects include ocular irritation and oropharyngeal, esophageal, and gastric burns. Other disadvantages are corrosiveness to metals in high concentrations (>500 ppm), inactivation by organic matter, bleaching of fabrics, and release of toxic chlorine gas when mixed with ammonia or acid (e.g. household cleaning agents).
The microbicidal activity of chlorine is attributed largely to undissociated hypochlorous acid (HOCl). The disinfecting efficacy of chlorine decreases with an increase in pH. Alternative compounds that release chlorine and are used in the healthcare setting include demand-release chlorine dioxide, sodium dichloroisocyanurate, and chloramine-T. The advantage of these compounds over the hypochlorites is that they retain chlorine longer and so exert a more prolonged bactericidal effect. Sodium dichloroisocyanurate tablets are stable, the total available chlorine is released in phases, and the solutions of sodium dichloroisocyanurate are acidic, thus making it a better disinfectant.
A new disinfectant, “superoxidized water,” with the concept of electrolyzing saline to create a disinfectant has been developed. The main products of this water are hypochlorous acid (e.g. at a concentration of about 144 mg/L) and chlorine. This method is inexpensive and end product—water is not detrimental to the environment. Although superoxidized water is intended to be generated fresh at the point of use, when tested under clean conditions the disinfectant was effective from 5 minutes to 48 hours after preparation. In 2002, the FDA cleared superoxidized water as a high-level disinfectant.
Mode of action: The exact mechanism by which free chlorine destroys microorganisms is not completely understood. Role of oxidation of sulfhydryl enzymes and amino acids; ring chlorination of amino acids; loss of intracellular contents; decreased uptake of nutrients; inhibition of protein synthesis; decreased oxygen uptake; oxidation of respiratory components; decreased adenosine triphosphate production; breaks in DNA; and depressed DNA synthesis has been proposed. The actual mechanism of action might involve a combination of these factors.
Uses: Hypochlorites are widely used in healthcare facilities in different dilutions for a variety of disinfection purposes. Disinfection of countertops and floors; decontamination of blood spills; as an irrigating agent in endodontic treatment; as a disinfectant for manikins, laundry, dental appliances, hydrotherapy tanks; in treatment of medical waste before disposal; and decontaminating water distribution system in hemodialysis centers and hemodialysis machines.
 
Formaldehyde12,17,28,3335
Formaldehyde is used as a disinfectant and sterilant in both its liquid and gaseous states. Formaldehyde is used principally as a water-based solution called formalin, which is 37% formaldehyde by weight. The aqueous solution is a bactericide, tuberculocide, fungicide, virucide and sporicide. Formaldehyde should be handled in the workplace as a potential carcinogen and its exposure should be limited to an 8-hour time-weighted average exposure concentration of 0.75 ppm. Ingestion of formaldehyde can be fatal; and long-term exposure to low levels in the air or on the skin can cause asthma-like respiratory problems and skin irritation, such as dermatitis and itching. For these reasons, employees should have limited direct contact with formaldehyde; and these considerations limit its role in sterilization and disinfection processes.
Mode of action: Formaldehyde inactivates microorganisms by alkylating the amino and sulfhydral groups of proteins and ring nitrogen atoms of purine bases.
Uses: Although formaldehyde-alcohol is a chemical sterilant and formaldehyde is a high-level disinfectant, the healthcare uses of formaldehyde are limited by its irritating fumes and its pungent odour even at very low levels (<1 ppm). For these reasons and its role as a suspected human carcinogen, its use is limited in healthcare settings; when it is used, direct exposure to employees is generally avoided. Formaldehyde is used in the healthcare setting to prepare viral vaccines 10(e.g. poliovirus and influenza); as an embalming agent; and to preserve anatomic specimens. Previously, it was used for fumigation of operation theatres and critical care areas; however, that has almost been replaced by other methods. Paraformaldehyde, a solid polymer of formaldehyde, which can be vaporized by heat, is used for the gaseous decontamination of laminar flow biologic safety cabinets.
 
Glutaraldehyde12,17,3639
Glutaraldehyde is a saturated dialdehyde that has gained popularity as a high-level disinfectant and chemical sterilant. Aqueous solutions of glutaraldehyde are acidic and generally in this state are not sporicidal. Only when the solution is “activated” by use of alkylating agents and made alkaline to pH 7.5–8.5 does the solution become sporicidal. Once activated, these solutions have a shelf-life of 14 days. New glutaraldehyde formulations (e.g. glutaraldehyde-phenol-sodium phenate, potentiated acid glutaraldehyde, stabilized alkaline glutaraldehyde) have a shelf-life of up to 30 days.
Mode of action: The biocidal activity of glutaraldehyde results from its alkylation of sulfhydryl, hydroxyl, carboxyl, and amino groups of microorganisms, which alters RNA, DNA, and protein synthesis.
Uses: Glutaraldehyde is most commonly used as a high-level disinfectant for medical equipment such as endoscopes, spirometry tubing, dialyzers, transducers, anesthesia, hemodialysis proportioning and dialysate delivery systems, respiratory therapy equipment and reuse of laparoscopic disposable plastic trocars. It is noncorrosive to metal and does not damage lensed instruments, plastics or rubber. It should not be used for cleaning noncritical surfaces because it is too toxic and expensive.
Colitis from residual glutaraldehyde in endoscopes; keratopathy and corneal decompensation from improperly rinsed ophthalmic instruments; dermatitis, mucositis and pulmonary symptoms with chronic exposure have been reported.
 
Hydrogen Peroxide12,17,4042
Hydrogen peroxide has been ascribed good bactericidal, virucidal, sporicidal, and fungicidal activities. Many products containing hydrogen peroxide are used as liquid chemical sterilants and high-level disinfectants. Concentrations of hydrogen peroxide from 6% to 25% show promise as chemical sterilants. The product marketed as a sterilant is a premixed, ready-to-use chemical that contains 7.5% hydrogen peroxide and 0.85% phosphoric acid to maintain a low pH. A new, rapid-acting 13.4% hydrogen peroxide formulation (that is not yet FDA-cleared) has demonstrated sporicidal, fungicidal, mycobactericidal and virucidal efficacy. Manufacturer data demonstrate that this solution sterilizes in 30 minutes and provides high-level disinfection in 5 minutes.
Mode of action: Hydrogen peroxide works by producing destructive hydroxyl free radicals that can attack membrane lipids, DNA, and other essential cell components. Catalase which is produced by aerobes and facultative anaerobes that possess cytochrome systems, can protect cells from metabolically produced hydrogen peroxide by degrading hydrogen peroxide to water and oxygen. This defense needs to be overcome by the concentrations used for disinfection.
Uses: Commercially available 3% hydrogen peroxide is a stable and effective disinfectant when used on inanimate surfaces. It is commonly used in concentrations of 3–6% for disinfecting soft contact lenses, tonometer biprisms, ventilators, fabrics, and endoscopes. Some cases of enteritis and colitis due to residual hydrogen peroxide in endoscopes have been reported.
 
Iodophors12,17,4345
Iodine solutions or tinctures have long been used as antiseptics on skin or tissue. An iodophor is a combination of iodine and a solubilizing agent or carrier; the resulting complex provides a sustained-release reservoir of iodine and releases small amounts of free iodine in aqueous solution. The best-known and most commonly used iodophor is povidone-iodine, a compound of polyvinylpyrrolidone with iodine. Iodophors retain the germicidal efficacy of iodine but unlike iodine generally are nonstaining and relatively nontoxic and nonirritant. Iodophors have been used both as antiseptics and disinfectants. FDA has not cleared any liquid chemical sterilant or high-level disinfectants with iodophors as the main active ingredient. Free iodine (I2) contributes to the bactericidal activity of iodophors and dilutions of iodophors demonstrate more rapid bactericidal action than does a full-strength povidone-iodine solution. Therefore, iodophors must be diluted according to the manufacturers’ directions to achieve antimicrobial activity.11
Mode of action: Iodine can penetrate the microbial cell wall quickly, and the lethal effects are believed to result from disruption of protein and nucleic acid structure and synthesis.
Uses: Besides their use as an antiseptic, iodophors have been used for disinfecting blood culture bottles and medical equipment, such as hydrotherapy tanks, thermometers, and endoscopes. Antiseptic iodophors are not suitable as hard-surface disinfectants because of concentration differences. Iodophors formulated as antiseptics contain less free iodine than those formulated as disinfectants. Iodine or iodine-based antiseptics should not be used on silicone catheters because they can adversely affect the silicone tubing.
 
Ortho-phthalaldehyde12,17,4648
Ortho-phthalaldehyde (OPA) is a high-level disinfectant that received FDA clearance in October 1999. It contains 0.55% 1,2-benzenedicarboxaldehyde. OPA solution is a clear, pale-blue liquid with a pH of 7.5.
Mode of action: Proposed mechanism is interaction with amino acids and affecting proteins of the microorganisms. The sporicidal activity of OPA is attributed to the blockage of the spore germination process.
Uses: OPA has several potential advantages over glutaraldehyde. It has excellent stability over a wide pH range (pH 3–9), is not a known irritant to the eyes and nasal passages, has a barely perceptible odor, does not require exposure monitoring, and requires no activation. It has excellent material compatibility. A disadvantage of OPA is that it stains proteins gray (including unprotected skin) and thus must be handled with caution. OPA residues remaining on inadequately water-rinsed transesophageal echo probes can stain the patient's mouth. Personal protective equipment should be worn while working and equipment must be thoroughly rinsed postdisinfection to prevent discoloration of skin or mucous membrane.
Recently, cases have been reported of anaphylaxis-like reactions in patients who underwent repeated cystoscopy with the scopes which had been reprocessed using OPA.
 
Peracetic Acid12,17,4952
Peracetic, or peroxyacetic, acid is characterized by rapid action against all microorganisms. Advantages of peracetic acid are that the decomposition products, i.e. acetic acid, water, oxygen and hydrogen peroxide are not harmful; it enhances removal of organic material; and leaves no residue. It remains effective in the presence of organic matter and is sporicidal even at low temperatures. Peracetic acid can corrode copper, bronze, brass, plain steel, and galvanized iron but these effects can be reduced by additives and pH modifications. It is considered unstable, especially when diluted; for example, a 1% solution loses half its strength through hydrolysis in 6 days, whereas 40% peracetic acid loses 1–2% of its active ingredients per month.
Mode of action: Similar to other oxidizing agents, the proposed mechanism is denaturation of proteins, disruption of the cell wall permeability, and oxidation of sulfhydryl and sulfur bonds in proteins, enzymes, and other metabolites.
Uses: Peracetic acid is used to chemically sterilize medical (e.g. endoscopes, arthroscopes), surgical, and dental instruments. The sterilant, 35% peracetic acid, is diluted to 0.2% with filtered water at 50°C. Simulated-use and clinical trials have demonstrated excellent microbicidal activity.
 
Peracetic Acid and Hydrogen Peroxide12,17,52,53
Two chemical sterilants are available that contain peracetic acid plus hydrogen peroxide in different percentages. It has been demonstrated that this combination inactivated all microorganisms including glutaraldehyde resistant Mycobacteria, except bacterial spores within 20 minutes.
 
Phenolics12,17,54
Joseph Lister in his revolutionary work on antiseptic surgery, used phenol as a germicide to prevent surgical infections. In the past few decades, work has been done on the phenol derivatives or phenolics and their antimicrobial properties. Phenol derivatives originate when a functional group (e.g. alkyl, phenyl, benzyl, halogen) replaces one of the hydrogen atoms on the aromatic ring of phenol. Two phenol derivatives commonly found as constituents of hospital disinfectants are ortho-phenylphenol and ortho-benzyl-para-chlorophenol. The antimicrobial properties of these compounds and many other phenol derivatives are much improved over those of the parent chemical. Phenolics are absorbed by porous materials, 12and the residual disinfectant can irritate tissue. In 1970, depigmentation of the skin was reported to be caused by phenolic germicidal detergents containing para-tertiary butylphenol and para-tertiary amylphenol.
Mode of action: In high concentrations, phenol acts as a protoplasmic poison, penetrating and disrupting the cell wall and precipitating the cell proteins. Low concentrations of phenol and higher molecular-weight phenol derivatives lead to bacterial death by inactivation of essential enzyme systems and leakage of essential metabolites from the cell wall.
Uses: Many phenolic germicides are used as disinfectants for use on environmental surfaces (e.g. bedside tables, laboratory surfaces and bedrails) and noncritical medical devices. Phenolics are not FDA-cleared as high-level disinfectants for use with semicritical items but could be used to preclean or decontaminate critical and semicritical devices before terminal sterilization or high-level disinfection.
 
Quaternary Ammonium Compounds12,17,55,56
Quaternary ammonium compounds are widely used as disinfectants. Increased water hardness decreases their microbicidal activity due to formation of insoluble precipitates; and materials such as cotton and gauze pads can absorb the active ingredients thus decreasing their efficacy. As with several other disinfectants, (e.g. phenolics, iodophors) gram-negative bacteria can survive or grow in them. A few case reports have documented occupational asthma as a result of exposure to benzalkonium chloride.
Mode of action: The bactericidal action of the quaternaries has been attributed to the inactivation of energy-producing enzymes, disruption of the cell membranes and denaturation of essential cell proteins.
Uses: The quaternaries commonly are used in ordinary environmental sanitation of noncritical surfaces, such as floors, walls and furniture. EPA-registered quaternary ammonium compounds are appropriate to use for disinfecting medical equipment that contacts intact skin (e.g. blood pressure cuffs).
 
Heavy Metals12,5759
The anti-infective activity of some heavy metals has been known for long. Silver has been used for prophylaxis of conjunctivitis of the newborn, bonding to indwelling catheters and topical therapy for burn wounds. The use of heavy metals as antiseptics or disinfectants is again being explored. Preliminary data suggests that metals are effective against a wide variety of microbes.
 
Ultraviolet Radiation12,22
The wavelength of ultraviolet (UV) radiation ranges from 328 nm to 210 nm (3280 A to 2100 A). The maximum bactericidal effect occurs at 240–280 nm. Mercury vapor lamps emit more than 90% of their radiation at 253.7 nm, which is near the maximum microbicidal activity. Inactivation of microorganisms results from nucleic acid through induction of thymine dimers. UV radiation has been employed in the disinfection of drinking water, air, contact lenses and titanium implants. Bacteria and viruses are more readily killed by UV light than are bacterial spores. The application of UV radiation in the healthcare environment (i.e. operating rooms, biologic safety cabinets and isolation rooms) is limited to destruction of airborne organisms or inactivation of microorganisms on surfaces.
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