Guideline for Disinfection and Sterilization in Healthcare Facilities, 2008
Inactivation of Bioterrorist Agents
Publications have highlighted concerns about the potential for biological terrorism306, 307. CDC has categorized several agents as "high priority" because they can be easily disseminated or transmitted from person to person, cause high mortality, and are likely to cause public panic and social disruption 308. These agents include Bacillus anthracis (the cause of anthrax), Yersinia pestis (plague), variola major (smallpox), Clostridium botulinum toxin (botulism), Francisella tularensis (tularemia), filoviruses (Ebola hemorrhagic fever, Marburg hemorrhagic fever); and arenaviruses (Lassa [Lassa fever], Junin [Argentine hemorrhagic fever]), and related viruses308.
A few comments can be made regarding the role of sterilization and disinfection of potential agents of bioterrorism309. First, the susceptibility of these agents to germicides in vitro is similar to that of other related pathogens. For example, variola is similar to vaccinia 72, 310, 311 and B. anthracis is similar to B. atrophaeus (formerly B. subtilis)312, 313. B. subtilis spores, for instance, proved as resistant as, if not more resistant than, B. anthracis spores (>6 log10 reduction of B. anthracis spores in 5 minutes with acidified bleach [5,250 ppm chlorine])313. Thus, one can extrapolate from the larger database available on the susceptibility of genetically similar organisms314. Second, many of the potential bioterrorist agents are stable enough in the environment that contaminated environmental surfaces or fomites could lead to transmission of agents such as B. anthracis, F. tularensis, variola major, C. botulinum toxin, and C. burnetti 315. Third, data suggest that current disinfection and sterilization practices are appropriate for managing patient-care equipment and environmental surfaces when potentially contaminated patients are evaluated and/or admitted in a health-care facility after exposure to a bioterrorist agent. For example, sodium hypochlorite can be used for surface disinfection (see http://www.epa.gov/pesticides/factsheets/chemicals/bleachfactsheet.htm). In instances where the health-care facility is the site of a bioterrorist attack, environmental decontamination might require special decontamination procedures (e.g., chlorine dioxide gas for B. anthracis spores). Because no antimicrobial products are registered for decontamination of biologic agents after a bioterrorist attack, EPA has granted a crises exemption for each product (see http://www.epa.gov/pesticides/factsheets/chemicals/bleachfactsheet.htm). Of only theoretical concern is the possibility that a bioterrorist agent could be engineered to be less susceptible to disinfection and sterilization processes 309.
Toxicological, Environmental and Occupational Concerns
Health hazards associated with the use of germicides in healthcare vary from mucous membrane irritation to death, with the latter involving accidental injection by mentally disturbed patients316. Although their degrees of toxicity vary 317-320, all disinfectants should be used with the proper safety precautions 321 and only for the intended purpose.
Key factors associated with assessing the health risk of a chemical exposure include the duration, intensity (i.e., how much chemical is involved), and route (e.g., skin, mucous membranes, and inhalation) of exposure. Toxicity can be acute or chronic. Acute toxicity usually results from an accidental spill of a chemical substance. Exposure is sudden and often produces an emergency situation. Chronic toxicity results from repeated exposure to low levels of the chemical over a prolonged period. Employers are responsible for informing workers about the chemical hazards in the workplace and implementing control measures. The OSHA Hazard Communication Standard (29 CFR 1910.1200, 1915.99, 1917.28, 1918.90, 1926.59, and 1928.21) requires manufacturers and importers of hazardous chemicals to develop Material Safety Data Sheets (MSDS) for each chemical or mixture of chemicals. Employers must have these data sheets readily available to employees who work with the products to which they could be exposed.
Exposure limits have been published for many chemicals used in health care to help provide a safe environment and, as relevant, are discussed in each section of this guideline. Only the exposure limits published by OSHA carry the legal force of regulations. OSHA publishes a limit as a time-weighted average (TWA), that is, the average concentration for a normal 8-hour work day and a 40-hour work week to which nearly all workers can be repeatedly exposed to a chemical without adverse health effects. For example, the permissible exposure limit (PEL) for EtO is 1.0 ppm, 8 hour TWA. The CDC National Institute for Occupational Safety and Health (NIOSH) develops recommended exposure limits (RELs). RELs are occupational exposure limits recommended by NIOSH as being protective of worker health and safety over a working lifetime. This limit is frequently expressed as a 40-hour TWA exposure for up to 10 hours per day during a 40-hour work week. These exposure limits are designed for inhalation exposures. Irritant and allergic effects can occur below the exposure limits, and skin contact can result in dermal effects or systemic absorption without inhalation. The American Conference on Governmental Industrial Hygienists (ACGIN) also provides guidelines on exposure limits 322. Information about workplace exposures and methods to reduce them (e.g., work practices, engineering controls, PPE) is available on the OSHA (http://www.osha.gov) and NIOSH (http://www.cdc.gov/niosh) websites.
Some states have excluded or limited concentrations of certain chemical germicides (e.g., glutaraldehyde, formaldehyde, and some phenols) from disposal through the sewer system. These rules are intended to minimize environmental harm. If health-care facilities exceed the maximum allowable concentration of a chemical (e.g., >5.0 mg/L), they have three options. First, they can switch to alternative products; for example, they can change from glutaraldehyde to another disinfectant for high-level disinfection or from phenolics to quaternary ammonium compounds for low-level disinfection. Second, the health-care facility can collect the disinfectant and dispose of it as a hazardous chemical. Third, the facility can use a commercially available small-scale treatment method (e.g., neutralize glutaraldehyde with glycine).
Safe disposal of regulated chemicals is important throughout the medical community. For disposal of large volumes of spent solutions, users might decide to neutralize the microbicidal activity before disposal (e.g., glutaraldehyde). Solutions can be neutralized by reaction with chemicals such as sodium bisulfite 323, 324 or glycine 325.
European authors have suggested that instruments and ventilation therapy equipment should be disinfected by heat rather than by chemicals. The concerns for chemical disinfection include toxic side effects for the patient caused by chemical residues on the instrument or object, occupational exposure to toxic chemicals, and recontamination by rinsing the disinfectant with microbially contaminated tap water 326.
Disinfection in Ambulatory Care, Home Care, and the Home
With the advent of managed healthcare, increasing numbers of patients are now being cared for in ambulatory-care and home settings. Many patients in these settings might have communicable diseases, immunocompromising conditions, or invasive devices. Therefore, adequate disinfection in these settings is necessary to provide a safe patient environment. Because the ambulatory-care setting (i.e., outpatient facility) provides the same risk for infection as the hospital, the Spaulding classification scheme described in this guideline should be followed (Table 1) 17.
The home environment should be much safer than hospitals or ambulatory care. Epidemics should not be a problem, and cross-infection should be rare. The healthcare provider is responsible for providing the responsible family member information about infection-control procedures to follow in the home, including hand hygiene, proper cleaning and disinfection of equipment, and safe storage of cleaned and disinfected devices. Among the products recommended for home disinfection of reusable objects are bleach, alcohol, and hydrogen peroxide. APIC recommends that reusable objects (e.g., tracheostomy tubes) that touch mucous membranes be disinfected by immersion in 70% isopropyl alcohol for 5 minutes or in 3% hydrogen peroxide for 30 minutes. Additionally, a 1:50 dilution of 5.25%–6.15% sodium hypochlorite (household bleach) for 5 minutes should be effective 327-329. Noncritical items (e.g., blood pressure cuffs, crutches) can be cleaned with a detergent. Blood spills should be handled according to OSHA regulations as previously described (see section on OSHA Bloodborne Pathogen Standard). In general, sterilization of critical items is not practical in homes but theoretically could be accomplished by chemical sterilants or boiling. Single-use disposable items can be used or reusable items sterilized in a hospital 330, 331.
Some environmental groups advocate "environmentally safe" products as alternatives to commercial germicides in the home-care setting. These alternatives (e.g., ammonia, baking soda, vinegar, Borax, liquid detergent) are not registered with EPA and should not be used for disinfecting because they are ineffective against S. aureus. Borax, baking soda, and detergents also are ineffective against Salmonella Typhi and E.coli; however, undiluted vinegar and ammonia are effective against S. Typhi and E.coli 53, 332, 333. Common commercial disinfectants designed for home use also are effective against selected antibiotic-resistant bacteria 53.
Public concerns have been raised that the use of antimicrobials in the home can promote development of antibiotic-resistant bacteria 334, 335. This issue is unresolved and needs to be considered further through scientific and clinical investigations. The public health benefits of using disinfectants in the home are unknown. However, some facts are known: many sites in the home kitchen and bathroom are microbially contaminated 336, use of hypochlorites markedly reduces bacteria 337, and good standards of hygiene (e.g., food hygiene, hand hygiene) can help reduce infections in the home 338, 339. In addition, laboratory studies indicate that many commercially prepared household disinfectants are effective against common pathogens 53 and can interrupt surface-to-human transmission of pathogens 48. The "targeted hygiene concept"—which means identifying situations and areas (e.g., food-preparation surfaces and bathroom) where risk exists for transmission of pathogens—may be a reasonable way to identify when disinfection might be appropriate 340.
Susceptibility of Antibiotic-Resistant Bacteria to Disinfectants
As with antibiotics, reduced susceptibility (or acquired "resistance") of bacteria to disinfectants can arise by either chromosomal gene mutation or acquisition of genetic material in the form of plasmids or transposons 338, 341-343, 344 , 345, 346. When changes occur in bacterial susceptibility that renders an antibiotic ineffective against an infection previously treatable by that antibiotic, the bacteria are referred to as "resistant." In contrast, reduced susceptibility to disinfectants does not correlate with failure of the disinfectant because concentrations used in disinfection still greatly exceed the cidal level. Thus, the word "resistance" when applied to these changes is incorrect, and the preferred term is "reduced susceptibility" or "increased tolerance" 344, 347. No data are available that show that antibiotic-resistant bacteria are less sensitive to the liquid chemical germicides than antibiotic-sensitive bacteria at currently used germicide contact conditions and concentrations.
MRSA and vancomycin-resistant Enterococcus (VRE) are important health-care–associated agents. Some antiseptics and disinfectants have been known for years to be, because of MICs, somewhat less inhibitory to S. aureus strains that contain a plasmid-carrying gene encoding resistance to the antibiotic gentamicin 344. For example, gentamicin resistance has been shown to also encode reduced susceptibility to propamidine, quaternary ammonium compounds, and ethidium bromide 348, and MRSA strains have been found to be less susceptible than methicillin-sensitive S. aureus (MSSA) strains to chlorhexidine, propamidine, and the quaternary ammonium compound cetrimide 349. In other studies, MRSA and MSSA strains have been equally sensitive to phenols and chlorhexidine, but MRSA strains were slightly more tolerant to quaternary ammonium compounds 350. Two gene families (qacCD [now referred to as smr] and qacAB) are involved in providing protection against agents that are components of disinfectant formulations such as quaternary ammonium compounds. Staphylococci have been proposed to evade destruction because the protein specified by the qacA determinant is a cytoplasmic-membrane–associated protein involved in an efflux system that actively reduces intracellular accumulation of toxicants, such as quaternary ammonium compounds, to intracellular targets 351.
Other studies demonstrated that plasmid-mediated formaldehyde tolerance is transferable from Serratia marcescens to E. coli 352 and plasmid-mediated quaternary ammonium tolerance is transferable from S. aureus to E. coli.353. Tolerance to mercury and silver also is plasmid borne 341, 343-346.
Because the concentrations of disinfectants used in practice are much higher than the MICs observed, even for the more tolerant strains, the clinical relevance of these observations is questionable. Several studies have found antibiotic-resistant hospital strains of common healthcare-associated pathogens (i.e., Enterococcus, P. aeruginosa, Klebsiella pneumoniae, E. coli, S. aureus, and S. epidermidis) to be equally susceptible to disinfectants as antibiotic-sensitive strains 53, 354-356. The susceptibility of glycopeptide-intermediate S. aureus was similar to vancomycin-susceptible, MRSA 357. On the basis of these data, routine disinfection and housekeeping protocols do not need to be altered because of antibiotic resistance provided the disinfection method is effective 358, 359. A study that evaluated the efficacy of selected cleaning methods (e.g., QUAT-sprayed cloth, and QUAT-immersed cloth) for eliminating VRE found that currently used disinfection processes most likely are highly effective in eliminating VRE. However, surface disinfection must involve contact with all contaminated surfaces 358. A new method using an invisible flurorescent marker to objectively evaluate the thoroughness of cleaning activities in patient rooms might lead to improvement in cleaning of all objects and surfaces but needs further evaluation360.
Lastly, does the use of antiseptics or disinfectants facilitate the development of disinfectant-tolerant organisms? Evidence and reviews indicate enhanced tolerance to disinfectants can be developed in response to disinfectant exposure 334, 335, 346, 347, 361. However, the level of tolerance is not important in clinical terms because it is low and unlikely to compromise the effectiveness of disinfectants of which much higher concentrations are used 347, 362.
The issue of whether low-level tolerance to germicides selects for antibiotic-resistant strains is unsettled but might depend on the mechanism by which tolerance is attained. For example, changes in the permeability barrier or efflux mechanisms might affect susceptibility to both antibiotics and germicides, but specific changes to a target site might not. Some researchers have suggested that use of disinfectants or antiseptics (e.g., triclosan) could facilitate development of antibiotic-resistant microorganisms 334, 335, 363. Although evidence in laboratory studies indicates low-level resistance to triclosan, the concentrations of triclosan in these studies were low (generally <1 μg/mL) and dissimilar from the higher levels used in antimicrobial products (2,000–20,000 μg/mL) 364, 365. Thus, researchers can create laboratory-derived mutants that demonstrate reduced susceptibility to antiseptics or disinfectants. In some experiments, such bacteria have demonstrated reduced susceptibility to certain antibiotics 335. There is no evidence that using antiseptics or disinfectants selects for antibiotic-resistant organisms in nature or that such mutants survive in nature366. ). In addition, the action of antibiotics and the action of disinfectants differ fundamentally. Antibiotics are selectively toxic and generally have a single target site in bacteria, thereby inhibiting a specific biosynthetic process. Germicides generally are considered nonspecific antimicrobials because of a multiplicity of toxic-effect mechanisms or target sites and are broader spectrum in the types of microorganisms against which they are effective 344, 347.
The rotational use of disinfectants in some environments (e.g., pharmacy production units) has been recommended and practiced in an attempt to prevent development of resistant microbes 367, 368. There have been only rare case reports that appropriately used disinfectants have resulted in a clinical problem arising from the selection or development of nonsusceptible microorganisms 369.