Nosocomial infection

Nosocomial infection
Classification and external resources

Contaminated surfaces increase cross-transmission
ICD-10 Y95

A nosocomial infection (nos-oh-koh-mi-al), also known as a hospital-acquired infection or HAI, is an infection whose development is favoured by a hospital environment, such as one acquired by a patient during a hospital visit or one developing among hospital staff. Such infections include fungal and bacterial infections and are aggravated by the reduced resistance of individual patients.[1]

In the United States, the Centers for Disease Control and Prevention estimate that roughly 1.7 million hospital-associated infections, from all types of microorganisms, including bacteria, combined, cause or contribute to 99,000 deaths each year.[2] In Europe, where hospital surveys have been conducted, the category of Gram-negative infections are estimated to account for two-thirds of the 25,000 deaths each year. Nosocomial infections can cause severe pneumonia and infections of the urinary tract, bloodstream and other parts of the body. Many types are difficult to attack with antibiotics, and antibiotic resistance is spreading to Gram-negative bacteria that can infect people outside the hospital.[2]

Contents

Known nosocomial infections

Epidemiology

Nosocomial infections are commonly transmitted when hospital officials become complacent and personnel do not practice correct hygiene regularly. Also, increased use of outpatient treatment means that people who are hospitalized are more ill and have more weakened immune systems than may have been true in the past. Moreover, some medical procedures bypass the body's natural protective barriers. Since medical staff move from patient to patient, the staff themselves serve as a means for spreading pathogens. Essentially, the staff act as vectors.

Categories and treatment

Among the categories of bacteria most known to infect patients are the category MRSA, Gram-positive bacteria and Helicobacter, which is Gram-negative. While there are antibiotic drugs that can treat diseases caused by Gram-positive MRSA, there are currently few effective drugs for Acinetobacter. However, Acinetobacter germs are evolving and becoming immune to existing antibiotics. "In many respects it’s far worse than MRSA," said a specialist at Case Western Reserve University.[2]

Another growing disease, especially prevalent in New York City hospitals, is the drug-resistant Gram-negative germ, Klebsiella pneumoniae. An estimated more than 20 percent of the Klebsiella infections in Brooklyn hospitals "are now resistant to virtually all modern antibiotics. And those supergerms are now spreading worldwide."[2]

The bacteria, classified as Gram-negative because of their reaction to the Gram stain test, can cause severe pneumonia and infections of the urinary tract, bloodstream, and other parts of the body. Their cell structures make them more difficult to attack with antibiotics than Gram-positive organisms like MRSA. In some cases, antibiotic resistance is spreading to Gram-negative bacteria that can infect people outside the hospital. "For Gram-positives we need better drugs; for Gram-negatives we need any drugs," said Dr. Brad Spellberg, an infectious-disease specialist at Harbor-UCLA Medical Center, and the author of Rising Plague, a book about drug-resistant pathogens.[2]

One-third of nosocomial infections are considered preventable. The CDC estimates 2 million people in the United States are infected annually by hospital-acquired infections, resulting in 20,000 deaths.[3] The most common nosocomial infections are of the urinary tract, surgical site and various pneumonias.[4]

Country estimates

The methods used differ from country to country (definitions used, type of nosocomial infections covered, health units surveyed, inclusion or exclusion of imported infections, etc.), so that international comparisons of nosocomial infection rates should be made with the utmost care.

United States: The Centers for Disease Control and Prevention (CDC) estimates that roughly 1.7 million hospital-associated infections, from all types of bacteria combined, cause or contribute to 99,000 deaths each year.[2] Other estimates indicate that 10%, or 2 million, patients a year become infected, with the annual cost ranging from $4.5 billion to $11 billion. In the USA the most frequent type of infection hospitalwide is urinary tract infection (36%), followed by surgical site infection (20%), bloodstream infection (BSI), and pneumonia (both 11%).[2]

France: estimates ranged from 6.7% in 1990 to 7.4% (patients may have several infections).[5] At national level, prevalence among patients in health care facilities was 6.7% in 1996,[6] 5.9% in 2001[7] and 5.0% in 2006.[8] The rates for nosocomial infections were 7.6% in 1996, 6.4% in 2001 and 5.4% in 2006.

In 2006, the most common infection sites were urinary tract infections (30,3%), pneumopathy (14,7%), infections of surgery site (14,2%). infections of the skin and mucous membrane (10,2%), other respiratory infections (6,8%) and bacterial infections / blood poisoning (6,4%).[9] The rates among adult patients in intensive care were 13,5% in 2004, 14,6% in 2005, 14,1% in 2006 and 14.4% in 2007.[10]

It has also been estimated that nosocomial infections make patients stay in the hospital 4-5 additional days. Around 2004-2005, about 9,000 people died each year with a nosocomial infection, of which about 4,200 would have survived without this infection.[11]

Italy: since 2000, estimates show that about 6.7% infection rate, i.e. between 450,000 and 700,000 patients, which caused between 4,500 and 7,000 deaths.[12] A survey in Lombardy gave a rate of 4.9% of patients in 2000.[13]

United Kingdom: estimates of 10% infection rate,[14] with 8.2% estimated in 2006.[15]

Switzerland: estimates range between 2 and 14%.[16] A national survey gave a rate of 7.2% in 2004.[17]

Finland: estimated at 8.5% of patients in 2005[18]

Transmission

The drug-resistant Gram-negative germs for the most part threaten only hospitalized patients whose immune systems are weak. The germs can survive for a long time on surfaces in the hospital and enter the body through wounds, catheters, and ventilators.[2]

Main routes of transmission
Route Description
Contact transmission the most important and frequent mode of transmission of nosocomial infections.
Droplet transmission occurs when droplets are generated from the source person mainly during coughing, sneezing, and talking, and during the performance of certain procedures such as bronchoscopy. Transmission occurs when droplets containing germs from the infected person are propelled a short distance through the air and deposited on the host's body.
Airborne transmission occurs by dissemination of either airborne droplet nuclei (small-particle residue {5 µm or smaller in size} of evaporated droplets containing microorganisms that remain suspended in the air for long periods of time) or dust particles containing the infectious agent. Microorganisms carried in this manner can be dispersed widely by air currents and may become inhaled by a susceptible host within the same room or over a longer distance from the source patient, depending on environmental factors; therefore, special air handling and ventilation are required to prevent airborne transmission. Microorganisms transmitted by airborne transmission include Legionella, Mycobacterium tuberculosis and the rubeola and varicella viruses.
Common vehicle transmission applies to microorganisms transmitted to the host by contaminated items such as food, water, medications, devices, and equipment.
Vector borne transmission occurs when vectors such as mosquitoes, flies, rats, and other vermin transmit microorganisms.

Contact transmission is divided into two subgroups: direct-contact transmission and indirect-contact transmission.

Routes of contact transmission
Route Description
Direct-contact transmission involves a direct body surface-to-body surface contact and physical transfer of microorganisms between a susceptible host and an infected or colonized person, such as occurs when a person turns a patient, gives a patient a bath, or performs other patient-care activities that require direct personal contact. Direct-contact transmission also can occur between two patients, with one serving as the source of the infectious microorganisms and the other as a susceptible host.
Indirect-contact transmission involves contact of a susceptible host with a contaminated intermediate object, usually inanimate, such as contaminated instruments, needles, or dressings, or contaminated gloves that are not changed between patients. In addition, the improper use of saline flush syringes, vials, and bags has been implicated in disease transmission in the US, even when healthcare workers had access to gloves, disposable needles, intravenous devices, and flushes.[19]

Risk factors

Factors predisposing a patient to infection can broadly be divided into three areas:

Prevention

Hospitals have sanitation protocols regarding uniforms, equipment sterilization, washing, and other preventative measures. Thorough hand washing and/or use of alcohol rubs by all medical personnel before and after each patient contact is one of the most effective ways to combat nosocomial infections.[20] More careful use of antimicrobial agents, such as antibiotics, is also considered vital.[21]

Despite sanitation protocol, patients cannot be entirely isolated from infectious agents. Furthermore, patients are often prescribed antibiotics and other antimicrobial drugs to help treat illness; this may increase the selection pressure for the emergence of resistant strains.

Sterilization

Sterilization goes further than just sanitizing. Sterilizing kills all microorganisms on equipment and surfaces through exposure to chemicals, ionizing radiation, dry heat, or steam under pressure.

Isolation

Isolation precautions are designed to prevent transmission of microorganisms by common routes in hospitals. Because agent and host factors are more difficult to control, interruption of transfer of microorganisms is directed primarily at transmission.

Handwashing and gloving

Handwashing frequently is called the single most important measure to reduce the risks of transmitting skin microorganisms from one person to another or from one site to another on the same patient. Washing hands as promptly and thoroughly as possible between patient contacts and after contact with blood, body fluids, secretions, excretions, and equipment or articles contaminated by them is an important component of infection control and isolation precautions. The spread of nosocomial infections, among immunocompromised patients is connected with Health Care Workers hand contamination in almost 40% of cases and it is a real challenging problem in the modern hospitals. The best way for Health Care Workers to overcome this problem is acting right hand hygiene procedures, this is why the WHO launched in 2005 the GLOBAL Patient Safety Challenge.[22] Two categories of micro organisms can be present on Health Care Workers hands: transient flora and resident flora. The first one is represented by the micro organisms taken by Health Care Workers from the environment, and the bacteria in it are capable of surviving on the human skin and sometimes to grow. The second group on the other hand, is represented by the permanent micro organisms that lived on the skin surface (on the stratum corneum or immediately under it). They are capable of surviving on the human skin and to grow freely on it. They have low pathogenicity and infection rate, and they create a kind of protection from the colonization from other more pathogenic bacteria. The skin of Health Care Workers is colonized by 3.9 x 104 – 4.6 x 106 cfu / cm2. The micro organisms creating the resident flora are: Staphylococcus epidermidis, Staphylococcus hominis, Microccoci, Propionibacterium, Corynebacterium, Dermobacterium, Pitosporum, while in the transitional could be found Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter spp, Enterobacter spp and Candida spp. The goal of hand hygiene is to eliminate the transient flora with a careful and proper performance of hand wash, using different kind of soap, from the normal one to the antiseptic, and alcohol based gel. The main problems found in the practice of hand hygiene is connected with the lack of available sinks and time consuming performance of hand washing. An easy way to resolve this problem could be the use of alcohol based hand rub, because of its faster application compared to a correct hand washing.[23]

Although handwashing may seem like a simple process, it is often performed incorrectly. Healthcare settings must continuously remind practitioners and visitors on the proper procedure in washing their hands to comply with responsible handwashing. Simple programs such as Henry the Hand, and the use of handwashing signals can assist healthcare facilities in the prevention of nosocomial infections.

All visitors must follow the same procedures as hospital staff to adequately control the spread of infections. Visitors and healthcare personnel are equally to blame in transmitting infections. Moreover, multidrug-resistant infections can leave the hospital and become part of the community flora if steps are not taken to stop this transmission.

In addition to handwashing, gloves play an important role in reducing the risks of transmission of microorganisms. Gloves are worn for three important reasons in hospitals. First, gloves are worn to provide a protective barrier and to prevent gross contamination of the hands when touching blood, body fluids, secretions, excretions, mucous membranes, and nonintact skin. In the USA, the Occupational Safety and Health Administration has mandated wearing gloves to reduce the risk of bloodborne pathogen infection.[24] Second, gloves are worn to reduce the likelihood that microorganisms present on the hands of personnel will be transmitted to patients during invasive or other patient-care procedures that involve touching a patient's mucous membranes and nonintact skin. Third, gloves are worn to reduce the likelihood that hands of personnel contaminated with microorganisms from a patient or a fomite can transmit these microorganisms to another patient. In this situation, gloves must be changed between patient contacts, and hands should be washed after gloves are removed.

Wearing gloves does not replace the need for handwashing, because gloves may have small, non-apparent defects or may be torn during use, and hands can become contaminated during removal of gloves. Failure to change gloves between patient contacts is an infection control hazard.

Surface sanitation

Sanitizing surfaces is an often overlooked, yet crucial component of breaking the cycle of infection in health care environments. Modern sanitizing methods such as NAV-CO2 have been effective against gastroenteritis, MRSA, and influenza. Use of hydrogen peroxide vapor has been clinically proven to reduce infection rates and risk of acquisition. Hydrogen peroxide is effective against endospore-forming bacteria, such as Clostridium difficile, where alcohol has been shown to be ineffective.[25]

Antimicrobial surfaces

Microorganisms are known to survive on inanimate ‘touch’ surfaces for extended periods of time.[26] This can be especially troublesome in hospital environments where patients with immunodeficiencies are at enhanced risk for contracting nosocomial infections.

Touch surfaces commonly found in hospital rooms, such as bed rails, call buttons, touch plates, chairs, door handles, light switches, grab rails, intravenous poles, dispensers (alcohol gel, paper towel, soap), dressing trolleys, and counter and table tops are known to be contaminated with Staphylococcus, Methicillin-resistant Staphylococcus aureus (MRSA), one of the most virulent strains of antibiotic-resistant bacteria and Vancomycin-resistant Enterococcus (VRE).[27] Objects in closest proximity to patients have the highest levels of staphylococcus, MRSA, and VRE. This is why touch surfaces in hospital rooms can serve as sources, or reservoirs, for the spread of bacteria from the hands of healthcare workers and visitors to patients.

Copper alloy surfaces have intrinsic properties to destroy a wide range of microorganisms. In the interest of protecting public health, especially in heathcare environments with their susceptible patient populations, an abundance of peer-reviewed antimicrobial efficacy studies have been and continue to be conducted around the world regarding copper’s efficacy to destroy E. coli O157:H7, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus, Clostridium difficile, influenza A virus, adenovirus, and fungi.[28]

Much of this antimicrobial efficacy work has been or is currently being conducted at the University of Southampton and Northumbria University (United Kingdom), University of Stellenbosch (South Africa), Panjab University (India), University of Chile (Chile), Kitasato University (Japan), the Instituto do Mar[29] and University of Coimbra (Portugal), and the University of Nebraska and Arizona State University (U.S.A.). A summary of the antimicrobial copper touch surfaces clinical trials to date is available[30]

In 2007, U.S. Department of Defense’s Telemedicine and Advanced Technologies Research Center (TATRC) began to study the antimicrobial properties of copper alloys in a multi-site clinical hospital trial conducted at the Memorial Sloan-Kettering Cancer Center (New York City), the Medical University of South Carolina, and the Ralph H. Johnson VA Medical Center (South Carolina).[31] Commonly-touched items, such as bed rails, over-the-bed tray tables, chair arms, nurse's call buttons, IV poles, etc. were retrofitted with antimicrobial copper alloys in certain patient rooms (i.e., the “coppered” rooms) in the Intensive Care Unit (ICU). Early results disclosed in 2011 indicate that the coppered rooms demonstrated a 97% reduction in surface pathogens versus the non-coppered rooms. This reduction is the same level achieved by “terminal” cleaning regimens conducted after patients vacate their rooms. Furthermore, of critical importance to health care professionals, the preliminary results indicated that patients in the coppered ICU rooms had a 40.4% lower risk of contracting a hospital acquired infection versus patients in non-coppered ICU rooms.[32][33][34] The U.S. Department of Defense investigation contract, which is ongoing, will also evaluate the effectiveness of copper alloy touch surfaces to prevent the transfer of microbes to patients and the transfer of microbes from patients to touch surfaces, as well as the potential efficacy of copper-alloy based components to improve indoor air quality.

In the U.S., the Environmental Protection Agency regulates the registration of antimicrobial products. After extensive antimicrobial testing according to the Agency’s stringent test protocols, 355 copper alloys, including many brasses, were found to kill more than 99.9% of methicillin-resistant Staphylococcus aureus (MRSA), E. coli O157:H7, Pseudomonas aeruginosa, Staphylococcus aureus, Enterobacter aerogenes, and vancomycin-resistant Enterococci (VRE) within two hours of contact.[35][36] Normal tarnishing was found to not impair antimicrobial effectiveness.

On February 29, 2008, the United States Environmental Protection Agency (EPA) granted its first registrations of five different groups of copper alloys as “antimicrobial materials” with public health benefits.[37] The registrations granted antimicrobial copper as "a supplement to and not a substitute for standard infection control practices." Subsequent registration approvals of additional copper alloys have been granted. The results of the EPA-supervised antimicrobial studies, demonstrating copper's strong antimicrobial efficacies across a wide range of alloys, have been published.[38] These copper alloys are the only solid surface materials to be granted “antimicrobial public health claims” status by EPA.

The EPA registrations state that laboratory testing has shown that when cleaned regularly:

The registrations state that “antimicrobial copper alloys may be used in hospitals, other healthcare facilities, and various public, commercial and residential buildings.” A list of antimicrobial copper products approved by the EPA is available.[39]

Aprons

Wearing an apron during patient care reduces the risk of infection. The apron should either be disposable or be used only when caring for a specific patient.

Mitigation

The most effective technique of controlling nosocomial infection is to strategically implement QA/QC measures to the health care sectors and evidence-based management can be a feasible approach. For those VAP/HAP diseases (ventilator-associated pneumonia, hospital-acquired pneumonia), controlling and monitoring hospital indoor air quality needs to be on agenda in management[40] whereas for nosocomial rotavirus infection, a hand hygiene protocol has to be enforced.[41][42][43] Other areas that the management needs to be covered include ambulance transport.

See also

References

  1. ^ "Nosocomial Infection". A Dictionary of Nursing. Oxford Reference Online. 2008. http://www.oxfordreference.com/views/ENTRY.html?subview=Main&entry=t62.e6134. Retrieved 2011-08-15. 
  2. ^ a b c d e f g h Pollack, Andrew. "Rising Threat of Infections Unfazed by Antibiotics" New York Times, Feb. 27, 2010
  3. ^ Ricks, Delthia (2007). "Germ Warfare". Ms. Magazine: 43–5. http://www.msmagazine.com/spring2007/germwarfare.asp. 
  4. ^ Klevens RM, Edwards JR, Richards CL, et al. (2007). "Estimating health care-associated infections and deaths in U.S. hospitals, 2002". Public Health Rep 122 (2): 160–6. PMC 1820440. PMID 17357358. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1820440. 
  5. ^ Quenon JL, Gottot S, Duneton P, Lariven S, Carlet J, Régnier B, Brücker G. Enquête nationale de prévalence des infections nosocomiales en France : Hôpital Propre (octobre 1990). BEH n° 39/1993.
  6. ^ Comité technique des infections nosocomiales (CTIN), Cellule infections nosocomiales, CClin Est, CClin Ouest, CClin Paris-Nord, CClin Sud-Est, CClin Sud-Ouest, avec la participation de 830 établissements de santé. Enquête nationale de prévalence des infections nosocomiales,1996, BEH n° 36/1997, 2 sept. 1997, 4 pp.. Résumé.
  7. ^ Lepoutre A, Branger B, Garreau N, Boulétreau A, Ayzac L, Carbonne A, Maugat S, Gayet S, Hommel C, Parneix P, Tran B pour le Réseau d’alerte, d’investigation et de surveillance des infections nosocomiales (Raisin). Deuxième enquête nationale de prévalence des infections nosocomiales, France, 2001, Surveillance nationale des maladies infectieuses, 2001-2003. Institut de veille sanitaire, sept. 2005, 11 pp. Résumé.
  8. ^ Institut de veille sanitaire Enquête nationale de prévalence des infections nosocomiales, France, juin 2006, Volume 1 – Méthodes, résultats, perspectives, mars 2009, ii + 81 pp. Volume 2 – Annexes, mars 2009, ii + 91 pp. Synthèse des résultats, Mars 2009, 11 pp.
  9. ^ Institut de veille sanitaire Enquête nationale de prévalence des infections nosocomiales, France, juin 2006, Vol. 1, Tableau 31, p. 24.
  10. ^ Réseau REA-Raisin « Surveillance des infections nosocomiales en réanimation adulte. France, résultats 2007 », Institut de veille sanitaire, Sept. 2009, ii + 60 pp.
  11. ^ Vasselle, Alain « Rapport sur la politique de lutte contre les infections nosocomiales », Office parlementaire d'évaluation des politiques de santé, juin 2006, 290 pp. (III.5. Quelle est l’estimation de la mortalité attribuable aux IN ?).
  12. ^ L'Italie scandalisée par "l'hôpital de l'horreur", Éric Jozsef, Libération, January 17, 2007 (French)
  13. ^ Liziolia A, Privitera G, Alliata E, Antonietta Banfi EM, Boselli L, Panceri ML, Perna MC, Porretta AD, Santini MG, Carreri V. Prevalence of nosocomial infections in Italy: result from the Lombardy survey in 2000. J Hosp Infect 2003;54:141-8.
  14. ^ Aodhán S Breathnacha, Nosocomial infections, Medicine, 2005: 33, 22-26
  15. ^ Press release for The Third Prevalence Survey of Healthcare-associated Infections in Acute Hospitals. Hospital Infection Society, Londres, 27/10/06.
  16. ^ Facts sheet - Swiss Hand Hygiene Campaign. (.doc)
  17. ^ Sax H, Pittet D pour le comité de rédaction de Swiss-NOSO et le réseau Swiss-NOSO Surveillance. Résultats de l’enquête nationale de prévalence des infections nosocomiales de 2004 (snip04). Swiss-NOSO 2005;12(1):1-4.
  18. ^ Lyytikainen O, Kanerva M, Agthe N, Mottonen T and the Finish Prevalence Survey Study Group. National Prevalence Survey on Nosocomial Infections in Finnish Acute Care Hospitals, 2005. 10th Epiet Scientific Seminar. Mahon, Menorca, Spain, 13–15 October 2005 [Poster].
  19. ^ Jain SK, Persaud D, Perl TM, et al. (July 2005). "Nosocomial malaria and saline flush". Emerging Infect. Dis. 11 (7): 1097–9. PMID 16022788. http://www.cdc.gov/ncidod/EID/vol11no07/05-0092.htm. 
  20. ^ McBryde ES, Bradley LC, Whitby M, McElwain DL (October 2004). "An investigation of contact transmission of methicillin-resistant Staphylococcus aureus". J. Hosp. Infect. 58 (2): 104–8. doi:10.1016/j.jhin.2004.06.010. PMID 15474180. 
  21. ^ Lautenbach E (2001). "Chapter 14. Impact of Changes in Antibiotic Use Practices on Nosocomial Infections and Antimicrobial Resistance—Clostridium difficile and Vancomycin-resistant Enterococcus (VRE)". In Markowitz AJ. Making Health Care Safer: A Critical Analysis of Patient Safety Practices. Agency for Healthcare Research and Quality. http://www.ahrq.gov/clinic/ptsafety/chap14.htm. 
  22. ^ World Alliance for patient safety. WHO Guidelines on Hand Hygiene in Health Care. http://www.who.int/rpc/guidelines/9789241597906/en/. 2009
  23. ^ (5) Hugonnet S, Perneger TV, Pittet D. Alcohol based hand rub improves compliance with hand hygiene in intensive care units. Arch Intern med 2002; 162: 1037-1043.
  24. ^ "Occupational Exposure to Bloodborne Pathogens;Needlestick and Other Sharps Injuries; Final Rule. - 66:5317-5325". Osha.gov. http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_id=16265&p_table=FEDERAL_REGISTER. Retrieved 2011-07-11. 
  25. ^ Otter JA, French GL (January 2009). "Survival of nosocomial bacteria and spores on surfaces and inactivation by hydrogen peroxide vapor". J. Clin. Microbiol. 47 (1): 205–7. doi:10.1128/JCM.02004-08. PMC 2620839. PMID 18971364. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2620839. 
  26. ^ Wilks, S.A., Michels, H., Keevil, C.W., 2005, The Survival of Escherichia Coli O157 on a Range of Metal Surfaces, International Journal of Food Microbiology, Vol. 105, pp. 445–454. and Michels, H.T. (2006), Anti-Microbial Characteristics of Copper, ASTM Standardization News, October, pp. 28-31
  27. ^ U.S. Department of Defense-funded clinical trials, as presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington, D.C., October 28, 2008
  28. ^ Copper Touch Surfaces
  29. ^ http://www.imar.pt
  30. ^ Antimicrobial copper-alloy touch surfaces#Clinical trials of antimicrobial copper alloy touch surfaces in healthcare facilities
  31. ^ http://www.biomedcentral.com/content/pdf/1753-6561-5-s6-o53.pdf and http://www.coppertouchsurfaces.org
  32. ^ http://www.biomedcentral.com/content/pdf/1753-6561-5-s6-o53.pdf
  33. ^ http://www.coppertouchsurfaces.org/press/releases/20110701.html
  34. ^ World Health Organization’s 1st International Conference on Prevention and Infection Control (ICPIC) in Geneva, Switzerland on July 1st, 2011
  35. ^ EPA registers copper-containing alloy products, May 2008, http://www.epa.gov/opp00001/factsheets/copper-alloy-products.htm
  36. ^ 355 Copper Alloys Now Approved by EPA as Antimicrobial, Jun 28, 2011, http://www.appliancemagazine.com/news.php?article=1498614&zone=0&first=1
  37. ^ EPA registers copper-containing alloy products, May 2008
  38. ^ Collery, Ph., Maymard, I., Theophanides, T., Khassanova, L., and Collery, T., Editors, Metal Ions in Biology and Medicine: Vol. 10., John Libbey Eurotext, Paris © 2008, Antimicrobial regulatory efficacy testing of solid copper alloy surfaces in the USA, by Michels, Harold T. and Anderson, Douglas G. (2008), pp. 185-190.
  39. ^ http://en.wikipedia.org/wiki/Antimicrobial_copper-alloy_touch_surfaces#Approved_products
  40. ^ Leung M, Chan AH (March 2006). "Control and management of hospital indoor air quality". Med. Sci. Monit. 12 (3): SR17–23. PMID 16501436. http://www.medscimonit.com/fulltxt.php?ICID=447117. 
  41. ^ Chan PC, Huang LM, Lin HC, et al. (April 2007). "Control of an outbreak of pandrug-resistant Acinetobacter baumannii colonization and infection in a neonatal intensive care unit". Infect Control Hosp Epidemiol 28 (4): 423–9. doi:10.1086/513120. PMID 17385148. 
  42. ^ Traub-Dargatz JL, Weese JS, Rousseau JD, Dunowska M, Morley PS, Dargatz DA (July 2006). "Pilot study to evaluate 3 hygiene protocols on the reduction of bacterial load on the hands of veterinary staff performing routine equine physical examinations". Can. Vet. J. 47 (7): 671–6. PMC 1482439. PMID 16898109. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1482439. 
  43. ^ Katz JD (September 2004). "Hand washing and hand disinfection: more than your mother taught you". Anesthesiol Clin North America 22 (3): 457–71, vi. doi:10.1016/j.atc.2004.04.002. PMID 15325713.