Antimicrobial properties of copper

Last updated

Copper and its alloys (brasses, bronzes, cupronickel, copper-nickel-zinc, and others) are natural antimicrobial materials. Ancient civilizations exploited the antimicrobial properties of copper long before the concept of microbes became understood in the nineteenth century. [1] [2] [3] [ unreliable medical source? ] In addition to several copper medicinal preparations, it was also observed centuries ago that water contained in copper vessels or transported in copper conveyance systems was of better quality (i.e., no or little visible slime or biofouling formation) than water contained or transported in other materials. [4]

Contents

The antimicrobial properties of copper are still under active investigation. Molecular mechanisms responsible for the antibacterial action of copper have been a subject of intensive research. Scientists are also actively demonstrating the intrinsic efficacy of copper alloy "touch surfaces" to destroy a wide range of microorganisms that threaten public health. [5]

Mechanisms of action

In 1852 Victor Burq discovered those working with copper had far fewer deaths to cholera than anyone else, and did extensive research confirming this. In 1867 he presented his findings to the French Academies of Science and Medicine, informing them that putting copper on the skin was effective at preventing someone from getting cholera. [6]

The oligodynamic effect was discovered in 1893 as a toxic effect of metal ions on living cells, algae, molds, spores, fungi, viruses, prokaryotic, and eukaryotic microorganisms, even in relatively low concentrations. [7] This antimicrobial effect is shown by ions of copper as well as mercury, silver, iron, lead, zinc, bismuth, gold, and aluminium.

In 1973, researchers at Battelle Columbus Laboratories [8] conducted a comprehensive literature, technology, and patent search that traced the history of understanding the "bacteriostatic and sanitizing properties of copper and copper alloy surfaces", which demonstrated that copper, in very small quantities, has the power to control a wide range of molds, fungi, algae, and harmful microbes. Of the 312 citations mentioned in the review across the time period 1892–1973, the observations below are noteworthy:

A subsequent paper [15] probed some of copper's antimicrobial mechanisms and cited no fewer than 120 investigations into the efficacy of copper's action on microbes. The authors noted that the antimicrobial mechanisms are very complex and take place in many ways, both inside cells and in the interstitial spaces between cells.

Examples of some of the molecular mechanisms noted by various researchers include the following:

Currently, researchers believe that the most important antimicrobial mechanisms for copper are as follows:

These potential mechanisms, as well as others, are the subject of continuing study by academic research laboratories around the world.

Antimicrobial efficacy of copper alloy touch surfaces

Copper alloy surfaces have intrinsic properties to destroy a wide range of microorganisms. In the interest of protecting public health, especially in healthcare environments with their susceptible patient populations, an abundance of peer-reviewed antimicrobial efficacy studies have been conducted in the past ten years regarding copper's efficacy to destroy E. coli O157:H7, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus , Clostridium difficile , influenza A virus, adenovirus, and fungi. [27] Stainless steel was also investigated because it is an important surface material in today's healthcare environments. The studies cited here, plus others directed by the United States Environmental Protection Agency, resulted in the 2008 registration of 274 different copper alloys as certified antimicrobial materials that have public health benefits.

E. coli

E. coli O157:H7 is a potent, highly infectious, ACDP (Advisory Committee on Dangerous Pathogens, UK) Hazard Group 3 foodborne and waterborne pathogen. The bacterium produces potent toxins that cause diarrhea, severe aches, and nausea in infected persons. Symptoms of severe infections include hemolytic colitis (bloody diarrhea), hemolytic uremic syndrome (kidney disease), and death. E. coli O157:H7 has become a serious public health threat because of its increased incidence and because children up to 14 years of age, the elderly, and immunocompromised individuals are at risk of incurring the most severe symptoms.

Efficacy on copper surfaces

Recent studies have shown that copper alloy surfaces kill E. coli O157:H7. [24] [28] More than 99.9% of E. coli microbes are killed after just 1–2 hours on copper. On stainless steel surfaces, the microbes can survive for weeks.

Results of E. coli O157:H7 destruction on an alloy containing 99.9% copper (C11000) demonstrate that this pathogen is rapidly and almost completely killed (more than 99.9% kill rate) within ninety minutes at room temperature (20 °C). [24] At chill temperatures (4 °C), more than 99.9% of E. coli O157:H7 are killed within 270 minutes. E. coli O157:H7 destruction on several copper alloys containing 99%–100% copper (including C10200, C11000, C18080, and C19700) at room temperature begins within minutes. [28] At chilled temperatures, the inactivation process takes about an hour longer. No significant reduction in the amount of viable E. coli O157:H7 occurs on stainless steel after 270 minutes.

Studies have been conducted to examine the E. coli O157:H7 bactericidal efficacies on 25 different copper alloys to identify those alloys that provide the best combination of antimicrobial activity, corrosion/oxidation resistance, and fabrication properties. [28] [29] [30] Copper's antibacterial effect was found to be intrinsic in all of the copper alloys tested. As in previous studies, [31] [32] no antibacterial properties were observed on stainless steel (UNS S30400). Also, in confirmation with earlier studies, [31] [32] the rate of drop-off of E. coli O157:H7 on the copper alloys is faster at room temperature than at chill temperature.

For the most part, the bacterial kill rate of copper alloys increased with increasing copper content of the alloy. [29] [30] This is further evidence of copper's intrinsic antibacterial properties.

Efficacy on brass, bronze, copper-nickel alloys

Brasses, which were frequently used for doorknobs and push plates in decades past, also demonstrate bactericidal efficacies, but within a somewhat longer time frame than pure copper. [28] All nine brasses tested were almost completely bactericidal (more than 99.9% kill rate) at 20 °C within 60–270 minutes. Many brasses were almost completely bactericidal at 4 °C within 180–360 minutes.

The rate of total microbial death on four bronzes varied from within 50–270 minutes at 20 °C, and from 180 to 270 minutes at 4 °C.

The kill rate of E. coli O157 on copper-nickel alloys increased with increasing copper content. Zero bacterial counts at room temperature were achieved after 105–360 minutes for five of the six alloys. Despite not achieving a complete kill, alloy C71500 achieved a 4-log drop within the six-hour test, representing a 99.99% reduction in the number of live organisms.

Efficacy on stainless steel

Unlike copper alloys, stainless steel (S30400) does not exhibit any degree of bactericidal properties against E. coli O157:H7. [28] This material, which is one of the most common touch surface materials in the healthcare industry, allows toxic E. coli O157:H7 to remain viable for weeks. Near-zero bacterial counts are not observed even after 28 days of investigation. Epifluorescence photographs have demonstrated that E. coli O157:H7 is almost completely killed on copper alloy C10200 after just 90 minutes at 20 °C; whereas a substantial number of pathogens remain on stainless steel S30400. [25]

MRSA

Methicillin-resistant Staphylococcus aureus (MRSA) is a dangerous bacteria strain because it is resistant to beta-lactam antibiotics. [33] [34] Recent strains of the bacteria, EMRSA-15 and EMRSA-16, are highly transmissible and durable. This is of extreme importance to those concerned with reducing the incidence of hospital-acquired MRSA infections.

In 2008, after evaluating a wide body of research mandated specifically by the United States Environmental Protection Agency (EPA), registration approvals were granted by EPA in 2008 granting that copper alloys kill more than 99.9% of MRSA within two hours.

Subsequent research conducted at the University of Southampton (UK) compared the antimicrobial efficacies of copper and several non-copper proprietary coating products to kill MRSA. [35] [36] At 20 °C, the drop-off in MRSA organisms on copper alloy C11000 is dramatic and almost complete (more than 99.9% kill rate) within 75 minutes. However, neither a triclosan-based product nor two silver-based antimicrobial treatments (Ag-A and Ag-B) exhibited any meaningful efficacy against MRSA. Stainless steel S30400 did not exhibit any antimicrobial efficacy.

In 2004, the University of Southampton research team was the first to clearly demonstrate that copper inhibits MRSA. [37] On copper alloys — C19700 (99% copper), C24000 (80% copper), and C77000 (55% copper) — significant reductions in viability were achieved at room temperatures after 1.5 hours, 3.0 hours, and 4.5 hours, respectively. Faster antimicrobial efficacies were associated with higher copper alloy content. Stainless steel did not exhibit any bactericidal benefits.

Leyland Nigel S., Podporska-Carroll Joanna, Browne John, Hinder Steven J., Quilty Brid, Pillai Suresh C. (2016). "Highly Efficient F, Cu doped TiO2 anti-bacterial visible light active photocatalytic coatings to combat hospital-acquired infections". Scientific Reports. 6: 24770. Bibcode:2016NatSR...624770L. doi: 10.1038/srep24770 . PMC   4838873 . PMID   27098010.{{cite journal}}: CS1 maint: multiple names: authors list (link)

Clostridium difficile

Clostridium difficile, an anaerobic bacterium, is a major cause of potentially life-threatening disease, including nosocomial diarrheal infections, especially in developed countries. [38] C. difficile endospores can survive for up to five months on surfaces. [39] The pathogen is frequently transmitted by the hands of healthcare workers in hospital environments. C. difficile is currently a leading hospital-acquired infection in the UK, [40] and rivals MRSA as the most common organism to cause hospital acquired infections in the U.S. [41] It is responsible for a series of intestinal health complications, often referred to collectively as Clostridium difficile Associated Disease (CDAD).

The antimicrobial efficacy of various copper alloys against Clostridium difficile was recently evaluated. [42] The viability of C. difficile spores and vegetative cells were studied on copper alloys C11000 (99.9% copper), C51000 (95% copper), C70600 (90% copper), C26000 (70% copper), and C75200 (65% copper). Stainless steel (S30400) was used as the experimental control. The copper alloys significantly reduced the viability of both C. difficile spores and vegetative cells. On C75200, near total kill was observed after one hour (however, at six hours total C. difficileincreased, and decreased slower afterward). On C11000 and C51000, near total kill was observed after three hours, then total kill in 24 hours on C11000 and 48 hours on C51000. On C70600, near total kill was observed after five hours. On C26000, near total kill was achieved after 48 hours. On stainless steel, no reductions in viable organisms were observed after 72 hours (three days) of exposure and no significant reduction was observed within 168 hours (one week).

Influenza A

Influenza, commonly known as flu, is an infectious disease from a viral pathogen different from the one that produces the common cold. Symptoms of influenza, which are much more severe than the common cold, include fever, sore throat, muscle pains, severe headache, coughing, weakness, and general discomfort. Influenza can cause pneumonia, which can be fatal, particularly in young children and the elderly.

After incubation for one hour on copper, active influenza A virus particles were reduced by 75%. [43] [44] After six hours, the particles were reduced on copper by 99.999%. Influenza A virus was found to survive in large numbers on stainless steel.

Once surfaces are contaminated with virus particles, fingers can transfer particles to up to seven other clean surfaces. [45] Because of copper's ability to destroy influenza A virus particles, copper can help to prevent cross-contamination of this viral pathogen.

Adenovirus

Adenovirus is a group of viruses that infect the tissue lining membranes of the respiratory and urinary tracts, eyes, and intestines. Adenoviruses account for about 10% of acute respiratory infections in children.[ citation needed ] These viruses are a frequent cause of diarrhea.

In a recent study, 75% of adenovirus particles were inactivated on copper (C11000) within one hour. Within six hours, 99.999% of the adenovirus particles were inactivated. Within six hours, 50% of the infectious adenovirus particles survived on stainless steel. [44]

Fungi

The antifungal efficacy of copper was compared to aluminium on the following organisms that can cause human infections: Aspergillus spp., Fusarium spp., Penicillium chrysogenum , Aspergillus niger and Candida albicans . [46] An increased die-off of fungal spores was found on copper surfaces compared with aluminium. Aspergillus niger growth occurred on the aluminium coupons [ clarification needed ] growth was inhibited on and around copper coupons.

See also

Related Research Articles

<i>Escherichia coli</i> O157:H7 Serotype of the bacteria Escherichia coli

Escherichia coli O157:H7 is a serotype of the bacterial species Escherichia coli and is one of the Shiga-like toxin–producing types of E. coli. It is a cause of disease, typically foodborne illness, through consumption of contaminated and raw food, including raw milk and undercooked ground beef. Infection with this type of pathogenic bacteria may lead to hemorrhagic diarrhea, and to kidney failure; these have been reported to cause the deaths of children younger than five years of age, of elderly patients, and of patients whose immune systems are otherwise compromised.

<span class="mw-page-title-main">Rhinovirus</span> Genus of viruses (Enterovirus)

The rhinovirus is a positive-sense, single-stranded RNA virus belonging to the genus Enterovirus in the family Picornaviridae. Rhinovirus is the most common viral infectious agent in humans and is the predominant cause of the common cold.

<span class="mw-page-title-main">Disinfectant</span> Antimicrobial agent that inactivates or destroys microbes

A disinfectant is a chemical substance or compound used to inactivate or destroy microorganisms on inert surfaces. Disinfection does not necessarily kill all microorganisms, especially resistant bacterial spores; it is less effective than sterilization, which is an extreme physical or chemical process that kills all types of life. Disinfectants are generally distinguished from other antimicrobial agents such as antibiotics, which destroy microorganisms within the body, and antiseptics, which destroy microorganisms on living tissue. Disinfectants are also different from biocides—the latter are intended to destroy all forms of life, not just microorganisms. Disinfectants work by destroying the cell wall of microbes or interfering with their metabolism. It is also a form of decontamination, and can be defined as the process whereby physical or chemical methods are used to reduce the amount of pathogenic microorganisms on a surface.

<span class="mw-page-title-main">Hospital-acquired infection</span> Infection that is acquired in a hospital or other health care facility

A hospital-acquired infection, also known as a nosocomial infection, is an infection that is acquired in a hospital or other healthcare facility. To emphasize both hospital and nonhospital settings, it is sometimes instead called a healthcare-associated infection. Such an infection can be acquired in a hospital, nursing home, rehabilitation facility, outpatient clinic, diagnostic laboratory or other clinical settings. A number of dynamic processes can bring contamination into operating rooms and other areas within nosocomial settings. Infection is spread to the susceptible patient in the clinical setting by various means. Healthcare staff also spread infection, in addition to contaminated equipment, bed linens, or air droplets. The infection can originate from the outside environment, another infected patient, staff that may be infected, or in some cases, the source of the infection cannot be determined. In some cases the microorganism originates from the patient's own skin microbiota, becoming opportunistic after surgery or other procedures that compromise the protective skin barrier. Though the patient may have contracted the infection from their own skin, the infection is still considered nosocomial since it develops in the health care setting. Nosocomial infection tends to lack evidence that it was present when the patient entered the healthcare setting, thus meaning it was acquired post-admission.

An antimicrobial is an agent that kills microorganisms (microbicide) or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals are used against fungi. They can also be classified according to their function. The use of antimicrobial medicines to treat infection is known as antimicrobial chemotherapy, while the use of antimicrobial medicines to prevent infection is known as antimicrobial prophylaxis.

<span class="mw-page-title-main">Quaternary ammonium cation</span> Polyatomic ions of the form N(–R)₄ (charge +1)

In organic chemistry, quaternary ammonium cations, also known as quats, are positively-charged polyatomic ions of the structure [NR4]+, where R is an alkyl group, an aryl group or organyl group. Unlike the ammonium ion and the primary, secondary, or tertiary ammonium cations, the quaternary ammonium cations are permanently charged, independent of the pH of their solution. Quaternary ammonium salts or quaternary ammonium compounds are salts of quaternary ammonium cations. Polyquats are a variety of engineered polymer forms which provide multiple quat molecules within a larger molecule.

<span class="mw-page-title-main">Tigecycline</span> Chemical compound

Tigecycline, sold under the brand name Tygacil, is a tetracycline antibiotic medication for a number of bacterial infections. It is a glycylcycline administered intravenously. It was developed in response to the growing rate of antibiotic resistant bacteria such as Staphylococcus aureus, Acinetobacter baumannii, and E. coli. As a tetracycline derivative antibiotic, its structural modifications has expanded its therapeutic activity to include Gram-positive and Gram-negative organisms, including those of multi-drug resistance.

<span class="mw-page-title-main">Bedpan</span> Toilet device for someone confined to bed

A bedpan or bed pan is a device used as a receptacle for the urine and/or feces of a person who is confined to a bed and therefore not able to use a toilet or chamber pot.

Infection prevention and control is the discipline concerned with preventing healthcare-associated infections; a practical rather than academic sub-discipline of epidemiology. In Northern Europe, infection prevention and control is expanded from healthcare into a component in public health, known as "infection protection". It is an essential part of the infrastructure of health care. Infection control and hospital epidemiology are akin to public health practice, practiced within the confines of a particular health-care delivery system rather than directed at society as a whole.

Virulence factors are cellular structures, molecules and regulatory systems that enable microbial pathogens to achieve the following:

<span class="mw-page-title-main">Contamination control</span> Activities aiming to reduce contamination

Contamination control is the generic term for all activities aiming to control the existence, growth and proliferation of contamination in certain areas. Contamination control may refer to the atmosphere as well as to surfaces, to particulate matter as well as to microbes and to contamination prevention as well as to decontamination.

Antimicrobial copper-alloy touch surfaces can prevent frequently touched surfaces from serving as reservoirs for the spread of pathogenic microbes. This is especially true in healthcare facilities, where harmful viruses, bacteria, and fungi colonize and persist on doorknobs, push plates, railings, tray tables, tap (faucet) handles, IV poles, HVAC systems, and other equipment. These microbes can sometimes survive on surfaces for more than 30 days.

An antimicrobial surface is coated by an antimicrobial agent that inhibits the ability of microorganisms to grow on the surface of a material. Such surfaces are becoming more widely investigated for possible use in various settings including clinics, industry, and even the home. The most common and most important use of antimicrobial coatings has been in the healthcare setting for sterilization of medical devices to prevent hospital associated infections, which have accounted for almost 100,000 deaths in the United States. In addition to medical devices, linens and clothing can provide a suitable environment for many bacteria, fungi, and viruses to grow when in contact with the human body which allows for the transmission of infectious disease.

Pathogenic <i>Escherichia coli</i> Strains of E. coli that can cause disease

Escherichia coli is a gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms (endotherms). Most E. coli strains are harmless, but pathogenic varieties cause serious food poisoning, septic shock, meningitis, or urinary tract infections in humans. Unlike normal flora E. coli, the pathogenic varieties produce toxins and other virulence factors that enable them to reside in parts of the body normally not inhabited by E. coli, and to damage host cells. These pathogenic traits are encoded by virulence genes carried only by the pathogens.

<span class="mw-page-title-main">Rifalazil</span> Antibiotic

Rifalazil is an antibiotic substance that kills bacterial cells by blocking off the β-subunit in RNA polymerase. Rifalazil is used as a treatment for many different diseases. The most common are Chlamydia infection, Clostridium difficile associated diarrhea (CDAD), and tuberculosis (TB). Using rifalazil and the effects that coincide with taking rifalazil for treating a bacterial disease vary from person to person, as does any drug put into the human body. Food interactions and genetic variation are a few causes for the variation in side effects from the use of rifalazil. Its development was terminated in 2013 due to severe side effects.

Carbapenem-resistant Enterobacteriaceae (CRE) or carbapenemase-producing Enterobacteriaceae (CPE) are Gram-negative bacteria that are resistant to the carbapenem class of antibiotics, considered the drugs of last resort for such infections. They are resistant because they produce an enzyme called a carbapenemase that disables the drug molecule. The resistance can vary from moderate to severe. Enterobacteriaceae are common commensals and infectious agents. Experts fear CRE as the new "superbug". The bacteria can kill up to half of patients who get bloodstream infections. Tom Frieden, former head of the Centers for Disease Control and Prevention has referred to CRE as "nightmare bacteria". Examples of enzymes found in certain types of CRE are KPC and NDM. KPC and NDM are enzymes that break down carbapenems and make them ineffective. Both of these enzymes, as well as the enzyme VIM have also been reported in Pseudomonas.

<span class="mw-page-title-main">Nemonoxacin</span> Chemical compound

Nemonoxacin is a non-fluorinated quinolone antibiotic undergoing clinical trials. It has the same mechanism of action as fluouroquinolones; it inhibits DNA gyrase, preventing DNA synthesis, gene duplication, and cell division. At the end of 2016, it had reached market in Taiwan, Russia, the Commonwealth Independent States, Turkey, mainland China, and Latin America under the brand name Taigexyn. Nemonoxacin has completed phase 2 trials in the US and has moved on to phase 3 trials. The U.S. Food and Drug Administration (FDA) has granted nemonoxacin qualified infectious disease product (QIDP) and fast track designations for community-acquired bacterial pneumonia (CAP) and acute bacterial skin and skin-structure infections (ABSSSI).

<i>Clostridioides difficile</i> Species of bacteria

Clostridioides difficile is a bacterium known for causing serious diarrheal infections, and may also cause colon cancer. It is known also as C. difficile, or C. diff, and is a Gram-positive species of spore-forming bacteria. Clostridioides spp. are anaerobic, motile bacteria, ubiquitous in nature and especially prevalent in soil. Its vegetative cells are rod-shaped, pleomorphic, and occur in pairs or short chains. Under the microscope, they appear as long, irregular cells with a bulge at their terminal ends. Under Gram staining, C. difficile cells are Gram-positive and show optimum growth on blood agar at human body temperatures in the absence of oxygen. C. difficile is catalase- and superoxide dismutase-negative, and produces up to three types of toxins: enterotoxin A, cytotoxin B and Clostridioides difficile transferase. Under stress conditions, the bacteria produce spores that are able to tolerate extreme conditions that the active bacteria cannot tolerate.

Proteobiotics are natural metabolites which are produced by fermentation process of specific probiotic strains. These small oligopeptides were originally discovered in and isolated from culture media used to grow probiotic bacteria and may account for some of the health benefits of probiotics.

References

  1. Dollwet, H. H. A. and Sorenson, J. R. J. "Historic uses of copper compounds in medicine", Trace Elements in Medicine, Vol. 2, No. 2, 1985, pp. 80–87.
  2. "Medical Uses of Copper in Antiquity". Copper Development Association Inc. June 2000.
  3. "A Brief History of The Health Support Uses of Copper"
  4. Morrison, Jim. "Copper's Virus-Killing Powers Were Known Even to the Ancients". Smithsonian Magazine. Retrieved 2021-10-06.
  5. Zaleski, Andrew, As hospitals look to prevent infections, a chorus of researchers make a case for copper surfaces , STAT, September 24, 2020
  6. Love, Shayla (2020-03-18). "Copper Destroys Viruses and Bacteria. Why Isn't It Everywhere?". Vice. Retrieved 2020-03-18.
  7. Nägeli, Karl Wilhelm (1893), "Über oligodynamische Erscheinungen in lebenden Zellen", Neue Denkschriften der Allgemeinen Schweizerischen Gesellschaft für die Gesamte Naturwissenschaft, XXXIII (1)
  8. Dick, R. J.; Wray, J. A.; Johnston, H. N. (1973), "A Literature and Technology Search on the Bacteriostatic and Sanitizing Properties of Copper and Copper Alloy Surfaces", Phase 1 Final Report, INCRA Project No. 212, June 29, 1973, contracted to Battelle Columbus Laboratories, Columbus, Ohio
  9. Chang, S. M. and Tien, M. (1969), Effects of Heavy Metal Ions on the Growth of Microorganisms, Bulletin of the Institute of Chemistry, Academia Sinica, Vol. 16, pp. 29–39.
  10. Avakyan Z. A.; Rabotnova I. L. (1966). "Determination of the Copper Concentration Toxic to Micro-Organisms". Microbiology. 35: 682–687.
  11. Feldt, A. (no year), Tubercle Bacillus and Copper, Munchener medizinische Wochenschrift, Vol. 61, pp. 1455–1456
  12. Johnson, FH; Carver, CM; Harryman, WK (1942). "Luminous Bacterial Auxanograms in Relation to Heavy Metals and Narcotics, Self-Photographed in Color". Journal of Bacteriology. 44 (6): 703–15. doi:10.1128/jb.44.6.703-715.1942. PMC   374804 . PMID   16560610.
  13. Oĭvin, V. and Zolotukhina, T. (1939), Action Exerted From a Distance by Metals on Infusoria, Bulletin of Experimental Biology and Medicine USSR, Vol. 4, pp. 39–40.
  14. Colobert, L (1962). "Sensitivity of poliomyelitis virus to catalytic systems generating free hydroxyl radicals". Revue de Pathologie Generale et de Physiologie Clinique. 62: 551–5. PMID   14041393.
  15. 1 2 Thurman R. B.; Gerba C. P. (1989). "The Molecular Mechanisms of Copper and Silver Ion Disinfection of Bacteria and Viruses". CRC Critical Reviews in Environmental Control. 18 (4): 295–315. doi:10.1080/10643388909388351.
  16. Kuwahara, June; Suzuki, Tadashi; Funakoshi, Kyoko; Sugiura, Yukio (1986). "Photosensitive DNA cleavage and phage inactivation by copper(II)-camptothecin". Biochemistry. 25 (6): 1216–21. doi:10.1021/bi00354a004. PMID   3008823.
  17. Vasudevachari, M; Antony, A (1982). "Inhibition of avian myeloblastosis virus reverse transcriptase and virus inactivation by metal complexes of isonicotinic acid hydrazide". Antiviral Research. 2 (5): 291–300. doi:10.1016/0166-3542(82)90052-3. PMID   6185090.
  18. Sterritt, RM; Lester, JN (1980). "Interactions of heavy metals with bacteria". The Science of the Total Environment. 14 (1): 5–17. Bibcode:1980ScTEn..14....5S. doi:10.1016/0048-9697(80)90122-9. PMID   6988964.
  19. Samuni, A; Aronovitch, J; Godinger, D; Chevion, M; Czapski, G (1983). "On the cytotoxicity of vitamin C and metal ions. A site-specific Fenton mechanism". European Journal of Biochemistry. 137 (1–2): 119–24. doi: 10.1111/j.1432-1033.1983.tb07804.x . PMID   6317379.
  20. Samuni, A.; Chevion, M.; Czapski, G. (1984). "Roles of Copper and Superoxide Anion Radicals in the Radiation-Induced Inactivation of T7 Bacteriophage". Radiat. Res. 99 (3): 562–572. doi:10.2307/3576330. JSTOR   3576330. PMID   6473714.
  21. Manzl, C; Enrich, J; Ebner, H; Dallinger, R; Krumschnabel, G (2004). "Copper-induced formation of reactive oxygen species causes cell death and disruption of calcium homeostasis in trout hepatocytes". Toxicology. 196 (1–2): 57–64. doi:10.1016/j.tox.2003.11.001. PMID   15036756.
  22. Domek, MJ; Lechevallier, MW; Cameron, SC; McFeters, GA (1984). "Evidence for the role of copper in the injury process of coliform bacteria in drinking water". Applied and Environmental Microbiology. 48 (2): 289–93. Bibcode:1984ApEnM..48..289D. doi:10.1128/aem.48.2.289-293.1984. PMC   241505 . PMID   6385846.
  23. Domek, MJ; Robbins, JE; Anderson, ME; McFeters, GA (1987). "Metabolism of Escherichia coli injured by copper". Canadian Journal of Microbiology. 33 (1): 57–62. doi:10.1139/m87-010. PMID   3552166.
  24. 1 2 3 Michels, H. T.; Wilks, S. A.; Noyce, J. O.; Keevil, C. W. (2005), Copper Alloys for Human Infectious Disease Control Archived December 11, 2010, at the Wayback Machine , Presented at Materials Science and Technology Conference, September 25–28, 2005, Pittsburgh, PA; Copper for the 21st Century Symposium
  25. 1 2 Michels, Harold T. (October 2006), "Anti-Microbial Characteristics of Copper", ASTM Standardization News, 34 (10): 28–31, retrieved 2014-02-03
  26. BioHealth Partnership Publication (2007): Lowering Infection Rates in Hospitals and Healthcare Facilities - The Role of Copper Alloys in Battling Infectious Organisms, Edition 1, March.
  27. "Copper Touch Surfaces". Archived from the original on 2012-07-23. Retrieved 2010-04-07.
  28. 1 2 3 4 5 Wilks, SA; Michels, H; Keevil, CW (2005). "The survival of Escherichia coli O157 on a range of metal surfaces". International Journal of Food Microbiology. 105 (3): 445–54. doi:10.1016/j.ijfoodmicro.2005.04.021. PMID   16253366.
  29. 1 2 Michels, H. T.; Wilks, S. A.; Keevil, C. W. 2004, "Effects of Copper Alloy Surfaces on the Viability of Bacterium, E. coli 0157:H7", The Second Global Congress Dedicated to Hygienic Coatings & Surface Conference Papers, Orlando, Florida, US, 26–28 January 2004, Paper 16, Paint Research Association, Middlesex, UK
  30. 1 2 Michels, H. T.; Wilks, S. A.; Keevil, C. W. (2003), The Antimicrobial Effects of Copper Alloy Surfaces on the Bacterium E. coli O157:H7, Proceedings of Copper 2003 - Cobre 2003, The 5th International Conference, Santiago, Chile, Vol. 1 - Plenary Lectures, Economics and Applications of Copper, pp. 439–450, The Canadian Institute of Mining, Metallurgy and Petroleum, Montreal, Quebec, Canada, (presented in Santiago, Chile, November 30–December 3, 2003)
  31. 1 2 Keevil, C. W.; Walker, J. T.; and Maule, A. (2000), Copper Surfaces Inhibit Escherichia coli O157, Seminario Cobre y Salud, Nov. 20, 2000, CEPAL/Comision Chilena del Cobre/ICA, Santiago, Chile
  32. 1 2 Maule, A. and Keevil, C. W. (2000), Long-Term Survival of Verocytotoxigenic Escherichia coli O157 on Stainless Steel Work Surfaces and Inhibition on Copper and Brass, ASM-P-119
  33. Ug, A; Ceylan, O (2003). "Occurrence of Resistance to Antibiotics, Metals, and Plasmids in Clinical Strains of Staphylococcus spp". Archives of Medical Research. 34 (2): 130–6. doi:10.1016/S0188-4409(03)00006-7. PMID   12700009.
  34. Mulligan, ME; Murray-Leisure, KA; Ribner, BS; Standiford, HC; John, JF; Korvick, JA; Kauffman, CA; Yu, VL (1993). "Methicillin-resistant Staphylococcus aureus: a consensus review of the microbiology, pathogenesis, and epidemiology with implications for prevention and management". The American Journal of Medicine. 94 (3): 313–28. doi:10.1016/0002-9343(93)90063-U. PMID   8452155.
  35. Michels, H. T.; Noyce, J. O.; Keevil, C. W. (2009). "Effects of temperature and humidity on the efficacy of methicillin-resistant Staphylococcus aureus challenged antimicrobial materials containing silver and copper" (PDF). Letters in Applied Microbiology. 49 (2): 191–5. doi:10.1111/j.1472-765X.2009.02637.x. PMC   2779462 . PMID   19413757. Archived from the original (PDF) on 2011-07-07. Retrieved 2010-04-10.
  36. Keevil, C. W.; Noyce, J. O. (2007), Antimicrobial Efficacies of Copper, Stainless Steel, Microban, BioCote and AgIon with MRSA at 20 °C, unpublished data
  37. Noyce, J. O. and Keevil, C. W. (2004), The Antimicrobial Effects of Copper and Copper-Based Alloys on Methicillin-resistant Staphylococcus aureus, Copper Development Association Poster Q-193 from Proceedings of the Annual General Meeting of the American Society for Microbiology, 24–27 May 2004, New Orleans; presented at the American Society for Microbiology General Meeting, New Orleans, Louisiana May 24
  38. Dumford Dm, 3rd; Nerandzic, MM; Eckstein, BC; Donskey, CJ (2009). "What is on that keyboard? Detecting hidden environmental reservoirs of Clostridium difficile during an outbreak associated with North American pulsed-field gel electrophoresis type 1 strains". American Journal of Infection Control. 37 (1): 15–9. doi:10.1016/j.ajic.2008.07.009. PMID   19171247.{{cite journal}}: CS1 maint: numeric names: authors list (link)
  39. Kim, KH; Fekety, R; Batts, DH; Brown, D; Cudmore, M; Silva Jr, J; Waters, D (1981). "Isolation of Clostridium difficile from the environment and contacts of patients with antibiotic-associated colitis". The Journal of Infectious Diseases. 143 (1): 42–50. doi:10.1093/infdis/143.1.42. PMID   7217711.
  40. Health Protection Agency, Surveillance of Healthcare Associated Infections Report 2007
  41. McDonald, LC; Owings, M; Jernigan, DB (2006). "Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996–2003". Emerging Infectious Diseases. 12 (3): 409–15. doi:10.3201/eid1205.051064. PMC   3291455 . PMID   16704777.
  42. Weaver, L; Michels, HT; Keevil, CW (2008). "Survival of Clostridium difficile on copper and steel: futuristic options for hospital hygiene". The Journal of Hospital Infection. 68 (2): 145–51. doi:10.1016/j.jhin.2007.11.011. PMID   18207284.
  43. Noyce, JO; Michels, H; Keevil, CW (2007). "Inactivation of Influenza A Virus on Copper versus Stainless Steel Surfaces". Applied and Environmental Microbiology. 73 (8): 2748–50. Bibcode:2007ApEnM..73.2748N. doi:10.1128/AEM.01139-06. PMC   1855605 . PMID   17259354.
  44. 1 2 "Viruses Influenza A". Archived from the original on 2009-10-18. Retrieved 2010-04-07.
  45. Barker, J; Vipond, IB; Bloomfield, SF (2004). "Effects of cleaning and disinfection in reducing the spread of Norovirus contamination via environmental surfaces". The Journal of Hospital Infection. 58 (1): 42–9. doi:10.1016/j.jhin.2004.04.021. PMID   15350713.
  46. Weaver, L.; Michels, H. T.; Keevil, C. W. (2010). "Potential for preventing spread of fungi in air-conditioning systems constructed using copper instead of aluminium". Letters in Applied Microbiology. 50 (1): 18–23. doi: 10.1111/j.1472-765X.2009.02753.x . PMID   19943884.