Scientific References

Peer-reviewed research papers discussing the antimicrobial properties of copper-based metals

Here is a library of published papers and conference posters covering the laboratory and clinical studies conducted on the antimicrobial characteristics of solid copper and copper alloys over the last 20 years.  Some papers are accessible here as pdfs, others have links to entries in various scientific libraries where full papers can be accessed via a subscription or for a cost.

If you have a paper to suggest we include here, please contact Marleine Williams, Project Co-ordinator, Copper Development Association.

Browse the entire list or use the category filters below.


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Copper Surfaces Reduce the Microbial Burden in Out-Patient Infectious Disease Practice
B E Hirsch, H Attaway, R Nadan, S Fairey, J Hardy, G Miller, S Rai, D Armellino, M Schilling, W Moran, P Sharpe, A Estelle, J H Michel, H T Michels, M G Schmidt, Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston, MA, 2010

Copper alloy surfaces are known to kill bacteria and decrease the environmental microbial bio-burden (MB) in ICUs. Out-patients share risk factors including co-morbidities, antibiotic exposure plus recent hospitalisation. The transient and high volume of potentially infectious and vulnerable subjects renders the out-patient clinic a significant locus of transmission that is often overlooked. This study shows the benefit of copper surfaces for their ability to reduce the MB in an infectious disease out-patient practice.  These findings support the clinical trial findings from Selly Oak, Calama and MUSC and, in addition, show a halo effect - reduced contamination in the vicinity of the copper surfaces. The calculated ratio of patients to the median burden enabled the conclusion to be drawn that use of the chair with the copper arm tops resulted in a 17-fold lower risk of exposure to environmental microbes than when patients used the standard chair.

Antimicrobial surfaces to prevent healthcare-associated infections: a systematic review: a different view
Schmidt MG, Salgado CD, Freeman KD, John Jr. JF, Cantey RJ, Sharpe PA, Michels HT. Journal of Hospital Infection, February 2018

Letter explaining randomisation, blinding and the link between touch surface bioburden and acquisition of HCAIs in a multi-centre copper clinical trial, in response to comments in the following review: Antimicrobial surfaces to prevent healthcare-associated infections: a systematic review. Muller MP, MacDougall C, Lim M; Ontario Agency for Health Protection and Promotion Public Health Ontario; Provincial Infectious Diseases Advisory Committee on Infection Prevention and Control; Provincial Infectious Diseases Advisory Committee on Infection Prevention and Control.J Hosp Infect. 2016 Jan;92(1):7-13. doi: 10.1016/j.jhin.2015.09.008. Epub 2015 Oct 3.

Antimicrobial Effect of Copper Alloys on Acinetobacter Species Isolated from Infections and Hospital Environment
Anna Różańska, Agnieszka Chmielarczyk, Dorota Romaniszyn, Grzegorz Majka, Małgorzata Bulanda. BioMed Central, January 2018

Background: An increased proportion of Gram-negative bacteria have recently been reported among etiologic agents of infection. In Poland, Acinetobacter baumannii is a big problem for hospitals, especially intensive care units. Touch surfaces made from materials with antimicrobial properties, especially copper alloys, are recommended as a supplementary method of increasing biological safety in the hospital environment.

Aim of the study: The objective of this study is to determine the susceptibility to selected copper alloys of three clinical Acinetobacter baumannii strains, one Acinetobacter lwoffi and an A. pittii strain isolated from the hospital environment.

Material and method: The modification of the Japanese Standard, which the ISO 22196:2011 norm was used for testing antimicrobial properties of CuZn37, CuSn6 and CuNi18Zn20 and Cu-ETP and stainless steel as positive and negative control, respectively.

Results: The highest cidal efficiency, expressed as both time and the degree of reduction of the initial suspension density, against all of the tested Acinetobacter strains was found for ETP copper. But, the results of our study also confirmed effective activity (bacteriocidal or bacteriostatic) of copper alloys selected for the study, contrary to the stainless steel. The reduction in bacterial suspension density is significantly different depending on the strain and copper alloy composition.

Conclusions: The results of our study confirmed the effective antibacterial activity of copper and its selected alloys against clinical Acinetobacter baumannii and Acinetobacter lwoffii strains, and Acinetobacter pittii strain isolated from the hospital environment.

Pure and Oxidized Copper Materials as Potential Antimicrobial Surfaces for Spaceflight Activities
Hahn C., Hans M., Hein C., Mancinelli R.L., Mücklich F., Wirth R., Rettberg P., Hellweg C.E., and Moeller R.. Astrobiology. December 2017, 17(12): 1183-1191.

Microbial biofilms can lead to persistent infections and degrade a variety of materials, and they are notorious for their persistence and resistance to eradication. During long-duration space missions, microbial biofilms present a danger to crew health and spacecraft integrity. The use of antimicrobial surfaces provides an alternative strategy for inhibiting microbial growth and biofilm formation to conventional cleaning procedures and the use of disinfectants. Antimicrobial surfaces contain organic or inorganic compounds, such as antimicrobial peptides or copper and silver, that inhibit microbial growth. The efficacy of wetted oxidized copper layers and pure copper surfaces as antimicrobial agents was tested by applying cultures of Escherichia coli and Staphylococcus cohnii to these metallic surfaces. Stainless steel surfaces were used as non-inhibitory control surfaces. The production of reactive oxygen species and membrane damage increased rapidly within 1 h of exposure on pure copper surfaces, but the effect on cell survival was negligible even after 2 h of exposure. However, longer exposure times of up to 4 h led to a rapid decrease in cell survival, whereby the survival of cells was additionally dependent on the exposed cell density. Finally, the release of metal ions was determined to identify a possible correlation between copper ions in suspension and cell survival. These measurements indicated a steady increase of free copper ions, which were released indirectly by cells presumably through excreted complexing agents. These data indicate that the application of antimicrobial surfaces in spaceflight facilities could improve crew health and mitigate material damage caused by microbial contamination and biofilm formation. Furthermore, the results of this study indicate that cuprous oxide layers were superior to pure copper surfaces related to the antimicrobial effect and that cell density is a significant factor that influences the time dependence of antimicrobial activity. Key Words: Contact killing—E. coli—S. cohnii—Antimicrobial copper surfaces—Copper oxide layers—Human health—Planetary protection.

Life-like Assessment of Antimicrobial Surfaces by a New Touch Transfer Assay Displays Strong Superiority of a Copper Alloy Compared to Silver Containing Surfaces.
Knobloch JK-M, Tofern S, Kunz W, SchuÈtze S, Riecke M, Solbach W, et al. PLoS ONE 12(11): e0187442.

Transmission of bacteria from inanimate surfaces in healthcare associated environments is an important source of hospital acquired infections. A number of commercially available medical devices promise to fulfill antibacterial activity to reduce environmental contamination. In this study we developed a touch transfer assay modeling fingerprint transmission to investigate the antibacterial activity of surfaces, with confirmed antibacterial activity by a modified ISO 22196 (JIS Z801) assay to test such surfaces under more realistic conditions. Bacteria were taken up from a dry standardized primary contaminated surface (PCS) with disinfected fingers or fingers covered with sterile and moistened cotton gloves. Subsequently, bacteria were transferred by pressing on secondary contaminated surfaces (SCS) with or without potential antibacterial activity and the relative reduction rate was determined after 24 h. A stable transmission rate between PCS and SCS was observed using moistened sterile gloves. A copper containing alloy displayed at least a tenfold reduction of the bacterial load consistently reaching less than 2.5 cfu/cm2. In contrast, no significant reduction of bacterial contamination by silver containing surfaces and matured pure silver was observed in the touch transfer assay. With the touch transfer assay we successfully established a new reproducible method modeling cross contamination. Using the new method we were able to demonstrate that several surfaces with confirmed antimicrobial activity in a modified ISO 22196 (JIS Z 2801) assay lacked effectiveness under defined ambient conditions.This data indicate that liquid based assays like the ISO 22196 should be critically reviewed before claiming antibacterial activity for surfaces in the setting of contamination of dry surfaces by contact to the human skin. We suggest the newly developed touch transfer assay as a new additional tool for the assessment of potential antimicrobial surfaces prior utilization in hospital environments.

Reduction of Bacterial Burden by Copper Alloys on High-touch Athletic Center Surfaces
Z Ibrahim, A Petrusan, P Hooke, S Hinsa-Leasure. American Journal of Infection Control, August 2017

Highlights: Copper alloys significantly decrease bacterial burden on athletic center surfaces. Dumbbells were found to harbor significant concentrations of bacteria. Staphylococcus was the most common type of bacteria found on athletic surfaces.

Background: Athletic centers have been locations for the transmission of community-acquired infections. This study assessed the capacity of copper alloys to reduce the bacterial burden associated with high-touch athletic center equipment. Copper alloy weights and grips were rotated with rubber coated and stainless steel controls in an undergraduate college athletic center over a 16-month period. The athletic center is used by college athletic teams, student body, and local community.

Methods: The primary outcome was to compare bacterial burdens on copper and control grips by swabbing surfaces. Significance was determined using the nonparametric Mann-Whitney U test with significance assessed at P < .05. Secondary outcomes included characterizing bacterial communities on surfaces and conducting antibiotic susceptibility testing using the Kirby-Bauer disk diffusion method.

Results: Control athletic center components carried bacterial loads 94% larger than those found on copper alloy components. Bacterial community characterization revealed Staphylococcus to be the most common bacterial genus found on grip surfaces. Antibiotic resistance testing of the Staphylococcus isolates revealed that all isolates were susceptible to vancomycin and linezolid, whereas 35% of copper alloy isolates and 44% of control isolates were resistant to erythromycin.

Conclusions: Copper alloys can mitigate the bacterial burden on high-touch surfaces. Strategically placing copper alloys in areas of high human contact can augment infection control efforts and potentially decrease community-acquired infections in athletic centers.

Antibiotic Resistance, Ability to Form Biofilm and Susceptibility to Copper Alloys of Selected Staphylococcal Strains Isolated from Touch Surfaces in Polish Hospital Wards
A Różańska, A Chmielarczyk, D Romaniszyn, M Bulanda, M Walkowicz, P Osuch and T Knych. Antimicrobial Resistance & Infection Control, August 2017

Background: Despite the employment of sanitary regimes, contact transmission of the aetiological agents of hospital infections is still exceedingly common. The issue of microbe transmission becomes particularly important when facing multidrug-resistant microorganisms such as methicillin-resistant staphylococci. In the case of deficiencies in cleaning and disinfection procedures, hospital equipment made of copper alloys can play an important role, complementing traditional hospital hygiene procedures. The objective of this study was to characterize staphylococcal strains isolated from touch surfaces in Polish hospital wards in terms of their drug resistance, ability to form biofilm and susceptibility to antimicrobial activity of copper alloys.

Methods: The materials for the study were 95 staphylococcal strains isolated from touch surfaces in 13 different hospital wards from Małopolska province (the south of Poland). Phenotypic and genotypic antibiotic resistance were checked for erythromycin, clindamycin, gentamycin, ciprofloxacin, trimethoprim/sulfamethoxazole and mupirocin. Biofilm formation ability for the tested strains was checked with the use of culture on Congo red agar. Susceptibility to copper, tin bronze, brass and new silver was tested using a modification of the Japanese standard.

Results: Over 67% of the analysed staphylococcal strains were methicillin-resistant (MR). Four strains were resistant to all of the tested antibiotics, and 14 were resistant to all except mupirocin. Strains classified as MR had significantly increased resistance to the remaining antibiotic groups. About one-third of the analysed strains revealed biofilm-forming ability. Among the majority of species, biofilm-forming and non-biofilm-forming strains were distributed evenly; in the case of S. haemolyticus only, negative strains accounted for 92.8%. Susceptibility to copper alloys was different between strains and rather lower than in the case of the SA strain selected for comparison.

Conclusions: Coagulase-negative staphylococci, the most commonly isolated in Polish hospital wards, should not be neglected as an infection risk factor due their high antibiotic resistance. Our experiments confirmed that touch surfaces made of copper alloys may play an important role in eliminating bacteria from the hospital environment.

Antimicrobial Properties of Selected Copper Alloys on Staphylococcus aureus and Escherichia coli in Different Simulations of Environmental Conditions: With vs. without Organic Contamination
A Różańska,A Chmielarczyk, D Romaniszyn, A Sroka-Oleksiak, M Bulanda, M Walkowicz, P Osuch, T Knych. International Journal of Environmental Research and Public Health, July 2017

Hospital equipment made from copper alloys can play an important role in complementing traditional methods of disinfection. Aims of the study: The aim of this study was to assess the dynamics of the antimicrobial properties of selected copper alloys in different simulations of environmental conditions (with organic contamination vs. without organic contamination), and to test alternatives to the currently used testing methods. Materials and Methods: A modification of Japanese standard JIS Z 2801 as well as Staphylococcus aureus (SA) and Escherichia coli (EC) suspended in NaCl vs. tryptic soy broth (TSB) were used in tests performed on seven commonly used copper alloys, copper, and stainless steel. Results: A much faster reduction of the bacterial suspension was observed for the inoculum prepared in NaCl than in TSB. A faster reduction for EC than for SA was observed in the inoculum prepared in NaCl. The opposite results were found for the inoculum based on TSB. A significant correlation between the copper concentration in the copper alloys and the time and degree of bacterial suspension reduction was only observed in the case of EC. Conclusions: This study confirmed the antimicrobial properties of copper alloys, and additionally showed that Staphylococcus aureus was more resistant than Escherichia coli in the variant of the experiment without organic contamination. However, even for SA, a total reduction of the bacterial inoculum’s density took no longer than 2 h. Under conditions simulating organic contamination, all of the tested alloys were shown to have bactericidal or bacteriostatic properties, which was contrary to the results from stainless steel

Reduction of Environmental Contamination With Multidrug-Resistant Bacteria by Copper-Alloy Coating of Surfaces in a Highly Endemic Setting
Maria Souli, Anastasia Antoniadou, Ioannis Katsarolis, Irini Mavrou. Infection Control & Hospital Epidemiology, May 2017

To evaluate the efficacy of copper-coating in reducing environmental colonization in an intensive-care unit (ICU) with multidrug-resistant-organism (MDRO) endemicity. Interventional, comparative crossover trial.The general ICU of Attikon University hospital in Athens, Greece. Those admitted to ICU compartments A and B during the study period. Before any intervention (phase 1), the optimum sampling method using 2 nylon swabs was validated. In phase 2, 6 copper-coated beds (ie, with coated upper, lower, and side rails) and accessories (ie, coated side table, intravenous [i.v.] pole stands, side-cart handles, and manual antiseptic dispenser cover) were introduced as follows: During phase 2a (September 2011 to February 2012), coated items were placed next to noncoated ones (controls) in both compartments A and B; during phase 2b (May 2012 to January 2013), all copper-coated items were placed in compartment A, and all noncoated ones (controls) in compartment B. Patients were randomly assigned to available beds. Enenvironmental samples were cultured quantitatively for clinically important bacteria. Clinical and demographic data were collected from medical records. Copper coating significantly reduced the percentage of colonized surfaces (55.6% vs 72.5%; P<.0001), the percentage of surfaces colonized by MDR gram-negative bacteria (13.8% vs 22.7%; P=.003) or by enterococci (4% vs 17%; P=.014), the total bioburden (2,858 vs 7,631 cfu/100 cm2; P=.008), and the bioburden of gram-negative isolates, specifically (261 vs 1,266 cfu/100 cm2; P=.049). This effect was more pronounced when the ratio of coated surfaces around the patient was increased (phase 2b). Copper-coated items in an ICU setting with endemic high antimicrobial resistance reduced environmental colonization by MDROs.

Killing of Bacteria by Copper, Cadmium, and Silver Surfaces Reveals Relevant Physicochemical Parameters
J Luo, C Hein, F Mücklich, M Solioz. Biointerphases 12,020301, 2017

The killing of bacteria on metallic copper surfaces in minutes to hours is referred to as contact killing. Why copper possesses such strong antimicrobial activity has remained enigmatic. Based on the physicochemical properties of metals, it was recently predicted that cadmium should also be active in contact killing [Hans et al., Biointerphases 11, 018902 (2010)]. Here, the authors show that cadmium is indeed antimicrobial. It kills three logs of bacteria in 9 h, compared to copper which kills eight logs of bacteria. Metallic silver kills less than one log of bacteria in 9 h. These findings support the novel concept whereby oxide formation, metal ion dissolution, and a Pearson soft character are the key factors for a metal to be antibacterial. Based on these parameters, copper and cadmium are expected to be the two most antibacterial metals.

The Role of Copper Surfaces in Reducing the Incidence of Healthcare-associated infections: A Systematic Review and Meta-analysis
Ignacio Pineda, Richard Hubbard,Francisca Rodríguez. Canadian Journal of Infection Control, Spring 2017

Background: Healthcare-associated infections are a major public health problem, with an important clinical and economic burden on health systems worldwide. In-vitro and in-vivo studies have shown that copper has the potential to kill microorganisms on contact. It has been described as the “contact killer”. Despite this, the preventive role of antimicrobial copper on the reduction of healthcare-associated infections is not clear yet.

Aims & Objectives:To assess the role of copper surfaces on the reduction of healthcare-associated infections.

Methods A systematic review of the literature with a meta-analysis. The search was carried out in five electronic databases, grey literature and reference list of included studies. Two researchers independently screened and judged the quality of the included studies. The GRADE approach was used to assess the quality of the body of evidence.

Results: Fourteen studies met the inclusion criteria. Overall, the introduction of antimicrobial copper alloys surfaces in high-touch surfaces reduced the incidence of healthcare-associated infections by around a quarter (IRR 0.74, 95% CI 0.56 to 0.97; p = 0.03; low quality of the evidence). Additionally, the probability of achieving the recommended concentration of less than 250 colony forming units/100cm2 was 2.73 times higher in copper surfaces than in regular surfaces (RR 2.73, 95% CI 1.83 to 4.07; p <0.00001; moderate quality of the evidence). No signifi cant difference was observed in the mortality rate.

Conclusion: This systematic review and meta-analyses suggest that the introduction of antimicrobial copper alloys in replacement of high-touch surfaces may have a positive effect on the incidence rate of HAIs. Larger clinical trials will be needed to show an impact on mortality.

Potential of Copper Alloys to Kill Bacteria and Reduce Hospital Infection Rates
Michels and Michels, Internal Medicine Review, March 2017

A large body of peer-reviewed literature has demonstrated in laboratory testing that placing bacteria in a highly concentrated bacterial inoculum onto copper alloy surfaces results in their rapid death.  A smaller but convincing number of studies indicate that bacteria die on the surfaces of hospital room components made from copper alloys.  Will the ability of copper alloys to kill bacteria translate into an ability to reduce the rate of hospital-acquired infections (HAIs)?  This review addresses this question. In particular, the results of a clinical trial in which HAI rates are significantly reduced after introducing copper alloys components into Intensive Care Units of three hospitals will be presented. The findings suggest that copper alloys enhance hospital hygiene protocols because they act passively 24/7/365 requiring neither training nor human intervention to kill bacteria and reduce hospital-acquired infections.

Antimicrobial Copper Alloys Decreased Bacteria on Stethoscope Surfaces
Michael G. Schmidt et al. American Journal of Infection Control. 2017.

Background: Stethoscopes may serve as vehicles for transmission of bacteria among patients. The aim of this study was to assess the efficacy of antimicrobial copper surfaces to reduce the bacterial concentration associated with stethoscope surfaces.

Methods: A structured prospective trial involving 21 health care providers was conducted at a pediatric emergency division (ED) (n = 14) and an adult medical intensive care unit located in tertiary care facilities (n = 7). Four surfaces common to a stethoscope and a facsimile instrument fabricated from U.S. Environmental Protection Agency–registered antimicrobial copper alloys (AMCus) were assessed for total aerobic colony counts (ACCs), methicillin-resistant Staphylococcus aureus, gram-negative bacteria, and vancomycin-resistant enterococci for 90 days.

Results: The mean ACCs collectively recovered from all stethoscope surfaces fabricated from the AMCus were found to carry significantly lower concentrations of bacteria (pediatric ED, 11.7 vs 127.1 colony forming units [CFU]/cm2, P < .00001) than their control equivalents. This observation was independent of health care provider or infection control practices. Absence of recovery of bacteria from the AMCu surfaces (66.3%) was significantly higher (P < .00001) than the control surfaces (22.4%). The urethane rim common to the stethoscopes was the most heavily burdened surface; mean concentrations exceeded the health care–associated infection acquisition concentration (5 CFU/cm2) by at least 25×, supporting that the stethoscope warrants consideration in plans mitigating microbial cross-transmission during patient care.

Conclusions: Stethoscope surfaces fabricated with AMCus were consistently found to harbor fewer bacteria.

Copper as an Antibacterial Material in Different Facilities
J. Inkinen, R. Mäkinen, M.M. Keinänen-Toivola, K. Nordström, M. Ahonen. Letters in Applied Microbiology, Vol. 64, Issue 1, January 2017

The present study was performed in real life settings in different facilities (hospital, kindergarten, retirement home, office building) with copper and copper alloy touch surface products (floor drain lids, toilet flush buttons, door handles, light switches, closet touch surfaces, corridor hand rails, front door handles and toilet support rails) in parallel to reference products. Pure copper surfaces supported lower total bacterial counts (16 ± 45 vs 105 ± 430 CFU cm−2, n = 214, P < 0·001) and a lower occurrence of Staphylococcus aureus (2·6 vs 14%, n = 157, P < 0·01) and Gram-negatives (21 vs 34%, n = 214, P < 0·05) respectively than did reference surfaces, whereas the occurrence of enterococci (15%, n = 214, P > 0·05) was similar. The studied products could be assigned to three categories according to their bacterial loads as follows (P < 0·001): floor drain lids (300 ± 730 CFU cm−2, n = 32), small area touch surfaces (8·0 ± 7·1 to 62 ± 160 CFU cm−2, n = 90) and large area touch surfaces (1·1 ± 1·1 to 1·7 ± 2·4 CFU cm−2, n = 92). In conclusion, copper touch surface products can function as antibacterial materials to reduce the bacterial load, especially on frequently touched small surfaces.

Influence of Copper and its Alloys Against Resistant Strains of Coagulase-negative Staphylococci Isolated from Touch Surfaces of Polish Hospital Units
A. Różańska, A. Chmielarczyk, D. Romaniszyn, M. Bulanda. Journal of Hospital Infection, Supplement 1, November 2016.

Background: Coagulase-negative staphylococci (CNS) are the predominant contaminant flora of the Polish hospital environment.

Aim/Objective: The objective of the study was to evaluate the antimicrobial properties of copper and selected copper alloys, against CNS highly resistant to antibiotics, isolated from touch surfaces of Polish hospital units.

Method: Modification of Japanese standard – a method for testing antimicrobial properties of surfaces made of non-porous materials was used in the study. Assessment of antimicrobial properties was performed on copper alloys: CuZn37, CuSn6, CuNi12Zn24 and Cu-ETP as positive control and stainless steel as negative control. Bacterial strains used in the study were: Staphylococcus haemolyticus and Staphylococcus epidermidis – strains resistant to beta-lactam antibiotics, aminoglycosides, fluoroquinolones, clindamycin, erythromycin and trimethoprim/sulfamethoxazole vs. strains of these species forming a biofilm and, for comparison–Stapylococcus aureus.

Results: The strongest antimicrobial properties against the tested strains were found for pure copper –total elimination of bacteria from the level of 107 CFU/mL was observed after approximately 180 min. A faster total reduction of the density of bacterial suspension was also observed in case of SA comparing to CNS strains. Effectiveness comparable to that of pure copper was demonstrated for tin bronze (CuSn6).

Discussion and/or Conclusion: The results demonstrated that copper alloy materials exhibit strong antimicrobial properties against the study strains. It means that the use of equipment made of materials with antimicrobial properties can help to limit the spread of antibiotic resistance genes in the hospital environment. The work was carried out in the framework of the NCBiR project PBS3/ A9/32/2015.

Reduce Infections in Military and Disaster Medicine with a New Weapon: Continuously Active Antimicrobial Copper Alloy Surfaces
AA Estelle, J Rutherford, MG Schmidt. Poster presented at DiMiMED, the International Conference on Disaster and Military Medicine. 15–16 November 2016, Düsseldorf, Germany

Antimicrobial copper surfaces are proven to inactivate lethal viruses and kill infectious bacteria that cause healthcare-associated infections (HAIs) responsible for substantial patient morbidity and mortality. These continuously active metal surfaces can be integrated into rapidly deployable military medical clinics and military medical treatment facilities to reduce the risk of infectious outbreaks thereby increasing productivity and improving mission effectiveness.

Copper Alloy Surfaces Sustain Terminal Cleaning Levels in a Rural Hospital
Shannon M. Hinsa-Leasure, Queenster Nartey, Justin Vaverka, Michael G. Schmidt. American Journal of Infection Control, 28 September 2016

Objective: To assess the ability of copper alloy surfaces to mitigate the bacterial burden associated with commonly touched surfaces in conjunction with daily and terminal cleaning in rural hospital settings.

Design: A prospective intention-to-treat trial design was used to evaluate the effectiveness of cooper alloy surfaces and respective controls to augment infection control practices under pragmatic conditions.

Setting: Half of the patient rooms in the medical-surgical suite in a 49-bed rural hospital were outfitted with copper alloy materials. The control rooms maintained traditional plastic, metal, and porcelain surfaces.

Methods:The primary outcome was a comparison of the bacterial burden harbored by 20 surfaces and components associated with control and intervention areas for 12 months. Locations were swabbed regardless of the occupancy status of the patient room. Significance was assessed using nonparametric methods employing the Mann-Whitney U test with significance assessed at P < .05.

Results: Components fabricated using copper alloys were found to have significantly lower concentrations of bacteria, at or below levels prescribed, upon completion of terminal cleaning. Vacant rooms were found to harbor significant concentrations of bacteria, whereas those fabricated from copper alloys were found to be at or below those concentrations prescribed subsequent to terminal cleaning.

Conclusions: Copper alloys can significantly decrease the burden harbored on high-touch surfaces, and thus warrant inclusion in an integrated infection control strategy for rural hospitals.

Small Colony Variants are More Susceptible to Copper-mediated Contact Killing for Pseudomonas Aeruginosa and Staphylococcus Aureus
Sha Liu and Xue-Xian Zhang, Journal of Medical Microbiology (2016), 65, 1143–1151

Applying self-sanitizing copper surfaces to commonly touched places within hospital facilities is an emerging strategy to prevent healthcare-associated infections. This is due to the fact that bacterial pathogens are rapidly killed on copper, a process termed contact killing. However, the mechanisms of contact killing are not fully understood, and the potential of bacterial pathogens to develop resistance has rarely been explored. Here, we hypothesize that bacteria are predominantly killed by a burst release of toxic copper ions, resulting from chemical reactions between bacterial cell surface components and metallic copper. To test this, we isolated and characterized small colony variants (SCVs) derived from Pseudomonas aeruginosa and Staphylococcus aureus. SCVs overproduce extracellular polymeric substances (EPS), which will enhance copper ion release, causing more rapid death on copper. Indeed, all 13 SCVs tested were more rapidly killed than wild-types on the surfaces of both pure copper and brass (63.5% Cu). Next, using the non-pathogenic Pseudomonas fluorescens SBW25 as a model, we examined the roles of specific cell surface components in contact killing, including EPS, LPS, capsule, flagella and pili. We also subjected P. fluorescens SBW25 to daily serial passage of sub-lethal conditions on brass. After 100 transfers, there was a slight increase of survival rate, but ~97% of cells can still be killed within 60 min on brass. Together, our data implicate that the rate of contact killing on copper is largely determined by the cell surface components, and bacteria have limited ability to evolve resistance to metallic copper.

Perspectives From the Field in Response to “It is Time to Revise our Approach to Registering Antimicrobial Agents for Health Care Settings”
Michael G. Schmidt, Joseph J. John Jr., Katherine D. Freeman, Peter A. Sharpe, Adam A. Estelle, Harold T. Michels. American Journal of Infection Control, 9 August 2016

The recent commentary, “It is time to revise our approach to registering antimicrobial agents for health care settings” by Alvarez et al1 provides welcome recognition that antimicrobial touch surfaces, such as copper alloys, offer a promising method to augment our capacity to combat health care-associated infections (HAIs). We agree that replacing high-touch surfaces in hospitals and elsewhere with continuously active, antimicrobial copper alloys provides an important means of reducing microbial burden during intervals between routine and terminal environmental cleanings.

Copper Alloys - The New ‘Old’ Weapon in the Fight Against Infectious Disease
Harold T. Michels, Corinne A. Michels, Current Trends in Microbiology, Vol. 10 2016

Exposure to dry copper alloy surfaces, such as brass, kills a wide spectrum of microorganisms including Gram-negative and Gram-positive bacteria and fungi, and permanently inactivates several types of viruses.

A large body of published evidence reports that greater than 99.9% killing occurred within a 2-hour period when the microorganism was exposed to the copper alloy samples at room temperature and typical indoor humidity levels. Included in these studies were disease-causing bacteria such as E. coli O157:H7 as well as hospital “super-bugs” such as Methicillin- Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococci(VRE). The results of these laboratory-based tests are reviewed here.

The mechanism(s) of action of copper alloy surface killing is still under investigation and progress on this important area of research will be described. It is important to note that mutations that provide resistance to copper alloy surface exposure have not been reported. These results suggest that copper alloy surfaces could be a powerful tool against the transmission of infectious disease in public settings, most particularly hospitals.

In a clinical trial, summarized here, the amount of live bacteria found on components made of copper alloys was compared to that found on components made from standard materials and shown to be 83% lower. Most significantly, when infection rates were tracked in these hospital rooms with the copper components and compared to rooms containing the standard components, it was found that the infection rates were reduced by a statistically significant 58%.

Thus, the widespread deployment of copper alloy components to frequently touched surfaces, such as door knobs and hand rails, has the potential to significantly reduce the rate of transmission of infections in the clinical settings and public-use spaces such as schools and transit systems.

Antimicrobial Applications of Copper
Marin Vincent, Philippe Hartemann, Marc Engels-Deutsch. International Journal of Hygiene and Environmental Health. doi:10.1016/j.ijheh.2016.06.003

Copper has long been known to have antimicrobial activity and is used in drinking water treatment and transportation. It has been recognized by the American Environmental Protection Agency as the first metallic antimicrobial agent in 2008. With ongoing waterborne hospital-acquired infections and antibiotic resistance, research on copper as an antimicrobial agent is again very attractive.

Many studies have shown that the use of copper surface and copper particles could significantly reduce the environmental bioburden. This review highlights in its first part all the conditions described in the literature to enhance copper antimicrobial activity. Secondly, the different antimicrobial applications of copper in water treatment, hospital care units and public applications are presented. Finally, the future research needs on copper as an antimicrobial agent are discussed.

Potential Effectiveness of Copper Surfaces in Reducing Health Care–associated Infection Rates in a Pediatric Intensive and Intermediate Care Unit: A Nonrandomized Controlled Trial
Bettina von Dessauer Maria S. Navarrete, Dona Benadof, Carmen Benavente, Michael G. Schmidt. American Journal of Infection Control. doi:10.1016/j.ajic.2016.03.053

Background: Studies have consistently shown that copper alloyed surfaces decrease the burden of microorganisms in health care environments. This study assessed whether copper alloy surfaces decreased hospital-associated infections in pediatric intensive and intermediate care units.

Methods: Admitted infants were assigned sequentially to a room furnished with or without a limited number of copper alloyed surfaces. Clinical and exposure to intervention data were collected on a daily basis. To avoid counting infections present prior to admission, patients who stayed in the hospital <72 hours were excluded from analysis. Health care–associated infections (HAIs) were confirmed according to protocol definitions.

Results: Clinical outcomes from 515 patients were considered in our analysis: 261 patients from the intervention arm of the study, and 254 from the control arm. Crude analysis showed an HAI rate of 10.6 versus 13.0 per 1,000 patient days for copper- and non–copper-exposed patients, respectively, for a crude relative risk reduction (RRR) of 0.19 (90% confidence interval, 0.46 to -0.22). Conducting clinical trials to assess interventions that may impact HAI rates is very challenging. The results here contribute to our understanding and ability to estimate the effect size that copper alloy surfaces have on HAI acquisition.

Conclusions: Exposure of pediatric patients to copper-surfaced objects in the closed environment of the intensive care unit resulted in decreased HAI rates when compared with noncopper exposure; however, the RRR was not statistically significant. The clinical effect size warrants further consideration of this intervention as a component of a systems-based approach to control HAIs.

Lack of Involvement of Fenton Chemistry in Death of Methicillin-Resistant and Methicillin-Sensitive Strains of Staphylococcus aureus and Destruction of Their Genomes on Wet or Dry Copper Alloy Surfaces
S. L. Warnes and C. W. Keevil. Applied and Environmental Microbiology 2016, 10.1128/AEM.03861-15

The pandemic of hospital acquired infections caused by methicillin-resistant Staphylococcus aureus (MRSA) has declined but the evolution of strains with enhanced virulence, toxins and the increase of community-associated infections is still a threat. In previous studies, simulated droplet contamination of MRSA was killed on copper and brass surfaces within 90 minutes. However, contamination of surfaces is often via finger tips which dries rapidly and may be overlooked by cleaning regimes unlike visible droplets. In this new study a 5-log reduction of a hardy epidemic strain of MRSA (EMRSA-16) was observed following 10 minutes contact with copper and 4-log reduction observed on copper nickel and cartridge brass alloys in 15 minutes. A methicillin-sensitive strain (MSSA), from an osteomyelitis patient, was killed on copper surfaces in 15 minutes and a 4-log and 3-log reduction occurred within 20 minutes contact with copper nickel and cartridge brass, respectively. Bacterial respiration was compromised on copper surfaces and superoxide generated as part of the killing mechanism. In addition, destruction of genomic DNA occurs on copper and brass surfaces allaying concerns about horizontal gene transfer and copper resistance. Incorporation of copper alloy biocidal surfaces could help to reduce the spread of this dangerous pathogen.

Physicochemical Properties of Copper Important for its Antibacterial Activity and Development of a Unified Model
Michael Hans, Salima Mathews, Frank Mücklich and Marc Solioz, Biointerphases 11, 018902 (2016)

Contact killing is a novel term describing the killing of bacteria when they come in contact with metallic copper or copper-containing alloys. In recent years, the mechanism of contact killing has received much attention and many mechanistic details are available. The authors here review some of these mechanistic aspects with a focus on the critical physicochemical properties of copper which make it antibacterial. Known mechanisms of contact killing are set in context to ionic, corrosive, and physical properties of copper. The analysis reveals that the oxidation behavior of copper, paired with the solubility properties of copper oxides, are the key factors which make metallic copper antibacterial. The concept advanced here explains the unique position of copper as an antibacterial metal. Based on our model, novel design criteria for metallic antibacterial materials may be derived.

Copper Surfaces are Associated with Significantly Lower Concentrations of Bacteria on Selected Surfaces within a Pediatric Intensive Care Unit
Michael G. Schmidt PhD; Bettina von Dessauer MD; Carmen Benavente MD; Dona Benadof MD; Paulina Cifuentes RN; Alicia Elgueta RN; Claudia Duran MS; Maria S. Navarrete MD MPH. American Journal of Infection Control, Corrected proof. doi:10.1016/j.ajic.2015.09

Background: Health care associated infections result in significant patient morbidity and mortality. Although cleaning can remove pathogens present on hospital surfaces, those surfaces may be inadequately cleaned or recontaminated within minutes. Because of copper’s inherent and continuous antimicrobial properties, copper surfaces offer a solution to complement cleaning. The objective of this study was to quantitatively assess the bacterial microbial burden coincident with an assessment of the ability of antimicrobial copper to limit the microbial burden associated with 3 surfaces in a pediatric intensive care unit.

Methods: A pragmatic trial was conducted enrolling 1,012 patients from 2 high acuity care units within a 249-bed tertiary care pediatric hospital over 12 months. The microbial burden was determined from 3 frequently encountered surfaces, regardless of room occupancy, twice monthly, from 16 rooms, 8 outfitted normally and 8 outfitted with antimicrobial copper.

Results: Copper surfaces were found to be equivalently antimicrobial in pediatric settings to activities reported for adult medical intensive care units. The log10 reduction to the microbial burden from antimicrobial copper surfaced bed rails was 1.996 (99%). Surprisingly, introduction of copper objects to 8 study rooms was found to suppress the microbial burden recovered from objects assessed in control
rooms by log10 of 1.863 (73%).

Conclusion: Copper surfaces warrant serious consideration when contemplating the introduction of no-touch disinfection technologies for reducing burden to limit acquisition of HAIs.

Copper and copper alloys are engineering materials that are durable, colourful and recyclable and are widely available in various product forms suitable for a range of manufacturing purposes. Copper and its alloys offer a suite of materials for designers of functional, sustainable and cost-effective products.

Copper and certain copper alloys have intrinsic antimicrobial properties (so-called ‘Antimicrobial Copper’) and products made from these materials have an additional, secondary benefit of contributing to hygienic design. Products made from Antimicrobial Copper are a supplement to, not a substitute for standard infection control practices. It is essential that current hygiene practices are continued, including those related to the cleaning and disinfection of environmental surfaces.

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