Références scientifiques

Articles scientifiques publiés par les revues à comités de lecture internationaux sur les propriétés antimicrobiennes du cuivre et de ses alliages

Compte-tenu du nombre de publications, il est conseillé de passer par le moteur de recherche (la quasi totalité des articles sont en anglais) :

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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); http://dx.doi.org/10.1116/1.4935853

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 careeassociated 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.

Human Coronavirus 229E Remains Infectious on Common Touch Surface Materials
Warnes SL, Little ZR, Keevil CW. 2015. Human coronavirus 229E remains infectious on common touch surface materials. mBio 6(6):e01697-15. doi:10.1128/mBio.01697-15.

The evolution of new and reemerging historic virulent strains of respiratory viruses from animal reservoirs is a significant threat to human health. Inefficient human-to-human transmission of zoonotic strains may initially limit the spread of transmission, but an infection may be contracted by touching contaminated surfaces. Enveloped viruses are often susceptible to environmental stresses, but the human coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) have recently caused increasing concern of contact transmission during outbreaks. We report here that pathogenic human coronavirus 229E remained infectious in a human lung cell culture model following at least 5 days of persistence on a range of common nonbiocidal surface materials, including polytetrafluoroethylene (Teflon; PTFE), polyvinyl chloride (PVC), ceramic tiles, glass, silicone rubber, and stainless steel. We have shown previously that noroviruses are destroyed on copper alloy surfaces. In this new study, human coronavirus 229E was rapidly inactivated on a range of copper alloys (within a few minutes for simulated fingertip contamination) and Cu/Zn brasses were very effective at lower copper concentration. Exposure to copper destroyed the viral genomes and irreversibly affected virus morphology, including disintegration of envelope and dispersal of surface spikes. Cu(I) and Cu(II) moieties were responsible for the inactivation, which was enhanced by reactive oxygen species generation on alloy surfaces, resulting in even faster inactivation than was seen with nonenveloped viruses on copper. Consequently, copper alloy surfaces could be employed in communal areas and at any mass gatherings to help reduce transmission of respiratory viruses from contaminated surfaces and protect the public health.

From Laboratory Research to a Clinical Trial: Copper Alloy Surfaces Kill Bacteria and Reduce Hospital-Acquired Infections
Michels, H.T. 2015. From Laboratory Research to a Clinical Trial: Copper Alloy Surfaces Kill Bacteria and Reduce Hospital-Acquired Infections. Health Environments Research & Design Journal. 1–16.

Bacteria die on copper alloy surfaces in both the laboratory and the hospital rooms. Infection rates were lowered in those hospital rooms containing copper components. Thus, based on the presented information, the placement of copper alloy components, in the built environment, may have the potential to reduce not only hospital-acquired infections but also patient treatment costs.

Antimicrobial Properties of Copper in Gram-Negative and Gram-Positive Bacteria
Meyer, T.J. 2015. Antimicrobial Properties of Copper in Gram-Negative and Gram-Positive Bacteria. International Journal of Biological, Biomolecular, Agricultural, Food and Biotechnological Engineering. Vol:9, No:3.

For centuries humans have used the antimicrobial properties of copper to their advantage. Yet, after all these years the underlying mechanisms of copper mediated cell death in various microbes remain unclear. We had explored the hypothesis that copper mediated increased levels of lipid peroxidation in the membrane fatty acids is responsible for increased killing in Escherichia coli.

In this study we show that in both gram positive (Staphylococcus aureus) and gram negative (Pseudomonas aeruginosa) bacteria there is a strong correlation between copper mediated cell death and increased levels of lipid peroxidation.

Interestingly, the non-spore forming gram positive bacteria as well as gram negative bacteria show similar patterns of cell death, increased levels of lipid peroxidation, as well as genomic DNA degradation, however there is some difference in loss in membrane integrity upon exposure to copper alloy surface.

Antimicrobial Activity of Copper Alloys Against Invasive Multidrug-Resistant Nosocomial Pathogens
Koseoglu Eser O, Ergin A, Hascelik G, Current Microbiology, 5 June 2015

The emergence and spread of antibiotic resistance demanded novel approaches for the prevention of nosocomial infections, and metallic copper surfaces have been suggested as an alternative for the control of multidrug-resistant (MDR) bacteria in surfaces in the hospital environment.

This study aimed to evaluate the antimicrobial activity of copper material for invasive MDR nosocomial pathogens isolated over time, in comparison to stainless steel. Clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) (n:4), OXA-23 and OXA-58 positive, MDR Acinetobacter baumannii (n:6) and Pseudomonas aeruginosa (n:4) were evaluated.

The antimicrobial activity of coupons containing 99 % copper and a brass alloy containing 63 % copper was assessed against stainless steel. All the materials demonstrated statistically significant differences within each other for the logarithmic reduction of microorganisms. Among the three materials, the highest reduction of microorganisms was seen in 99 % copper and the least in stainless steel.

The result was statistically significant especially for 0, 2, and 4 h (P = 0.05). 99 % copper showed a bactericidal effect at less than 1 h for MRSA and at 2 h for P. aeruginosa. 63 % copper showed a bactericidal effect at 24 h for P. aeruginosa strains only. Stainless steel surfaces exhibited a bacteriostatic effect after 6 h for P. aeruginosa strains only.

99 % copper reduced the number of bacteria used significantly, produced a bactericidal effect and was more effective than 63 % copper.

The use of metallic copper material could aid in reducing the concentration of bacteria, especially for invasive nosocomial pathogens on hard surfaces in the hospital environment.

Destruction of the Capsid and Genome of GII.4 Human Norovirus Occurs During Exposure to Metal Alloys Containing Copper
C. S. Manuel, M. D. Moore and L.A. Jaykus, Applied and Environmental Microbiology, 15 May 2015

Human norovirus (HuNoV) represents a significant public health burden worldwide and can be environmentally transmitted. Copper surfaces have been shown to inactivate the cultivable surrogate murine norovirus, but no such data exist for HuNoV.

The purpose of this study was to characterize the destruction of GII.4 HuNoV and virus-like particles (VLPs) when exposed to copper alloy surfaces. Fecal suspensions positive for a GII.4 HuNoV outbreak strain or GII.4 virus-like particles (VLPs) were exposed to copper alloys or stainless steel for 0 to 240 min and recovered by elution. HuNoV genome integrity was assessed by RT-qPCR (without RNase treatment), and capsid integrity was assessed by RT-qPCR (with RNase treatment), transmission electron microscopy (TEM), SDS-PAGE/Western blot analysis, and a histo-blood group antigen (HBGA) binding assay.

Exposing fecal suspensions to pure copper for 60 min reduced GII.4 HuNoV RNA copy number by approximately 3 log 10 when analyzed by RT-qPCR without RNase treatment, and 4 log 10 when a prior RNase treatment was used.

The rate of reduction in HuNoV RNA copy number was approximately proportional to the percent copper in each alloy. Exposing GII.4 HuNoV VLPs to pure copper surfaces resulted in noticeable aggregation and destruction within 240 min, an 80% reduction in VP1 major capsid protein band intensity in 15 min, and near complete loss of HBGA receptor binding within 8 min. In all experiments, HuNoV remained stable on stainless steel.

These results suggest that copper surfaces destroy HuNoV, and may be useful in preventing environmental transmission of the virus in at-risk settings.

Inactivation of murine norovirus on a range of copper alloy surfaces is accompanied by loss of capsid integrity
S. L. Warnes, E. N. Summersgill and C.W. Keevil, Applied and Environmental Microbiology, 1 December 2014

Norovirus is one of the most common causes of acute viral gastroenteritis. The virus is spread via faecal oral route, most commonly from infected food and water, but several outbreaks have originated from contamination of surfaces with infectious virus.

In this study a close surrogate of human norovirus causing gastrointestinal disease in mice, murine norovirus type 1 (MNV-1), retained infectivity for more than 2 weeks following contact with a range of surface materials including Teflon (polytetrafluoroethylene, PTFE), polyvinyl chloride (PVC), ceramic tiles, glass, silicone rubber and stainless steel. Persistence was, slightly prolonged on ceramic surfaces.

A previous study in our laboratory observed that copper and copper alloy dry surfaces rapidly inactivated MNV-1 and destroyed the viral genome. In this new study we have observed that a relatively small change in percentage copper, between 70-80% in copper nickels and 60-70% in brasses, had significant influence on the ability of the alloy to inactivate norovirus. Nickel alone did not affect virus but zinc did have some antiviral effect which had a synergistic effect with copper and resulted in increased efficacy of brasses at lower percentage copper.

Electron microscopy of purified MNV-1 that had been exposed to copper and stainless steel surfaces suggested a massive breakdown of the viral capsid had occurred on copper. In addition, MNV-1 that had been exposed to copper and treated with RNase demonstrated a reduction in viral gene copy number. This suggests capsid integrity is compromised on contact with copper, allowing copper ion access to the viral genome.

Inactivation of Bacterial and Viral Biothreat Agents on Metallic Copper Surfaces
Pauline Bleichert, Christophe Espirito Santo, Matthias Hanczaruk, Hermann Meyer, Gregor Grass, BioMetals, International Biometals Society, 7 August 2014

In recent years several studies in laboratory settings and in hospital environments have demonstrated that surfaces of massive metallic copper have intrinsic antibacterial and antiviral properties.  Microbes are rapidly inactivated by a quick, sharp shock known as contact killing.  The underlying mechanism is not yet fully understood; however, in this process the cytoplasmic membrane is severely damaged.  Pathogenic bacterial and viral high-consequence species able to evade the host immune system are among the most serious lethal microbial challenges to human health.  Here, we investigated contact-killing mediated by copper surfaces of Gram-negative bacteria (Brucella melitensis, Burkholderia mallei, Burkholderia pseudomallei, Francisella tularensis tularensis and Yersinia pestis) and of Gram-positive endospore-forming Bacillus anthracis.  Additionally, we also tested inactivation of monkeypox virus and vaccinia virus on copper.  This group of pathogens comprises biothreat species (or their close relatives) classified by the Center for Disease and Control and Prevention (CDC) as microbial select agents posing severe threats to public health and having the potential to be deliberately released.  All agents were rapidly inactivated on copper between 30 s and 5 min with the exception of B. anthracis endospores.  For vegetative bacterial cells prolonged contact to metallic copper resulted in the destruction of cell structure.

Antimicrobial Copper (Cu+) Implementation and its Influence to the Epidemiological Data in Elementary School Population
P Efstathiou, E Kouskouni, K Karageorgou, M Tseroni, Z Manolidou, S Papanikolaou, E Logothetis, H Tzouma, C Petropoulou, I Agrafa. Antimicrobial Resistance and Infection Control 2013, 2(Suppl 1):P370

Meeting extract - Antimicrobial Resistance and Infection Control, 2nd International Conference on Prevention and Infection Control (ICPIC 2013), Geneva, Switzerland, 25-28 June 2013.

Objectives: Aim of this study was to evaluate the epidemiological data in elementary school students after implementing Cu+ in multi-touch surfaces.

Methods: Antimicrobial copper alloy  (Cu 63% - Zn 37%, Low Lead) was used to cover or replace multi-touch surfaces (handrails, stair railings), in five elementary schools (N=1596 students).  Epidemiological surveillance of flu-like symptoms was conducted from the 40th week of 2011 to 15th week of 2012 and recorded absenteeism among students based on a specific protocol.

Results: A significant reduction of pathogenic strains and viruses after the implementation of antimicrobial copper Cu+ influenced the occurrence of respiratory infections of viral etiology.  A decrease of seasonal influenza (Influenza Like Illness) was recorded on the students of these schools.  Clinical morbidity index of students was recorded at 36.01% (average 5 schools), while in the community the same period (2011-2012) the rate was 48.8%.

Conclusion: The use of antimicrobial copper in places with great population concentrations and crowded places such as schools is an innovative application, which in combination with hand hygiene contributes significantly to the reduction of viral respiratory tract infections and emerging as one of the most important allies to the Public health.

Disclosure of interest: None declared.

(Poster 370)

Norovirus Inactivation on Antimicrobial Touch Surfaces
B Keevil, S Warnes, Centre for Biological Sciences, University of Southampton, UK. Antimicrobial Resistance and Infection Control 2013, 2(Suppl 1):P25.

Meeting extract - Antimicrobial Resistance and Infection Control, 2nd International Conference on Prevention and Infection Control (ICPIC 2013), Geneva, Switzerland, 25-28 June 2013.

Introduction: Norovirus is the most common cause of gastroenteritis worldwide, primarily because of high infectivity, uncontrollable aerosol formation via vomitus and faeces, resistance to cleaning agents and persistence in the environment.  Even low level surface contamination is a transmission risk because of the low infectious dose and inadequate hand hygiene.

Objectives: Laboratory studies and clinical trials have demonstrated the use of antimicrobial copper alloy touch surfaces to reduce the spread of bacterial pathogens and antibiotic resistance gene transfer.  Here we investigate the efficacy of copper alloys to inactivate norovirus.

Methods: In the absence of infectivity assays for human norovirus, infectivity of surrogate murine MNV-1 norovirus, untreated or exposed to touch surfaces, was assessed by plaque assay in a RAW 264.7 monocyte macrophage cell line.  Copper alloy surfaces were compared to stainless steel as touch surfaces.  Results are expressed as plaque forming units (pfu) per cm2.  The role of Cu(I) or Cu(II) ions and reactive oxygen species (ROS) was assessed using specific chelators and quenchers.  Viral RNA was extracted and purified and separated in non-denaturing gel electrophoresis.

Results: Complete inactivation of approx 5 x 104 pfu per cm2 was observed on copper and copper-nickel in 5-10 minutes or in 20 hours at room temperature for alloys containing lower percentage copper with an inoculum that dried in seconds, simulating hand contact.  Virus exposed to stainless steel retained high infectivity at 2 hours.  Inactivation was slower if the virus was inoculated as a wet inoculum simulating vomitus: complete inactivation occurred in 1 hour for copper and copper-nickel, with significant reduction on other alloys but not stainless steel.  The highest rate of inactivation was observed on immediate contact.  These results were similar if virus burden was increased 50-fold.  Virus inactivation was faster at 37oC and slower at 4oC.  Cu(II) and particularly Cu(I) ions wer essential for loss of infectivity but not superoxide or hydroxyl radicals.  Exposure to copper alloys resulted in destruction of the viral genome, preventing potential mutation to copper resistance.

Conclusion: The results support the use of antimicrobial copper surfaces to reduce the spread of norovirus in high risk areas such as closed environments including healthcare facilities and cruise ships.

Disclosure of interest: B Keevil - Grant/Research support from International Copper Association, S Warnes - Grant/Research support from International Copper Association.

(Poster 25)

Experimental Tests of Copper Components in Ventilation Systems for Microbial Control
Charles Feigley, Jamil Khan, Deborah Salzberg, James Hussey, Hubert Attaway, Lisa Steed, Michael Schmidt and Harold Michels, (2013), HVAC&R Research, 19:1, 53-62

Colonization of HVAC systems by microbes may lead to release of hazardous bioaerosols containing allergens, irritants, odorants or infectious agents to outdoor air, possibly adversely affecting system performance.  Unlike the many common materials used in HVAC systems, copper and copper alloys have ben shown in laboratory investigations to kill bacteria and fungi on contact after several hours.  This study tested copper's antimicrobial properties in comparison with aluminium in full-scale, carefully controlled air-conditioning systems, four with copper heat exchanger facilities and four with aluminium assemblies, at identical airflow rates, temperatures, humidity, and input microbe levels.  Fungal and bacterial loads on copper surfaces in heat exchangers were lower than on aluminium surfaces by factors of 3500 and more than 500, respectively, over a 4-month period.  No statistically significant difference in the release of airborne microbes was detected between copper and aluminium heat exchangers.  The moderate conditions employed in this study, while still within the range commonly found in HVAC systems, possibly prevented the high microbial loading on aluminium heat exchanger surfaces from translating into significant differences in airborne concentrations betweeen copper and aluminium systems.

Sustained Reduction of Microbial Burden on Common Hospital Surfaces through Introduction of Copper
Michael G Schmidt, Hubert H Attaway, Peter A Sharpe, Joseph John Jr, Kent A Sepkowitz, Andrew Morgan, Sarah E Fairey, Susan Singh, Lisa L Steed, J Robert Cantey, Katherine D Freeman, Harold T Michels, Cassandra D Salgado J Clin Microbiol July 2012 vol 50

The contribution of environmental surface contamination with pathogenic organisms to the development of healthcare-associated infections (HAI) has not been well defined.  The microbial burden (MB) associated with commonly touched surfaces in intensive care units (ICUs) was determined by sampling six objects in 16 rooms in ICUs in three hospitals over 43 months.

At month 23, copper-alloy surfaces, with inherent antimicrobial properties, were installed onto six monitored objects in 8 of 16 rooms, and the effect that this application had on the intrinsic MB present on the six objects was assessed.Census continued in rooms with and without copper for an additional 21 months.

In concert with routine infection control practices, the average MB found for the six objects assessed in the clinical environment during the preintervention phase was 28 times higher (6,985 CFU/100 cm2; n = 3,977 objects sampled) than levels proposed as benign immediately after terminal cleaning (<250 CFU/100 cm2).

During the intervention phase, the MB was found to be significantly lower for both the control and copper-surfaced objects. Copper was found to cause a significant (83%) reduction in the average MB found on the objects (465 CFU/100 cm2; n = 2714 objects) compared to the controls (2,674 CFU/100 cm2; n = 2,831 objects [P < 0.0001]).

The introduction of copper surfaces to objects formerly covered with plastic, wood, stainless steel, and other materials found in the patient care environment significantly reduced the overall MB on a continuous basis, thereby providing a potentially safer environment for hospital patients, health care workers (HCWs), and visitors.

Supplemental Materials and Methods:

Table S1 - Assessment of the intrinsic microbial burden found on commonly encountered objects before an intervention with antimicrobial copper

Table S2 - Determination of the intrinsic microbial burden associated with six high-touch objects with or without copper surfaces within three ICUs

Figure S1 - Distribution of the microbial burden in the built environment is subject to stochastic forces

Figure S2 - Copper surfaces attenuate the inherent variability of the MB recovered from high-touch objects in the ICU

J Clin Microbiol July 2012 vol. 50 no. 7 2217-2223. Published ahead of print 2 May 2012, doi: 10.1128/JCM.01032-12.

An evaluation of the antimicrobial properties of healthcare fomites (furnishings and equipment) made of copper alloys
T J Karpanen, A L Casey, P A Lambert, B D Cookson, P Nightingale, L Miruszenko, T S J Elliott. 7th International Conference of the Hospital Infection Society, Liverpool, October 2010.

Results presented at the 7th International Conference of the Hospital Infection Society in Liverpool, October 2010, confirm the role of antimicrobial copper touch surfaces as a supplement to routine cleaning to improve environmental hygiene in clinical environments.

The results showed that the highest contamination was found in the patient bathrooms, particularly on the chrome-plated toilet flush lever handles and tap handles, and on the plastic light pulls and toilet seats.

Copper-containing items, including door push plates, door pull handles, tap handles, toilet flush lever handles, patient over-bed tables, dressing trolleys, socket switches and light pull cord toggles - were found to have significantly fewer microorganisms on their surfaces than the controls and vancomycin-resistant enterococci, meticillin-sensitive Staphylococcus aureus and coliform bacteria were recovered less frequently from these.

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.

Biocidal Efficacy of Copper Alloys against Pathogenic Enterococci Involves Degradation of Genomic and Plasmid DNA
S L Warnes, S M Green, H T Michels, C W Keevil, Appl. Environ. Microbiol. doi:10.1128/AEM.03050-09, 2010

The increasing incidence of nosocomial infections caused by glycopeptide-resistant enterococci is a global concern. Enterococcal species are also difficult to eradicate with existing cleaning regimes; they can survive for long periods on surfaces thus contributing to cases of reinfection and spread of antibiotic resistant strains. We have investigated the potential use of copper alloys as bactericidal surfaces. Clinical isolates of vancomycin-resistant Enterococcus faecalis and Enterococcus faecium were inoculated onto copper alloy and stainless steel surfaces. Samples were assessed for the presence of viable cells by conventional culture, detection of actively respiring cells and assessment of cell membrane integrity. Both species survived for up to several weeks on stainless steel. However, no viable cells were detected on any alloys following exposure for 1 hour at an inoculum concentration of ≤104 colony forming units per cm2. Analysis of genomic and plasmid DNA from bacterial cells recovered from metal surfaces indicates substantial disintegration of the DNA following exposure to copper surfaces that is not evident in cells recovered from stainless steel. The DNA fragmentation is so extensive, and coupled with the rapid cell death which occurs on copper surfaces, that it suggests mutation is less likely to occur. It is therefore highly unlikely that genetic information can be transferred to receptive organisms re-contaminating the same area. A combination of effective cleaning regimes and contact surfaces containing copper could be useful to not only prevent spread of viable pathogenic enterococci but also to mitigate against the occurrence of potential resistance to copper, biocides or antibiotics, and spread of genetic determinants of resistance to other species.

A Pilot Study to Determine the Effectiveness of Copper in Reducing the Microbial Burden (MB) of Objects in Rooms of Intensive Care Unit (ICU) Patients
C D Salgado, A Morgan, K A Sepkowitz et al. Poster 183, 5th Decennial International Conference on Healthcare-Associated Infections, Atlanta, March 29, 2010

The first results from the US Department of Defense-funded 3-centre copper clinical trial show a significant reduction in bioburden on copper items compared to controls. Neither VRE nor MRSA were found on any copper items.

Effects of Temperature and Humidity on the Efficacy of Methicillin-resistant Staphylococcus Aureus Challenged Antimicrobial Materials Containing Silver and Copper
H T Michels, J O Noyce, and C W Keevil, Letters in Applied Microbiology, 49 (2009) 191-195

Demonstrates that commercially available silver ion-containing coatings marketed as antimicrobial do not exhibit any meaningful reduction of MRSA under typical indoor conditions. Copper alloys exhibited antimicrobial efficacy under all tested conditions.

Effectiveness of copper contact surfaces in reducing the microbial burden (MB) in the intensive care unit (ICU) of Hospital del Cobre, Calama, Chile
V Prado, C Durán, M Crestto, A Gutierrez, P Sapiain, G Flores, H Fabres, C Tardito, M Schmidt. Poster 56.044, presented at the 14th International Conference on Infectious Diseases, Miami, March 11, 2010.

First results from the Calama Hospital copper clinical trial show a significant reduction in bioburden on copper compared to control surfaces.

Survival of Bacteria on Metallic Copper Surfaces in a Hospital Trial
André Mikolay, Susanne Huggett, Ladji Tikana, Gregor Grass, Jörg Braun and Dietrich H Nies. Applied Microbial and Cell Physiology,DOI 10.1007/s00253-010-2640-1. May 2010

Basic chemistry of copper is responsible for its Janus-faced feature: on one hand, copper is an essential trace element required to interact efficiently with molecular oxygen. On the other hand, interaction with reactive oxygen species in undesired Fenton-like reactions leads to the production of hydroxyl radicals, which rapidly damage cellular macromolecules. Moreover, copper cations strongly bind to thiol compounds disturbing redox-homeostasis and may also remove cations of other transition metals from their native binding sites in enzymes. Nature has learned during evolution to deal with the dangerous yet important copper cations. Bacterial cells use different efflux systems to detoxify the metal from the cytoplasm or periplasm. Despite this ability, bacteria are rapidly killed on dry metallic copper surfaces. The mode of killing likely involves copper cations being released from the metallic copper and reactive oxygen species. With all this knowledge about the interaction of copper and its cations with cellular macromolecules in mind, experiments were moved to the next level, and the antimicrobial properties of copper-containing alloys in an "everyday" hospital setting were investigated. The alloys tested decreased the number of colony-forming units on metallic copper-containing surfaces by one third compared to control aluminum or plastic surfaces. Moreover, after disinfection, repopulation of the surfaces was delayed on copper alloys. This study bridges a gap between basic research concerning cellular copper homeostasis and application of this knowledge. It demonstrates that the use of copper-containing alloys may limit the spread of multiple drug-resistant bacteria in hospitals.

Performance of Ultramicrofibre Cleaning Technology with or without Addition of a Novel Copper-Based Biocide
D Hamilton, A Foster, L Ballantyne, P Kingsmore, D Bedwell, T J Hall, S S Hickok, A Jeanes, P G Coen, V A Gant, Journal of Hospital Infection (2010) 74, 62-71. doi:10.1016/j.jhin.2009.08.006.

This study compared the bacterial removal performance of ultromicrofibre cloths and mops (UMF) moistened with water (UMF + water) with those moistened with a novel copper-based biocide (UMF + CuWB50, 300 ppm) in several working hospital environments, specifically Accident and Emergency (A&E) and three other wards.

A total of 13 defined sampling sites (10 sites per ward) were sampled in order to retrieve, culture, and enumerate total viable (bacterial) counts (TVC) for each site.  We sampled 1h before, and 1 and 4h after, cleaning three times per week.  The trial ran for 7 weeks.  Two wards were cleaned with UMF + water for 3 weeks and UMF + CuWB50 for 4 weeks.  The reverse applied to the other two wards in a cross-over design fashion, to eliminate ward- and time-specific bias.  Multivariate statistical analyses were used to establish extent and significance of any perceived differences, and to eliminate the effects of potential confounders.  Cleaning with UMF + water reduced TVC on the test surfaces by 30%, whereas cleaning with TVC + CuWB50 reduced TVC by 56%.  CuWB50 had two separate effects; a direct antibacterial effect (evident shortly after cleaning), and a residual antibacterial effect that lasted approx 2 weeks.  The residual effect requires regular application of CuWB50 if it is to persist.  This 'real life' hospital implementation study demonstrates encouraging microbiological cleaning performance for UMF, which is further enhanced with CuWB50.

Role of Copper in Reducing Hospital Environment Contamination
A L Casey, D Adams, T J Karpanen, P A Lambert, B D Cookson, P Nightingale, L Miruszenko, R Shillam, P Christian and T S J Elliott, J Hosp Infect (2009), doi:10.1016/j.jhin.2009.08.018.

The environment may act as a reservoir for pathogens that cause healthcare-associated infections (HCAIs). Approaches to reducing environmental microbial contamination in addition to cleaning are thus worthy of consideration. Copper is well recognised as having antimicrobial activity but this property has not been applied to the clinical setting. We explored its use in a novel cross-over study on an acute medical ward. A toilet seat, set of tap handles and a ward entrance door push plate each containing copper were sampled for the presence of micro-organisms and compared to equivalent standard, non-copper-containing items on the same ward. Items were sampled once weekly for 10 weeks at 07:00 and 17:00. After five weeks, the copper-containing and non-copper-containing items were interchanged.

The total aerobic microbial counts per cm2 including the presence of 'indicator micro-organisms' were determined. Median numbers of microorganisms harboured by the copper-containing items were between 90% and 100% lower than their control equivalents at both 07:00 and 17:00. This reached statistical significance for each item with one exception. Based on the median total aerobic cfu counts from the study period, five out of ten control sample points and zero out of ten copper points failed proposed benchmark values of a total aerobic count of <5 cfu/cm2. All indicator micro-organisms were only isolated from control items with the exception of one item during one week. The use of copper-containing materials for surfaces in the hospital environment may therefore be a valuable adjunct for the prevention of HCAIs and requires further evaluation.

Potential for Preventing Spread of Fungi in Air-Conditioning Systems Constructed Using Copper Instead of Aluminium
L Weaver, H T Michels, C W Keevil, Letters in Applied Microbiology ISSN 0266-8254 (2010) 50 (1): 18. doi:10.1111/j.1472-765X.2009.02753.x. PMID 19943884.

As copper has been previously suggested as an antimicrobial surface, the effectiveness of copper was investigated as an antifungal surface which could be used in air-conditioning systems as an alternative to aluminium.

Methods and Results:
Coupons of copper (C11000) and aluminium were inoculated with fungal isolates (Aspergillus spp., Fusarium spp., Penicillium chrysogenum and Candida albicans) for various time periods. Culture on potato dextrose agar and an in situ viability assay using the fluorochrome FUN-1 were used to determine whether spores had survived. The results showed increased die off of fungal isolates tested compared to aluminium. In addition, copper also prevented the germination of spores present, thereby reducing the risk of the release of spores.

Copper offered an antifungal surface and prevented subsequent germination of spores present. FUN-1 demonstrated that fungal spores entered into a viable but not culturable (VBNC) state on copper indicating the importance of using such methods when assessing the effect of an antifungal as culture alone may give false results.

Significance and impact of study:
Copper offers a valuable alternative to aluminium which could be used in air-conditioning systems in buildings, particularly in hospital environments where patients are more susceptible to fungal infections.

Characterization and Control of the Microbial Community Affiliated with Copper or Aluminum Heat Exchangers of HVAC Systems
Michael G Schmidt, Hubert H Attaway, Silva Terzieva, Anna Marshall, Lisa L Steed, Deborah Salzberg, Hameed A Hamoodi, Jamil A Khan, Charles E Feigley, Harold T Michels. Curr Microbiol, 2012 May 9.

Microbial growth in heating ventilation and airconditioning (HVAC) systems with the subsequent contamination of indoor air is of increasing concern. Microbes and the subsequent biofilms grow easily within heat exchangers. A comparative study where heat exchangers fabricated from antimicrobial copper were evaluated for their ability to limit microbial growth was conducted using a full-scale HVAC system under conditions of normal flow rates using single-pass outside air. Resident bacterial and fungal populations were quantitatively assessed by removing triplicate sets of coupons from each exchanger commencing the fourth week after their installation for the next 30 weeks.

The intrinsic biofilm associated with each coupon was extracted and characterized using selective and differential media. The predominant organisms isolated from aluminum exchangers were species of Methylobacterium of which at least three colony morphologies and 11 distinct PFGE patterns we found; of the few bacteria isolated from the copper exchangers, the majority were species of Bacillus. The concentrations and type of bacteria recovered from the control, aluminum, exchangers were found to be dependent on the type of plating media used and were 11,411-47,257 CFU cm-2 per coupon surface. The concentration of fungi was found to average 378 CFU cm-2. Significantly lower concentrations of bacteria, 3 CFU cm-2, and fungi, 1 CFU cm-2, were recovered from copper exchangers regardless of the plating media used. Commonly used aluminum heat exchangers developed stable, mixed, bacterial/fungal biofilms in excess of 47,000 organisms per cm2 within 4 weeks of operation, whereas the antimicrobial properties of metallic copper were able to limit the microbial load affiliated with the copper heat exchangers to levels 99.97 % lower during the same time period.

Antimicrobial metallic copper surfaces kill Staphylococcus haemolyticus via membrane damage
Christophe Espírito Santo, Davide Quaranta, Gregor Grass. MicrobiologyOpen, Volume 1, Issue 1, pages 46–52, March 2012, DOI: 10.1002/mbo3.2

Molecular knowledge of the mode-of-action exerted by metallic Cu on microbes is certainly not strictly necessary for widespread application of antimicrobial surfaces in hygiene-sensitive areas. Currently, it is agreed-upon that genomic material will eventually degrade on metallic Cu (Weaver et al. 2011; Warnes and Keevil 2010; Espirito Santo and Grass, unpublished observations) but it is controversial if this process is causative for or subsequent to cell death (Weaver et al. 2010; Espirito Santo et al. 2011). We propose that current data favor the model that membranes are damaged first, causing lethality, followed by protein oxidation (Nandakumar et al. 2011) and DNA-degradation. In depth understanding of the sensitive cellular targets of Cu toxicity and the order of events leading to death, however, can be expected to provide new opportunities for improving the efficacy of Cu surfaces against microbes.

Le cuivre et les alliages de cuivre sont des matériaux techniques, résistants, colorés et recyclables. Ils sont disponibles dans une grande variété de formes et de produits, adaptés à des usages très divers. Le cuivre et ses alliages offrent pour les concepteurs une large gamme de matériaux pour la fabrication de produits fonctionnels, durables et rentables.

Le cuivre et certains de ses alliages possèdent des propriétés antimicrobiennes intrinsèques (sous la désignation de cuivre antimicrobien ou antibactérien, autrement dit Antimicrobial Copper en anglais). Les produits fabriqués à partir de ces matériaux spécifiques ont un avantage supplémentaire, participant à l'hygiène. Les produits en cuivre antimicrobien constituent une aide supplémentaire, et non un substitut, dans le cadre des pratiques usuelles visant le contrôle des infections. Il reste primordial que toutes les mesures d'hygiène courantes soient maintenues, y compris celles liées au nettoyage et à la désinfection des surfaces environnementales.

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