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Role of antimicrobial copper in preventing HAIs

The introduction of copper alloys to decrease microbial bioburden on surfaces in healthcare settings in addition to regular cleaning/disinfection is encouraging based the results of recent in situ studies
 
Jean-Yves Maillard PhD DSc
Cardiff School of Pharmacy and Pharmaceutical Sciences,
Cardiff University, UK
 
Healthcare-acquired infections (HAIs) are associated with high mortality and morbidity. Their impact on the public and regulator’s perception of healthcare facilities is harmful as well as costly to the National Health Service. The deadly outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) ten years ago, and of Clostridium difficile (C. difficile) more recently, have increased public awareness of microbial infections and led to high media coverage. Unfortunately, improvement for hospital hygiene remains slow despite sporadic negative media coverage and the increased availability of biocidal products tailored for the healthcare environment. Such a slow progress is linked to the lack of recognition of the link between surface contamination with microorganisms and infection in patients, despite the increasing amount of evidence in the scientific literature.
 
It should be recognised that surfaces can act as a microbial reservoir,(1–3) and that the level of microbial contamination increases with infected patients who shed large amount of microorganisms in their proximal environment. With this in mind, high-touch surfaces, such as those proximal to patients (for example, bedside cabinet, chair, bed handles, call button), but also door handles and push plates, have been particularly well examined for their level of microbial contamination. Microbial pathogens can also survive for a long period of time on surfaces despite cleaning/disinfection regimens; this is particularly the case for C. difficile spores.(4) It has been proposed that the acceptable level of surface contamination in healthcare facilities should be as low as <5CFU/cm2 for total aerobic colony count and <1CFU/cm2 for ‘indicator’ microorganisms such as C. difficile spores, Staphylococcus aureus, multiply resistant Gram-negative bacilli and vancomycin-resistant enterococci (VRE).(1) Although these figures are gaining support among infection control professionals, the challenge is how to achieve such targets considering the diversity of cleaning regimens and how well cleaning is performed.(5) Bacterial contamination of surfaces in healthcare settings have been reported to range between <5CFU/cm2 to hundreds of CFUs/cm2.(2) 
 
Reducing surface contamination
There are different methods to reduce microbial contamination on surfaces and one of the most widely approach is the use of detergent or disinfectant in combination with wipes,(6) or mops for cleaning floors. A more radical approach makes use of fumigation with, for example, vaporised hydrogen peroxide. This approach has been mainly used (and should probably be reserved) for ‘deep cleaning’ in combination with a pre-cleaning stage with a detergent/wipe combination. Such technologies have been used successfully to control outbreaks of pathogenic microorganisms (for example, Norovirus, multiply drug resistant bacteria and C. difficile outbreaks). There are now other devices available or on trial, such as UV-based systems for surface decontamination, but it might be too early to provide an assessment as to their efficacy in situ
 
Problems with detergent/disinfectant
The main issue with the use of detergent or disinfectant in combination with wiping or mopping is their application in practice.(6) Although regular cleaning of open surfaces is paramount, there is an important diversity in the standard of cleaning and in the regimen in place.(5) For example, one US study involving 23 hospitals described the overall inadequacy or limitations of terminal cleaning performed following a patient discharge.(7) There may be several reasons for such poor cleaning performance, including the lack of motivation, supervision and training of cleaning staff, the reluctance of cleaning staff and their supervisors to adopt a new technique and/or a new cleaning/disinfection regimen. In addition, some products labelled as antimicrobial/bactericidal/sporicidal used in healthcare facilities might not necessarily perform adequately.(8) With these limitations in mind, it is not surprising that bacterial pathogens are found on healthcare surfaces, sometimes in high numbers. It is also clear that there is a scope to introduce other measures to decrease microbial bioburden on healthcare surfaces in addition to regular cleaning/disinfection. 
 
Copper as an antimicrobial surface
Antimicrobial surfaces may offer an additional control measure of microbial pathogens.(2,3,9) The main advantage of antimicrobial surfaces is that, used in the appropriate conditions, they should produce a sustained microbicidal or microbistatic activity. Copper and its alloys is a common microbicide used in antimicrobial surfaces,(9,10) and since 2008, copper surfaces having an antimicrobial activity have been granted recognition from the US Environmental Protection Agency. The number of publications on copper/copper alloys’ antimicrobial efficacy, and interactions with micro-organisms has increased significantly over the past ten years, reflecting the recognition of copper as an antimicrobial and substantial increased research investments. Copper and its alloys have been reported to be microbicidal against a number of pathogens (such as MRSA, Klebsiella pneumonia, Pseudomonas aeruginosa, Acinetobacter baumannii, Mycobacterium tuberculosis and the yeast Candida albicans) although killing rate is slow, taking hours or sometimes days. It has also been claimed that copper alloys might have some slow sporicidal activity. Recent evidence has shown that bacterial killing might occur at a much faster rate, within minutes, in the presence of moisture.(9,11)
 
The continuous release of copper ions from surfaces is essential to maintain high antimicrobial activity of the surface.(12) A bactericidal activity within 24h can be easily demonstrated in the presence of moisture/water, which facilitates the diffusion of metallic ions. In reality, the relative humidity (RH) in UK hospitals may vary between 30% and 60%.(11) In these conditions of low–medium RH, the diffusion of the microbicide might not readily occur and, as a consequence, the microbicidal activity of the surface will be decreased severely. This is the main criticism of the standard efficacy test (JIS Z 2801/ISO 20743) used by manufacturers to demonstrate activity of their antimicrobial surface. This test relies on 100% humidity to measure antimicrobial activity and, as such, should be used only during product development to demonstrate some activity of the product, but not to make a claim of antimicrobial activity. 
 
There have been a number of in situ studies investigating the efficacy of copper surfaces in controlling microbial bioburden on surfaces.(3) A recent US study in intensive care units of three hospitals demonstrated a significant reduction of incident HAI and/or patient colonisation with MRSA or VRE following the introduction of copper alloy high-touch surfaces.(13) One possible limitation for the use of a copper surface is the possible incompatibilities of commonly used cleaning and disinfectants used in healthcare settings. Incompatible chemistries might lead to the bioburden  being fixed onto surfaces, thereby decreasing the efficacy of cleaning and disinfection regimens.
 
Bactericidal efficacy
The bactericidal efficacy of copper is not surprising as a number of copper-bacterial interactions mechanisms have been described(14) including the inhibition of bacterial respiration, membrane damage and the production of free radicals highly damaging for bacterial cell components.(12) Copper/copper alloys have also been shown to be able to degrade bacterial DNA, which has the potential to negate against the spread of genetic resistance determinants. Despite the microbicidal efficacy of copper, genetic evidence of bacterial resistance to copper is emerging, although there has been no report of bacteria becoming resistant to copper where copper alloys surfaces have been used. 
 
Copper has been used for other applications in the healthcare environments with more or less success. The control of pathogenic water-borne bacteria by using copper in water distribution systems has been well reported.(12) The effectiveness of copper impregnated textile to control microbial pathogens remains to be demonstrated.(13)
 
The cost of fitting copper alloy surfaces in healthcare settings needs to be justified. The reduction of the microbial surface bioburden below the 5CFU/cm2 threshold for total aerobic colony count and below 1CFU/cm2 for ‘indicator’ microorganisms would be an appropriate performance indicator but it needs to be followed with a decrease in infection and patient decolonisation. 
 
Conclusions
With this in mind, the introduction of copper alloys to decrease microbial bioburden on surfaces in healthcare settings in addition to regular cleaning/disinfection is encouraging based the results of recent in situ studies. Finally, the copper industry needs to reflect on incompatible chemistries with copper/copper alloy surfaces. To respond to this issue, the use of a ‘copper-compatible’ logo for cleaning and biocidal products should be encouraged.
 
References
  1. Dancer SJ. How do we assess hospital cleaning? A proposal for microbiological standards for surface hygiene in hospitals. J Hosp Infect 2004;56:10–5.
  2. Page K, Wilson M, Parklin IP. Antimicrobial surfaces and their potential in reducing the role of the inanimate environment in the incidence of hospital-acquired infections. J Mat Chem 2009;19:3819–31.
  3. Weber DJ, Rutala WA. Self-disinfecting surfaces: Review of current methodologies and future prospects. Am J Infect Control 2013;41:S31–5.
  4. Maillard J-Y. Innate resistance to sporicides and potential failure to decontaminate. J Hosp Infect 2011;77: 204–9. 
  5. Dancer SJ. The role of environmental cleaning in the control of hospital-acquired infection. J Hosp Infect 2009;73:378–85.
  6. Sattar SA, Maillard J-Y. The crucial role of wiping in decontamination of high-touch environmental surfaces: review of current status and directions for the future. Am J Infect Control 2013;41:S97–S104.
  7. Carling PC, Parry MF, Von Beheren SM. Identifying opportunities to enhance environmental cleaning in 23 acute care hospitals. Infect Control Hosp Epidemiol 2008;29:1–7.
  8. Siani H, Cooper CJ, Maillard J-Y. Efficacy of ‘sporicidal’ wipes against Clostridium difficile. Am J Infect Control 2011;39:212–8.
  9. Grass G, Rensing C, Solioz M. Metallic copper as an antimicrobial surface. Appl Environ Microbiol 2011;77:1541–7.
  10. O’Gorman J, Humphreys H. Application of copper to prevent and control infection. Where are we now? J Hosp Infect 2012;81:217–23.
  11. Ojeil M et al. Evaluation of antimicrobial surface activity with a newly developed in vitro efficacy test reflective of conditions found in UK hospitals, J Hosp Infect 2013;85:274–281.
  12. Warnes SL, Caves V, Keevil CW. Mechanism of copper surface toxicity in Escherichia coli O157:H7 and Salmonella involves immediate membrane depolarization followed by slower rate of DNA destruction which differs from that observed for Gram-positive bacteria. Environ Microbiol 2012;14:1730–43. 
  13. Salgado CD et al. Copper surfaces reduce the rate of healthcare-acquired infections in the intensive care unit. Infect Control Hosp Epidemiol 2013;34:479–86.
  14. Lemire JA, Harrison JJ, Turner RJ. Antimicrobial activity of metals: mechanisms, molecular targets and applications. Nat Rev Microbiol 2013; 11:371–84.
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