Antimicrobial Copper changing the course of Medicine History on the 21st century.

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1 Antimicrobial Copper changing the course of Medicine History on the 21st century. Panos A. Efstathiou M.D., D.Sc. Orthopedic Surgeon Secretary General of Hellenic College of Orthopedic Surgeon On the 19th century Louis Pasteur has developed the germ theory of disease and its affect on the human body. On the 20th century Alexander Fleming 1 discovered an infection-fighting agent, widely known as penicillin. They were both major discoveries that would change the course of Medicine History. On the 21st century Antimicrobial Copper Alloys has proved to be the most sufficient, accurate and low cost antibacterial agents, reducing significantly the microbial flora on touch surfaces. Copper use from different civilizations in the course of time Copper and its beneficial actions in humans are already known since the early years. The name origins from the Latin name curpus indicating the name of the island of Cyprus which was the main source of mineral cooper in antiquity 2. The use of containers of drinking water from copper and the installation of metal shaving in the wounds for disinfection is reported in Egypt 3. The Aztecs used cooper to treat various skin diseases 2. Hippocrates, the father of Medicine ( B.C.E) recommended the use of copper for leg ulcers related to varicose veins 2. In France during the cholera epidemic of 1850 A.C.E, it was observed that workers in copper mines were not affected by the disease 3. In 1970, antimicrobial copper activity has been observed by the American College of Chest Physicians, and compiled the first publication on Antibacterial Action of Copper in Respiratory Therapy Apparatus. The oligodynamic effects of introducing copper into large reservoir nebulizers used in respiratory therapy has resulted in the nebulizer contents remaining in a sterile state 4. In 1983, a hospital study showing cooper s effectiveness in lowering the E.Coli count on doorknobs was published in the United States of America 5. During the next decades the major concern within the medical community is Health Care Associated Infections (HCAI), or nosocomial infections. These infections affect patients in a hospital or other health care facility, and are not present or incubating at the time of admission. They also include infections acquired by patients in the hospital or facility but appearing after discharge, and occupational infections among staff 6. According to fact sheet of WHO (2011) most countries lack surveillance systems for health care-associated infections 7. Those that do have systems often struggle with the complexity and lack of standardized criteria for diagnosing the infections. 1

2 While this makes it difficult to gather reliable global information on health care associated infections, results from studies clearly indicate that each year, hundreds of millions of patients are affected by them around the world 7. Health care-associated infections usually only receive public attention when there are epidemics. Although often hidden from public attention, the very real endemic, on-going problem is one that no institution or country can claim to have solved, despite many efforts. Recently the E. Coli-0104:H4 outbreak in Germany, which is known (never before seen) as a country with strong and well organised health system, points out the difficulty of discovering the source of epidemic 8. Prevalence of health care-associated infection in high income countries, (WHO Report on the Burden of Endemic Health Care-Associated Infection World wide2011 The European Centre for Disease Prevention and Control reports an average prevalence of HCAI is 7.1% in European Countries. The Centre estimates that patients are affected by approximately episodes of health careassociated infection every year in Europe 9. The estimated incidence rate in the United States of America (USA) was 4.5% in 2002, corresponding to 9.3 infections per patient-days and 1.7 million affected patients 10. According to a recent European multicenter study, the proportion of infected patients in intensive care units can be as high as 51%; most of these are health care-associated 11. Approximately 30% of patients in ICUs are affected by at least one episode of health care associated infection. The longer patients stay in an ICU, the more at risk they become of acquiring an infection. On average, the cumulative incidence of infection in adult-high risk patients is 17.0 episodes per 1000 patient-days 11. 2

3 The measures taken for eliminating-reducing microbes transportation through frequently touch surfaces started the last decade with the Clean Care is Safer Care campaign (WHO) 12. In many healthcare systems, specific guideline was given to healthcare professionals, in order to activate their awareness and eliminate nosocomial infections. In 2001 in the UK, the epic Project: Developing National Evidence-based Guidelines for Preventing Healthcare associated Infections among the other good practices, points out touch surfaces as one of the major components of microbes concentration and transfer 13. Laboratory studies In 1995 first laboratory researches from the University of Southampton showed that the copper cast alloys was able to control E.-Coli 0157 in cross contamination food procedures 14. The results of the above research showed that although stainless steel surfaces may appear to be clean, bacteria can survive on these surfaces for considerable periods of time. In comparison, survival on many copper alloys is limited to just a few hours or even minutes. Due to the intrinsic characteristics of copper alloys, i.e. homogenous and solid, superior lifetime antimicrobial efficacy, wear resistance, and durability, they could be utilized in facilities where bacterial contamination cannot be tolerated 14. On the following years in many laboratory researches, germicide activity of copper alloys has been identified 15, 16and 17. Clinical Trials First clinical trial results in Kitasato University Hospital in Japan, Selly Oak Hospital in the UK and Calama Hospital in Chile, showed that surface contamination was greatest on surfaces near the patient. The second results showed 90% reductions in contamination on copper surfaces compared to controls. Neither MRSA nor VRE were found on any copper 18, 19, and 20 surface sampled In an outpatient study, not only was the reduction in Microbial Burden confirmed but a halo effect was observed-reduced contamination in the vicinity of the copper surfaces. The copper surfaces were also shown to reduce the risk of exposure to environmental microbes by 17% 7. Other clinical trials come to confirm the significant reduction in contamination on the copper compared to the control components. (Asklepios Hospital, Hamburg, Germany) 21 In addition first results show higher levels of contamination on the non-copper items and presence of faecal and urinary bacteria (Staphylococcus aureus, E.Coli and Candida albicans) only on stainless steel, plastic and chromium components. On copper and copper alloy surfaces, only Gram positive bacilli and cocci and normal environmental and skin flora were found. (Helsinki University: Department of Public Health, Finland.) 22 3

4 Antimicrobial Copper Alloys Registration During the 2008, in the US, laboratory results were independently verified by the Environmental Protection Agency (EPA), leading to EPA having the only public health registration for a touch surface material. The innovation was that for the first time a solid material has been registered and approved for its germicide efficacy, suitable for public health usage. Researches took place in 3 US hospitals, Memorial Sloan-Kettering Cancer Center, NY, Ralph H. Johnson Veterans Administration Medical Center, NY and Medical University of South Carolina, Charleston, SC. 23 The trials are being executed in three stages. The first stage established the baseline microbial burden on frequently-touched objects in ICU rooms. The second stage, which has just been completed, compared the microbial burden on Antimicrobial Copper surfaces with the microbes found on non copper equivalent surfaces. The third stage will assess the incidence of hospital-acquired infections in ICU rooms with and without Antimicrobial Copper Objects. 23 The connection between contamination on frequently-touched surfaces and patient acquisition of infections evaluated in order to determine, that Antimicrobial Copper has a clinical benefit to patients. Findings from the first stage of the program show that the most heavily contaminated objects are those in closest proximity to the patients: bed rails, call buttons and chairs were found to the highest levels of Staphylococcus aureus, methicillinresistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). These pathogens can survive for extended periods of time on such objects, which may act as reservoirs for the bacteria. The average microbial burden on objects was nearly 17,000 Colony forming Units per 100 square centimetres. 23 Similar researches from the WHO 7 and the Medical University of South Carolina show that objects located close to the patient are most heavily contaminated. These objects are mainly bed rails and call buttons 24. In general Antimicrobial Copper Alloys are effective against bacteria viruses, fungi and moulds, including Staphylococcus aureus (MRSA), Influenza A (H1N1), Enterobacter aerogenes, Pseudomonas aeruginosa, E.Coli O157:H7 and Vancomycin-resistant Enterococcus faecalis. According to a research by Hospital Attikon, Medical School of Athens, Greece, scientists came to the conclusion that Copper alloys reduced the number of viable carbapenemaseproducing bacteria significantly in 3 hours and produced a bactericidal effect in 5 hours. The pure Cu99% was more effective than cooper alloy Cu64% -Zn36%. These data suggest that the use of copper as surface material in the hospital could aid in diminishing the environmental reservoir of Methicillin Drug Resistant Gram-negatives 25. Further Activities Up until now, all researches and applications appear to have great potential regarding the effectiveness of Antimicrobial Copper Alloys against bacteria and other pathogenic organisms. 4

5 There are several theories for the mechanism by which copper kills bacteria, including: Causing leakage of potassium or glutamate through the outer membrane of bacteria Disturbing osmotic balance Binding to proteins that do not require copper Causing oxidative stress by generating hydrogen peroxide. The use of a Copper Alloy surface is a supplement to, and not a substitute for, standard infection control practices; users must continue to follow all current infection control practices, including those practices related to cleaning and disinfection of environmental surfaces. The Copper Alloy surface material has been shown to reduce microbial contamination, but it does not necessarily prevent cross contamination. Indicative objects or touch surfaces that can be replaced by objects made of Antimicrobial Copper Alloys. (Antimicrobial Copper - A Global Overview Tokuda Hospital, Sofia -1April 2011) 30 Further to the research s results, manufactures have shown great interest in producing a variety of objects that are used frequently in nosocomial areas(e.g. ICU etc.), using Antimicrobial Copper Alloys. However, the implementation outside hospital areas where microbial flora is at high levels, with increased risk of contamination worries public health planners. In Laval France, the new Center Inter-Generational Multi Accueil (CIGMA) 26, a nursery for 35 infants and a 60 bed care home for dependent elderly people copperized all handrails and doorhandles. In Tokyo, Japan the Mejiro Daycare Center for Children copperized all touch surfaces 27. In Athens Greece a big private elementary school with 2500 students changed all the handrails, doorhandles and touch surfaces of doors with cooper alloy Cu64% -Zn36%. 5

6 The first results showed % less contamination on them than on standard non copper surfaces 28. Antimicrobial Copper objects costs is a combination of raw material cost and manufacturing cost. In general the total cost is not high 31. Due to the antimicrobial efficacy, cost of object replacement and implementation, cannot be compared to the cost of objects made by other type of materials (stainless steel, plastic etc.) Microbial flora decrease results to antibiotics usage decrease, which leads to the reduction of patient s hospitalization. Cooper Alloys antimicrobial activity when compared to amnoglycocides against mutidrag resistance bacteria (Escherichia coli, Klebsiella spp, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus faecium) isolated from blood culture patients with signs of infection of fever appearing any time after 8 days of admission into ICU, showed that the inhibition zone of antimicrobial copper where equal to those of Aminoglycosides (2011). The above research took place at Hospital ARETAIEIO Medical School of Athens, Greece 29. Acknowledgements I thank, Prof.E. Kouskouni M.D.,Ph.D., K. Karageorgou M.D.,D.Sc, A. Vilaeti M.D., Z. Manolidou R.N.,M.Sc., M. Tseroni R.N.,M.Sc., I. Agrafa for expert advices in the study. In times where multi - resistant to antibiotics bacteria are increased, and the possibility of the end of antibiotics is near, Antimicrobial Copper Era has come to light. Corresponding author: Mailing address: Artis 17, Amarousio P.C.15125,GREECE Phone: , Fax: panosefstathiou@usa.net 6

7 BIBLIOGRAFY 1. Fleming Alexander, Biography- Wikipedia. The free encyclopedia. 2. Efstathiou P., Antimicrobial Copper a revolution in the field of prevention ESNE NATIONAL CONGRESS, CHIOS- GREECE, May Efstathiou P., Antimicrobial action of Copper, 2 nd Copper Day, H.I.C.D.- Thessaloniki -Greece, 5 Οct Robert S. Deane, M.B.B. Ch., Ernest L. Mills, M.D. and Aubert J. Hamel Antimicrobial Action of Cooper in Respiratory Therapy Apparatus, Chest, Vol. 58, No 4, Oct Kuhn P.J. Doorknobs: A source of Nosocomial infection? Diagnostic Medicine, Nov/Dec Poultsides LA., Liaropoulos LL, and Malizos KN.: The Socioeconomic Impact of Musculoskeletal Infections - Journal of Borne & Joint Surg. Am. 2010; 92: WHO, Health Care Associated Infections Fact Sheet, ECDC, Rapid Risk Assessment outbreak of Shiga toxin-producing. E.Coli (stec)in Germany 27May European Centre for Disease Prevention and Control (ECDC) Annual Epidemiological report Public Health Reports Estimating Health Care-Associated Infections and Deaths in U.S. Hospital s, 2002 Research Articles 160, March April 2007 / Volume Hirsch B.E.,Schmidt M.G., et all, Copper Surfaces Reduce Microbial Burden in Out-Patients Infections Disease Practice.poster at the ICAAC Boston, MA Sept 13, WHO, Report on the Burden of Endemic Health Care-Associated Infection Worldwide Clean Care is Safer Care, EPIC Guidelines for Preventing Health Care Associated Infections, Journal of Hospital Infection (2001) 47 (Supplement):S1doi: /jhin Noyce J.O., H.Michels, C.W. Keevil Use of Copper Cast Alloys to Control Escherichia Coli O157 Cross- Contamination during Food Processing, Applied and Environmental Microbiology, June 2006, p NoyceJ.O. H.Michels and C.W.Keevil1. Inactivation of Influenza A Virus on Copper versus Stainless Steel Surfaces. Applied and Environmental Microbiology, Apr.2007, p , Vol.73, No Weavera L., H.T. Michelsb, C.W. Keevila. Survival of Clostridium difficile on copper and steel: Futuristic options for hospital hygiene. J Hosp Infect (2008), doi: /j.jhin Wheeldon L.J., T. Worthington1, P.A. Lambert, A.C. Hilton,.J. Lowden and T.S.J. Elliot.. Antimicrobial efficacy of copper surfaces against spores and vegetative cells of Clostridium difficile: the germination theory. Journal of Antimicrobial Chemotherapy (2008) 62, , doi: /jac/dkn219, 10 June Sasahara T, Niiyama N and Ueno M. Use of Copper and its Alloys to Reduce Bacterial Contamination in Hospitals (Invited lecture), Journal of the JRICu Vol.46 No.1 (2007). 19. Casey Al et al. Role of copper in reducing hospital environment 7

8 contamination, J Hosp. Infect (2009), doi: /j.jhin Prado V, Duran C, Crestto M et al. Effectiveness of copper contact surfaces in reducing the microbial burden (MB) in the intensive care unit (ICU) of Hospital del Cobre, Calama, Chile. Poster , 14th.International Conference on Infectious Diseases, Miami, March 11, Reducing the risk of HCAI AskLepios Hospital, Homburg, and Germany. CDA196. p6, Reducing the risk of HCAI Helsinki University, Finland. CDA196. P6, Michels HT and Anderson DG. Antimicrobial regulatory efficacy testing of solid copper alloy surfaces in the USA,. pp , Metal Ions in Biology and Medicine: Vol Salgado CD, Morgan A, Sepkowitz KA et al. 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. Poster 183, 5th Decennial International Conference on Healthcare- Associated Infections, Atlanta, March 19, Armaganidis A., et al. Evaluation of copper-containing items for reducing environmental contamination with multidrug-resistant bacteria in a University Hospital ICU-2nd Department of Critical Care Medicine, Athens University School of Medicine, University General Hospital ATTIKO. 26. Pioneering Eco Care Home Specifies Antimicrobial Copper Laval, France- CDA, PR799-9Feb Antimicrobial Copper to Protect Children against Infections-Tokyo, Japan-CDA-PR797-Jan Efstathiou P.,et al. Elementary schools in Athens -Application of Antimicrobial Copper. XVI Congreso Nacional y V Internacional de la Sociedad Española de Medicina Preventiva Salud Publica e Higiene, Maspalomas, Gran Canaria 25/27 May Kouskouni E., I. Tsouma, I. Patikas, K. Karageorgou, Z. Manolidou, M. Tseroni, M. Agrafa, P.Efstathiou (ATHENS, Gr) Antimicrobial Activity of Copper Alloys compared to Aminoglycosides against multidrug resistant bacteria ECCMID-ICC Abst. Nr Vessey Angela, Antimicrobial Copper - A Global Overview, European Antimicrobial Copper Programme Tokuda Hospital, Sofia,Bulgaria - 1April Peter Sharpe -Business Case for AM Copper Alloys (presentation) February 11,