What is Copper & Silver Ionisation?

Copper and silver ionisation is a relatively new modality for the control of Legionella, Pseudomonas and other pathogens in water systems. The use of copper and silver ionisation was first recorded in the USA in 1990 (Lin et al., 2011), although it was pioneered by NASA in the 1960s (Albright et al., 1967). The ProEconomy copper and silver ionisation system is known by its trade name of Orca.
  • How does copper and silver ionisation work?
    Copper and silver ionisation involves the generation of copper and silver ions in water by water flowing through a turbine of a flow sensor. This sends a signal to the control unit, which then passes a low DC current between two copper and two silver electrodes located in an electrode chamber. The current causes ionisation, i.e. the release of copper and silver ions into the flowing water. Being electrically charged the copper and silver ions seek opposite polarity and find this in the negatively charged sites on cell wall of bacteria, such as Legionella, Pseudomonas and E.coli. The ions distort and weaken the cell wall and then damage the cell by binding at specific sites to DNA, RNA, cellular protein and respiratory enzymes denying all life support systems to the cell, causing death.
  • Clinical Infectious Diseases
    Liu Z., Stout, J.E., Boldin, M., Rugh, J., Diven, W.F., and Yu, V.L., (1998), Intermittent use of copper-silver ionization for Legionella control in water distribution systems: a potential option in buildings housing individuals at low risk of infection. Clin Infect Dis 26: 138–140. Of three buildings colonised with Legionella, two were fitted with copper-silver ionisation systems, with the third building left as a control. Positive tests for Legionella in the first building dropped to zero within four weeks, and to zero within the second building within twelve weeks. Recolonisation didn’t occur in the first test building for 6-12 weeks after the CSI system had been switched off, and in the second building for 8-12 weeks. The control building remained positive throughout.
  • Infection Control Hospital Epidemiology
    Stout, J.E. & Yu, V.L., (2003), Experiences of the first 16 hospitals using copper-silver ionisation for Legionella control: implications for the evaluation of other disinfection modalities, Infect Control Hosp Epidemiol 24(8): 563-8. The first 16 hospitals in the USA to install copper-silver ionisation were surveyed twice, in 1995 with a follow-up in 2000. All had reported cases of hospital-acquired legionnaires’ disease prior to installation, and 75% had attempted other control methods. In 1995 50% of the hospitals reported 0% positivity, and 43% still reported 0% in 2000. Moreover, no cases of hospital-acquired legionnaires’ disease had occurred in any hospital since 1995.
  • American Journal of Infection Control
    Miuetzner, S. et al, (1997), Efficacy of thermal treatment and copper-silver ionization for controlling Legionella pneumophila in high-volume hot water plumbing systems in hospitals, American Journal of Infection Control, Vol. 25, No. 6, p. 452-457. Hot water (>60 oC) was flushed through fixtures for 10 minutes. Copper-silver ionisation units were installed upstream from hot water tanks. It was found that four heat-flush treatments failed to provide long-term control of Legionella, whereas ionisation reduced the recovery rate of Legionella from 108 outlets from 72% to 2% within 1 month and maintained effective control for at least 22 months.
  • Clinical Infectious Diseases
    Mòdol, J. et al, (2007), Hospital-Acquired Legionnaires Disease in a University Hospital: Impact of the Copper-Silver Ionization System, Clinical Infectious Diseases, Vol. 44, No. 2, p. 263-265 Hospital-acquired legionnaires’ disease had been endemic in a Barcelona hospital for many years, with various control methods tried and failed. After installation of a copper-silver ionisation system, Legionella colonisation decreased significantly and the incidence of hospital-acquired legionnaires’ disease decreased dramatically from 2.45 to 0.18 cases per 1000 patient discharges.
  • The Journal of Infectious Diseases
    Liu, Z. et al (1994), Controlled Evaluation of Copper-Silver Ionization in Eradicating Legionella pneumophila from a Hospital Water Distribution System, The Journal of Infectious Diseases, Vol. 169, No. 4, pp. 919-922 A copper-silver ionisation system was effective in eradicating Legionella from the hot water distribution system of a hospital building were identified as easy installation and maintenance, non-toxic by products well below EPA standards, stable and easily measured residual that was unaffected by high temperatures, and a margin of safety if the system stopped working as recolonisation by Legionella required more than 2 months.

Effect on Legionella

Legionella

Legionella pneumophila is a disease-causing microorganism well known for causing Legionellosis (Legionnaires’ disease and Pontiac fever). It is particularly dangerous for hospital patients that have a compromised immune system. L. pneumophila can survive in water temperatures from 0°C to 63°C (Nguyen et al. 1991), with an optimum growth range between 38°C and 46°C. It thrives and multiples rapidly in untreated or ineffectively treated water, and finds its way into a human system when it is inhaled as aerosols emitted by showers, taps cooling towers and fountains.
Cases of Legionnaires’ disease have quadrupled between 2000 and 2014 in the USA and are still on the rise (Figure 1), hence the importance of not only being aware of it but also having a robust system in place to control Legionella. More cases occur in the summer than in other times of the year because Legionella thrives in warmer water temperatures commonly seen in summer months.
The number of reported cases of Legionnaires’ disease in England and Wales between 1 January and 31 December 2016 was 496 (PHE 2016).
Temperature control has been the traditionally applied method for the control of Legionella in water distribution systems. This entails obtaining 50°C and above after running any hot water tap for 1 minute and 20°C and below after running any cold water tap for 2 minutes (HTM04-01 2016). However, only 13% of the results of tests carried out by the UK Building Services Research and Information Association (BSRIA) in 1996 using temperature control were free of Legionella.
Intermittent shock injection of chlorine into the water, to achieve 20 to 50 mg/L of chlorine throughout the system, can be effective in the short term. Bacterial re-colonisation often occurs, however, after the disinfectant levels decrease (Lin et al. 1998). Unfortunately, protozoan cysts of species such as amoeba that harbour Legionella survive free chlorine levels of 50mg/L (Kilvington & Price 1990). Chlorine also reacts with organic materials and accelerates the production of trihalomethanes (THMs), carcinogens which are the only regulated disinfection by-product in the UK. It is required by law that the sum of four THMs does not exceed 100 μg/L (Bougeard et al. 2010).
Chlorine Dioxide: The UK Drinking Water Inspectorate have prescribed that a level of 0.5mg/L of chlorine dioxide should not be exceeded. Studies on models indicate that concentrations of between 0.3 and 0.5mg/L can control Legionella, but maintaining this level in hospital water systems difficult as the chlorine dioxide will decompose to chlorite and chlorate, and decays over distance and at elevated temperatures (Sidari et al. 2004).
Chlorite and chlorate are not only toxic but also less active than chlorine dioxide against Legionella, and are inactive against protozoa and biofilm.
There are health hazards to humans and environmental concerns associated with chlorine dioxide, and to this effect the UK Health Protection Agency has produced a guide on how to deal with chlorine dioxide incidents.
Copper and silver ionisation is a relatively new modality for the control of Legionella, Pseudomonas and other pathogens in water systems. The use of copper and silver ionisation was first recorded in the USA in 1990 (Lin et al. 2011), although it was pioneered by NASA in the 1960s (Albright et al. 1967). The ProEconomy copper and silver ionisation system is known by its trade name Orca.

Effective Legionella control using copper and silver ionisation

ProEconomy have been analysing water since 1993 and have built up a substantial databank. Their results show that when silver ion concentrations at outlets are maintained between 0.02 and 0.08 mg/L and copper ion concentrations between 0.2 and 0.4 mg/L, Legionella contamination is avoided.
Much more research proving the efficacy of the Orca system is available and Dr Birgitta Bedford, a founder member of ProEconomy and who has a PhD in Legionella control from Cranfield University, has compiled a list of references of over 40 scientific papers that support copper and silver water ionisation. Some of them are listed at the end of this Fact Sheet.
Data sets from hospitals using the Orca system demonstrate excellent control of Legionella and an example is given in Figure 2 (Barbosa & Thompson 2016). The graph records results for a large hospital on the outskirts of London and show 100% control for the last 15 months.
Fig 2. Number of samples tested, Legionella positives and percent positives, 2011-2015.

Further evidence from published papers

Conclusions from a study carried out by the University of Pittsburgh, USA (Lin et al. 1998) stated that for Legionella control, copper and silver ionisation outperformed conventional treatment techniques such as hyperchlorination, chlorine dioxide, superheating and flush and UV light systems due to the following advantages:
  1. Installation and maintenance are easy.
  2. Efficacy is not affected by high water temperatures, unlike chlorine dioxide and UV light systems.
  3. Residual disinfectant protection occurs throughout the system, unlike UV light.
  4. Recolonisation is delayed as the copper and silver ions kill rather than suppress Legionella bacteria.
A study into the long-term (5 to 11 years) efficacy of copper and silver ionisation for Legionella control in 16 hospital water systems concluded that it reduced the incidence of hospital-acquired Legionnaires’ disease, and furthermore was the only modality to have fulfilled all evaluation criteria that the USA recommend be applied to Legionella control approaches (Stout and Yu 2003).

Residual Effect of Copper and Silver

A 1994 study on copper and silver ionisation of a hospital water distribution system found complete inactivation of Legionella pneumophila and L. bozemanii when exposed to 0.4 mg/L copper and 0.04 mg/L silver, and continued residual inactivation two months after the copper and silver water ionisation unit was switched off (Liu et al. 1994).
Another study by Liu et al. (1998) evaluated copper-silver ionisation systems installed onto the hot water recirculation lines of two hospital buildings colonised with L. pneumophila, compared with a control also colonised with L. pneumophila. Four weeks after activation of the system, distal site positivity for Legionella in the first test building dropped to zero. After operating for 16 weeks the system was disconnected and installed onto the second test building. Twelve weeks of disinfection reduced the distal site positivity for Legionella in the second test building to zero. Legionella recolonisation did not occur in the first test building for 6-12 weeks and in the second test building for 8-12 weeks after inactivation of the system. A significantly higher copper concentration was found in the biofilm taken from a sampling device than in than that from water, and this was taken to be the reason the copper-silver ionisation system had a residual effect and prevented early recolonisation.

Copper and silver ionisation complements temperature

Results of tests carried out during a research project completed in 1996 by BSRIA in the UK showed that copper and silver ionisation was effective against Legionella bacteria in both cold and hot water systems with water temperatures as low as 35°C. Therefore, when temperature is lower than the recommended by the authorities, having copper and silver as a secondary Legionella control modality will ensure the water system is still protected.

Effect on Pseudomonas

Pseudomonas aeruginosa

Pseudomonas aeruginosa is a common biofilm-forming Gram-negative bacterium, often found in soil and ground water, which is implicated in diseases, especially of the lungs. It can, however, cause a wide range of infections in almost any organ or tissue, particularly in patients with a weakened immune system, such as cancer patients, newborns and those with severe burns, diabetes mellitus or cystic fibrosis (DH, Estates & Facilities, 2013). It is an opportunistic pathogen that rarely affects healthy individuals.
Pseudomonas is known to flourish particularly well where it has access to a higher level of oxygen and the temperature is between 11˚C - 44˚C, although some are able to multiply at just 4˚C.
As a direct result of the deaths of four neonates in Northern Ireland in 2012, an addendum to Health Technical Memorandum 01-04 (DH, England, 2013) was produced to advise National Health Service managers on how to deal with the presence of P. aeruginosa in augmented care units. The guidance was based on current expert opinion and limited scientific evidence (Walker and Moore, 2015), and was concerned with controlling and/or minimising the risk of mortality due to P. aeruginosa associated with water outlets.
P. aeruginosa is more difficult to control in water systems than Legionella. This is because Pseudomonas is a successful organism in terms of biofilm formation and colonisation, and evidence suggests that the presence of microorganisms within a biofilm substantially increases the problems associated with decontamination of those water systems. Unlike Legionella, Pseudomonas can infect patients directly via hospital workers touching a wound, for example, and by both staff and patients touching contaminated surfaces. P. aeruginosa is also commonly associated with antibiotic resistance.
An important source of P. aeruginosa contamination is biofilms (Bedford et al. 2012). A study by Quick et al. (2015) showed that plumbing components such as flow straighteners, shower rosettes, flexible hoses, solenoid valves and thermostatic mixer valves (TMVs) are particularly at risk of biofilm formation due to factors including surface areas, complex designs and inadequate pasteurisation. Their study confirmed the presence of P. aeruginosa in scrapings from a TMV from a shower room, and the species covered 95% of the base reference genome used in the study. Although most bacteria will remain fixed within biofilms, some will become detached resulting in free-floating or planktonic forms that can contaminate the water (DH, Estates & Facilities, 2013).

Copper and Silver Ionisation

Copper and silver ionisation is a relatively new modality for the control of Legionella, Pseudomonas and other pathogens in water systems. The use of copper and silver ionisation was first recorded in the USA in 1990 (Lin et al. 2011), although it was pioneered by NASA in the 1960s (Albright et al. 1967). The ProEconomy copper and silver ionisation system is known by its trade name Orca.
Copper and silver ionisation involves the generation of copper and silver ions in water by water flowing through a turbine of a flow sensor. This sends a signal to the control unit, which then passes a low DC current between two copper and two silver electrodes located in an electrode chamber. The current causes ionisation, i.e. the release of copper and silver ions into the flowing water. Being electrically charged the copper and silver ions seek opposite polarity and find this in the negatively charged sites on cell wall of bacteria, such as Legionella, Pseudomonas and E.coli. The ions distort and weaken the cell wall and then damage the cell by binding at specific sites to DNA, RNA, cellular protein and respiratory enzymes denying all life support systems to the cell, causing death.

Controlling P. aeruginosa with Copper and Silver Ionisation

A study by Huang et al. (2008) showed that all copper ion concentrations tested, at the concentration applied to Legionella control, in their study (0.1–0.8 mg/L) achieved more than 99.9% reduction of P. aeruginosa which appears to be more susceptible to copper ions than S. maltophilia and A. baumannii. Silver ions concentration of 0.08 mg/L achieved more than 99.9% reduction of P. aeruginosa, S. maltophilia and A. baumannii, after 6, 12 and 96 h, respectively. A combination of copper and silver ions exhibited a synergistic effect against P. aeruginosa and A. baumannii, while the combination exhibited an antagonistic effect against S. maltophilia. They concluded that ionization may have a potential to eradicate P. aeruginosa, S. maltophilia and A. baumannii from hospital water systems.
ProEconomy has compiled data from seven UK hospitals using the copper and silver ionisation Orca system for pathogens control in water systems and table 1 shows the summary data. It can be observed that from a total of 6037 samples obtained from all hospitals over a five-year period, only 545 samples (9%) were contaminated with P. Aeruginosa.

How to reduce Pseudomonas contamination

Taps and sinks cleaning: Taps should be cleaned before the rest of the hand basin as set out by the NHS Cleaning Manual. During cleaning, there is a risk of contaminating tap outlets with microorganisms if the same cloth is used to clean the bowl of the hand basin before the tap. These may be of patient origin, so it is possible that bacteria, including antibiotic resistant organisms, could seed the outlet, become resident in any biofilm and have the potential to be transmitted to other patients.
Body fluids disposal: Do not dispose of body fluids at the wash-hand basin – use the dirty utility area.
Patient equipment: Do not wash any patient equipment in wash-hand basins.
Storage: Do not use wash-hand basins for storing used equipment awaiting decontamination.
Safe water: Wash patients, including neonates, on augmented care units with water from outlets demonstrated as safe by risk assessments and, if necessary, by water sampling.
Environmental fluid: Do not dispose of used environmental cleaning fluids at wash-hand basins.
Flushing: Regularly Flush all taps that are used infrequently on augmented care units, at least daily in the morning for 1 minute (HTM 04-01 Part B).
Replace TMVs: There is some evidence that the more complex the design of the outlet assembly, for example sensor-operated taps, the more prone to Pseudomonas colonisation the outlet may be (DH, 2012). Reports from infection prevention and control groups suggest that those estates that replaced TMV-IR/non-touch taps with more conventional elbow or knee actuated devices saw an end to the outbreak and associated Pseudomonas contamination for the reported period (DH, 2012).
Clean and descale outlets: Regularly clean and descale or replace water outlets/shower heads where there may be direct or indirect water contact with patients (see HTM 04-01).

Effect on pathogens other than Legionella

HTM04-01 recommendations

Following the publication of the new updated version of the HTM04-01 last year, duty holders now must ensure the safety of all water used by patients, residents, staff and visitors to healthcare facilities so as to minimise the risk of infection associated with all waterborne pathogens. This therefore applies to other waterborne pathogens, not just Legionella, including Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Mycobacteria.
S. maltophilia is considered an emerging multidrug-resistant opportunistic pathogen, and the increasing incidence of nosocomial and community-acquired infections is of particular concern for immune-compromised individuals as this pathogen is associated with a significant fatality/case ratio (Brooke 2012).
S. maltophilia, previously known as Pseudomonas maltophilia and later Xanthomonas maltophilia is commonly found in a free-living state, mainly in soil and water but also in animals and foods. It is associated with wet surfaces and aqueous solutions and its cells have the ability to survive with minimal nutrients, e.g. in drinking water, ultrapure water, treated water and dialysate effluent.
S. maltophilia has become an important pathogen as it can acquire genes from other bacteria species including those involved in antibiotic resistance (Brooke 2012). It can also transfer antibiotic resistance to other bacteria (Babalova et al. 1995).

The HTM04-01 and Stenotrophomonas

The HTM04-01 states that “There are at least 14 species of Stenotrophomonas; the most important waterborne pathogen is S. maltophilia. This is an emerging opportunistic environmental pathogen that causes healthcare-associated infections and is found in aqueous habitats including water sources. S. maltophilia is an organism with various molecular mechanisms for colonisation and infection, and can be recovered most notably from the respiratory tract of cystic fibrosis patients with P. aeruginosa. Its habits within the healthcare environment are very similar to P. aeruginosa; however, it is more heat-sensitive and will not grow above 40°C. Good temperature management should reduce the risk of colonisation. It has been associated with the colonisation of taps/tap water, sinks/sink traps, showers, hydrotherapy pools, ice-makers, disinfectant solutions, haemodialysers, nebuliser chambers, humidifier reservoirs, bronchoscopes and ventilator circuits. S. maltophilia isolated from tap water has been shown to be responsible for the colonisation/infection of five neonates in a neonatal intensive-care unit. Where clinical results indicate water may be a vector in the transmission of Stenotrophomonas spp., then water sampling should be carried out as per P. Aeruginosa.” (See page 20 of HTM04-01 linked in references list below)

S. maltophilia control in water systems

Tolerance is a problem when trying to control microorganisms, and S. maltophilia is of particular concern because of its resistance to some biocides. Brooke (2012) presented a comprehensive review of studies on S. maltophilia which includes its biocide tolerance. The study showed that:
  • S. macrophilia was recovered in large numbers (5.1 x 105 – 4.8 x 106) in sputum suction tubing after exposure to 0.1% sodium hypochlorite for 2 h.
  • Resistance to Triclosan (2,4,4’-trichloro-2’-hydroxydiphenylether) and sodium dodecyl sulphate (SDS) was also demonstrated, with clinical isolate X26332 surviving and persisting in a 0.02% solution of SDS for 14 days at 30⁰C.
  • Silver nitrate, at the recommended dose of 100 µg/L, did not significantly prevent biofilms formation in drinking water, and that only when concentration of silver nitrate reached around 10,000 µg/L was it able to inhibit biofilm formation.
Brooke’s study also discussed metal resistance in clinical and environmental settings. It showed that S. maltophilia cells have gene clusters used for the import, storage and efflux of metals.

How copper and silver ionisation control pathogens

Chaudri et al. (1999) showed that toxicity to microorganisms due to zinc in soil was due to free Zn2+, its ionic form. Metals applied in a compound as a biocide are bound to other atoms, for example as nitrate in silver nitrate, and hence may not be bio-available. For metals to show toxicity to microorganisms they must be present in their ionic, and hence bio-available, state.
Copper and silver ionisation involves the generation of copper and silver ions in water. This happens when water flows through the turbine of a flow sensor sending a signal to the system control unit, which then passes a low DC current between two copper and two silver electrodes located in an electrode chamber. The current causes the release of copper and silver ions into the flowing water. Being electrically charged the copper and silver ions seek opposite polarity and find this in the negatively charged sites on the cell wall of Legionella bacteria. The ions distort and weaken the cell wall and then bind at specific sites to DNA, RNA, cellular protein and respiratory enzymes denying all life support systems to the cell, causing death. Therefore, biocide tolerance in S. maltophilia is unlikely to occur when using copper and silver ionisation to control pathogens in water systems.

Copper and silver ionisation control of S. maltophilia and other pathogens in water systems

As stated in HTM04-01, S. maltophilia is heat-sensitive and will not grow above 40°C. Good temperature management should, therefore, reduce the risk of colonisation. Use of the word ‘should’, however, implies that control is not guaranteed.
It has been demonstrated that copper and silver ionisation is effective against Legionella, P. aeruginosa and Mycobacteria as well as S. maltophilia (Liu et al. 1994, Miuetzner et al. 1997, Liu et al. 1998, Stout et al. 1998, Biurrun et al. 1999, Rohr et al. 1999, Kusnetsov et al. 2001, Stout and Yu 2003, Chen et al. 2008, Lin et al. 2011, Bedford 2012, Barbosa & Thompson 2016). This is most probably because the copper and silver are in their ionic state which is the form that is able to kill microbial cells, hence their success in controlling pathogens in water systems.

Effect on Biofilms (1)

What is biofilm?

Biofilms are layers of microbial cells that become attached to surfaces submerged in water. They are complex structures formed by bacterial communities comprising multiple species that grow on a solid surface. Legionella is one of the important bacteria species that contaminate water systems in public water supplies and borehole waters, and colonise these systems from biofilms, where they are protected from disinfection.

How are biofilms formed?

Yan et al. (2016) from Princeton have shown the mechanism of how bacteria build biofilms cell by cell. Vibrio cholerae was chosen as model biofilm organism in their study because of its history as a threat to human health. It causes diarrheal disease cholera.
The bacterium first attaches itself to a surface and begins to reproduce, and the growing colony members secrete a sticky substance to both keep themselves from getting washed away and to protect themselves from competing bacteria.
At first, the bacterial colony expands horizontally on the surface (Fig 1). As each cell splits, the resulting daughter cells become firmly attached to the surface alongside the parent cells. Squeezed by increasing numbers of offspring bacteria, however, the cells at the heart of the expanding colony are forced to detach from the surface and project vertically. The bacterial colony thus changes from a flat two-dimensional mass to an expanding three-dimensional globule that is held together by slime in the developing biofilm.
The Princeton team had a close look into the genetics behind this cellular behaviour. A single gene, RbmA, was found to be key to the process by which new cells connect in such a way as to develop a three-dimensional biofilm.
When the gene was deactivated, a big diffuse and floppy biofilm formed. When RbmA performed as normal, though, a denser and stronger biofilm was formed as the cells stayed linked to each other. Thus, RbmA provides the biofilms’ resilience.

How important are biofilms in Legionella control in water systems?

Biofilms play an important role in the spread of Legionella, as they provide nutrients for their growth as well as a protective environment, enabling them to survive water treatment processes (Lin et al. 1998; Kuiper et al. 2004). Biofilms also harbour other pathogenic bacteria, such as Pseudomonas spp. and Acinetobacter baumannii. It is essential to control biofilm formation to control pathogens in water systems.

Which parts of the system are more prone to biofilms?

Areas of low water flow and where water is allowed to stagnate are the places where biofilms are most likely to form. Not surprisingly, biofilms are thus found in water systems in dead-end pipes that are closed at one end and through which no water passes, and dead-leg pipes through which water only passes when it is draw-off from the fitting. Complicated tap/mixer taps fittings are also ideal places for biofilms to form. Often, we come across new taps and tap fittings with complicated designs aimed at solving the problem of pathogen contamination. Rather than solving the problem, however, these fittings might actually add to it due to the additional nooks and crannies providing an ideal environment for biofilms to build-up. Preventing Legionella and Pseudomonas contamination of these systems is, therefore, a difficult technological challenge.

Which materials are more prone to biofilm formation?

Biofilms appear as a patchy mass in some pipe sections and may lead to deterioration of water quality, amplification of corrosion and generation of bad tastes and odours. Characteristics of biofilm formation were studied by Shin et al. (2007) for different pipe materials, water treatment processes and temperature. The results of the study showed that heterotrophic plate count (HPC) increased with time and decreased with a decrease in temperature. The highest HPC was observed on cast iron pipe (CIP) material for all treatment processes. The lowest HPC was observed on cured-in-place pipe (CIPP) liner and stainless steel pipe (SSP) material. The highest HPC was observed in the pipe feeding tap water. The mean HPC at room temperature was higher than that at low temperature. The results of pilot test showed that the HPC of ductile cast iron pipe (DCIP) was higher than that of CIPP. Pseudomonas spp. were identified as the dominant bacteria spp. in the biofilm.

Can copper and silver ionisation control biofilms?

Yes, the Orca copper and silver ionisation water treatment system has been shown to control biofilms more effectively than any other Legionella control modality. By controlling biofilm formation, it reduces maintenance on tanks, taps, mixing valves, shower heads and other water-bearing equipment. Several studies describe the effectiveness of copper and silver ionisation in the control of biofilms and Pseudomonas spp. and A. baumannii associated with these biofilms.
A BSRIA project (BSRIA TN6/96) demonstrated how biofilm can be controlled in a rig by using copper and silver ionisation. Biofilms were analysed in the copper pipework circuits and the glass reinforced plastic (GRP) tanks by removing small copper coupons from the copper pipework circuits and GRP coupons from the tanks. These coupons were covered with biofilms and disinfected by copper-silver ionisation. The cistern GRP and cold water circuit copper coupon samples of the rig that were supplied with hard water demonstrated a 30% drop in biofilm coverage on commencement of disinfection. After 14 days of disinfection, the percentage coverage on the surface of the hot water circuit copper coupon was reduced to less than 5%. The percentage coverage on the cistern GRP coupon sample began, however, to increase again to 30% after 21 days. The authors suggested that biofouling returned on the cistern GRP coupon because it was difficult to maintain silver concentrations above 0.01 mg/L due to scaling of the silver electrodes, which obstructed the release and presence of silver. We found in our own study that scaling can be successfully removed by switching the electrode polarity. Copper and silver ionisation disinfection resulted in a rapid decrease in biofilm coverage on the cold water copper coupon samples of the rig that was supplied with softened water, from over 50% to less than 5%. A more gradual constant decrease was noted, to less than 10%, on the cistern GRP and the hot water copper coupons. The study showed that where operated at concentrations of 0.4mg/L copper and 0.04 mg/L silver, copper and silver ionisation was effective for the control of biofouling.
Shih and Lin (2010) also demonstrated that copper and silver ionisation was effective in controlling biofilms. A model plumbing system consisting of four transparent PVC biofilm sampling pipes was designed. A 14-day inoculation period was followed by 120 hours of disinfection. The inocula solutions consisted of a bacterial suspension (3 x 106 cfu/ml) comprising environmental isolates of P. aeruginosa, S. maltophilia, and A. baumannii, that are biofilm-associated sessile pathogens. Copper and silver ion concentrations were maintained between 0.2 mg/L copper/0.02 mg/L silver and 0.8 mg/L copper/0.08 mg/L silver. Complete inactivation of the biofilm-associated P. aeruginosa was achieved within the first 24 hours. Biofilm-associated S. maltophilia was completely inactivated in 48 hours, and 99.9% of biofilm-associated A. baumannii was killed in 12 hours.
A study by Liu et al. (1998) also found that a significantly higher copper concentration was found in the biofilm taken from a sampling device than was in the surrounding water. This was taken to be the reason for the residual effect of the copper and silver ionisation system and its prevention of early re-colonisation.

Effect on Biofilms (2)

Biofilms

Biofilms are of great importance to public health because microorganisms, such as Legionella and Pseudomonas aeruginosa, that thrive and hide in them, can infect people and cause disease.
A biofilm is an assembly of microbial cells that is irreversibly associated (not removed by gentle rinsing) with a surface and enclosed in a matrix of primarily polysaccharide material. Non-cellular materials such as mineral crystals, corrosion particles, clay or silt particles and blood components can also be found in the biofilm matrix depending on the environment in which the biofilm has developed.
Biofilms form on a wide variety of surfaces, including living tissues, indwelling medical devices, industrial and water system plumbing materials and natural aquatic systems.
In a water system, biofilms are more likely to form where there are areas of low water flow and where water is allowed to stagnate, and are, therefore, found in dead-end pipes, (which are closed at one end through which no water passes), and dead-leg pipes, (through which water only passes when there is draw-off from the fitting).
Biofilms play an important role in the spread of disease as they provide both nutrients and a protective environment for pathogens, enabling them to grow and survive water treatment processes such as elevated temperatures, chlorine and other biocides (Newsome, 2001 and Kuiper et al., 2004). Thermal disinfection with 70°C was, for instance, was not effective in eliminating Legionella in a 2010 study evaluating heat shock treatment (Farhat et al., 2010). Oxidising chemicals such as chlorine and chlorine dioxide do not penetrate established biofilms well, as these chemicals decay over distance and at elevated temperatures, and, therefore, cannot control any pathogen that hides in the biofilms (Sidari et al. 2004).
Bacteria such as Legionella and Pseudomonas enter the water system through the incoming mains or through borehole water.
Once in the water system some bacteria can form a dormant, protective spore-like form until the right conditions for growth occur.
When the right conditions become available they hatch out, become ‘swimmers’ and then ‘stickers’ that can attach to any plumbing material, especially rubber, eroded galvanized steel, and plastics. Copper is less affected due to its biocidal properties (BSRIA Technical Note TN 9/96, Geldreich and Le Chevalier, 1999, Estates & Facilities Alert Department of Health, 2010).
Once attached to a surface the bacteria multiply, secreting sticky slime to form slime ‘houses’. This multiplication continues, fueled by food from the water, to form slime stacks.
Pathogens in these slime houses and are protected from biocides and high temperatures and can even communicate with each other by a process called quorum sensing. This enables them to respond to the availability of nutrients, defend against other microorganisms that may compete for the same nutrients, and avoid toxic compounds.
Bacteria, including Legionella and Pseudomonas aeruginosa, either remain and multiply in the slime houses and stacks, (‘persisters’), or they swim away from the biofilm when conditions are favourable. The whole process then begins again elsewhere in the water system. Pathogens persisting in biofilms have been found to be much more resistant to treatment processes than free floating (planktonic) cells of the same isolate (Tachikawa et al., 2005). In addition, species of a one-celled animal, the amoeba, can be found moving around and feeding in the biofilm. These organisms engulf bacteria, but instead of being broken down microbes such as Legionella multiply. Eventually the amoeba breaks open, releasing them into the biofilm some distance from where the original microbes were taken in (DeClerck et al., 2009).
From the above, it’s clear that any method applied to control pathogens in a water system must be able to also remove biofilm, otherwise recolonization will rapidly occur. If the biofilm remains, long-term control of pathogens such as Legionella and Pseudomonas is impossible. So, how can we control the biofilms and, therefore, pathogens in water systems?
Temperature control has been the method traditionally applied to control Legionella in water systems. It entails having to obtain 55°C and above after running any hot water tap for 1 minute, and 20°C and below after running any cold water tap for 2 minutes (DH HTM04-01 2016). Unfortunately, pathogens in biofilms are protected as penetration by temperature is limited. Worse, this may cause pieces of the top layers of biofilm to break loose under the action of shear forces from the water, which can then settle elsewhere in the water system (Center for Biofilm Engineering). Furthermore, mixing valves are often used to avoid the risk of scalding. These valves will mix the water to a temperature at which pathogens grow most rapidly, and their inner components often include materials that encourage biofilm formation (DH HTM04-01, 2016).
Oxidising chemicals, such as chlorine and chlorine dioxide have some effect on biofilm but decay over distance and at elevated temperatures. This means that they will have limited penetration of established biofilms, particularly in large systems, (Sidari et al. 2004). Oxidising chemicals can also enhance the formation of easily biodegradable organic substances which can be used by bacteria as an energy source, thus actually promoting biofilm formation (Lund and Ormerod, 1995).
Ultra Violet light (UV) and Ozone (O3), according to HSE HSG274 and HTM04-01, are not intended to be dispersive and are designed to have their effect only at or very close to the point of application. Removing biofilm in water systems is, therefore, difficult if not impossible.

Effective biofilm control using copper and silver ionisation

Copper and silver ionisation involves the continuous release of copper and silver ions in water. With the Orca copper and silver ionisation system, the ions are generated by passing a low electrical current between two pure copper and two pure silver electrodes.
The biocidal efficacy of copper and silver is well documented. It has been suggested that the silver ion primarily affects the function of membrane-bound enzymes of bacteria, such as those in the respiratory chain, through binding to thiol groups. Yamanaka et al. (2005), however, found that the silver ion also readily infiltrated the interior of bacteria rather than remaining in the cell membrane area, and that one of the major bactericidal actions of the silver ion was caused by its interaction with the ribosome and subsequent suppression in the expression of enzymes and proteins essential to ATP production.
Studies carried out in-vitro with biofilm demonstrated that its formation was controlled by copper and silver ionisation (BSRIA TN6/96, Walker et al, 1997, Shih and Lin, 2010). Evaluation tests of copper and silver ionisation units that were treating actual hot and cold water systems in hospitals demonstrated that L. pneumophila was controlled (Liu et al., 1994, Miuetzner et al, 1997, Liu et al, 1998, Stout et al., 1998, Biurrun et al., 1999, Kusnetsov et al, 2001, Stout and Yu, 2003, Chen et al., 2008, Bedford, 2013).
A residual effect of copper and silver throughout treated systems was also observed. Studies carried out in 1994 and 1998 by Liu et al demonstrated that the residual copper and silver produced by ionisation continued to control Legionella for as long as 3 months after the copper and silver ionisation system was switched off (Liu et al., 1994, Liu et al., 1998).

Effectivness at High & Low Water Temeperatures

Legionella pneumophila is a disease-causing microorganism well known for causing Legionellosis (Legionnaires’ disease and Pontiac fever). It is particularly dangerous for hospital patients that have a compromised immune system. L. pneumophila and other species of the genus Legionella thrives in temperatures between 20 and 45°C and multiplies rapidly in untreated or ineffectively treated water systems.

Legionella control in cold and hot water systems

Various methods are used for controlling Legionella in water systems, but not all of them will work for both cold and hot water.
In the UK, the HTM04-01 (2016) states that temperature control is the traditional method applied for the control of Legionella in water distribution systems in the UK. This control method entails obtaining 55 ⁰C and above, after running any hot water tap for 1 minute, and 20 ⁰C and below, after running any cold water tap for 2 minutes (HTM04-01, 2016). Many premises use the temperature control together with an additional modality, including chlorine dioxide and copper-silver ionisation, to control Legionella and other pathogens in water systems. In fact, item 4.7 of the HTM says that:
“In addition to maintaining a temperature control regimen, there may be occasions where additional biocidal treatment is required for the effective control of Legionella and other opportunistic waterborne pathogens. However, the selection of suitable treatment is complex and depends on a number of parameters, and the chosen biocide should be properly managed. This is particularly the case with cold water services compared with hot water services where, with the benefit of circulation, water is returned to the calorifier/water heater and is then pasteurised. However, it should be taken into consideration that effective concentrations of some biocides are difficult to achieve in hot water systems due to gassing off.”
This is indeed the case with chlorine dioxide, which is discussed under item 2.96, page 36 of the HSE document HSG274 Part 2 (2014). It states that:
“In the case of hot water distribution systems with calorifiers/water heaters operating conventionally (i.e. at 60 °C), there will be a tendency for chlorine dioxide to be lost by ‘gassing off’, especially if the retention time in a vented calorifier/water heater is long. In most cases, however, some level of total oxidant should be found in the hot water, although at concentrations far less than the 0.5 mg/l injected.” Lower concentrations of the biocide will of course render it ineffective.
Item 2.98 of the same document states that:
“Excessive levels of chlorine dioxide should be avoided since they can encourage the corrosion of copper and steel pipework and high levels of chlorine dioxide can degrade certain types of polyethylene pipework particularly at elevated temperatures. Users of chlorine dioxide systems will need to consider these issues and when choosing a system these points should be checked to ensure that the supplier addresses them satisfactorily.”

How copper and silver ionisation for Legionella control works at low and high water temperatures

Copper and silver ionisation for Legionella control, on the other hand, is one of the current techniques that not only have been shown to be effective for Legionella control (Landeen et al. 1989, Lin et al. 2011, Lin et al. 1996, BSRIA TN6/96) but also works at both hot and cold water temperature (Liu et al. 1994, Liu et al. 1998, Stout et al. 1998, Kusnetsov et al. 2001, Stout and Yu 2003 and Chen et al. 2008).
Studies of hot water systems in hospitals in the USA suggested that copper and silver ionisation eliminated L. pneumophila contamination in systems with relatively low water volume (<200 L) and without hot water storage tanks (Liu et al. 1994, Coville et al. 1993).
A new hospital building in London has been using the Orca copper and silver ionisation system since opening in 2011 with deliberately reduced water temperatures. A 100% Legionella control and 90% Pseudomonas control at temperatures between 17 and 45 °C has been achieved. The installation of a copper and silver ionisation system also minimised the use of thermostatic mixing valves due to the lower temperatures, thus eliminating the need for mixing valve maintenance regimes and corresponding costs. In addition, by allowing the system to operate at lower temperatures, a 33% reduction in energy consumption associated with heating water was achieved.

About Dialysis Water Filtration Systems

Approximately 400 litres of water are used weekly for producing dialysis fluid. It is, therefore, important to know and monitor the chemical and microbiological purity of this water (Pontoriero et al 2003). Hospital dialysis units have to deliver high purity water which is free from contaminants and, therefore, metals and chemical compounds should be removed from it. To ensure the water is free from impurities standard drinking water undergoes additional treatments such as filtration and reverse osmosis.

What can contaminate dialysis units?

Water used for the preparation of dialysis fluid should ideally be ultrapure water or at least meet the minimum standard of purity given in Table 1 (Mactier 2007). The table includes contaminants that should always be included in routine testing as they occur in relatively high levels and are not restricted in drinking water (chlorine, calcium, magnesium), those for which drinking water limit is more than five times the recommended limit for water for dialysis, and all contaminants for which the drinking water limit is 2 to 5 times the recommended limit for dialysis. In water treated by reverse osmosis, these contaminants will only exceed the limits in table 1 if they occur at relatively high levels in the water supplied to the unit. These contaminants can be omitted from routine tests if data is available to show that the levels in the water supplied to the unit rarely exceed the limit in the table. These data should be obtained from the municipal water supplier or from tests on the raw water if it is obtained from a private source (Mactier 2007).
Table 1 is from the Renal Association’s document “Clinical Practice Guidelines Module 2: Haemodialysis” and shows the list of possible contaminants and their maximum recommended concentration in water for dialysis. As shown in the table, contaminants include the chemical elements that are widely used in products and processes and thus can end up in water courses (e.g. aluminium, calcium, potassium, sodium, magnesium, chlorine, chloride, fluorine, fluoride, copper, cadmium, lead, mercury, silver, tin, zinc); chemical compounds (e.g. nitrate, ammonium, sulphate) as well as bacterial contaminants (e.g. bacteria, TVCs and endotoxins). Removal of these contaminants from water, therefore, has to be carried out to ensure that maximum concentrations of chemical and microbial contaminants allowed in dialysis water are not exceeded, and this is usually done by filtration (Figure 1). If the filtration equipment fails then contamination of the dialysis water and the patient’s blood could occur.
Table 1: Maximum recommended concentrations for chemical and microbial contaminants in water for dialysis:
dialysis-filtration-systems-table-1
Note: Antimony (AAMI limit 0.006 mg/L) and selenium (AAMI and ISO limit 0.09 mg/L) have been excluded from this table as the limit for drinking water in the UK is lower than the limit for water for dialysis.

Legionella in water systems

Legionella pneumophila is a disease-causing microorganism, which is ubiquitous in water systems and can infect people, being particularly dangerous for hospital patients that have a compromised immune system. L. pneumophila is well known for causing Legionellosis (Legionnaire’s disease and Pontiac fever). Legionella can survive extreme water temperature ranges, 0°C to 63°C (Nguyen et al. 1991), with an optimum temperature growth range between 38°C and 46°C and multiples rapidly in untreated or ineffectively treated water systems. No doubt, Legionella has to be controlled in water systems, especially in hospitals to protect patients. Many control strategies exist, but where dialysis units are in place, the Legionella control system cannot interfere with or contaminate the dialysis system.

Which Legionella control method is less likely to contaminate Dialysis water units?

The dialysis filtration system can fail if using compounds like silver hydrogen peroxide as a biocide to control Legionella in the water system, as happened in Leicester General Hospital some years ago (Martin 2008). The filtration system was not able to cope with the high concentration of silver hydrogen peroxide in the water, resulting in contamination of the dialysis water. This would not have happened if the hospital was using pure Copper and Silver Ionisation for pathogens control in the water systems, i.e. the dialysis water filtration system would have been able to cope without any problems. This is because the levels of ions of copper and silver released into the water by the copper and silver ionisation system are extremely small (0.200-0.800 mg/L for copper and 0.020-0.080 mg/L for silver). Sometimes people get confused with these two systems and, therefore, we will take this opportunity to point out that there is a huge difference between copper and silver ionisation and silver hydrogen peroxide – the two modalities are completely different. The concentrations of silver salts (not ions) used in silver hydrogen peroxide are between 8 to 12 mg/L (more than 400 times the level used in Cu-Ag ionisation).
Reverse osmosis is capable of excluding metal ions, aqueous salts and molecules from the treated water (Coulliette & Arduino 2013). Ultrafiltration and endotoxin-retentive filters can be included after the deioniser, immediately after the storage tank, and/or before delivery to the dialyser depending on the design of the system (Ward 2004) to remove bacteria and endotoxin by using a positively charged filter surface and size exclusion.
ProEconomy Ltd, who are the only providers of the Orca pure copper and silver ionisation system for pathogens control in water has carried out analysis to measure levels of copper and silver before and after dialysis water filtration equipments and the results are shown in Table 2, where it can be seen that the copper concentration before the RO unit was 0.246 mg/L and after the unit was <0.003 mg/L, showing almost complete removal to well below the recommended levels (0.1 mg/L). The silver concentration before the unit was 0.059 mg/L and after it was 0.0004 mg/L, which again shows almost complete removal to well below the allowed levels (0.005 mg/L) as shown in Table 1.
Table 2: Copper and Silver Before and After Dialysis Water Filtration:
Sample Id Copper (mg/L) Silver (mg/L)
Maximum recommended concentration (Renal Association, AAMI-ISO) 0.1 0.005
Renal Dialysis Before osmosis 0.246 0.0593
Renal Dialysis After osmosis <0.003 0.0004

Article: Copper and silver ionisation is essential for Legionella control

HSE has backed copper as a biocide for essential use.
ProEconomy have worked tirelessly over the last 20 years to create the reputation that they have and they have helped establish copper and silver ionisation as an essential method for Legionella control.
Nick Bedford MD of ProEconomy is positive about the derogation; ‘the review of copper as a biocide by the EC had a big impact on us and we are glad that HSE backed copper and silver ionisation as an essential water treatment method. We hope to build on this and are positive that there will be positive changes for copper and silver ionisation in the new ACoP L8. It’s time that ionisation’s contribution to Legionella control has a more balanced standing within official legislation.’
For more information contact Nick Bedford at nick@proeconomy.com.

References

Albright C.F., Nachum R., Lechtman M.D. (1967) Development of an electrolytic silver-ion generator for water sterilization in Apollo spacecraft water systems: Final Report. Apollo Applications Program, Manned Spacecraft Center, NASA:Houston. Available online: http://www.clearwaterpoolsystems.com/nasa-connection.html (Accessed July 2015).
Barbosa, V.L., Thompson, K.C. (2016) Controlling Legionella in a UK hospital using copper and silver ionisation - a case study. Journal of Environmental Chemical Engineering 4(3): 3330 3337.
Bougeard C.M.M., Goslan E.H., Jefferson B., Parsons S.A. (2010). Comparison of the disinfection by-product formation potential of treated waters exposed to chlorine and monochloramine. Water Research 2010;44(3):729-740.
Building Services Research and Information Services (1996). Application Guide AG 2/93. Water treatment for building services systems. Building Services Research and Information Services (BSRIA) Technical Notes TN6/96 1996. Ionisation water treatment for hot and cold water services.
DH Estates and Facilities Division (2016) Health Technical Memorandum 04-01: Safe water in healthcare premises, Part A: Design, installation and commissioning 2016. Health Technical Memorandum 04-01: Safe water in healthcare premises, Part B: Operational management. Department of Health. 2016. London, UK. [Online]. Available from: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/524882/DH_HTM_0401_PART_B_acc.pdf [Accessed April 2017].  
Kilvington S., Price J. (1990) Survival of Legionella pneumophila within cysts of Acanthamoeba polyphaga. Journal of Applied Bacteriology 68:519-525.
Lin Y., Stout J.E., Yu V.L. (2011). Controlling Legionella in Hospital Drinking Water: An Evidence-Based Review of Disinfection Methods. Infection Control and Hospital Epidemiology. 32(2):166-173.
Lin Y.E., Vidic R.D., Stout J.E., Yu V.L. (1998). Legionella in water distribution systems. J Am Water Works Assoc. 90:112–21.
Liu Z., Stout J.E., Tedesco L., Boldin M., Hwang C., Diven W.F., Yu V.L. (1994). Controlled evaluation of copper-silver ionisation in eradicating Legionella from a hospital water distribution system. J. Infectious Disease. 169:919-922.
Liu Z., Stout J.E., Boldin M., Rugh J., Diven W.F., Yu V.L. (1998). Intermittent use of copper-silver ionisation for Legionella control in water distribution systems: A potential option in buildings housing individuals at low risk of infection. Clinical Infectious Diseases. 26:138-140.
Nguyen M.H, Stout J.E., Yu, V.L. (1991) Legionellosis.  Infect Dis Clin N Am 5(3):561-584.
PHE (2017). Monthly Legionella Report: December 2016. PHE publications gateway number: 2016569  https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/582431/Monthly_LD_Report_-_December_16.pdf
Sidari F.P., Stout J.E., van Briesen J.M. (2004). Keeping Legionella out of water systems. J. Am. Water Works Assoc 96:111-119.
Stout J.E., Yu V.L. (2003). Experiences of the first 16 hospitals using copper silver ionisation for Legionella control: Implications for the valuation of other disinfection modalities. Infection Control and Hospital Epidemiology 24(8):563-568.

References

Albright C.F., Nachum R., Lechtman M.D. (1967) Development of an electrolytic silver-ion generator for water sterilization in Apollo spacecraft water systems: Final Report. Apollo Applications Program, Manned Spacecraft Center, NASA:Houston. Available online: http://www.clearwaterpoolsystems.com/nasa-connection.html (Accessed July 2015).
Bedford, B. (2012) Legionella control in water systems using copper and silver ion generation systems. PhD thesis. Cranfield University, UK.
DH (2012). Report on the review of evidence regarding the contamination of wash-hand basin water taps within augmented care units with Pseudomonads. 43 pp.
DH, Estates and Facilities (2013). HTM 04-01 - Addendum: Pseudomonas aeruginosa – advice for augmented care units. 37 pp. <a href="https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/140105/Health_Technical_Memorandum_04-01_Addendum.pdf">https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/140105/Health_Technical_Memorandum_04-01_Addendum.pdf</a>
Huang, H-I;  Shih, H-Y;  Lee, C-M; Yang, TC;  Lay, J-J; Lin, YE (2008). In vitro efficacy of copper and silver ions in eradicating Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter baumannii: Implications for on-site disinfection for hospital infection control.  Water Research 42(1-2): 73–80.
Lin Y., Stout J.E., Yu V.L. (2011). Controlling Legionella in Hospital Drinking Water: An Evidence-Based Review of Disinfection Methods. Infection Control and Hospital Epidemiology. 32(2):166-173.
Liu Z., Stout J.E., Tedesco L., Boldin M., Hwang C., Diven W.F., Yu V.L. (1994). Controlled evaluation of copper-silver ionisation in eradicating Legionella from a hospital water distribution system. J. Infectious Disease. 169:919-922.
Liu Z., Stout J.E., Boldin M., Rugh J., Diven W.F., Yu V.L. (1998). Intermittent use of copper-silver ionisation for Legionella control in water distribution systems: A potential option in buildings housing individuals at low risk of infection. Clinical Infectious Diseases. 26:138-140.
Quick J., Cumley N., Wearn C.M., Niebel M., Constantinidou C., Thomas C.M., Pallen M.J., Moiemen N.S., Bamford A., Oppenheim B., Loman N.J. (2014). Seeking the source of Pseudomonas aeruginosa infections in a recently opened hospital: an observational study using whole-genome sequencing. British Medical Journal Open 2014(4):e006278. Doi:10.1136/bmjuopen-2014-006278.
Walker J., Moore G. (2015). Pseudomonas aeruginosa in hospital water systems: biofilms, guidelines, and practicalities. Journal of Hospital Infection 89(4):324–327.

References

Babalova M., Blahova J., Lesicka-Hupkova M., Krcmery V., Kubonova K. (1995). Transfer of ceftazidime and aztreonam resistance from nosocomial strains of Xanthomonas (Stenotrophomonas) maltophilia to a recipient strain of Pseudomonas aeruginosa ML-1008. Eur. J. Clin. Microbiol. Infect. Dis. 14:925-927.
Barbosa V.L., Thompson K.C. (2016). Controlling Legionella in a UK hospital using copper and silver ionisation - a case study. Journal of Environmental Chemical Engineering 4(3):3330-3337.
Bedford B. (2012) Legionella control in water systems using copper and silver ion generation systems. PhD thesis, Cranfield University, UK. Available from: https://dspace.lib.cranfield.ac.uk/bitstream/1826/7983/1/Birgitta_Bedford_Thesis_2012.pdf
Biurrun A., Caballero L., Pelaz C., Leon E., Gago A. (1999). Treatment of a Legionella pneumophila colonized water distribution system using copper-silver ionization and continuous chlorination. Infect. Control. Hosp. Epidemiol. 20:426-428.
Bollet C., Davin-Regli A., De Micco P. (1995) A simple method for selective isolation of Stenotrophomonas maltophilia from environmental samples. Applied and Environmental Microbiology 61(4):1653–1654. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1388425/pdf/hw1653.pdf
Brooke J.S. (2012) Stenotrophomonas maltophilia: an emerging global opportunistic pathogen. Clin Microbiol Rev 25(1):2–41. 10.1128/CMR.00019-11
Chaudri A.M., Knight B.P, Barbosa-Jefferson V.L., Preston S., Paton G.I., Killham K., Coad N., Nicholson F.A., Chambers B.J., McGrath S.P. (1999) Determination of acute Zn toxicity in pore water from soils previously treated with sewage sludge using bioluminescence assays. Environ. Sci. and Technol. 33: 11. 1880–1885.
Chen Y.S., Lin Y.E., Liu Y.C., Huang W.K., Shih H.Y., Wann S.R., Lee S.S. et al. (2008). Efficacy of point-of-entry copper-silver ionisation system in eradicating Legionella pneumophila in a tropical tertiary care hospital: implications for both hospitals contaminated with Legionella in both hot and cold water. Journal of Hospital Infection. 68:152-158.
DoH Estates and Facilities Division (2016) Health Technical Memorandum 04-01: Safe water in healthcare premises, Part A: Design, installation and commissioning 2016. Health Technical Memorandum 04-01: Safe water in healthcare premises, Part B: Operational management. Department of Health. 2016. London, UK. [Online]. Available from: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/524882/DH_HTM_0401_PART_B_acc.pdf [Accessed April 2017].
Kusnetsov J., Livanainen E., Elomaa N., Zacheus O., Martikainen P.J. (2001). Copper and silver ions more effective against Legionellae then against Mycobacteria in a hospital warm water system. Wat. Res. 35(17):4217-4225.
Lin Y., Stout J.E., Yu V.L. (2011). Controlling Legionella in Hospital Drinking Water: An Evidence-Based Review of Disinfection Methods. Infection Control and Hospital Epidemiology. 32(2):166-173.
Liu Z., Stout J.E., Tedesco L., Boldin M., Hwang C., Diven W.F., Yu V.L. (1994). Controlled evaluation of copper-silver ionisation in eradicating Legionella from a hospital water distribution system. J. Infectious Disease. 169:919-922.
Liu Z., Stout J.E., Boldin M., Rugh J., Diven W.F. Yu V.L. (1998). Intermittent use of copper-silver ionisation for Legionella control in water distribution systems: A potential option in buildings housing individuals at low risk of infection. Clinical Infectious Diseases. 26:138-140.
Miuetzner S., Schwille R.C., Farley A., Wald R.R., Ge J.H., States S.J., Libert T., Wadowsky R.M. (1997). Efficacy of thermal treatment and copper-silver ionization for controlling Legionella pneumophila in high-volume hot water plumbing systems in hospitals. The Association for Professionals in Infection Control and Epidemiology, Inc. 17(46):813-866.
Rohr U., Senger M., Selenka F., Turley R., Wilhelm M. (1999). Four years of experience with silver-copper ionization for control of Legionella in a German university hospital hot water plumbing system. Clinical Infectious Diseases. 29:1507-1511.
Stout J.E., Lin Y.E., Goetz A.M., Muder R.R. (1998). Controlling Legionella in hospital water systems: Experience with the superheat-and-flush method and copper silver ionization. Infection control and Hospital Epidemiology. 19(12):911-914.

References

Building Services Research and Information Services (1996) Application Guide AG 2/93. Water treatment for building services systems. Building Services Research and Information Services (BSRIA) Technical Notes TN6/96 1996. Ionisation water treatment for hot and cold water services.
Chen, Y.S.; Lin, Y.E.; Liu, Y.C.; Huang, W.K.; Shih, H.Y.; Wann, S.R.; Lee, S.S.; Tsai, H.C.; Li, C.H.; Chao, H.L.; Ke, C.M.; Lu, H.H.; Chang, C.L. (2008). Efficacy of point-of-entry copper-silver ionisation system in eradicating Legionella pneumophila in a tropical tertiary care hospital: implications for both hospitals contaminated with Legionella in both hot and cold water. Journal of Hospital Infection 68:152-158.
Colville, A.; Crowley, J.; Dearden, D.; Slack, R.C.B.; Lee, J.V. (1993). Outbreak of Legionnaires’ disease at University Hospital, Nottingham: epidemiology, microbiology and control. Epidemiol Infect 110:105-16.
DH Estates and Facilities Division (2016) Health Technical Memorandum 04-01: Safe water in healthcare premises, Part A: Design, installation and commissioning 2016. Health Technical Memorandum 04-01: Safe water in healthcare premises, http://www.wales.nhs.uk/sites3/Documents/254/WHTM%2004%2D01%20Part%20A%202016.pdf Part B: Operational management. Department of Health. 2016. London, UK. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/524882/DH_HTM_0401_PART_B_acc.pdf [Accessed April 2017].
Kusnetsov, J.; Iivanainen, E.; Elomaa, N.; Zacheus, O.; Martikainen, P.J. (2001). Copper and silver ions more effective against Legionella then against Mycobacteria in a hospital warm water system. Wat. Res. 35(17):4217-4225
Landeen, L.K.; Yahya, M.T.; Gerba, C.R. (1989) Efficacy of copper and silver ions and reduced levels of free chlorine in inactivation of Legionella pneumophila. Appl Environ Microbiol 55:3045-50.
Lin, Y.; Stout, J.E.; Yu, V.L. (2011) Controlling Legionella in Hospital Drinking Water: An Evidence-Based Review of Disinfection Methods. Infection Control and Hospital Epidemiology 32:166-173.
Lin, Y.S.E.; Vidic, R.D.; Stout, J.E.;Yu, V.L. (1996) Individual and combined effects of copper and silver ions on inactivation of Legionella pneumophila. Wat. Res. 30:1905-1913.
Liu, Z.; Stout, J.E.; Tedesco, L.; Boldin, M.; Hwang, C.; Divert, W.F.; et al. (1994). Controlled evaluation of copper-silver ionization in eradicating LegionelIa pneumophila from a hospital water distribution system. J Infect Dis 169:919-22.
Liu, Z.; Stout, J.E.; Boldin, M.; Rugh, J.; Diven, W.F.; Yu, V.L. (1998). Intermittent use of copper-silver ionisation for Legionella control in water distribution systems: A potential option in buildings housing individuals at low risk of infection. Clinical Infectious Diseases 26:138-140.
Stout J.E., Y.E. Lin, A.M. Goetz, and R.R. Muder. (1998). Controlling Legionella in hospital water systems: Experience with the superheat-and-flush method and copper silver ionization. Infection control and Hospital Epidemiology 19(12):911-914.
Stout J.E.; Yu, V.L. (2003). Experiences of the first 16 hospitals using copper silver ionisation for Legionella control: Implications for the valuation of other disinfection modalities. Infection Control and Hospital Epidemiology 24(8):563-568.

ProEconomy's reputation speaks volumes and the Orca system is highly regarded by those who have installed it.