(See the article by Souli et al, on pages 765–771.)

Despite dramatic decreases in the incidence of healthcare-associated infections (HAIs) in recent years, a large prevalence study of US acute-care hospitals estimated that ~722,000 HAIs occurred in 2011, resulting in ~75,000 deaths.Reference Magill, Edwards and Bamberg ¹ Several decades ago, WeinsteinReference Weinstein ² theorized that pathogens causing HAIs in the intensive care unit (ICU) had several sources: the patients’ endogenous flora (40%–60%), cross-infection via the hands of healthcare personnel (HCP; 20%–40%), antibiotic-driven changes in flora (20%–25%), and other causes (including contamination of the environment; 20%).Reference Weinstein ² More recently, accumulating scientific evidence has indicated that contamination of environmental surfaces in hospital rooms plays an important role in the transmission of several key healthcare-associated pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp (VRE), Clostridium difficile, Acinetobacter spp, and norovirus.Reference Boyce ^{3 –} Reference Otter, Yezli, Salkeld and French ⁶ In general, all of these pathogens share the following characteristics: ability to survive for prolonged periods of time on environmental surfaces, ability to remain virulent after environmental exposure, frequent contamination of the hospital environment, ability to colonize patients, ability to contaminate or transiently colonize the hands of HCP, and transmission via the contaminated hands of HCP.Reference Boyce ^{3 –} Reference Otter, Yezli, Salkeld and French ⁶ Evidence supporting the role of contaminated surfaces in the transmission of key healthcare-associated pathogens includes the following observations. (1) The surfaces in rooms of colonized or infected patients are frequently contaminated with the pathogen.Reference Boyce ^{3 –} Reference Otter, Yezli, Salkeld and French ⁶ (2) Contact with hospital-room surfaces or medical equipment by HCP frequently leads to contamination of hands and/or gloves.Reference Otter, Yezli, Salkeld and French ⁶ (3) The patient admitted to a room previously occupied by a patient colonized or infected with a pathogen (eg, MRSA, VRE, C. difficile, Acinetobacter) has a substantially increased likelihood (ie, 39%–353%) of developing colonization or infection with that pathogen.Reference Otter, Yezli, Salkeld and French ⁶ (4) Improved terminal cleaning of rooms decreases environmental pathogensReference Carling ⁷ and the rate of individual patient colonization and/or infections; it also leads to a decreased facility-wide rate of colonization and/or infection.Reference Donskey ⁸

Unfortunately, inadequate terminal room disinfection is common.Reference Carling ⁷ In fact, studies have demonstrated that <50% of room surfaces are cleaned.Reference Carling ⁷ Therefore, and not surprisingly, many room surfaces remain contaminated with a multidrug-resistant organisms (MDROs) following terminal room disinfection.Reference Weber, Anderson and Rutala ^{5 ,} Reference Otter, Yezli, Salkeld and French ⁶ Although enhanced education of environmental service staff with feedback regarding cleaning effectiveness (eg, fluorescent dye) improves cleaning effectiveness, overall cleaning remains suboptimal.Reference Carling ⁷ For this reason, “no-touch” methods of terminal room disinfection have been developed.Reference Otter, Yezli, Perl, Barbut and French ^{9 –} Reference Boyce ¹⁴ No-touch methods that use ultraviolet (UV) light devices or hydrogen peroxide systems for terminal room disinfection when the occupant has been colonized or infected with a MDRO have been demonstrated to reduce the risk of the subsequent room occupant developing colonization and/or an HAI.Reference Rutala and Weber ^{11 ,} Reference Weber, Rutala, Anderson, Chen, Sickbert-Bennett and Boyce ¹³ Importantly, some studies have demonstrated a facility-wide reduction of HAIsReference Boyce, Havill and Otter ^{15 ,} Reference Vianna, Dale, Simmons, Stibich and Licitra ¹⁶ ; furthermore, these reductions were not related to improved hand hygiene or to environmental cleaning compliance.Reference Pegues, Han, Gilmar, McDonnell and Gaynes ^{17 ,} Reference Anderson, Chen and Weber ¹⁸

One of the limitations of currently available UV devices or hydrogen peroxide systems is that they can only be used for terminal disinfection because patients and HCP must evacuate the room prior to use. Because daily room disinfection has been shown to reduce contamination of HCP hands and gloves,Reference Kundrapu, Sunkesula, Jury, Sitzlar and Donskey ¹⁹ there has been interest in developing “no-touch” methods for decreasing MDRO surface contamination on a continuous basis.Reference Otter, Yezli, Perl, Barbut and French ⁹ Such methods have been reviewed and include self-disinfecting surfaces using heavy metals, light-activated photosensitizers, high-intensity narrow-spectrum light, low-dose continuous hydrogen peroxide, photocatalytic disinfection, bacteriophage-modified surfaces, and altered surface topography.Reference Weber, Kanamori and Rutala ^{12 ,} Reference Boyce ^{14 ,} Reference Weber and Rutala ^{20 –} Reference Muller, MacDougall and Lim ²² Of these potential methods, the best studied is the use of heavy metals (eg, silver, copper) with copper-coated or impregnated surfaces; it is the only method that has been assessed in clinical trials.Reference Weber and Rutala ^{20 –} Reference Muller, MacDougall and Lim ²²

The studies assessing the effectiveness of no-touch methods including self-disinfecting surfaces for disinfection of room surfaces in hospitals can be divided into 3 general approaches. (1) the effectiveness of the self-disinfecting surface to kill or inhibit microbes artificially placed on the self-disinfecting surface, (2) the level of contamination on self-disinfecting surfaces in actual patient rooms compared to a “control” surface and (3) most importantly, clinical trials of a self-disinfecting surface to reduce HAIs.

Copper is an essential trace element in most living organisms, and >30 types of copper-containing proteins have been described.Reference Weber and Rutala ²⁰ The use of copper by humans dates back to the fifth and sixth millennia bc.Reference Grass, Rensing and Solioz ²³ Ancient civilizations used copper or copper compounds to prevent the growth of barnacles on the hulls of ships and as a medicinal agent.Reference Weber and Rutala ²⁰ In the 19th and 20th centuries, inorganic copper preparations were used to treat chronic adenitis, eczema, impetigo, tuberculous infections, and syphilis.Reference Grass, Rensing and Solioz ²³ The cause of bacterial cell death to exposure to copper may relate to its ability to accept and donate single electrons leading to the generation of reactive oxygen species, resulting is cell lysis.Reference Boyce ^{14 ,} Reference Weber and Rutala ^{20 ,} Reference Humphreys ^{21 ,} Reference Grass, Rensing and Solioz ²³ In healthcare facilities, the most well-studied use of copper has been as a “self-disinfecting” surface, but many other uses have been studied, including copper-containing paints, fabrics, hand rubs, microfiber cleaning cloths, pens, and fins within air-conditioning units.Reference Weber and Rutala ²⁰

Multiple studies have assessed the contact killing of microbes by copper surfaces.Reference Grass, Rensing and Solioz ²³ Contact with copper has been demonstrated to kill a variety of healthcare-associated pathogens including Staphylococcus aureus (including methicillin-resistant S. aureus), Enterococcus spp, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Mycobacterium tuberculosis. Reference Weber and Rutala ²⁰ In general, contact killing of vegetative bacteria and fungi occurs rapidly with >6-log₁₀ inactivation per hour. Spores (eg, C. difficile) are inactivated more slowly, but >3-log₁₀ are inactivated within 24 hours.Reference Grass, Rensing and Solioz ^{23 ,} Reference Weaver, Michels and Keevil ²⁴

In this issue of Infection Control and Hospital Epidemiology, Souli et alReference Souli, Antoniadou and Katsarolis ²⁵ report on the frequency and level of contamination of multiple copper-coated surfaces (ie, patient beds, side table, IV pole, side cart handles, and manual antiseptic dispenser) compared to control surfaces in a patient room in an intensive care unit.Reference Souli, Antoniadou and Katsarolis ²⁵ The study was performed in a Greek ICU setting in which evidence showed that the environment was considerably more contaminated than other settings and where highly resistant organisms predominated. For example, 62% of K. pneumoniae isolated from the environment were resistant to carbapenems and 100% were multidrug resistant; similarly, 98% of A. baumannii were resistant to carbapenems and 99% were multidrug resistant. Their study was conducted in 2 phases: In phase 1, enhanced environmental sampling was performed to identify the most microbiologically contaminated items to ‘copperize’; this targeted use of copper items is an important strength of the study. Phase 2 was the intervention phase; in phase 2a, copper-coated objects were placed next to uncoated objects (controls); and in phase 2b, cooper-coated objects were all placed in a single ICU compartment and non–copper-coated objects were placed in a different ICU compartment (controls). Combining the data for phases 2a and 2b revealed that copper-coated surfaces were less likely to be microbially contaminated (ie, 55.6% vs 72.5% for controls, P<.0001). Copper-coated surfaces were significantly less likely to be contaminated with gram-negative bacilli or Enterococcus spp, but no statistical reduction for A. baumannii, K. pneumoniae, or S. aureus was observed. Overall, the level of contamination was reduced by ~0.7-log₁₀ (P=.049). Importantly, no significant reduction was observed in phase 2a, in which copper items were placed next to uncoated objects, suggesting a possible interaction between the number of copper items and the level of reduction, which requires further investigation. The statistical approach used did not take into account the full range of variables; most importantly, indicators of hand-hygiene compliance and patient-level variables could have been included in a model with copper items as a separate variable. Souli et al reported no difference in hand-hygiene compliance during the study, but the effectiveness of environmental clean/disinfection was not assessed. Other limitations include the use of alcohol spray for daily disinfection of surfaces, which is an unusual approach and may limit the generalizability of the study; lack of randomization of patients to beds with copper items; and the lack of clinical and cost-effectiveness outcomes.

Multiple studies of copper-coated surfaces or devices have been conducted in the healthcare setting comparing the level and frequency of surface contamination to control surfaces (for a review of studies, see Weber and Rutala,Reference Weber and Rutala ²⁰ Humphreys,Reference Humphreys ²¹ Muller et al,Reference Muller, MacDougall and Lim ²² Weaver et al,Reference Weaver, Michels and Keevil ²⁴ and O’Gorman and HumphreysReference O’Gorman and Humphreys ²⁶ ). Studies have either used concurrent non–copper-coated control surfaces or a crossover design. Muller et alReference Muller, MacDougall and Lim ²² reported that 5 of 7 copper studies of copper-coated surfaces or fabrics reviewed demonstrated a significant reduction in quantitative bacterial contamination of <1-log₁₀ (range, <1-log₁₀ to 2-log₁₀). Limitations of the studies noted by Muller et alReference Muller, MacDougall and Lim ²² included lack of blinding, lack of randomization, and in general, failure to measure potential confounding factors (eg, hand hygiene compliance, effectiveness of cleaning by environmental services) or reported any patient-level data. Similar to previous studies, 2 more recent studies also demonstrated significant reductions of microbial contamination on copper-coated surfaces compared to control surfaces of 1- to 2-log₁₀.Reference Hinsa-Leasure, Nartey, Vaverka and Schmidt ^{27 ,} Reference Schmidt, von Dessauer and Benavente ²⁸

In addition, 3 clinical trials have been published in the English literature that assessed the effectiveness of cooper-coated surfaces to reduce HAIs (Table 1).Reference Grass, Rensing and Solioz ^{23 –} Reference Salgado, Sepkowitz and John ³¹ Of these 3 trials, 2 reported that the intervention arm (ie, copper) had a decreased incidence of HAIs,Reference Sifri, Burke and Enfield ^{30 ,} Reference Salgado, Sepkowitz and John ³¹ and 1 trial reported no significant reduction in HAIs.Reference von Dessauer, Navarrete, Benadof, Benavente and Schmidt ²⁹ Importantly, none of the trials assessed the effectiveness of environmental cleaning and disinfection using fluorescent dye or ATPase measurements, and 1 did not assess compliance with hand hygiene.Reference Salgado, Sepkowitz and John ³¹ Although Salgado et alReference Salgado, Sepkowitz and John ³¹ described their trial as a randomized clinical trial, Muller et alReference Muller, MacDougall and Lim ²² described this study as “low-quality evidence due to inappropriate randomization and lack of blinding.” An additional clinical trial has been published in the Spanish literature; it reported no differences in the frequency of nosocomial infections as well as no difference in the rates of ventilator-associated pneumonia, catheter-associated urinary tract infections, or central line-associated bloodstream infections.Reference Rivero, Brenner and Nercelles ³² However, this study was limited by its failure to achieve its intended sample size.

TABLE 1

Results of Selected Clinical Trials of Copper-Coated Versus Control Surfaces to Reduce Healthcare-Associated Infections

NOTE. Cu, copper; HH, hand hygiene; EVS, environmental service; HAI, healthcare-associated; RR, relative risk; PICU, pediatric intensive care unit; PIMCU, pediatric intermediate care unit; IV, intravenous; NS, not significant; MRSA, methicillin-resistant Staphylococcus aureus; VRE, vancomycin-resistant Enterococcus spp; RCT, randomized clinical trial.

The use of copper-coated surfaces to decrease contamination of hospital-room surfaces to decrease HAIs has several potential advantages over current technologies, but it also has several limitations, and several scientific questions remain unanswered (Table 2). Copper-coated surfaces have demonstrated the ability to inactivate many key pathogens associated with HAIs. Multiple studies have demonstrated that copper-coated surfaces can reduce the level of contamination on room surfaces by 1- to 2-log₁₀. Importantly, unlike the “no-touch” methods that use UV devices or hydrogen peroxide systems (which currently can only be used for terminal disinfection), copper-coated surface provide continuous disinfection. To date, clinical trials have reported only rare adverse reactions related to contact with a copper-coated surface.

TABLE 2

Advantages and Limitations in the Use of Copper as a Self-Disinfecting Surface in Hospital Rooms

However, currently available studies still leave many questions regarding the routine use of copper-coated surfaces in hospital rooms. First, it is unclear how many and which surfaces must be coated to achieve a reduction in HAIs. Second, the types of copper-coating that have been studied vary, and widely accepted standard for such surfaces do not exist. Third, only a limited number of clinical trials have been published that have assessed whether copper-coated surfaces reduce the incidence of HAIs, and among published studies, copper-coated surfaces have not uniformly been shown to reduce HAIs. Furthermore, the published studies have design flaws including failure to use a randomized design and failure to account for all possible confounding variables (eg, hand-hygiene compliance and cleaning effectiveness). Fourth, current studies investigating microbial reductions associated with copper-coated surfaces or clinical outcomes (ie, reduction of HAIs) have rarely assessed whether residual microbes had intrinsic or acquired resistance to copper. Survival on copper surfaces has been described and appears to be the consequence of endospore formation, survival on patches of dirt, or a special ability to endure a dry metallic copper surface.Reference Grass, Rensing and Solioz ²³ The frequency and importance of reduced susceptibility to copper among healthcare-associated pathogens remains poorly defined but likely will not be clinically significant. Fifth, the cost of purchasing, installing, and maintaining copper-coated surfaces has not been delineated. Sixth, the durability of copper-coated surfaces has been poorly described. Finally, no cost-effective analysis of the use of copper-coated surfaces has been published.

In conclusion, the use of copper-coated surfaces to provide continuous room disinfection is promising, but additional carefully designed and appropriately powered studies are required before this technology should be routinely adopted to prevent HAIs.