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Copper Continuously Limits the Concentration of Bacteria Resident on Bed Rails within the Intensive Care Unit


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Cleaning is an effective way to lower the bacterial burden (BB) on surfaces and minimize the infection risk to patients. However, BB can quickly return. Copper, when used to surface hospital bed rails, was found to consistently limit surface BB before and after cleaning through its continuous antimicrobial activity.
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Copper Continuously Limits the Concentration of Bacteria Resident on Bed Rails within the
Intensive Care Unit
Author(s): Michael G. Schmidt, PhD; Hubert H. Attaway III, MS; Sarah E. Fairey, BS; Lisa L.
Steed, PhD; Harold T. Michels, PhD; Cassandra D. Salgado, MD, MS
Infection Control and Hospital Epidemiology,
Vol. 34, No. 5, Special Topic Issue: The
Role of the Environment in Infection Prevention (May 2013), pp. 530-533
Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiology
of America
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infection control and hospital epidemiology may 2013, vol. 34, no. 5
concise communication
Copper Continuously Limits the
Concentration of Bacteria Resident on
Bed Rails within the Intensive Care
Michael G. Schmidt, PhD;
Hubert H. Attaway III, MS;
Sarah E. Fairey, BS;
Lisa L. Steed, PhD;
Harold T. Michels, PhD;
Cassandra D. Salgado, MD, MS
Cleaning is an effective way to lower the bacterial burden (BB) on
surfaces and minimize the infection risk to patients. However, BB
can quickly return. Copper, when used to surface hospital bed rails,
was found to consistently limit surface BB before and after cleaning
through its continuous antimicrobial activity.
Infect Control Hosp Epidemiol 2013;34(5):530-533
Microbes have an intrinsic ability to survive and colonize
commonly touched surfaces in hospitals. To prevent health-
care-associated infections (HAIs), infection control (IC)
guidelines recommend that, in concert with hand hygiene,
attention be paid to disinfection of patient-care surfaces, es-
pecially those designated high-touch objects (HTOs).
objects could contribute to transmission by contaminating
the hands of healthcare workers (HCWs) who subsequently
contact patients.
Routine and terminal cleaning of surfaces
and objects within the room using a hospital-grade disinfec-
tant has been an accepted method for controlling and limiting
the spread of infectious agents.
A concentration of less than
250 aerobic colony-forming units (cfu) of bacteria per 100
has been proposed as a benchmark where infectious risk
to patients is low.
In 2008, the United States Environmental Protection
Agency (US-EPA) registered 5 families of copper-containing
alloys as antimicrobial, which established that products man-
ufactured from these alloys kill 99.9% (log
2.0) of bacteria
within 2 hours of exposure.
Subsequently, copper has been
used to limit bacterial burden (BB) found on commonly
touched surfaces and objects in healthcare. Casey et al
served a median microbial reduction between 90% and 100%
1.95 to log
2.0) on copper-surfaced push plates, faucet
handles, and toilet seats, whereas Schmidt et al
an 83% (log
1.93) reduction in BB for copper-surfaced ob-
jects over the course of a 43-month multicenter trial.
Cleaning can effectively remove pathogens from surfaces,
but studies have shown that, more than half of the time,
surfaces were not adequately terminally cleaned and may be-
come recontaminated within minutes.
The rails of hospital
beds, as a consequence of coincident interactions with pa-
tients, HCWs, and visitors, are one of the most frequently
touched items in the patient care environment. In this study,
we quantitatively assessed the BB present on bed rails to
evaluate the effectiveness of the antimicrobial properties of
metallic copper to continuously limit the concentration of
bacteria resident before and after routine cleaning.
material and methods
This institutional review board–approved study was con-
ducted within a 17-bed medical intensive care unit (MICU)
of a 660-bed academic hospital. In accordance with hospital
policy, visitors were permitted between 8 am and 8 pm at the
discretion of staff. Each single-patient room contained an In
Touch Critical Care Bed (Stryker). Routine patient care was
provided throughout the course of the study, including teach-
ing rounds, resulting in numerous patient visits with direct
contact between the healthcare team, patients, and built
Standard In Touch beds have 4 plastic rails. Three beds
were custom fitted with copper (UNS# C110 99.9% metallic
copper) surface caps on the rails as described elsewhere by
Schmidt et al.
In accordance with MICU policy, all objects and surfaces
within the patient’s room, including the study bed rails, were
cleaned at least daily and upon patient discharge from the
hospital (ie, terminally cleaned) using the US-EPA–registered
disinfectant Virex II 256, which was dispensed from an au-
tomated dilution system (Use Solution, 0.07% n-alkyl di-
methyl benzyl ammonium chloride and 0.07% didecyl di-
methyl ammonium chloride; Johnson Diversey) as prescribed
by the manufacturer.
Bed rail sampling was conducted in candidate rooms if the
patient housed there would be continuously occupying the
room for the next 8 hours and if sampling at 2-hour intervals
would not affect care. Cleaning staff were not made aware
of the study. Plastic (control) and copper bed rails were sam-
pled immediately before cleaning (time 0) and then at 30
minutes and 2.5, 4.5, and 6.5 hours after cleaning. Samples
were taken on 5 separate occasions over a 3-month period.
Three patient-occupied beds with plastic rails (controls) and
3 with copper rails were sampled on each occasion, resulting
in evaluation of 30 beds. Samples were collected and pro-
cessed as described elsewhere.
The effectiveness with which copper reduced resident BB
was calculated by measuring the difference between the BB
on copper bed rails and that on plastic bed rails. A mean
reduction in BB was calculated for each type of bed rail and
compared using the Mann-Whitney and Wilcoxon rank test
(Epi Info, version 3.5.1). In a previous study, copper surfaces
were associated with an 83% (log
1.92) reduction in BB,
compared with plastic surfaces.
Based on this, we calculated
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copper continuously limits bacterial burden 531
figure 1. Copper continuously limits the concentration of bacteria on bed rails. Shown are the average total aerobic colony-forming
units per 100 cm
recovered from standard plastic bed rails (filled circles) and copper bed rails (open circles) before and after cleaning
with Virex 256. Five independent replicates are shown, and 3 beds of each type were sampled per time period. Dashed line represents the
suggested bacterial burden desired immediately after terminal cleaning (250 colony-forming units per 100 cm
table 1. Assessment of the Antimicrobial Activity of Copper to Control the Bacterial Burden betweenCleanings
with Virex 256
Plastic bed rails Copper bed rails
Time point
Colony count,
mean cfu/100 cm
(SE) Reduction, %
Colony count,
mean cfu/100 cm
(SE) Reduction, % P
Precleaning 6,102 2,572 698 368 .006
Hour 0.5 1,112 802 82 362 282 48 .069
Hour 2.5 1,560 936 74 530 530 24 .012
Hour 4.5 2,396 1,502 61 224 94 68 .013
Hour 6.5 5,198 2,386 15 434 236 38 .002
note. SE, standard error.
that a sample size of 7 beds per group was necessary to have
at least 90% power to detect an absolute BB decrease of 83%
between copper-surfaced bed rails and standard plastic bed
rails at a 5% significance level.
Average length of stay was 7.3 days for patients cared for in
the plastic-railed beds and 8.6 days for patients cared for in
the copper-railed beds. Compared with the mean BB found
on plastic rails, the mean found immediately before cleaning
on copper rails was significantly lower (6,102 cfu per 100 cm
or log
3.79 per 100 cm
vs 698 cfu per 100 cm
or log
per 100 cm
; Figure 1). Subsequent cleaning of bed rails re-
sulted in an immediate decrease in BB regardless of the bed
rail surface. The mean reduction was 82% (1,112 cfu per 100
or log
3.05 per 100 cm
) on plastic rails and 48% (362
cfu per 100 cm
or log
2.56 per 100 cm
) on copper rails.
Continued sampling subsequent to cleaning found that the
mean BB on copper rails remained significantly lower than
that on plastic rails (Table 1). Among the beds with unmo-
dified plastic rails, the highest initial BB recorded at any time
over the study period was 32,400 cfu per 100 cm
per 100 cm
), whereas the lowest was undetectable for 5
(6.6%) of the 75 plastic-railed beds. Among copper beds, the
highest initial BB was 5,310 cfu per 100 cm
2.56 per
100 cm
), whereas the lowest was undetectable for 37 (49.3%)
of 75 copper-railed beds sampled.
In assessing the frequency with which the BB on the sur-
faces of bed rails was below a proposed value that was sug-
gested as low risk immediately after terminal cleaning, 250
cfu per 100 cm
, it was found that the difference observed
between the copper-surfaced and plastic-surfaced rails was
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532 infection control and hospital epidemiology may 2013, vol. 34, no. 5
table 2. Frequency Bacterial Burden Was Below Suggested Terminal Cleaning Standard Immediately before and after Routine
Cleaning Conducted during Routine Patient Care
Bed rails with colony count !250 cfu/100 cm
Time point
Plastic rails associated
with 15 beds
Bed rail colony count
!250 cfu/100 cm
Copper rails associated
with 15 beds
Bed rail colony count
!250 cfu/100 cm
,% P(2-tailed)
Precleaning 4 27 10 67 .067
Hour 0.5 10 67 13 87 .86
Hour 2.5 7 47 12 80 .13
Hour 4.5 8 53 11 73 .44
Hour 6.5 5 33 12 80 .02
Overall 34/75 45 58/75 77 .0001
note. cfu, colony-forming units.
significant ( ). A total of 77% of copper-surfacedPp.0001
rails were below this level, whereas only 45% of plastic rails
were below this critical threshold (Table 2).
The patient room is a kinetic reservoir where hard surfaces,
equipment, furniture, and the belongings of patients serve as
fomites where casual touch may transfer resident microbes
to patients and HCWs. Here, we report the quantitative ef-
fectiveness with which copper surfaces were able to augment
routine cleaning practices to continuously limit the BB res-
ident on the rails of patient beds.
Bacteria responsible for many HAIs can survive for days,
weeks, or months on hospital surfaces in spite of the best
efforts of the healthcare team to keep the BB within limits
considered safe for patient care.
Some have argued that ter-
minal cleaning must achieve a threshold where fewer than
250 cfu per 100 cm
of aerobic bacteria are detectable to
minimize risk of transfer to HCWs or patients.
In previous
work, we described the rapid reestablishment of bacteria on
bed rail surfaces after cleaning with a hospital-grade disin-
These data suggested that, to keep the BB below the
risk-based threshold, surfaces would require cleaning at en-
hanced intervals and that this would result in increased work-
load for HCWs and environmental services. The current study
would suggest that this cleaning interval would need to com-
mence between every 2.5 and 4.5 hours for beds with standard
plastic rails. However, in concert with once-daily cleaning,
copper bed rails were routinely able to maintain a BB below
a low-risk threshold for the entire shift. Low-risk concentra-
tions were associated with 77% of the sampled copper beds.
The use of copper to control BB on surfaces found in
healthcare has been recently reviewed.
Here, we demonstrate
that the antimicrobial activity was continuous in its ability
to limit BB found on bed rails. Weber and Rutala,
in their
commentary of work conducted by Karpanen et al,
that it was impractical or impossible to coat each environ-
mental surface with copper. However, the data provided here
and in other studies suggest that the strategic placement of
copper in key high-touch areas offers a novel strategy to limit
BB on a continuous basis.
Other no-touch methods for room
disinfection (hydrogen peroxide vapor [HPV] and UV light)
rely on discontinuous modalities of application to reduce
environmental BB.
Consequently, like the US-EPA–regis-
tered disinfectants that are regularly used to disinfect patient
rooms subsequent to cleaning, both UV and HPV will likely
have the same limitation of rapid restoration of BB intrinsic
to HTOs. In contrast, copper-alloyed surfaces offer a contin-
uous way to limit and/or control the environmental burden.
Hospital and environmental services need not perform ad-
ditional steps, follow complex treatment algorithms, obtain
“buy-in” from other providers, or require additional training
or oversight.
It is intuitive to argue that, to minimize infectious risk to
a patient, any method that augments the effectiveness of hand
hygiene and routine cleaning will likely translate into lower
rates of HAIs and/or hospital-acquired colonizations with
epidemiologically important pathogens. The continuous an-
timicrobial activity of copper surfaces demonstrated here
should enhance routine and terminal-cleaning practices re-
quired of hospitals.
We acknowledge the assistance of Janet Byrne and the staff of the MUSC
MICU as well as Chuck Stark, Dennis Simon, and Kathy Zolman of Advanced
Technologies Institute; Adam Estelle, Wilton Moran, and Jim Michel of the
Copper Development Association; and Peter Sharpe of Sharpe and Associates
for assistance with developing the copper alloyed bed rails.
Financial support. Supported by the US Army Materiel Command Con-
tract W81XWH-07-C-0053. The views, opinions and/or findings presented
here are those of the authors and should not be construed as an official US
Department of the Army position.
Potential conflicts of interest. H.T.M. is senior vice president for research
and development for the Copper Development Association and was the
principal investigator of the funds awarded to support the study. Heprovided
expertise for antimicrobial alloy specifications. Similar to other authors, he
received salary support and funds to purchase supplies and materials. None
of the other authors received funds from the Copper Development Asso-
ciation for the conduct of this research. The Copper Development Association
did not provide any funds for the conduct of this research. In full disclosure,
the employer of H.T.M. promotes the active use of copper for industrial
applications. All other authors report no conflicts of interest relevant to this
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copper continuously limits bacterial burden 533
article. All authors submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest, and the conflicts that the editors consider relevant to
this article are disclosed here.
Affiliations: 1. Department of Microbiology and Immunology, Medical
University of South Carolina, Charleston, South Carolina; 2. Department of
Pathology and Laboratory Medicine, Medical University of South Carolina,
Charleston, South Carolina; 3. Copper Development Association, New York,
New York; 4. Division of Infectious Diseases, Department of Medicine, Med-
ical University of South Carolina, Charleston, South Carolina.
Address correspondence to Michael G. Schmidt, PhD, Medical University
of South Carolina, Department of Microbiology and Immunology, 173 Ashley
Avenue, BSB 319G, Charleston, SC 29425 (
Received June 3, 2012; accepted August 26, 2012; electronically published
April 9, 2013.
2013 by The Society for Healthcare Epidemiology of America. All rights
reserved. 0899-823X/2012/3405-0016$15.00. DOI: 10.1086/670224
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... Among the two, MRSA is of particular concern due to the increasing number of infections [27,52]. Against this backdrop, we note that recent studies have found that copper and its alloys can kill MRSA, Acinetobacter strains, E. coli, several other bacteria strains, and can inactivate norovirus, coronavirus (SARS-CoV and SARS-CoV-2), and many other viruses [3,51,[55][56][57][58]. Of considerable relevance here is that it has been shown that not only pure copper surfaces but copper alloys such as bronze and brass have also been shown to kill or inactivate potentially deadly microbes [59][60][61]. ...
... It was also noticed that placing copper alloy surfaces in the ICU rooms reduced the risk of HAI by more than half during the study period, and no HAI outbreak of epidemiologically important organisms occurred in copper-alloy equipped ICUs. A detailed study was conducted in another 16 ICU rooms (eight experimental rooms and eight control rooms) of three hospitals in the USA over 21 months, replacing the normal hand-touch steel surfaces with copper, and this study also found that copper materials at the hand-touch surfaces significantly reduced the microbial burden (698 vs. 6102 CFU per 100 cm 2 , 88% reduction) [57]. ...
... Other studies conducted in the health care environment have also reported the benefits of replacing plastic hospital beds with copper or copper alloys due to the significant reduction in the microbial burden [66][67][68][69]. However, the studies revealed that the contact-killing property increases with an increase in copper concentration, and a minimum of 60% copper concentration is required in alloys to get the best result [16,57,[70][71][72]. Souli et al. [72] studied the antibacterial efficacy of two copper coatings (99% and 63% copper concentrations) on various multi-drug resistant Gram-negative pathogens responsible for nosocomial infections such as E. coli, Enterobacter spp., K. pneumonia, P. aeruginosa, and Acinetobacter baumannii (A. ...
Full-text available
Pathogen transfer and infection in the built environment are globally significant events, leading to the spread of disease and an increase in subsequent morbidity and mortality rates. There are numerous strategies followed in healthcare facilities to minimize pathogen transfer, but complete infection control has not, as yet, been achieved. However, based on traditional use in many cultures, the introduction of copper products and surfaces to significantly and positively retard pathogen transmission invites further investigation. For example, many microbes are rendered unviable upon contact exposure to copper or copper alloys, either immediately or within a short time. In addition, many disease-causing bacteria such as E. coli O157:H7, hospital superbugs, and several viruses (including SARS-CoV-2) are also susceptible to exposure to copper surfaces. It is thus suggested that replacing common touch surfaces in healthcare facilities, food industries, and public places (including public transport) with copper or alloys of copper may substantially contribute to limiting transmission. Subsequent hospital admissions and mortality rates will consequently be lowered, with a concomitant saving of lives and considerable levels of resources. This consideration is very significant in times of the COVID-19 pandemic and the upcoming epidemics, as it is becoming clear that all forms of possible infection control measures should be practiced in order to protect community well-being and promote healthy outcomes.
... Copper alloys are the most commonly evaluated option for antimicrobial surfaces, and have demonstrated in vitro activity against a range of pathogens, and have been effective at reducing healthcare associated infections. [33][34][35] As shown in Figure 5, its use relies on the production of copper ions (Cu 2+ ) that are considered to be the predominant antimicrobial species. 36 Application: Touch surfaces in the clinical environment • The advantage of organosilane products is they can be attached to both soft and hard surfaces. ...
Full-text available
Issues: Contaminated surfaces and medical devices contribute to the transmission of healthcare-associated infection (HCAI) and the spread of antimicrobial resistance (AMR). Surface-attached biofilms (communities of microbial and non-microbial matter on surfaces) support microbial survival, persistence, and can protect microbes from attack by biocides and antibiotics. Biofilms also play a role in several important infection pathways including infections related to medical devices (e.g. catheter-associated urinary tract infections), prosthesis-related infections (e.g. infected hip joints), and water-borne infections (e.g. Pseudomonasand Legionalla contamination of hospital water systems). These pathways are increasingly recognised in the transmission of pathogens that can cause HCAI and increase AMR. A 2016 Public Health England survey of over 48,000 patient records found that 6.6% of patients acquired HCAI in hospitals. Solutions: Antimicrobial surfaces could disrupt the microbial habit by reducing microbial attachment and/or killing attached microbes. The design, manufacture and testing of antimicrobial surface technologies must involve multidisciplinary teams from molecular science, engineering, medicine and business. Potential application areas for antimicrobial surfaces include: Improving the design of medical devices in order to reduce the risk of infection; Reducing the risk of infection related to surgically implanted prosthesis (such as hip and knee joints); Transforming the clinical environment to have touch surfaces with antimicrobial properties (e.g. coated bed rails) particularly for the prevention of infection in vulnerable patient groups such as adults and neonates in intensive care. To make hospital water system less prone to contamination with bacteria such as Pseudomonas and Legionella. In addition to applications in the hospital environment of developed countries, antimicrobial surfaces should be developed with low and middle-income (LMIC) settings in mind, where these surfaces could mitigate the impact of additional challenges related to LMIC settings (such as lack of power and clean water). The spread of infection and antimicrobial resistance in the clinical environment cannot be tackled by antimicrobial surfaces alone, but be employed as part of a combined approach involving clinical and cleaning staff following protocols developed to prevent the spread of microbes, and the responsible distribution and use of antibiotics.
... Furthermore, there are also a number of experiments being conducted in clinics or hospitals. In those actual environments, various touched objects such as handles [22], bed rails [23,24], chairs [25], tables [24,26], pens [27], push plates, and even toilet seats [28] were newly equipped with different types of copper surfaces. These experiments usually lasted for weeks or months and many positive results have been obtained. ...
*Full text is available in the database* Metallic copper has been widely proved as a promising antibacterial surface. This work aims to investigate the copper corrosion phenomena mostly observed in a certain type of antibacterial efficiency test, the so-called droplet method. By performing various ex-situ metallurgical methods, chemical and morphological changes on copper surfaces were characterised, with which the copper ion content and antibacterial activity were correlated. All these findings not only help to understand the origin of the antibacterial copper ion release, but also shift the research focus back on the copper surface itself, suggesting how materials research can function in antibacterial surface design.
... Schmidt et al. [103] worked on the bioburden of the sole bedrails, arguing that these devices were at the cross-road of potential contaminations by patients, healthcare workers and visitors. This study was held on a limited number of beds but took into account the impact of cleaning practices by sampling the devices once before and multiple times after the daily cleaning routine. ...
Full-text available
Copper has been used for its antimicrobial properties since Antiquity. Nowadays, touch surfaces made of copper-based alloys such as brasses are used in healthcare settings in an attempt to reduce the bioburden and limit environmental transmission of nosocomial pathogens. After a brief history of brass uses, the various mechanisms that are thought to be at the basis of brass antimicrobial action will be described. Evidence shows that direct contact with the surface as well as cupric and cuprous ions arising from brass surfaces are instrumental in the antimicrobial effectiveness. These copper ions can lead to oxidative stress, membrane alterations, protein malfunctions, and/or DNA damages. Laboratory studies back up a broad spectrum of activity of brass surfaces on bacteria with the possible exception of bacteria in their sporulated form. Various parameters influencing the antimicrobial activity such as relative humidity, temperature, wet/dry inoculation or wear have been identified, making it mandatory to standardize antibacterial testing. Field trials using brass and copper surfaces consistently report reductions in the bacterial bioburden but, evidence is still sparse as to a significant impact on hospital acquired infections. Further work is also needed to assess the long-term effects of chemical/physical wear on their antimicrobial effectiveness.
... Although the antimicrobial mechanisms of Cu are not fully understood, Cu ions released from the Cu surface are largely believed to play a key role for inducing bacterial death [16,[20][21][22]. The infection chain in bacteria-favored environments has been shown to efficiently break via contact with Cu-based surfaces as a result of a considerable reduction in the number of bacteria, a process known as "contact killing" [22][23][24][25][26][27]. This remarkable reduction in number of microorganisms has been reported in studies both at laboratory conditions and at real settings in hospitals [28]. ...
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Metal-based high-touch surfaces used for indoor applications such as doorknobs, light switches, handles and desks need to remain their antimicrobial properties even when tarnished or degraded. A novel laboratory methodology of relevance for indoor atmospheric conditions and fingerprint contact has therefore been elaborated for combined studies of both tarnishing/corrosion and antimicrobial properties of such high-touch surfaces. Cu metal was used as a benchmark material. The protocol includes pre-tarnishing/corrosion of the high touch surface for different time periods in a climatic chamber at repeated dry/wet conditions and artificial sweat deposition followed by the introduction of bacteria onto the surfaces via artificial sweat droplets. This methodology provides a more realistic and reproducible approach compared with other reported procedures to determine the antimicrobial efficiency of high-touch surfaces. It provides further a possibility to link the antimicrobial characteristics to physical and chemical properties such as surface composition, chemical reactivity, tarnishing/corrosion, surface roughness and surface wettability. The results elucidate that bacteria interactions as well as differences in extent of tarnishing can alter the physical properties (e.g. surface wettability, surface roughness) as well as the extent of metal release. The results clearly elucidate the importance to consider changes in chemical and physical properties of indoor hygiene surfaces when assessing their antimicrobial properties.
... Since then, many more types of viruses have revealed their susceptibility to copper (e.g., single-or double-stranded DNA or RNA enveloped or nonenveloped viruses), one of which being HIV [145,148]. Additionally, copper used in hospital settings has shown that bed rails made out of copper reduce the bacterial burden and healthcare-acquired infections because of its continuous antimicrobial activity [149,150]. Moreover, linen with copper fabrics or impregnated with copper oxide has shown efficient reduction of healthcare-associated infections [151,152]. ...
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Thirty-five thousand people die as a result of more than 2.8 million antibiotic-resistant infections in the United States of America per year. Pseudomonas aeruginosa (P. aeruginosa) is classified a serious threat, the second-highest threat category of the U.S. Department of Health and Human Services. Among others, the World Health Organization (WHO) encourages the discovery and development of novel antibiotic classes with new targets and mechanisms of action without cross-resistance to existing classes. To find potential new target sites in pathogenic bacteria, such as P. aeruginosa, it is inevitable to fully understand the molecular mechanism of homeostasis, metabolism, regulation, growth, and resistances thereof. P. aeruginosa maintains a sophisticated copper defense cascade comprising three stages, resembling those of public safety organizations. These stages include copper scavenging, first responder, and second responder. Similar mechanisms are found in numerous pathogens. Here we compare the copper-dependent transcription regulators cueR and copRS of Escherichia coli (E. coli) and P. aeruginosa. Further, phylogenetic analysis and structural modelling of mexPQ-opmE reveal that this efflux pump is unlikely to be involved in the copper export of P. aeruginosa. Altogether, we present current understandings of the copper homeostasis in P. aeruginosa and potential new target sites for antimicrobial agents or a combinatorial drug regimen in the fight against multidrug resistant pathogens.
The rise in antimicrobial resistant bacteria have prompted the need for antibiotic alternatives. To address this problem, significant attention has been given to the antimicrobial use and novel applications of copper. As novel applications of antimicrobial copper increase, it is important to investigate how bacteria may adapt to copper over time. Here, we used experimental evolution with re-sequencing (EER-seq) and RNA-sequencing to study the evolution of copper resistance in Escherichia coli. Subsequently, we tested whether copper resistance led to rifampicin, chloramphenicol, bacitracin, and/or sulfonamide resistance. Our results demonstrate that E. coli is capable of rapidly evolving resistance to CuSO4 after 37 days of selection. We also identified multiple de novo mutations and differential gene expression patterns associated with copper, most notably those mutations identified in the cpx gene. Furthermore, we found that the copper resistant bacteria had decreased sensitivity when compared to the ancestors in the presence of chloramphenicol, bacitracin, and sulfonamide. Our data suggest that the selection of copper resistance may inhibit growth in the antimicrobials tested, resulting in evolutionary trade-offs. The results of our study may have important implications as we consider the antimicrobial use of copper and how bacteria may respond to increased use over time. Keywords: Escherichia coli; copper; experimental evolution; genomics; antibiotics
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Healthcare-associated infections (HAIs) contribute to patient morbidity and mortality with an estimated 1.7 million infections and 99,000 deaths costing USD $28–34 billion annually in the United States alone. There is little understanding as to if current environmental surface disinfection practices reduce pathogen load, and subsequently HAIs, in critical care settings. This evidence map includes a systematic review on the efficacy of disinfecting environmental surfaces in healthcare facilities. We screened 17,064 abstracts, 635 full texts, and included 181 articles for data extraction and study quality assessment. We reviewed ten disinfectant types and compared disinfectants with respect to study design, outcome organism, and fourteen indictors of study quality. We found important areas for improvement and gaps in the research related to study design, implementation, and analysis. Implementation of disinfection, a determinant of disinfection outcomes, was not measured in most studies and few studies assessed fungi or viruses. Assessing and comparing disinfection efficacy was impeded by study heterogeneity; however, we catalogued the outcomes and results for each disinfection type. We concluded that guidelines for disinfectant use are primarily based on laboratory data rather than a systematic review of in situ disinfection efficacy. It is critically important for practitioners and researchers to consider system-level efficacy and not just the efficacy of the disinfectant.
Objectives Estimated levels of microbial burden on hospital environmental surfaces vary substantially among published studies. Cultures obtained during a cluster-controlled crossover trial of a quaternary ammonium (Quat) disinfectant versus an improved hydrogen peroxide (IHP) disinfectant provided additional data on the amount of microbial burden on selected surfaces. Methods RODAC plates containing D/E neutralizing agar were used to sample a convenience sample of 5–8 high-touch surfaces in patient rooms on 2 medical wards, an intensive care unit, and a step-down unit at a large hospital. Before routine daily cleaning, samples were obtained in varying rooms over an 11-month period. RODAC plates (1 per surface sampled) were incubated for 72 hours, and aerobic colony counts per plate (ACCs) were determined. Statistical analysis was used to determine the potential impact on ACCs of study period, cleaning compliance rate, disinfectant used, ward, surface sampled, and isolation room status. Results Overall, 590 cultures were obtained on Quat wards and 589 on IHP wards. Multivariable regression analysis revealed that mean ACCs differed significantly by site ( P < .001), type of ward ( P < .001), isolation room status ( P = .039), and study period ( P = .036). The highest mean ACCs per RODAC plate were on toilet seats (112.8), bedside rails (92.0), and bathroom grab bars (79.5). Conclusions The combination of factors analyzed revealed that estimating microbial burden is complex and is affected by multiple factors. Additional studies should evaluate individual sites, ward types, cleaning and disinfection practices, and isolation room status.
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The interplay between atmospheric corrosion and antimicrobial efficiency of bare Cu and Cu5Zn5Al1Sn was studied upon exposures simulating high-touch surface conditions. The survival of the bacteria Bacillus subtilis during surface contact with Cu and Cu5Zn5Al1Sn was examined under different degrees of surface oxidation, tarnishing, wettability and copper ion release. Depending on surface conditions complete bacteria inhibition was obtained within 4 min on Cu and within 6 to 10 min on Cu5Zn5Al1Sn. The antibacterial efficiency increases slightly with copper release rate and is governed by complex interactions between the corroded metal surface, bacteria and extracellular polymeric substances produced by the bacteria.
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The contribution of environmental surface contamination with pathogenic organisms to the development of health care-associated infections (HAI) has not been well defined. The microbial burden (MB) associated with commonly touched surfaces in intensive care units (ICUs) was determined by sampling six objects in 16 rooms in ICUs in three hospitals over 43 months. At month 23, copper-alloy surfaces, with inherent antimicrobial properties, were installed onto six monitored objects in 8 of 16 rooms, and the effect that this application had on the intrinsic MB present on the six objects was assessed. Census continued in rooms with and without copper for an additional 21 months. In concert with routine infection control practices, the average MB found for the six objects assessed in the clinical environment during the preintervention phase was 28 times higher (6,985 CFU/100 cm(2); n = 3,977 objects sampled) than levels proposed as benign immediately after terminal cleaning (<250 CFU/100 cm(2)). During the intervention phase, the MB was found to be significantly lower for both the control and copper-surfaced objects. Copper was found to cause a significant (83%) reduction in the average MB found on the objects (465 CFU/100 cm(2); n = 2714 objects) compared to the controls (2,674 CFU/100 cm(2); n = 2,831 objects [P < 0.0001]). The introduction of copper surfaces to objects formerly covered with plastic, wood, stainless steel, and other materials found in the patient care environment significantly reduced the overall MB on a continuous basis, thereby providing a potentially safer environment for hospital patients, health care workers (HCWs), and visitors.
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Background: Commonly touched items are likely reservoirs from which patients, health care workers, and visitors may encounter and transfer microbes. A quantitative assessment was conducted of the risk represented by the intrinsic bacterial burden associated with bed rails in a medical intensive care unit (MICU), and how disinfection might mitigate this risk. Methods: Bacteria present on the rails from 36 patient beds in the MICU were sampled immediately before cleaning and at 0.5, 2.5, 4.5, and 6.5 hours after cleaning. Beds were sanitized with either a bottled disinfectant (BD; CaviCide) or an automated bulk-diluted disinfectant (ABDD; Virex II 256). Results: The majority of bacteria recovered from the bed rails in the MICU were staphylococci, but not methicillin-resistant Staphylococcus aureus. Vancomycin-resistant enterococci were recovered from 3 beds. Bottled disinfectant reduced the average bacterial burden on the rails by 99%. However, the burden rebounded to 30% of that found before disinfection by 6.5 hours after disinfection. ABDD reduced the burden by an average of 45%, but levels rebounded within 2.5 hours. The effectiveness of both disinfectants was reflected in median reductions to burden of 98% for BD and 95% for ABDD. Conclusions: Cleaning with hospital-approved disinfectants reduced the intrinsic bacterial burden on bed rail surfaces by up to 99%, although the population, principally staphylococci, rebounded quickly to predisinfection levels.
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To determine whether copper incorporated into hospital ward furnishings and equipment can reduce their surface microbial load. A crossover study. Acute care medical ward with 19 beds at a large university hospital. Fourteen types of frequent-touch items made of copper alloy were installed in various locations on an acute care medical ward. These included door handles and push plates, toilet seats and flush handles, grab rails, light switches and pull cord toggles, sockets, overbed tables, dressing trolleys, commodes, taps, and sink fittings. Their surfaces and those of equivalent standard items on the same ward were sampled once weekly for 24 weeks. The copper and standard items were switched over after 12 weeks of sampling to reduce bias in usage patterns. The total aerobic microbial counts and the presence of indicator microorganisms were determined. Eight of the 14 copper item types had microbial counts on their surfaces that were significantly lower than counts on standard materials. The other 6 copper item types had reduced microbial numbers on their surfaces, compared with microbial counts on standard items, but the reduction did not reach statistical significance. Indicator microorganisms were recovered from both types of surfaces; however, significantly fewer copper surfaces were contaminated with vancomycin-resistant enterococci, methicillin-susceptible Staphylococcus aureus, and coliforms, compared with standard surfaces. Copper alloys (greater than or equal to 58% copper), when incorporated into various hospital furnishings and fittings, reduce the surface microorganisms. The use of copper in combination with optimal infection-prevention strategies may therefore further reduce the risk that patients will acquire infection in healthcare environments.
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This study evaluated three methods for monitoring hospital cleanliness. The aim was to find a benchmark that could indicate risk to patients from a contaminated environment. We performed visual monitoring, ATP bioluminescence and microbiological screening of five clinical surfaces before and after detergent-based cleaning on two wards over a four-week period. Five additional sites that were not featured in the routine domestic specification were also sampled. Measurements from all three methods were integrated and compared in order to choose appropriate levels for routine monitoring. We found that visual assessment did not reflect ATP values nor environmental contamination with microbial flora including Staphylococcus aureus and meticillin-resistant S. aureus (MRSA). There was a relationship between microbial growth categories and the proportion of ATP values exceeding a chosen benchmark but neither reliably predicted the presence of S. aureus or MRSA. ATP values were occasionally diverse. Detergent-based cleaning reduced levels of organic soil by 32% (95% confidence interval: 16-44%; P<0.001) but did not necessarily eliminate indicator staphylococci, some of which survived the cleaning process. An ATP benchmark value of 100 relative light units offered the closest correlation with microbial growth levels <2.5 cfu/cm(2) (receiver operating characteristic ROC curve sensitivity: 57%; specificity: 57%). In conclusion, microbiological and ATP monitoring confirmed environmental contamination, persistence of hospital pathogens and measured the effect on the environment from current cleaning practices. This study has provided provisional benchmarks to assist with future assessment of hospital cleanliness. Further work is required to refine practical sampling strategy and choice of benchmarks.
The antimicrobial effect of copper has long been recognized and has a potential application in the healthcare setting as a mechanism to reduce environmental contamination and thus prevent healthcare-associated infection (HCAI). To review the rationale for copper use, the mechanism of its antimicrobial effect, and the evidence for its efficacy. A PubMed search of the published literature was performed. Extensive laboratory investigations have been carried out to investigate the biocidal activity of copper incorporated into contact surfaces and when impregnated into textiles and liquids. A limited number of clinical trials have been performed, which, although promising, leave significant questions unanswered. In particular there is a lack of consensus on minimum percentage copper alloys required for effectiveness, the impact of organic soiling on the biocidal effect of copper, and the best approach to routine cleaning of such surfaces. Limited information is available on the ability of copper surfaces to eradicate spores of Clostridium difficile. Additional studies to demonstrate that installing copper surfaces reduces the incidence of HCAI are required and the cost-effectiveness of such intervention needs to be assessed. Further research in a number of key areas is required before the potential benefits of using copper routinely in the clinical setting to prevent and control infection can be confirmed and recommended.
To compare the microbiological efficacy of hydrogen peroxide vapor (HPV) and ultraviolet radiation (UVC) for room decontamination. Prospective observational study. 500-bed teaching hospital. HPV and UVC processes were performed in 15 patient rooms. Five high-touch sites were sampled before and after the processes and aerobic colony counts (ACCs) were determined. Carrier disks with ∼10(6) Clostridium difficile (CD) spores and biological indicators (BIs) with 10(4) and 10(6) Geobacillus stearothermophilus spores were placed in 5 sites before decontamination. After decontamination, CD log reductions were determined and BIs were recorded as growth or no growth. 93% of ACC samples that had growth before HPV did not have growth after HPV, whereas 52% of sites that had growth before UVC did not have growth after UVC (P < .0001). The mean CD log reduction was >6 for HPV and ∼2 for UVC. After HPV 100% of the 10(4) BIs did not grow, and 22% did not grow after UVC, with a range of 7%-53% for the 5 sites. For the 10(6) BIs, 99% did not grow after HPV and 0% did not grow after UVC. Sites out of direct line of sight were significantly more likely to show growth after UVC than after HPV. Mean cycle time was 153 (range, 140-177) min for HPV and 73 (range, 39-100) min for UVC (P < .0001). Both HPV and UVC reduce bacterial contamination, including spores, in patient rooms, but HPV is significantly more effective. UVC is significantly less effective for sites that are out of direct line of sight.
Recent studies using direct covert observation or a fluorescent targeting method have consistently confirmed that most near patient surfaces are not being cleaned in accordance with existing hospital policies while other studies have confirmed that patients admitted to rooms previously occupied by patients with hospital pathogens have a substantially greater risk of acquiring the same pathogen than patients not occupying such rooms. These findings, in the context recent studies that have shown disinfection cleaning can be improved on average more than 100% over baseline, and that such improvement has been associated with a decrease in environmental contamination of high touch surfaces, support the benefit of decreasing environmental contamination of such surfaces. This review clarifies the differences between measuring cleanliness versus cleaning practices; describes and analyzes conventional and enhanced monitoring programs; addresses the critical aspects of evaluating disinfection hygiene in light of guidelines and standards; analyzes current hygienic practice monitoring tools; and recommends elements that should be included in an enhanced monitoring program.