When Hollywood tires of rounding up the usual suspects-gangsters and terrorists-they turn to an old reliable villain: the deadly virus that threatens to annihilate the entire human race. Sharks make a worthy villain, but if you don't swim in the ocean, you have a pretty good chance of never meeting up with a Great White. But a deadly virus, whether airborne or spread by monkeys, can reach anyone, anyplace at any time.
Koltnow 1
LETHAL MICROORGANISMS have terrorized man since the beginning of time, killing more human beings than anything else in history. The most infamous epidemic, the Black Death, wiped out almost half the population of Europe. Plague, malaria, and cholera are still dangerous today and are joined by modern pandemics such as AIDS and the bird and swine flus. H. G. Wells, a late 19th century biologist, science fiction writer, and celebrated "futurist" said, "adapt or perish, now as ever, is nature's inexorable imperative." Wells created doom's day scenarios that would rival the threat we face today by an army of invisible organisms that are spreading across the planet, evolving and adapting to the man's best weaponry.
Like hazardous shape-shifting objects of science fiction lore, these superbugs continually alter their structure, leaving antibiotics powerless at finding their targets.2 Superbugs are nature's revenge on humans for their ingenuity. For decades, antibiotics, which work by honing in on particular bacteria, have been the chief line of defense against infection. But superbugs have developed clever means of resisting medicines. Although this is a natural, evolutionary phenomenon, humans have hastened this portent with the global overuse of antibiotics.3 Why are bacteria so successful in fighting back? Many bacteria can divide as fast as every 20 minutes under ideal conditions, which allows them to adapt very rapidly to adverse environments. By acquiring pieces of DNA from other bacteria, strains are selected that have a fitness advantage and over time can build up a catalogue of genes that help them to survive. Acquiring DNA that codes for antibiotic resistance is a prime example of this process and is fuelled by antibiotic use.4 Further underlining their adversarial relationship with modern medicine, these organisms are particularly associated with hospitals, which are traditionally trusted safe havens for the most vulnerable. Hospitals have become fertile breeding grounds for these resilient opponents, which have come with great human expense. If left free to roam around unhindered, their potential for devastation is considerable.2,5,6
HUMAN AND FINANCIAL COSTS OF HOSPITAL-ACQUIRED INFECTIONS
In the United States, 4.5% of hospitalized patients develop hospital-acquired infections (HAIs), resulting in an estimated 100 000 deaths and adding $35.7 to $45 billion to health care costs. Furthermore, patients with HAIs have longer lengths of stay (21.6 vs 4.9 days), higher readmission rates within 30 days (29.8% vs 6.2%), and greater mortality (9.4% vs 1.8%). Hospital infections account for more deaths than the 18 000 people dying prematurely from being underinsured and more deaths than AIDS, breast cancer, and auto accidents combined. With 103 000 deaths per year, it is the fourth largest killer in the United States.7,8 To further inflame the situation, the costs of HAIs are progressively being allocated to providers. Selected in 2008 by the Centers for Medicare & Medicaid Services as "Never Events," HAIs were included in the Final Rule for exclusion from additional hospital reimbursement. Acknowledging these data, the Centers for Medicare & Medicaid Services is continuing to consider HAIs in its subsequent rule making.9
Intensive care unit (ICU) patients are at further risk for HAIs because of the severity of their illnesses, invasive procedures, and frequent interaction with health care workers (HCWs). Movement of organisms within hospitals is complex and may depend on microbes residing on environmental surfaces, indwelling devices, a patient's own flora, and transiently colonized HCWs' hands, clothing, and equipment. Environmental contamination can contribute to the acquisition of microbes responsible for HAIs and can persist for weeks on materials used to fabricate objects in hospitals.7
Both vertical and horizontal interventions to prevent HAIs require upfront investments to pay for components of the intervention such as supplies (eg, gowns and gloves) and laboratory resources (eg, tests, personnel). A business case can be made for these interventions, since the estimated median cost of a health care-associated infection ranges from $17 143 to $34 657 for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus (VRE) alone. Mathematical models in ICU studies have shown that targeted active surveillance and isolation of high-risk patients were more cost-effective than the savings from whole hospital, universal active surveillance (see Section B Chapter 7 AHRQ Infection HAI for references).
Universal active surveillance for MRSA may be optimal for hospitals with endemic MRSA throughout their hospital, whereas ICU-level universal contact precautions may be recommended for hospitals with multidrug-resistant Acinetobacter baumannii transmission in their ICU. Interventions such as active surveillance, contact precautions, and contact isolation should not be performed alone. Rather, these interventions must be performed in conjunction with other infection control interventions such as hand hygiene and antimicrobial stewardship (see Section B Chapter 7 AHRQ Infection HAI for references). No one strategy or method appears to stand out as the panacea we are searching for, leaving us debating on the value of means and methods to contaminant controls. One thing that is certain though is that infection control planning must start with an interdisciplinary team effort that includes all stakeholders, including the clinical infection control team, environmental services (ESs), clinical staff, ancillary services, quality assurance and patient safety committees, and administration for a successful program to mitigate the risk of HAI in critical care units.
HISTORICAL OVERVIEW
Hospitals started paying attention to infection control in the late 1880s, when mounting evidence showed unsanitary conditions were hurting patients. A renewed emphasis on hygiene was triggered by the emergence a decade ago of a nasty strain of Clostridium difficile. Community-associated C difficile infections, even among previously healthy people, have continued to rise, with diarrhea-causing C difficile now linked to 14 000 US deaths annually (increasing from 793 deaths in 1999), and in 2007, it was ranked among the 20 leading causes of mortality among Americans older than 65 years (see Section B Chapter 7 AHRQ Infection HAI for references).
In 2003, a coronavirus related to severe acute respiratory syndrome erupted in East Asia, leaping to humans from animal hosts, eventually killing some 800 people in a worldwide epidemic. In 2005, 18 650 patients with MRSA died, more than the number of Americans who died from HIV/AIDS in that same year. Despite decades of infection control interventions, HAIs continue to be a major burden on US hospitals. Currently, there is a rising wave of new emergent HAIs, including multidrug resistant strains of A baumannii, carbapenem-resistant Enterobacteriaceae (CRE), and Klebsiella pneumoniae (see Section B Chapter 7 AHRQ Infection HAI for references).
"From the perspective of contemporary drug-resistant organisms, (CRE) is the most serious threat, the most serious challenge we face to patient safety," says Arjun Srinivasan, Associate Director for Prevention of Health Care-Associated Infections at the Centers for Disease Control and Prevention (CDC). Since the first known case, at a North Carolina hospital, was reported in 2001, the bacteria's ability to defeat even the most potent antibiotics has conjured fears of illnesses that cannot be stopped. Death rates among patients with CRE infections can be 40%, far worse than other, better-known health care infections such as MRSA or C difficile, which have plagued hospitals for decades, increasing concerns that CRE could make its way beyond health facilities and into the general community (see Section B Chapter 7 AHRQ Infection HAI for references).10
On May 28, 2013, Dr Margaret Chan, head of the World Health Organization, at the 64th World Health Assembly, updated earlier reports of a deadly new respiratory virus. The Middle East Respiratory Syndrome Coronavirus was first identified in late 2012 and described in scientific journals mid-May 2013. It has emerged with a vengeance, killing half of the people known to be infected. The first samples of Middle East Respiratory Syndrome Coronavirus were obtained from an intensive care unit patient in Saudi Arabia, with documented cases being transmitted from index patients to family members. Although an animal reservoir is suspected, none has been discovered. Meanwhile, cases have ping-ponged across continents with clusters of infection, including patient-to-patient and patient to HCW transmissions. "We understand too little about this virus when viewed against the magnitude of its potential threat," Chan said.
We do not know where the virus hides in nature. We do not know how people are getting infected. Until we answer these questions, we are empty-handed when it comes to prevention. These are alarm bells. And we must respond. The novel coronavirus is not a problem that any single affected country can keep to itself or manage all by itself. It is a global threat.
An antibiotic apocalypse is looming as the cast of enemies continuing to grow.
Manufacturers have no new antibiotics ready to release that show promise, with only 2 new antibiotics being released since 2007 and historically a 10-year average lead time to market. There is little incentive for drug companies to invest in developing alternatives. Effective medications would be taken only until a patient recovered, making them far less profitable than lifelong drugs for chronic illnesses. Plus, CREs have developed new resistance so quickly that any new antibiotic is not likely to last.10 The era of the ready and rapid cure of common bacterial infections may be coming to an end, heralding a return to a time when such diseases were the most common cause of death.4 Thus, eradication of these superbugs may not be feasible; so for now, preventing the spread of these infections, not treatment, is the most sustainable strategy to control health care-associated infections.
MOBILE PATIENTS AND MOBILE BUGS: TRACKING AN ELUSIVE KILLER
The reservoir for many HAIs is primarily colonized or infected patients. Transiently colonized HCWs and contaminated items in the environment are often intermediates in the patient-to-patient transmission of these pathogens. Thus, breaking transmission from these reservoirs is the most important strategy to prevent HAIs (see Section B Chapter 7 AHRQ Infection HAI for references). There are many challenges to containing the spread of superbugs, but one of the most daunting and immediate is figuring out where it is showing up and getting a reliable national picture of prevalence or where cases are concentrated. Data are so isolated, and the reporting methodologies so varied that the reports are of little practical use. "If we don't know the scope and we don't know the distribution-how big is the problem and where is the problem-it's hard to know the next piece, which is what (prevention strategies) are you going to implement and where?" says Claudia Steiner, a physician and research officer at the U.S. Agency for Healthcare Research and Quality.10
It is especially important to know where CRE bacteria are emerging because they spread among patients who bounce between or among clinics, surgical centers, rehabilitation facilities, nursing homes, and, of course, hospitals. Not all of those infected are symptomatic: the bacteria can lurk, unseen, until a carrier's immune system is compromised or until the bug finds a path into the body and infection sets in. As those patients move from one facility to another, the bacteria move with them, often clinging to caregivers' hands-and moving to new victims. No facility is an island; if a nursing home patient is carrying CRE and gets sick in the night, the staff there just want to get him to a hospital; they may not know much about his (history), so that information does not come with him. But the bacteria do. Meanwhile, the bacteria cycle from one facility to the next-and back.10 So, how do we track these superbugs?
Database systems have been introduced and are evolving to automate the collection and monitoring of patients' laboratory results but, unfortunately, many facilities are still challenged with time-consuming manual infection control. Integrated computerized medical software can aid in making optimal treatment decisions. Data-driven ICU platforms are available that offer an infrastructure for infection surveillance, extended data mining, and modeling of critical illness to reduce improper use of antibiotics and to offer an earlier, more accurate detection of antibiotic resistant organisms and increased efficacy of patient care.
Halting the current emergence of ever-more resistant bacterial pathogens also requires attention to the root cause, which means rigorous control of antibiotic use. This is difficult to achieve on a global scale and has had little success in much of the developing world where antibiotics are available over the counter. In the meantime, control efforts rely on tracking the emergence and spread of multidrug-resistant strains and the rapid detection and containment of outbreaks. Researchers at the University of Cambridge believe that this is where technologies based on whole genome sequencing (WGS) could really make a difference in detecting these outbreaks quickly so that they can be efficiently controlled.4
Researchers, particularly in the case of CRE, realized that they were seeing a mobile genetic event; it looked like a single resistance gene was jumping among different bacteria from the Enterobacteriaceae family, creating new bugs before their eyes. A common resistance gene was identified among the different CRE bacteria. The gene was jumping, one by one, to other species of Enterobacteriaceae bacteria, creating new carbapenem-defying bugs. The doctors were seeing, in real time, a phenomenon that had worried researchers for years: the ability of CRE to share resistance genes across different members of the Enterobacteriaceae family. The big fear is that the genes may start to convey resistance to more common strains of the bacteria, turning routine illnesses, such as urinary tract infections, into untreatable nightmares. Worst-case scenario: resistance could move to bacteria outside of health care, so people could pick it up in the community through something as simple as a handshake.10 Integration of genomic and epidemiological data can yield actionable insights and facilitate the control of nosocomial transmission (see Section B Chapter 7 AHRQ Infection HAI for references). If there is any hint of resistance, we need to know about it. Genes are hitching a ride among bacteria on mobile pieces of DNA, called plasmids, that can move from one cell to another. Genetic tests have been developed that can identify those plasmids-and the bacteria they had affected-in days. Traditional tests to identify the resistance-carrying plasmids can take months.10
In a study published in June 2012 on MRSA, WGS was combined with the search for tiny variations in the sequence of different strains. This showed that "genetic fingerprints" could be used to distinguish between bacteria isolated from patients who were involved in an outbreak and bacteria isolated from those who were not. Subsequent studies showed that WGS could be used to detect the spread of MRSA from hospitals into the community and was used to identify a carrier in the hospital, helping to bring the outbreak to a close. Efforts are now under way to apply this technology to other bacteria, including multidrug-resistant gram-negative bacilli, a group that comprises some of the most pathogenic disease-causing bacteria.4
How does this approach differ from what we can already do? Current bacterial typing methods often lack sufficient discrimination to be able to distinguish between strains of the same bacterial species isolated from different people. This means that we cannot confirm whether transmission has taken place, and so typing is not used as part of routine infection control. Sequencing can now be done in less than a day, which means that information is produced in time to influence clinical practice.4
Whole genome sequencing technologies represent a major paradigm shift in public health microbiology, quickly emerging as the gold standard in bacterial typing and tracking worldwide epidemics and regional outbreaks. The continued improvements in turnaround time and accessibility of DNA sequencing technologies are now approaching a point where genomic data can be generated in a clinically relevant time frame (see Section B Chapter 7 AHRQ Infection HAI for references). While becoming faster and cheaper, there are still barriers to adopting these into routine clinical microbiology. It is currently lacking automated sequence interpretation tools that turn a string of genetic data into meaningful data that are useful mechanism for local, national, and global surveillance. A clear understanding of the cost versus benefit associated with the introduction of this technology is needed to distinguish under what circumstances the extra information provided by sequencing makes a difference to patient outcome, disease control, and when it is not worth doing.4
TARGET POPULATION: HIGH-RISK PATIENTS
High-risk patients in critical care units, burn units, emergency departments, surgical and trauma rooms, neutropenic units, and even in ambulances and patient transport vehicles are most susceptible to the ravages of superbugs. A 20-month retrospective cohort studied patients admitted to 8 ICUs performing routine admission and weekly screening for MRSA and VRE. The relative odds of acquisition were accessed among patients admitted to rooms in which the most recent occupants were MRSA-positive or VRE-positive, compared with patients admitted to other rooms. Among patients whose prior room occupant was MRSA-positive, 3.9% acquired MRSA, compared with 2.9% of patients whose prior room occupant was MRSA-negative (adjusted odds ratio, 1.4; P = .04). VRE, among patients whose prior room occupant was VRE-positive, these values were 4.5% and 2.8%, respectively (adjusted odds ratio, 1.4; P = .02). These excess risks accounted for 5.1% of all incident MRSA cases and 6.8% of all incident VRE cases, with a population attributable risk among exposed patients of less than 2% for either organism. Studies have led researchers to the conclusion that admission to a room previously occupied by a C difficile-, MRSA- or, a VRE-positive patient, the new occupant was at increased risk for acquiring these organisms, suggesting the persistence of organisms in the environment.7,11
STOPPING THE UNTREATABLE: HOW CAN WE OUTSMART THE SUPERBUG?
We sweep. We swab. We sterilize. And still the germs persist. Centers for Disease Control and Prevention guidance for controlling HAIs rests on the cornerstones of infection control strategy: rigorous hand cleaning by staff and visitors, isolating infected patients, and requiring gowns and gloves for anyone contacting them; it recommends cutting antibiotic use to slow the development of resistant bacteria and limiting use of invasive medical devices, such as catheters, that give bacteria a path into the body.7,10 But the measure that may hold the most promise is contentious: screening patients for the bacteria so that carriers can be isolated. There is disparate opinion over who should be screened. Every patient? Only those whose history puts them at high risk for infection? Only those showing symptoms?10 Screening, along with advanced methods of decontamination processes and technology, is enabling us to face the threat presented by emerging infectious organisms.
TRADITIONAL METHODS: BEYOND HAND WASHING
Accepted as the most reliable means for reducing HAI risk, hand washing compliance has become a critical issue for infection control. Hand washing sinks that are easily accessible, near the entrances to patient modules, are designed deep and wide enough to prevent splashing, and that are preferably equipped with elbow, knee, foot, or sonar-operated faucets are now required. There are tools to police performance as well. Scanners have been designed to monitor how many times HCWs use a sink or hand sanitizer. Touchless dispensing systems, such as electronic bath tissue, hand towel, and skin care dispensers, further reduce the spread of germs.12
Confirmed by the CDC as having a positive germicidal effect, UV-C lamps are now being used to enhance effective hand washing. Germicidal irradiation (UVGI) uses UV-C, the component of ultraviolet energy that breaks through the outer membrane of microbes such as yeast, mold, bacteria, viruses, or algae. When the UV-C energy reaches the DNA of the microbe, modifications cause the microbe to lose its ability to reproduce. UVGI lamps provide a powerful and concentrated dose of UV-C energy that sanitizes the air and surfaces, destroying pathogens that come in contact with the ultraviolet (UV) rays. This technology has been incorporated into hand sanitizers that are fully automatic and deliver UV-C at 3-second intervals, monitoring who is using it and how often. These units can verify if bare hands or gloved hands have been inserted. UV-C can inactivate all pathogens on the outer surface of a bare or gloved hand in 3 seconds, including C difficile spores, while producing no irritation whatsoever. Installing these units, which are priced to be approximately one-third the cost of alcohol rubs on a per-bed annual basis, is estimated to save $2 billion in material expenses for US hospitals.12
Another concern is hospital tap water, which has also been recognized as a source of infections. Plumbing system design and operation has a great impact on reducing the risk of HAIs. It has been demonstrated that hospital tap water contains microbial pathogens, and that biofilm in water systems resists disinfection and delivers pathogenic organisms to the point of care to at-risk patients through direct contact, ingestion, and inhalation of waterborne pathogens. It is vital that the water supply comes from a certified source, especially if hemodialysis is to be performed. Zone stop valves must be installed on pipes entering each ICU to allow service to be turned off should line breaks occur. Systemic water treatment technologies reduce levels of recognized waterborne pathogens; however, they cannot eradicate biofilm within health care facility plumbing. Existing point-of-use filtration technologies have been reported to interrupt clinical outbreaks of infection because of recognized waterborne pathogens and can represent a critical component of a comprehensive infection control strategy.9
While not a technological or design advance, a study worth noting was published in the May 2013 New England Journal of Medicine that evaluated strategies for controlling infections by superbugs by (1) testing ICU patients for MRSA, (2) isolating those infected, or (3) disinfecting all patients. The study found that hospitals can sharply reduce the spread of drug-resistant bacteria in the ICU by decontaminating all patients rather than screening them and focusing only on those found to be infected already. The study looked at 74 000 patients in 74 ICUs nationwide and found that cleaning all ICU patients with a special soap and ointment reduced all infections, including MRSA, by 44%. Dr Susan Huang from the University of California, Irvine, who led the study, said
This study helps answer a long-standing debate in the medical field about whether we should tailor our efforts to prevent infection to specific pathogens, such as MRSA, or whether we should identify a high risk group and give them all special treatment to prevent infection. The universal decolonization strategy was the most effective and easiest to implement. It eliminates the need for screening all ICU patients for MRSA.
The researchers cautioned, however, that physicians will have to watch closely to make sure the germs do not become resistant to disinfecting soaps and ointments.13
ENHANCED CLEANING PROTOCOLS
Environmental service staffs are essential members of a hospital's infection control team. As preventionists, they need to be educated and have clear ownership of their responsibilities in the cleaning process. The mean proportion of surfaces and objects in a patient room that are disinfected at terminal cleaning is only about 50%. Using the right cleaners and disinfectants to decontaminate surfaces can help reduce the risk of HAIs, but employing systems to monitor cleaning thoroughness, proper training and communication are also vital. Environmental service departments are receiving more pressure to perform at higher levels in cleaning and disinfecting surfaces, and vendors continue to search for ways to help hospitals meet new demands. "The microscope has moved from clinical areas to the support areas," says John Scherberger, a former hospital ES director and president of Healthcare Risk Mitigation Inc.14 Moving away from the focus on elbow grease and bleach, there has been a merger of the housekeeping and infection prevention staff that emphasizes that cleaning is less about being a maid's service and more about protecting patients from superbugs.
While studies have shown that effective ES cleaning and disinfection can reduce pathogens on hospital room surfaces, it is more challenging to demonstrate definitively that thorough cleaning will lead to reduced HAIs. The CDC Guidelines for Environmental Infection Control in Health-Care Facilities have concluded that showing an unequivocal correlation can be difficult because many factors can contribute to preventing infections, not just clean surfaces, identifying points to 3 basic problems with existing studies. First, while many studies report on changes in ES procedures and their impact on the numbers of pathogens on surfaces, the details of these cleaning procedures often are not given. Second, if other infection prevention practices are included in the same study that is attempting to evaluate the contribution of environmental cleaning and disinfection to disease control, the study design may not be set up to measure the impact of each factor individually. And third, many ES studies do not include an epidemiologic component to monitor infection transmission among patients before, during, and after the study. When the epidemiologic component is included, the evidence is much more supportive of ES cleaning procedures making a difference, but more well-designed studies are needed. Even with limitations of national studies, the CDC is confident that there is a correlation between low occurrence of HAIs and effective ES cleaning practices. When staff had checklists, complete processes, and good tools for cleaning rooms, HAI rates fell.12
A study done at University of California, Irvine, reviewed 13 000 hospital stays in 10 ICUs at a large tertiary care academic medical centers in Boston, focusing on how an enhanced cleaning protocol reduced the spread of MRSA to patients exposed to rooms in which the prior occupant had been colonized or infected. Regarding multimodal cleaning intervention, 3 parts proved effective and included (1) a change from using a pour bottle to bucket immersion for applying disinfectant to cleaning cloths; (2) an educational campaign involving the environmental service staff; and (3) feedback method using removal of intentionally applied marks visible only under UV lighting.14 Comprehensive environmental cleaning systems, including cleaners, tools, training, marking, and monitoring systems, are now readily available.
Advances in cleaning chemistry have impacted the decontamination process as well. The marketplace offers a variety of cleaning options, including disinfecting wipes and quaternary ammonium (Quat) compounds. Quat compounds continue to be used widely at hospitals because of their low cost. However, they require staff time to mix the compounds, and there is a chance for human error in achieving the correct concentration. In addition, the environmental protection agency required contact time for disinfection may entail rewetting the surface several times. Ready-to-use disinfectant wipes work quickly but generate waste. Bleach-based products that are environmental protection agency registered can kill 51 microorganisms, including C- diff, tuberculosis, and Norovirus, and are designed for multipurpose use, including use in critical care units.
It is estimated that 70% of hospitals now use microfiber mops and cloths to improve efficacy of cleaning products. Research reports that microfiber mops can remove 99.9% of microbes with water. Manufacturers have released a disposable microfiber mop that can be used for enhanced infection control in isolation areas, while the reusable mops can be used in patients' rooms and noncritical areas. Microdenier, a new type of microfiber, has also been introduced, with fibers that are smaller than the microbes they are wiping up, so the fabric works exceptionally well as a trap-and-remove cleaning tool.14 The challenge is to find the right products that are cost-effective, evidence-based, ready-to-use, and that will support infection control.
There are applied surface treatments that use electrostatic sprayers that apply electrically charged biocide particles onto a targeted area. The charged particles are attracted to all areas and are able to wrap around objects. When they are applied electrostatically, entire areas are completely covered. This results in a highly active molecule that has both tenacious bonding capabilities and excellent antimicrobial properties. This process is applied to break down biofilm and the pathogens protein wall and then physically dismember the organism into its component parts that have been demonstrated to control bacteria for extended periods of time.
PROCESS-MONITORING DEVICES
Adenosine triphosphate (ATP) is an energy source that is present in all living cells. An ATP-monitoring system can detect the amount of organic matter that remains after cleaning an environmental surface, a medical device, or a surgical instrument. Adenosine triphosphate has a light-producing reaction when it comes in contact with a natural oxidative enzyme called "luciferase." A cotton swab is used to collect a sample that is introduced to luciferase. Next, a handheld illuminometer reads the sample. This meter measures the amount of bioluminescence generated when the energy molecule "ATP" comes in contact with the luciferase. Results are measured in "relative light units," and the number is displayed on the screen. A high number means that the illuminometer detected a higher level of light created by a large amount of ATP. This concludes that the area sampled has a high level of contamination. A lower relative light units number means a lower level of ATP and a lower level of contamination.
Hospitals are using ATP-based monitoring systems to detect and measure the effectiveness of their facilities' sanitation efforts. The amount and location of where ATP is detected indicates areas and items in the health care setting that may need to be recleaned and the possible need for improvement in a health care facility's cleaning protocols.15 A quarter to a third of all hospitals are now using ATP, with instrumentation being developed that can track 5000 locations. Software has been improved, making it easier for tracking and trending data. The new functionality will allow a health care system to link data from multiple hospital networks, confirming efficacy and note outliers; it can validate what the hospital staff is doing correctly or motivate him or her to reach a higher level of cleaning for continuous improvement.12,14
EVIDENCE-BASED DESIGN AND TECHNOLOGICAL ADVANCES
Evidence-based design research has changed how decisions are made during hospital construction and renovation plans. Focus has moved from low per square foot costs, to justifying the incorporation of advanced technology and contemporary design models that focus on patients' safety and satisfaction. Studies have shown that the movement from semiprivate to private rooms alone can reduce HAI rates up to 45%. Treatment of nosocomial infections comprises a significant percentage of operational costs of hospitals and helps make the financial case for incorporating a greater investment in design elements that promote infection control. Contemporary elements that should be considered include the following:
DOOR SELECTION
Intended to maximize both space and functionality, a new generation of critical care self-closing door systems has been designed to shut the active leaf to a positive latch position that ensures a smooth, quiet action; helps fight infection; and prevents the door from being inadvertently left open. Antimicrobial coatings are available on latches or the entire door package that continuously suppresses the spread of bacteria. Available internal glass miniblinds eliminate the risk of infections and the cost of cleaning. Available touch-less sensors conveniently open doors and eliminates contact with handles to reduce the risk of spreading disease.
FLOORING
Flooring, carpet especially, is a big factor in infection control. Bacteria on hospital floors predominantly consist of organisms found commonly on skin. Infection risk from contaminated floors is small; however, the survival of microbes on carpeting is different where it is found in larger numbers, posing a greater risk. Carpeting should be avoided in high-risk areas because the cleaning process may aerosolize fungal spores. There are new generation, nonporous flooring options available, with antimicrobial properties that can be installed with heat welded seams to reduce chance for cultivation.
HEATING, VENTILATION, AND AIR CONDITIONING DESIGN
Computational fluid dynamic analysis is used to simulate and compare the removal of microbes using a number of different ventilation systems in hospitals. A turbulent airflow study performed in a hospital ICU stressed the prevention of airborne infections using computational fluid dynamic software that tracks massless contaminated particles. It has been observed that the remote pockets of the room, where air circulation is not proper, may serve as a source of pathogenic microorganisms. The need of precise determination of airflow pattern and temperature distribution in a room was realized at first by air conditioning engineers so as to provide comfort condition of temperature and air velocity throughout the occupied zone. In the modern era, people spend about 90% of the time in indoor environments; it has been shown that in hospitals occupants can be exposed to upward of 8000 chemical species and microorganisms. Studies show that the number of particles deposited on surfaces and vented out is greater in magnitude than the number killed by UV light, suggesting that ventilation plays an important role in controlling the contaminant level.16
UV-C, or UVGI, has been used for more than 70 years as a means to reduce or eliminate DNA-based contaminants (bacteria, viruses, and mold) from surfaces and in heating, ventilation, and air conditioning (HVAC) systems. UV-C has been recommended to enhance the existing filter systems that are in place, not instead of them. The filters capture particulate and the lights target the organisms that we want to eliminate from the system altogether. Fixtures in the HVAC system keep systems clean and save maintenance and energy dollars. Mold and bacteria from the outdoors are not welcome and will not be able to grow and flourish with UVC lights. Duct contamination is eliminated without the food source from the cooling coils. Evidence-based design studies have shown improved clinical outcomes and shorter hospital stays, resulting in reduced direct and indirect third party costs and legal liabilities. By continuously cleaning the coils and drain pan of biofilm, UVGI improves ventilation system heat transfer and efficiency, resulting in reduced energy costs.12
In June 2009, the American Society of Heating, Refrigerating and Air-Conditioning Engineers stated that, "Airborne infectious disease transmission can be reduced using dilution ventilation, specific in-room flow regimes, room pressure differentials, personalized and source capture ventilation, filtration and UVGI." UVGI strategies include installation into ventilating duct and irradiation of the upper zones of occupied spaces to destroy airborne viruses and bacteria that circulate throughout the system. UV-C will successfully deliver contaminant destruction rates above 90%, when properly installed and applied in combination with air exchange rates. UVGI supports health care facility bottom line goals by making a vital contribution to infection control, operational excellence, risk management, and environmental stewardship.12,17
ANTIMICROBIAL COATINGS AND SURFACE TECHNOLOGIES
Surfaces can act as reservoirs of microbes, allowing hands (gloved or ungloved) to become contaminated with organisms after touching such a surface. Studies have shown contamination by potentially harmful microbes of common, inanimate hospital surfaces such as room door handles, sterile packaging, mops, fabrics, plastics, HCWs' pens, keyboards and monitors, stethoscopes, and telephones when colonized individuals were present in hospital rooms.18 Complicated even further by contaminated surfaces outside of patient rooms-elevator buttons, thermostats, wheelchairs, toilet rooms, and so forth, that are vehicles for HCWs and visitors to carry organisms into the patient and even out into the community.
More significantly, it was found that 65% of nursing staff that had directly treated an infected individual, are contaminating their gowns/uniforms with the organism. MRSA on gloves was also observed in 42% of personnel who had no direct contact with the patient but had touched surfaces in infected patient's rooms. While appropriate hand washing by HCWs can control the further spread of the microorganism via hand-surface transmission, it cannot eradicate the surface contamination itself, nor the potential direct transfer by the. The efficacy of traditional cleaning methods to remove surface contamination is under debate. A recent study of MRSA contamination in the hospital environment detected MRSA on 74% of swab samples before cleaning and on 66% of swab samples after cleaning. To fully tackle the situation, it is clear that a bioactive surface that can either prevent bacterial contamination altogether or destroy adherent organism is required.18
It is well known that bacteria and mold grow in and on horizontal and vertical surfaces; however, it was not known until recently that sinks and countertops were studied as potential sites for the spread of disease. There are now several studies documenting that bacterium can grow around the rim of the sink and the interior of the sink and drain. There is sufficient evidence that transmission is possible from sinks to hands. When patients or HCWs use the sink to wash their hands, researchers discovered that while they may be cleaning their hands, the bacteria that has been washed from the hands may be deposited around the outside of the sink. When a patient or HCW washes his or her hands, he or she might be picking up bacteria from the person who previously used the sink. Despite cleaning the sink with a disinfectant, bacteria may survive around the rim of the basin.
Until 2006, when the Facility Guidelines Institute revised its recommendations in the Guidelines for the Design and Construction of Health Care Facilities for surface materials, most countertops that were used in patient-care areas where plastic laminate with a china set-on sink and set-on back splash. Laminate is porous and will absorb moisture over time. Countertops and the perimeter of the sink are almost always wet, with water collecting at the back splash, harboring bacteria and mold. One solution is to install solid surfaces that are more hygienic, nonporous, and inert-like stainless steel. Selected surfaces should meet all of the 18 characteristics of a preferred surface as defined in guidelines by the 2006 Facility Guidelines Institute. With solid surface, grout lines and open seams are replaced by impermeable, hygienic joints. Sinks can be integral, with a countertop creating 1 continuous surface without rims, caulk, or seams. Back splashes are coved up from the countertop, leaving no seams or voids for water to pool. Depending on the location, coved back splashes can go high enough up the wall to prevent water from soaking the wall and creating an environment for bacterial growth.19
Surfaces are also available to which microbes will find it hard to become attached. Antimicrobial surfaces and coatings are incorporated into wall paint, wall protection, doors, and furniture that can actively kill microbes. Ideally, these antimicrobial surfaces should be permanent, hard-wearing, and work under hospital conditions. The mode of action in killing microbes needs to function simultaneously through multiple pathways so that the development of resistance, as seen for antibiotics and diffusible antimicrobials, is avoided. In that context, the light-activated antimicrobials offer particular promise as they function by generating reactive oxygen species that act on multiple targets within microbes. Furthermore, titanium dioxide coatings offer both reactive oxygen species and a superhydrophilic surface that is both easy to clean and hard for a microbe to adhere to. The current widespread armory of antimicrobial coatings gives hope for reducing HAIs. However, these coatings, without a strict hygiene regime, will have limited benefit.18
MICROBIOCIDE-RELEASING SURFACES
One of the most heavily marketed and most widespread products for suppressing microbial growth is Microban (Microban International, Ltd, Huntersville, North Carolina). Microban incorporates triclosan-a broad spectrum phenolic antimicrobial-into a surface, normally a polymer. It works more like a disinfectant, that is, killing outside in, rather than an antibiotic, that is, inside out. With a Microban product, the antimicrobial leaches from the surface of the product to perform the antimicrobial function. This means that effectively they are nonpermanent. Triclosan is found in many products such as hand wash soaps, toothpastes, as well as on touch surfaces and items such as chopping boards and cling film. Microban has been shown to suppress bacterial growth within the domestic, especially kitchen, environments; however, it is not widely used within hospitals. One of the first uses of Microban as an antimicrobial in a hospital was at the John Radcliffe in Oxford at the end of 2006, where it was used as a coating on door handles. There has also been significant concern about possible development of triclosan resistance; furthermore, some studies suggest that triclosan can, under the action of UV light, produce dioxins, which are extremely hazardous to man.18
Another well-established method for preventing the adhesion of microbes, proteins, and mammalian cells to surfaces is to coat them with a layer of poly(ethylene glycol), or PEG. PEG modification was first shown to inhibit microbial adhesion in the late 1990s, with much research being carried out in this area subsequently. The principal drawback of this technology is that currently the deposition of a PEG surface requires 3 synthetic steps and can be done only to a surface during manufacturing.18
Diamond-like carbon coatings may be very useful to prevent infections due to invasive biomedical devices such as venous and renal catheters, which are a major source of HAIs. First prepared by an ion-beam technique in the 1970s, these materials are now more commonly produced in the laboratory by plasma-assisted/plasma-enhanced chemical vapor deposition. The physical and mechanical properties of these films, especially in the study of their tribology, meant that initial uses were as protective coatings at the interfaces between the magnetic storage platters and the read/write heads of hard disk drives. However, researchers have subsequently realized many other uses, in particular, that of diamond-like carbon as a biocompatible surface coating for biomedical devices such as stents or replacement joints.18
Silver has long been known to be an antimicrobial; the Greeks and the Romans used silver coins and vessels to make drinking water potable. Silver ions have a significant antimicrobial effect. Silver sulfadiazine creams have been applied topically to burn patients and in wound dressings to prevent infections. It has been used as an additive in catheters and other medical devices. Commercial coating products rely on the diffusion of silver ions from the substrate material and their subsequent action on adherent microbes as broad spectrum antimicrobials. To date, few organisms have developed resistance toward the silver ion as an antimicrobial. Despite the initial effectiveness of these existing antimicrobial coatings, they have 1 major drawback-they are nonpermanent, relying on diffusible antimicrobials to which microbes can develop resistance; however, the concentration of silver required for action is actually very low and varies between reports. One possible drawback of silver-based antimicrobials is the possibility of silver ion cytotoxicity toward mammalian cells, as recently reported. This could be an area of concern for antimicrobial devices or treatments coming into contact with human cells and tissues.18
Copper and copper alloy surfaces are another straightforward way to help eliminate microbial spread on health care surfaces. Laboratory testing shows that when surfaces in which copper is incorporated are cleaned regularly, 99.9% of bacteria are killed within 2 hours of exposure including MRSA, VRE, S aureus, Enterobacter aerogenes, Pseudomonas aeruginosa, and Escherichia coli. Science suggests that copper surfaces affect bacteria in 2 sequential steps: first is a direct interaction between the surface and the bacterial outer membrane, causing the membrane to rupture. The second is related to the holes in the outer membrane, through which the cell loses vital nutrients and water, causing a general weakening of the cell. Every cell's outer membrane, including that of a single-cell organism such as a bacterium, is characterized by a stable electrical microcurrent. This is often called "transmembrane potential" and is a voltage difference between the inside and the outside of a cell. It is strongly suspected that when a bacterium comes in contact with a copper surface, a short circuiting of the current in the cell membrane can occur. This weakens the membrane and creates holes. Now that the cell's main defense (its outer envelope) has been breached, there is an unopposed stream of copper ions entering the cell. This puts several vital processes inside the cell in danger. Copper literally overwhelms the inside of the cell and obstructs cell metabolism. These reactions are accomplished and catalyzed by enzymes. When excess copper binds to these enzymes, their activity grinds to a halt. After membrane perforation, copper can stop the cell from transporting or digesting nutrients, from repairing its damaged membrane, and from breathing or multiplying. It is also thought that this is why such a wide range of microorganisms are susceptible to contact action by copper.12
Antimicrobial copper surfaces in ICUs can reduce the risk of HAI by more than 40% according to study funded by the Department of Defense in 3 hospitals (July 2010 to May 2011) where 564 patients were randomly assigned to either a copper-coated room or a control room. The study found a 95% reduction in bacteria, including MRSA and VRE, with a 41% reduction in HAIs among patients in copper-coated rooms. Specifically, the infection rate in copper rooms was 8.95 cases per 1000 patient days, compared with 15.16 cases in control rooms.20 Antimicrobial copper surfaces are a supplement to and not a substitute for standard infection control practices. Just like other antimicrobial products, they have been shown to reduce microbial contamination but do not necessarily prevent cross contamination; users must continue to follow all current infection control practices.12
Stainless steel, in comparison with copper surfaces, was shown to be inert. Stainless steel coupons showed no change in bacterial load, even after 1 week of exposure. Studies show that, despite its association with hygiene, stainless steel surfaces may not be the best choice for areas where microbial surface contamination is an issue. While it is an easy material to clean, stainless steel has no ability to reduce the microbial load on its surface. Despite its excellent antimicrobial response, however, copper may not be a suitable replacement for stainless steel in a hospital environment. This is because of its mechanical properties in comparison with stainless steel and the fact that it oxidizes when exposed to the air. However, it has been shown that copper alloys, such as brass, also exhibit antimicrobial activity, albeit of smaller magnitude. These alloys have improved aesthetic and mechanical properties and may be more suited to hospital applications.18
Light-activated antimicrobial agents are an alternative method of disinfecting a surface by the use of a coating that produces reactive radical species. Radical species, unlike the antimicrobials previously discussed, have no specific target within a microbe, that is to say they are completely nonselective microbiocides. This has one very important implication-it avoids the potential problems of microbes developing resistance to a microbicidal treatment, since there is no one site within a microbe upon which they act. Resistance develops only when a specific site is targeted by a microbicide. There are 2 principal coating types that produce these reactive species and act as antimicrobial surfaces: (1) a coating comprising a photosensitizer immobilized in a coating and (2) a titanium dioxide-based photocatalyst coating. These materials fall under the broad classification of light-activated antimicrobial agents.18
Antimicrobial textiles are now used in the design of linens, privacy curtains, window treatments, and upholstered furnishings that are not cleanable by wiping down the surface, which makes them a common source of contamination. Privacy curtains should be eliminated in patients' rooms or should cover the smallest area possible and secured out of the path of traffic when not in use. Daily room cleaning should include all scrubbable surfaces that have been touched; privacy curtains should be changed between patients, although cost can be prohibitive in areas such as the emergency department.17 Fabric window coverings are not recommended.
NEW TECHNOLOGY
Portable UV light units have been developed to easily move from location to location where there are concerns about surface and air contamination by harmful pathogens. The units are capable of safely disinfecting a room using UV-C energy in as little as a few minutes by breaking the cell chain of the DNA in an organism. When the chain is broken, the cell cannot reproduce. Independent tests have looked at the effectiveness for surface disinfection at 8- and 17-ft distances in a controlled environment. Using S aureus as the test organism, a mobile room sanitizer was successful at destroying 99.9% of the target organisms in 5 minutes at the 8-ft range and in as little as 10 minutes at the 17-ft range. Ultraviolet lighting can be incorporated into light fixtures, for example, in operating rooms that if lights were modulated to full power between surgery cases can reduce MRSA by 2-log.12
Portable units cost upward to $125 000.00. Environmental service staff must still clean rooms, but the UV light treatment is the high-tech backup needed for the next level of decontamination. A small observational study within a hospital showed that C difficile infection rates fell by half and C difficile deaths fell from 14 to 2 during the last 2 years, compared with the 2 years before the machines were put into use. But, some experts say that there is not enough evidence to show that the machines are worth it. No national study has shown that these products have led to reduced deaths or infection rates, noted Dr L. Clifford McDonald of the CDC. His point: It takes only a minute for a nurse or a visitor with dirty hands to walk into a room, touch a vulnerable patient with germy hands, and undo the benefits of a recent space-age cleaning. "Environments get dirty again," McDonald said, and thorough cleaning with conventional disinfectants ought to do the job.12
HYDROGEN PEROXIDE VAPOR GENERATORS
Hydrogen peroxide vapor (HPV), an oxidizing agent, provides 3-dimensional sterilization of hospital rooms. Hydrogen peroxide vapor technology consists of a mobile vapor generator that releases 30% wt/wt aqueous hydrogen peroxide (H2O2) vapor to facilitate total disinfection of a room and equipment. When it comes into contact with microorganisms, it oxidizes the cells or spores, thus deactivating them. The generator delivers HPV at high speed, ensuring distribution to all parts of a room. A very fine layer of microcondensation is formed on all exposed surfaces, deactivating microorganisms.21
The HPV will kill off endospore-forming bacteria, including C difficile, on porous and nonporous materials. Although not a standalone procedure, HPV has been successfully deployed in numerous facilities to help reduce infection rates both long-term and in response to clusters or outbreaks in targeted locations. Hydrogen peroxide vapor can be used to reach awkward inaccessible areas. However, areas not exposed to the vapor are not disinfected, so all surfaces have to be positioned for optimum exposure. Soiling reduces the efficacy of HPV,3 so surfaces to be disinfected must be clear of soil. Hydrogen peroxide vapor disinfection must be used in addition to standard cleaning, not as a substitute for it. After an appropriate dwell time, typically 10 to 15 minutes, the aeration units are used to scrub the hydrogen peroxide from the air, breaking it down to form oxygen and water leaving the room free from residual biocides and ready for reoccupancy. This process eradicates organisms in comparison with other technologies that reduce only organism counts. The process is controlled from outside the room by a computer, which provides feedback about progress to the operators. Portable disinfecting units and aerators cost approximately $40 000 per pair.21 Connections can be designed into room construction with rotating ceiling distribution systems as well.
The Johns Hopkins Hospital in Baltimore started using HPV in December 2012 to disinfect ICU modules after an 18-month study determined that the technology reduced the risk of patients' acquisition of multidrug-resistant organisms compared with standard cleaning protocols. The study showed that use of an HPV system reduced by 64% the number of patients who later became contaminated with any of the most common multidrug-resistant organisms. According to the study, patients were 80% less likely to acquire VRE. In the study, which was conducted from January 2008 through June 2009, the prior occupants of the patient rooms were known to be infected or colonized with a multidrug-resistant organism in 22% of 6350 admissions in 180 private patient rooms. Nearly half of the rooms in the study were disinfected using HPV. After the study rooms underwent regular cleaning, the vents inside the rooms were covered, the 2 devices were placed inside, and the rooms were sealed. The HPV process was tracked with electronic monitors outside the rooms. After the first step was completed, a catalytic aerator unit converted the HPV to water vapor and oxygen and left a residue-free surface and safe environment.22-24
A study released on May 2013 from Case Western Reserve University School of Medicine looked at a 3-tiered sequential process over a 21-month period at a VA hospital, using (1) florescent markers, (2) UV radiation treatment, and (3) enhanced disinfection that utilized a dedicated team with supervisory assessment and clearance of rooms infected with C difficile. Efficacy was determined by obtaining cultures. The results were as follows,
The fluorescent marker intervention improved the thoroughness of cleaning of high-touch surfaces (from 47% to 81% marker removal; P < .0001). Relative to the baseline period, the prevalence of positive cultures from clinical documentation improvement (CDI) rooms was reduced by 14% (P = .024), 48% (P <.001), and 89% (P = .006) with interventions 1, 2, and 3, respectively. During the baseline period, 67% of CDI rooms had positive cultures after disinfection, whereas during interventions periods 1, 2, and 3 the percentages of CDI rooms with positive cultures after disinfection were reduced to 57%, 35%, and 7%, respectively.25
These results stress the importance of not only advanced cleaning processes but also a combination of methods for disinfection including advanced cleaning processes as well as culturing of CDI rooms as an assessment tool.
CONCLUSION: CONFRONTING THE NEMESIS
The emergence of deadly antibiotic resistant bacteria must be attacked on multiple fronts. Although many studies have been performed, there is still much debate as to which interventions should be implemented to prevent health care-associated infections. Right now, there is no magic bullet. No one method to contain, reduce, or eliminate all of our enemies. Critical care nurses are on the frontlines of this fight and are vital members of the infection control team. Current evidence should be considered by individual institutions to determine which interventions are right for their facility based on their patient population, problem pathogens, and ability to implement the plan.
Over the past 2 decades, there have been an ever-increasing number of bacterial species, particularly the gram negatives, which are resistant to all approved treatments. A promising study underway at the Department of Microbiology and Molecular Genetics, University of Pittsburgh, focuses on the design and testing of peptides, which have been designed de novo, and as such do not exist in nature. Previous studies have shown that these peptides have a broad spectrum of activity against both gram-positive and gram-negative organisms, including community-acquired MRSA and a pan-drug-resistant K pneumoniae strain that is resistant to all approved antibiotics among others. They have shown that single injections of the peptides were able to protect mice, in a dose-dependent manner, from a lethal P aeruginosa bacteremia. They are currently in the process of beginning preliminary preclinical studies to understand the pharmacokinetic and toxicity profile, establish a dosing scheme, and perform efficacy comparison studies against last resort standard-of-care antibiotics such as the carbapenems and colistin against carbapenem- and colistin-resistant bacteria, respectively. Outcomes so far have been positive; they plan to push forward to preclinical development studies that would culminate in filing an investigational new drug application with the Food and Drug Administration to allow clinical trials.
Jonathan Steckbeck, PhD, University of Pittsburgh Molecular Research Associate, working on the project stresses,
Given the current state of bacterial antibiotic resistance, it will be imperative over the coming years to incorporate evidence-based design and new technologies to help control hospital-acquired infections while the antibiotic pipeline is rebuilt. It is going to take a concerted effort among research scientists, healthcare professionals, and the general public to ensure that we do not relinquish the medical advances that antibiotics have provided us for the past 70 years. Comprehensive measures, including new antibiotic drugs, design and engineering advances, and public education, will help to ensure that we remain ahead of this reemerging bacterial threat.
In this melee, keeping one step ahead of our microscopic adversaries is essential. Man's battle plan in this conflict must continue to evolve-in order to adapt, not perish.
REFERENCES