key: cord-016426-aw3wirmb authors: Wohrley, Julie D.; Bartlett, Allison H. title: The Role of the Environment and Colonization in Healthcare-Associated Infections date: 2018-07-16 journal: Healthcare-Associated Infections in Children DOI: 10.1007/978-3-319-98122-2_2 sha: doc_id: 16426 cord_uid: aw3wirmb Healthcare-associated infections (HAIs) can be caused by endogenous host microbial flora or by exogenous microbes, including those found in the hospital environment. Efforts to decrease endogenous pathogens via decolonization and skin antisepsis may decrease the risk of infection in some settings. Controlling the spread of potential pathogens from the environment requires meticulous attention to cleaning and disinfection practices. In addition to selection of the appropriate cleaning agent, use of tools that assess the adequacy of cleaning and addition of no-touch cleaning technology may decrease environmental contamination. Hand hygiene is also a critical component of preventing transmission of pathogens from the environment to patients via healthcare worker hands. resulting from invasive devices or surgical procedures may be associated with a shift from colonization to infection. A complex interaction occurs throughout the body between commensal organisms and the barriers they colonize, with research on the skin and gastrointestinal tract microbiome shedding light on these interactions. The skin is a protective barrier with large numbers of colonizing bacteria. The skin microbiome is inhabited by bacteria, fungi, viruses, archaea, and mites; however most research has focused on bacteria. The presence of various microbes may influence disease as evidenced by the shift from Staphylococcus epidermidis cultured from healthy skin in young children [3] to Propionibacterium acnes in teenagers with acne [4, 5] . Children with atopic dermatitis have a propensity to infection with Staphylococcus aureus [6] . Loss of skin integrity, as with wounds, burns, inflammation, or invasive devices, allows pathogens to enter. The balance between host and flora is also important in the gut and is influenced by antibiotic usage, diarrheal diseases, and critical illness [7] [8] [9] . The gut provides both an essential immune response in maintaining health with normal flora stimulating proliferation of epithelial cells in small and large intestines, participating in development of competent gut-associated immune responses, as well as providing a physical barrier function against pathogen invasion through colonization resistance [10] [11] [12] . Inflammatory bowel disease is just one example of altered gut flora associated with a disease state. The secretory antibody system is important in the defense against mucosal infections. Specific secretory immunoglobulin A (IgA), transported through secretory epithelia to the mucosal surface, inhibits pathogen colonization through microorganism entrapment in mucus and promotion of clearance of entrapped microbes via peristalsis or mucociliary movement [13] . IgA also plays a role in mucosal protection of the gut by binding to a mucous layer that separates commensal bacteria from the apical surface of intestinal epithelial cells [14] . Patients admitted to the hospital bring with them their "normal" flora which may be very different in a previously healthy child than in a technology-dependent child who resides in a long-term care facility. Colonization of children with organisms specific to their individual clinical conditions, such as Pseudomonas aeruginosa in a tracheostomy-and ventilator-dependent child, or multidrug-resistant Enterobacteriaceae in the GI tract of a neurologically impaired adolescent with neurogenic bladder and a history of frequent urinary tract infections, may lead to infection with these pathogens. These resident organisms may be transferred to the environment where they can be acquired directly by other patients or transmitted indirectly by HCW hands. High-risk populations for acquisition of multidrug-resistant organisms include those who are critically ill, who are immunocompromised, or who have been hospitalized for long periods of time, either in acute care or long-term care settings. Additional risk factors include prolonged use of antibiotics and contact with colonized patients or the colonized/contaminated hands of HCW. Colonizing organisms may produce invasive infection whether or not colonization is acquired in the hospital or the community. Colonization with methicillinresistant Staphylococcus aureus (MRSA) is a risk factor for subsequent invasive MRSA infection [15] . A study of relatedness between colonizing strains of S. aureus and those associated with invasive disease in adults found that more than 80% of S. aureus blood isolates were identical to those colonizing the patient's anterior nares [16] . Genotypes of S. aureus strains from surgical site infections were also noted to be identical to colonizing strains in more than 80% of surgical patients [17] . The hospital environment represents a reservoir of organisms such as MRSA, vancomycin-resistant Enterococcus (VRE), and multidrug-resistant gram-negative pathogens as well as Clostridium difficile. Notably, these same drug-resistant organisms found on surfaces in acute care hospital settings can be found in outpatient settings [18] [19] [20] [21] . Transmission between patients and the environment may occur directly from contaminated fomites, indirectly from fomites on HCW hands, or indirectly from patient to patient on HCW hands. C. difficile may be spread in this indirect fashion. For example, this organism may be first identified in the stool of hospitalized patients and then later found to be contaminating the hospital room and its contents, with spread to HCW hands and the hospital environment. Hospital surfaces may serve as both a reservoir and a vehicle of transmission for pathogens. Specific pathogens such as MRSA [22] , Pseudomonas aeruginosa [23] , Acinetobacter [24] , and C. difficile can contaminate hospital surfaces because of their ability to survive in the environment. The amount of hospital surface contamination varies depending on body site of infection/colonization, patient type, and cleaning practices. VRE is commonly associated with environmental contamination, especially in the presence of diarrhea [25] . In a study of ICU patients, the rates of environmental contamination were higher for patients with more than one body site positive for VRE [26] . C. difficile is often identified from rooms of colonized and infected patients, proving difficult to eradicate due to resilience of the spores [27] . The frequency of positive environmental cultures for C. difficile is high; in one study 29% (11 of 38) of environmental cultures in rooms occupied by asymptomatic patients had positive cultures for C. difficile, and 49% (44 of 90) of cultures in rooms occupied by patients had C. difficile-associated diarrhea (p = 0.014) [25, 28] . Over 80% of the environmental isolates characterized in this study had an immunoblot type identical to that of the patient [28] . During an outbreak investigation in an adult long-term care facility, C. difficile skin isolates from asymptomatic patients and from environmental surfaces matched the source patient's isolate in 13/15 (87%) and 11/19 (58%) cases, respectively [29] . C. difficile has also been recovered from physician and nurse work areas [27, 30] . Given the potential for hospital surfaces to be contaminated with pathogens, it stands to reason that the hands, and even the gloves, of HCWs can become contaminated as well. Contamination of hands of HCWs occurs after direct patient care or contact with contaminated surfaces [31] [32] [33] . Positive environmental cultures were found to be a risk factor for development of hand/glove contamination [34] . Not surprisingly, the level of hand contamination has been shown to correlate with level of environmental contamination [35] . Prior room occupants infected with healthcare-associated (HCA) pathogens may provide a source of exposure to other patients [36, 37] . Admission to a room in which the prior occupant was infected or colonized with MRSA, VRE, Acinetobacter, or C. difficile is a risk factor for subsequent colonization or infection with these organisms [38] [39] [40] [41] . Special terminal cleaning (after the patient has been discharged) of rooms previously occupied by patients with C. difficile infection, including the use of hydrogen peroxide vapor, has been implemented to reduce rates of subsequent infection [42] . These procedures have led to reduced rates of infection in patients subsequently admitted to a room where a prior room occupant was infected or colonized with C. difficile [43, 44] . Since colonization may lead to infection, two basic strategies -horizontal and vertical -are employed to reduce HAIs. Horizontal strategies seek to broadly reduce the burden of common healthcare-associated pathogens including S. aureus, Enterococcus, gram-negative bacteria, and Candida through interventions such as hand hygiene and environmental cleaning. Vertical strategies target specific pathogens known to cause HAIs and utilize active surveillance testing as well as directed approaches to decrease colonization and prevent transmission and subsequent infection [45, 46] . General horizontal prevention strategies are approached elsewhere in this text and include hand hygiene, contact precautions, isolation, and PPE use (see Chap. 1, Principles of Infection Control). Strategies applied to patients known or at risk for pathogen colonization when viewed from a vertical approach fall into three broad categories: active surveillance testing (AST), pathogen-specific isolation, and decolonization. Screening (active surveillance testing, or AST) involves detection of colonized patients using culture or molecular methods and typically focuses on high-risk pathogens, including S. aureus (MRSA), Enterococcus (VRE), and C. difficile, that are transmitted from person-to-person from colonized or infected patients [45, 47, 48] . Some of the principles, strategies, challenges, and controversies of AST will be discussed below. Optimal samples for AST vary by pathogen. Specimens for MRSA testing are most frequently obtained from nares; however S. aureus also colonizes the skin, perineum, pharynx [49] [50] [51] [52] , GI tract [49] , vagina [53] , and axillae [49, 50] , and additional sites of screening may be indicated depending on the clinical scenario and potential consequences of infection. Specimens may undergo culture-based or molecular methods for detection of S. aureus/MRSA. VRE colonization is based on samples from stool, rectal, and perirectal swabs, using both molecular methods and culture-based methods [54] . Rectal or stool samples are also used for detection of multidrug-resistant gram-negative organisms such as extended-spectrum β-lactamase-producing Enterobacteriaceae, as well as carbapenemase-producing Enterobacteriaceae. Pseudomonas and Acinetobacter may be detected in multiple sites, depending on clinical situation, including the rectum, skin, nares, pharynx, wounds, urine, and trachea if the patient is mechanically ventilated. The use of AST without additional interventions to reduce risk for transmission has not proven effective. Universal screening effort for pathogens has been most widely studied for MRSA and is considered to be controversial due to questions regarding its effectiveness in controlling spread, as well as cost [45] . Screening alone has not shown to be effective in reducing colonization and infection for MRSA [55, 56] . Studies have failed to show benefit for a combination of AST and isolation in reducing VRE infection or colonization; however, outbreaks of VRE have been successfully controlled in hospital settings with use of active surveillance, contact precautions, patient isolation, and cohorting [57] . Similarly, active surveillance is most useful following outbreaks of MRSA [58] . A cluster randomized trial in intensive care units found that universal gown and glove use did not reduce overall acquisition of multidrug-resistant organisms (MDRO); there was, however, a small reduction in MRSA transmission noted as a secondary outcome [59] . Another prospective study of ICU patients failed to show a difference in MRSA transmission [60] , with additional concerns for the psychosocial effect that isolation places on patients [61] . In observational studies, single room isolation was shown to reduce MRSA acquisition and infection among hospitalized patients [62, 63] . Current recommendations for MRSA colonized and infected patients include isolation in single rooms or cohorting [64, 65] . However, experts have called for a review of the current recommendations for contact precautions and isolation for MRSA colonization in view of the above stated concerns [66] . The addition of targeted decolonization strategies to AST and isolation for control of spread of healthcare-associated pathogens has been most extensively studied to prevent MRSA spread in the hospital setting. Patients who are nasally colonized with S. aureus are more than twice as likely as non-colonized patients to develop S. aureus infection [1, 67, 68] . Carriage may be classified as persistent, intermittent, or noncarriage [69] . Persistent colonization is associated with an increased risk of infection compared with intermittent or non-carriers [70] . Carriers with high bacterial loads have a higher risk of infection and may be more likely to transmit the bacteria to their environment [70, 71] . Greater quantities of S. aureus are found in the nares of persistent S. aureus carriers compared with intermittent carriers [72, 73] . Much research exists regarding the efficacy of active surveillance cultures combined with decolonization to decrease S. aureus transmission and infection in adults, with growing literature in neonatal ICUs [74] [75] [76] . Intranasal antibiotics (mupirocin), with or without antibacterial skin washes (chlorhexidine), have been used in order to decrease the bacterial burden and prevent transmission and infection. Shortterm nasal mupirocin has been demonstrated to be effective in eradicating MRSA nasal carriage, with up to 90% success after 1 week of treatment, and 30-60% efficacy for longer duration of follow-up, depending on patient profile and body sites colonized [77, 78] . Nasal mupirocin use in high-risk settings has been demonstrated to be effective in eradicating S. aureus nasal colonization and reducing the number of infections in ICU, hemodialysis, surgical, and long-term care settings [79] [80] [81] [82] . In a study of nearly two million adult admissions, a significant reduction in the rate of MRSA transmission and infection was noted after introduction of an infection control bundle, which included decolonization of MRSA carriers and isolation [83, 84] as well as a hand hygiene program [84] . However, a crossover study of universal screening on surgical wards combined with targeted decolonization and contact precautions was unable to demonstrate reduction in MRSA infections despite high compliance with screening [85] . Nasal mupirocin decolonization of NICU infants with MRSA colonization in two units with high prevalence (>25%) of MRSA colonization decreased the rate of MRSA infections [86] . However, a retrospective study in the USA failed to demonstrate benefit when nasal mupirocin was used for 5 days in colonized neonates in a unit with a baseline prevalence of around 2% [87] . This study showed that some NICU infants develop infection prior to detection of colonization and infants who remain in the NICU can become recolonized over time [87] . Taken together, these data suggest that decolonization measures may be most beneficial when the baseline rate of colonization is high. Additional NICU studies have found a high correlation between colonizing strains and infecting strains and confirmed high rates (42%) of infections occurring before colonization is detected suggesting universal, rather than targeted, decolonization should be used to control the spread of MRSA [74] . Current recommendations suggest that decolonization may be considered in highrisk neonates during an MRSA outbreak or in cases of endemic MRSA when other measures are failing [88] . A recent Society for Hospital Epidemiology Association (SHEA) survey regarding practices for MRSA identification and eradication in NICUs noted that most (86%) performed surveillance screening (AST) for MRSA in neonates with variability in timing of samples, sites sampled, isolation protocols, and decolonization strategies employed [89] . Recommendations for MSSA are less clear. Invasive MSSA infections occur 2.5 times more frequently than invasive MRSA infections in neonates, leading to significant morbidity and mortality [90] . Targeted screening followed by MSSA decolonization in a single NICU reduced incidence rates of MSSA-positive clinical cultures and MSSA infections by more than 50% [91] . Mupirocin resistance among S. aureus isolates has been demonstrated in multiple studies, especially associated with prolonged use. High-level resistance has been associated with decolonization failure, and low-level resistance may be associated with early recolonization [71, 72] . Therefore, the long-term use of mupirocin is questioned, and alternatives to mupirocin for decolonization in those with mupirocin-resistant strains of MRSA are needed. However, in a long-term study examining use of mupirocin prophylaxis in the NICU over a 7-year period, the rate of S. aureus (MSSA and MRSA) infections decreased from 1.88 to 0.33 per 1000 patient days without any mupirocin-resistant isolates identified [92] . This finding is consistent with previous reports of low prevalence of resistance among S. aureus isolates from mupirocin-treated neonates [93] . The use of decolonization may be most effective for patients at risk of infection for short periods of time such as surgical patients, whose risk of infection may be less once the surgical site is closed, as well as ICU patients, whose risk may lower once they are discharged from the ICU [94, 95] . This is of import given that patients are recolonized within weeks or months following decolonization, and thus the effect is often shortlived [95, 96] . Mupirocin decolonization has been used specifically to reduce the risk of surgical site infections (SSIs) associated with gram-positive organisms. In a metaanalysis of 17 RCTs or quasi-experimental studies including adult cardiac and orthopedic surgery patients, mupirocin decolonization was found to be significantly protective against gram-positive SSIs, specifically S. aureus SSIs [46, 81, 97] . Preoperative S. aureus decolonization is not routinely recommended for most pediatric patients undergoing surgery, however the impact of preoperative colonization on risk of SSI in children has been examined in many small studies. Risk of SSI was not elevated in S. aureus-colonized children undergoing cardiac surgery [98] . Studies in adult cardiac surgery patients, however, suggest a benefit to mupirocinbased decolonization in prevention of SSI [99] ; this topic as it pertains to cardiac surgery is discussed further in Chap. 11. Chlorhexidine (CHG) is a widely used broad-spectrum topical antimicrobial agent [100] . The Centers for Disease Control and Prevention recommend its use as a skin cleanser prior to insertion of central venous catheters (CVC) in both children and adults but do not recommend its use in infants less than 2 months of age due to lack of safety and efficacy data in this population [101] . In spite of these cautions, a national survey of neonatology training program directors indicates that most NICUs use chlorhexidine for CVC site prep and maintenance but restrict use based on gestational age, chronological age, and birth weight [102] . Risks to premature infants relate to the increased potential for chemical burns and contact dermatitis in the setting of underdeveloped skin [100] and the possibility of systemic absorption of CHG, although no adverse events have been reported despite demonstrable blood CHG levels [100, [103] [104] [105] . Chlorhexidine bathing has been suggested as another adjunct to decrease colonization and has been studied in adults and children, including neonates. An adult randomized controlled trial demonstrated that daily chlorhexidine bathing did not reduce HAI including central line-associated bloodstream infection (CLABSI), catheter-associated urinary tract infection (CAUTI), or ventilator-associated pneumonia (VAP) [106] . A number of other studies (including clinical trials) in adults, however, have shown positive benefits of chlorhexidine-containing products when used as part of a bundle approach for HAI prevention [107] [108] [109] . In the Pediatric SCRUB Trial, daily chlorhexidine bathing was compared with standard bathing practices to evaluate effect on incidence of bacteremia in critically ill children [110] . There was a non-statistically significant reduction in bacteremia in the CHG group in the intention-to-treat analysis and a 36% decrease in bacteremia in the per protocol arm [110] . The use of universal decolonization raises concerns about the possibility of chlorhexidine resistance. A study from Texas Children's Hospital found that nearly half of nosocomial S. aureus carried one or both genes associated with chlorhexidine tolerance (qacA/qacB and smr), noting that smr-positive isolates were more often resistant to methicillin, ciprofloxacin, or clindamycin as well [111] . Mupirocin resistance was also noted in 2.8% of the isolates in this study [111] . Vertical and horizontal approaches to infection prevention have been compared in two studies: Huang et al. compared three approaches to MRSA prevention among 74 adult ICU patients in the REDUCE-MRSA study [112] . Vertical approaches consisted of AST with and without targeted decolonization of MRSA carriers with CHG bathing and intranasal mupirocin compared with a horizontal approach involving universal decolonization of all ICU patients regardless of MRSA status. Universal decolonization was found to be associated with the largest reduction in all-cause BSI (44%) and MRSA clinical culture rates (37%) [112] . Another group showed that improved hand hygiene in addition to universal CHG bathing reduced overall infection rate and specific rates of Candida CAUTI and Acinetobacter VAP [113] . Additionally, when there is high adherence to CHG bathing and hand hygiene, there is no additional benefit to AST and isolation to reduce MDRO acquisition rates [114] . Selective digestive decontamination (SDD) and selective oral decontamination (SOD) are additional methods of universal decolonization employed in an effort to reduce colonization with gram-negative organisms, particularly in critically ill patients. Both methods use a polymyxin, an aminoglycoside, and an antifungal, applied to the oropharynx as a paste or gel (SOD) or in a liquid form administered per nasogastric or orogastric tube (SDD), paired with systemic antimicrobials, usually an intravenous third-generation cephalosporin. These two strategies have been studied in more than 50 RCTs and have been examined in 12 metaanalyses with demonstrated efficacy in reduction of colonization, morbidity, and mortality in adult ICU patients [115] [116] [117] . Widespread acceptance has been limited by concern over selecting for resistant organisms in universal applications, although long-term follow-up in units employing these strategies have not demonstrated an increase in resistant organisms [118] . Microbiome studies of adults undergoing SDD compared to healthy adults revealed dramatic shifts in the gastrointestinal microbiome of SDD recipients (as would be expected) as well as an increase in the relative abundance of organisms expressing antimicrobial resistance genes [119] . The pediatric experience with these strategies is limited. In a single meta-analysis of 4 RCTs including 335 children, ventilator-associated pneumonia rates were 69% lower in in those children receiving SDD [120] . The use in neonatal populations has not been studied. The evidence for perioperative antimicrobial prophylaxis is well established, and the use of antimicrobials prior to incision reduces rates of SSI [121] by reducing the concentration of potential pathogens within or near the surgical incision. The basic tenets of antimicrobial use to prevent SSI include use of prophylaxis for all elective operations requiring entry into a hollow viscus, involving insertion of intravascular or orthopedic prosthetic devices or implants, or operations in which occurrence of SSI would pose catastrophic risk to the patient (e.g., sternotomy). The choice of antimicrobial is based upon a need for bactericidal activity against the expected pathogens for specific surgical procedures as well as agents which are known to be safe and cost-effective. The goal is to provide bactericidal concentrations in tissues and serum at the time of incision and to be continued throughout the entire operation until the wound is closed. Re-dosing of the antimicrobial agent may be required should the procedure last several hours or if there is significant blood loss. An important risk factor contributing to SSI risk is the number of organisms which gain entry into the wound intraoperatively. The greater the burden, the greater the risk of infection. When appropriate antimicrobial prophylaxis has been administered, a bacterial burden of 10 5 is required to cause SSI; however if a foreign body is present, the threshold to cause infection may be significantly reduced. Virulence of the organism also contributes to SSI risk. Pre-and perioperative antiseptics are utilized in order to decrease organism burden and thereby reduce the risk of SSI. Preoperative bathing with agents such as chlorhexidine has been shown to decrease the amount of endogenous flora on the skin but has not been shown to reduce rates of SSI in pooled analyses of adult surgical patients [122] . In certain very high-risk populations, however, such as cardiac and orthopedic surgery patients, preoperative chlorhexidine bathing has been associated with reduced rates of SSI (especially those due to S. aureus or MRSA) [123] [124] [125] . It is likely that the benefits of chlorhexidine bathing are influenced by the type of surgical procedure (i.e., high-risk vs. low-risk) as well as the baseline rate of SSI at a given institution. In spite of these controversies, the use of chlorhexidine body wash prior to surgery is routine. There are several options for preoperative skin antisepsis with either chlorhexidine-alcohol or povidone-iodine as the active agent. The authors of a Cochrane Review conclude that other characteristics of skin prep agents such as potential side effects and cost should be taken into consideration as well until there are definitive data showing clinical superiority of one agent over another [126] . New CDC Guidelines for Prevention of SSI recommend an alcohol-based skin antiseptic, such as either chlorhexidine-alcohol or iodophor-alcohol products [127] [128] [129] . Surgical site infections generally arise from endogenous sources such as bacteria present on skin surfaces or in a viscus, with greatest risk occurring while the wound is open. In addition to skin surface, bacteria may be found in skin appendages, including sebaceous glands, hair follicles, and sweat glands [130] . When infections related to exogenous sources occur, they may be sporadic or related to an outbreak. Exogenous sources include contamination of the operating room environment, surgical instruments, equipment, or colonized or infected personnel [131, 132] . Common nosocomial pathogens can persist for months on surfaces, contributing to transmission risk in the absence of regular and thorough cleaning and disinfection [133] . These pathogens importantly include gram-positive (Enterococcus, including VRE; S. aureus, including MRSA; and Streptococcus pyogenes) as well as gramnegative (Acinetobacter spp., E. coli, Klebsiella spp., p. aeruginosa, Serratia marcescens, or Shigella) organisms. Spore-forming bacteria, such as Clostridium difficile, can survive for months as can fungi and yeast. Viruses from the respiratory tract, such as coronavirus, influenza, coxsackie, and rhinovirus, survive a relatively short period of days, whereas viruses from the gastrointestinal tract, such as norovirus or rotavirus, may persist for up to 2 months [133] . Surfaces in rooms of patients infected or colonized with pathogens may (and frequently do) become contaminated. MRSA, VRE, Acinetobacter spp., norovirus, and C. difficile have been detected on environmental surfaces in rooms of infected or colonized patients, can colonize healthcare workers' hands, and can then be transmitted to others [134] . Contact with the environment is as likely as contact with the affected patient to result in contamination of HCW hands [32] . The presence of environmental contamination is a risk factor for HCW hand/glove contamination [33] . Admission to a room previously occupied by a patient colonized or infected with MRSA, VRE, Acinetobacter spp., or C. difficile has been shown to be a risk factor for subsequent development of colonization or infection by these pathogens [38, 40, 41] . Multiple studies have demonstrated that a lack of thorough cleaning [135, 136] contributes to persistence of environmental contamination. Assessing adequacy of cleaning can be performed using various methods including observation for visible soiling, culture-based colony counts, fluorescent dye, and ATP detection. For example, fluorescent dye can be applied as a dot to surfaces where it dries clear. If a surface was inadequately wiped, the area fluoresces when exposed to black light. ATP bioluminescence systems measure ATP, a marker for presence of residual organic material (e.g., human secretions or excretions and food). ATP, however, does not indicate presence of viable pathogens, and its absence does not rule out the presence of contamination, and as such, use of fluorescent dye correlates more closely with colony counts than does ATP bioluminescence [137] . Focused efforts to eradicate pathogens can improve cleaning efficacy, which may involve specialized teams [138] or through use of improved monitoring of cleaning practices with markers such as ATP and fluorescent dye [137, 139] . Feedback to environmental services (EVS) staff following use of enhanced methods has also been demonstrated to improve the frequency of achieving adequate cleaning [140, 141] . In a study of 36 acute care hospitals, only 48% (9910/20,646) of environmental surfaces were cleaned at baseline. After educational and procedural interventions combined with provision of objective performance feedback to EVS staff, 77% (7287/9464) of surfaces were cleaned (p < 0.001) [141] . In addition to ensuring each surface is cleaned, it is important to select the correct cleaning product as microorganisms vary in their resistance to disinfectants. For example, disinfection of a room potentially contaminated by C. difficile requires use of hypochlorite-based solutions [142] rather than phenols or quaternary ammonium compounds generally used for general hospital-based cleaning. In spite of enhanced cleaning methods aimed at improving cleaning thoroughness and monitoring of cleaning practices, many surfaces remain inadequately cleaned. For this reason, no-touch room disinfection units that decontaminate environmental surfaces and objects utilizing either ultraviolet (UV) light or hydrogen peroxide (HP) vapor have been developed [143, 144] . These technologies are considered an adjunct to standard cleaning and disinfection since surfaces must be physically clean and the room must be emptied of people prior to use. UV irradiation with certain wavelengths breaks the molecular bond in DNA, thereby destroying the organism. This has been shown to be effective against MRSA, VRE, and Acinetobacter baumannii, in experimentally contaminated rooms [145] . Systems utilizing HP vapor have been found to be effective in eradicating pathogens such as MRSA, Mycobacterium tuberculosis, Serratia, and C. difficile spores from rooms and equipment [146] . Both of these methods have been found to be effective at reducing HAIs [146] . Their advantages include ability to substantially reduce C. difficile spores [147] as well as achieve substantial reductions in vegetative bacteria. Failure to adequately clean and sterilize equipment may lead to transmission via contaminated equipment [148] . The level of disinfection or sterilization considered acceptable depends on the intended use of the object and is categorized as critical (items that come into contact with sterile tissue), semicritical (items contacting mucous membranes, such as endoscopes), and noncritical (items contacting skin, such as stethoscopes). These each require sterilization, high-level disinfection, or low-level disinfection, respectively. Cleaning should precede sterilization or disinfection. Among the many sources of infection within hospital environments, water remains of significant concern secondary to opportunity for exposure. Water is ubiquitous in its use throughout the hospital, not only for routine sanitation but also for air conditioning, mechanical ventilation, bathing, as well as the cleaning and processing of equipment. Certain organisms have special predilection for moist environments and include gram-negative bacilli, nontuberculous mycobacteria, fungi, and some viruses. In a recent review of waterborne healthcare-associated infections, 41 of 125 reports described hospitalized children [149] . The organisms primarily responsible included Legionella (hot water distribution systems), Pseudomonas (bottled water), and Burkholderia (distilled and sterile water contamination) [149] . Generally, tap water is the most frequently reported source of infection, with contamination at the sink, shower, and bathtub. Legionella was the primary cause of HAI among all the patients included in this review and was the predominant organism causing outbreaks [149] . Legionella outbreaks have been reported in premature neonates associated with the humidification trays of incubators [150] and in term neonates associated with cold mist humidifiers [151] . Environmental control measures are generally insufficient, and eradication requires use of a multistep control plan which includes education; use of sterile water for immunocompromised patients; use of periodic cleaning of showers, tubs, and sinks; and use of disinfection systems/filters on taps and shower heads. A team of specialists from all areas of infection control including engineers is required to eradicate contamination in the water system/supplies when it occurs [149] . Endogenous and exogenous microbes are a constant threat to hospitalized patients. Efforts to decrease endogenous pathogens via decolonization and skin antisepsis decrease the risk of infection in some settings. Controlling the spread of potential pathogens from the environment requires meticulous attention to cleaning and disinfection practices as well as hand hygiene. The role of nasal carriage in Staphylococcus aureus infections Variability and diversity of nasopharyngeal microbiota in children: a metagenomic analysis Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization The skin microbiome The role of Propionibacterium acnes in acne pathogenesis: facts and controversies Staphylococcal infections in patients with atopic dermatitis Antibiotic use and microbiome function The role of the microbiome in human health and disease: an introduction for clinicians Gut microbiota and host defense in critical illness Probiotics in critically ill children Bacterial colonization and intestinal mucosal barrier development The intestinal microbiota: its role in health and disease The function of immunoglobulin A in immunity Intestinal IgA production and its role in host-microbe interaction Methicillin-resistant Staphylococcus aureus colonization and its association with infection among infants hospitalized in neonatal intensive care units Nasal carriage as a source of Staphylococcus aureus bacteremia. Study Group Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections Epidemiology of community-acquired methicillin-resistant Staphylococcus aureus skin infections among healthcare workers in an outpatient clinic Outpatient vancomycin use and vancomycin-resistant enterococcal colonization in maintenance dialysis patients What's trending in the infection prevention and control literature? From HIS 2012 to HIS 2014, and beyond The importance of long-term acute care hospitals in the regional epidemiology of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae Controlling hospital-acquired infection: focus on the role of the environment and new technologies for decontamination Risk of acquiring multidrug-resistant gram-negative bacilli from prior room occupants in the intensive care unit Survival of Acinetobacter baumannii on dry surfaces Antibiotic exposure and room contamination among patients colonized with vancomycin-resistant enterococci Epidemiology of colonisation of patients and environment with vancomycin-resistant enterococci Isolation of Clostridium difficile from the environment and contacts of patients with antibiotic-associated colitis Nosocomial acquisition of Clostridium difficile infection Asymptomatic carriers are a potential source for transmission of epidemic and nonepidemic Clostridium difficile strains among long-term care facility residents What is on that keyboard? Detecting hidden environmental reservoirs of Clostridium difficile during an outbreak associated with North American pulsed-field gel electrophoresis type 1 strains A quantitative approach to defining "high-touch" surfaces in hospitals Contamination of hands with methicillin-resistant Staphylococcus aureus after contact with environmental surfaces and after contact with the skin of colonized patients Transfer of multidrug-resistant bacteria to healthcare workers' gloves and gowns after patient contact increases with environmental contamination Clinical and molecular epidemiology of sporadic and clustered cases of nosocomial Clostridium difficile diarrhea Transmission of health care-associated infections from roommates and prior room occupants: a systematic review Distribution of multi-resistant gram-negative versus gram-positive bacteria in the hospital inanimate environment Environmental contamination due to methicillin-resistant Staphylococcus aureus: possible infection control implications Risk of acquiring antibiotic-resistant bacteria from prior room occupants Disinfection and sterilization in health care facilities: an overview and current issues Methods for assessing the adequacy of practice and improving room disinfection Evaluation of hospital room assignment and acquisition of Clostridium difficile infection Does improving surface cleaning and disinfection reduce health care-associated infections? Impact of hydrogen peroxide vapor room decontamination on Clostridium difficile environmental contamination and transmission in a healthcare setting An evaluation of environmental decontamination with hydrogen peroxide vapor for reducing the risk of patient acquisition of multidrug-resistant organisms Approaches for preventing healthcare-associated infections: go long or go wide? Decolonization in prevention of health care-associated infections Infection control: the case for horizontal rather than vertical interventional programs Screening for MRSA: a flawed hospital infection control intervention Healthy carriage of Staphylococcus aureus: its prevalence and importance Carriage patterns of Staphylococcus aureus in a healthy non-hospital population of adults and children Effect of mupirocin treatment on nasal, pharyngeal, and perineal carriage of Staphylococcus aureus in healthy adults Perineal carriage of Staph. aureus Vaginal colonization with Staphylococcus aureus in healthy women: a review of four studies Resistance mechanisms, epidemiology, and approaches to screening for vancomycin-resistant Enterococcus in the health care setting Isolation measures in the hospital management of methicillin resistant Staphylococcus aureus (MRSA): systematic review of the literature Screening for methicillinresistant Staphylococcus aureus: a comparative effectiveness review Eradication of a large outbreak of a single strain of vanB vancomycin-resistant Enterococcus faecium at a major Australian teaching hospital Effectiveness of contact isolation during a hospital outbreak of methicillin-resistant Staphylococcus aureus Universal glove and gown use and acquisition of antibiotic-resistant bacteria in the ICU: a randomized trial Isolation of patients in single rooms or cohorts to reduce spread of MRSA in intensive-care units: prospective twocentre study Reconsidering isolation precautions for endemic methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus Single rooms may help to prevent nosocomial bloodstream infection and cross-transmission of methicillin-resistant Staphylococcus aureus in intensive care units To isolate or not to isolate? Analysis of data from the German Nosocomial Infection Surveillance System regarding the placement of patients with methicillin-resistant Staphylococcus aureus in private rooms in intensive care units Guidelines for the control and prevention of meticillin-resistant Staphylococcus aureus (MRSA) in healthcare facilities Strategies to prevent methicillin-resistant Staphylococcus aureus transmission and infection in acute care hospitals: 2014 update Screening and isolation to control meticillin-resistant Staphylococcus aureus: sense, nonsense, and evidence Outcomes of colonization with MRSA and VRE among liver transplant candidates and recipients Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks Follow-up of Staphylococcus aureus nasal carriage after 8 years: redefining the persistent carrier state Persistent (not intermittent) nasal carriage of Staphylococcus aureus is the determinant of CPD-related infections Nasal carriage of Staphylococcus aureus is a major risk factor for surgical-site infections in orthopedic surgery Quantitative analysis and molecular fingerprinting of methicillin-resistant Staphylococcus aureus nasal colonization in different patient populations: a prospective, multicenter study Effect of antibiotics on the bacterial load of meticillin-resistant Staphylococcus aureus colonisation in anterior nares Role of decolonization in a comprehensive strategy to reduce methicillin-resistant Staphylococcus aureus infections in the neonatal intensive care unit: an observational cohort study Eradication of methicillin-resistant Staphylococcus aureus from a neonatal intensive care unit by active surveillance and aggressive infection control measures Successful control of methicillin-resistant Staphylococcus aureus in endemic neonatal intensive care units -a 7-year campaign Randomized, placebo-controlled, double-blind trial to evaluate the efficacy of mupirocin for eradicating carriage of methicillin-resistant Staphylococcus aureus Eradication of methicillin-resistant Staphylococcus aureus carriage: a systematic review Mupirocin prophylaxis to prevent Staphylococcus aureus infection in patients undergoing dialysis: a metaanalysis Intranasal mupirocin for reduction of Staphylococcus aureus infections in surgical patients with nasal carriage: a systematic review Perioperative intranasal mupirocin for the prevention of surgical-site infections: systematic review of the literature and meta-analysis Mupirocin ointment for preventing Staphylococcus aureus infections in nasal carriers Universal surveillance for methicillin-resistant Staphylococcus aureus in 3 affiliated hospitals Veterans Affairs initiative to prevent methicillin-resistant Staphylococcus aureus infections Universal screening for methicillin-resistant Staphylococcus aureus at hospital admission and nosocomial infection in surgical patients Effect of mupirocin decolonization on subsequent methicillinresistant Staphylococcus aureus infection in infants in neonatal intensive care units Methicillin-resistant Staphylococcus aureus transmission and infections in a neonatal intensive care unit despite active surveillance cultures and decolonization: challenges for infection prevention Strategies to prevent methicillin-resistant Staphylococcus aureus transmission and infection in acute care hospitals: 2014 update Society for Healthcare Epidemiology of America's Pediatric Special Interest G. Identification and eradication of methicillin-resistant Staphylococcus aureus colonization in the neonatal intensive care unit: results of a national survey Burden of invasive Staphylococcus aureus infections in hospitalized infants Active surveillance cultures and decolonization to reduce Staphylococcus aureus infections in the neonatal intensive care unit Comprehensive strategy including prophylactic mupirocin to reduce Staphylococcus aureus colonization and infection in high-risk neonates Control of a methicillinresistant Staphylococcus aureus outbreak in a neonatal intensive care unit by unselective use of nasal mupirocin ointment Screening cardiac surgery patients for MRSA: an economic computer model Efficacy of mupirocin nasal ointment in eradicating Staphylococcus aureus nasal carriage in chronic haemodialysis patients The persistence of Staphylococcus aureus decolonization after mupirocin and topical chlorhexidine: implications for patients requiring multiple or delayed procedures Effectiveness of a bundled intervention of decolonization and prophylaxis to decrease gram positive surgical site infections after cardiac or orthopedic surgery: systematic review and meta-analysis Preoperative colonization in pediatric cardiac surgery and its impact on postoperative infections Preventing surgical-site infections in nasal carriers of Staphylococcus aureus Safety of chlorhexidine gluconate used for skin antisepsis in the preterm infant Summary of recommendations: guidelines for the prevention of intravascular catheter-related infections Chlorhexidine use in the neonatal intensive care unit: results from a national survey Percutaneous absorption of chlorhexidine in neonatal cord care Absorption of chlorhexidine from the intact skin of newborn infants Pilot trial to compare tolerance of chlorhexidine gluconate to povidone-iodine antisepsis for central venous catheter placement in neonates Chlorhexidine bathing and healthcare-associated infections: a randomized clinical trial Chlorhexidine bathing and health care-associated infections among adult intensive care patients: a systematic review and meta-analysis Effectiveness of chlorhexidine bathing to reduce catheter-associated bloodstream infections in medical intensive care unit patients Effect of daily chlorhexidine bathing on hospital-acquired infection Daily chlorhexidine bathing to reduce bacteraemia in critically ill children: a multicentre, cluster-randomised, crossover trial Clinical and molecular features of decreased chlorhexidine susceptibility among nosocomial Staphylococcus aureus isolates at Texas Children's Hospital Targeted versus universal decolonization to prevent ICU infection Impact of daily chlorhexidine baths and hand hygiene compliance on nosocomial infection rates in critically ill patients Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial Selective digestive or oropharyngeal decontamination and topical oropharyngeal chlorhexidine for prevention of death in general intensive care: systematic review and network meta-analysis Selective oropharyngeal decontamination versus selective digestive decontamination in critically ill patients: a meta-analysis of randomized controlled trials Selective digestive and oropharyngeal decontamination in medical and surgical ICU patients: individual patient data meta-analysis Selective decontamination of the oropharynx and the digestive tract, and antimicrobial resistance: a 4 year ecological study in 38 intensive care units in the Netherlands Comparative gut microbiota and resistome profiling of intensive care patients receiving selective digestive tract decontamination and healthy subjects Selective decontamination of the digestive tract in critically ill children: systematic review and meta-analysis The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection Preoperative bathing of the surgical site with chlorhexidine for infection prevention: systematic review with meta-analysis A randomized, clinical trial of preadmission chlorhexidine skin preparation for lower extremity total joint arthroplasty Preoperative Staphylococcus Aureus screening and targeted decolonization in cardiac surgery Preoperative bathing with chlorhexidine reduces the incidence of surgical site infections after total knee arthroplasty: a meta-analysis Preoperative skin antiseptics for preventing surgical wound infections after clean surgery Centers for Disease Control and Prevention guideline for the prevention of surgical site infection Chlorhexidine-alcohol versus povidone-iodine for surgical-site antisepsis Frequent contamination of nursing scrubs is associated with specific care activities Skin and skin structure infections in the patient at risk: carrier state of Staphylococcus aureus Prolonged outbreak of Staphylococcus aureus surgical site infection traced to a healthcare worker with psoriasis Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study How long do nosocomial pathogens persist on inanimate surfaces? A systematic review The role played by contaminated surfaces in the transmission of nosocomial pathogens Healthcare Environmental Hygiene Study G. Identifying opportunities to enhance environmental cleaning in 23 acute care hospitals Healthcare Environmental Hygiene Study G. Intensive care unit environmental cleaning: an evaluation in sixteen hospitals using a novel assessment tool Comparison of fluorescent marker systems with 2 quantitative methods of assessing terminal cleaning practices Reduction of Clostridium difficile and vancomycin-resistant Enterococcus contamination of environmental surfaces after an intervention to improve cleaning methods Monitoring the effectiveness of hospital cleaning practices by use of an adenosine triphosphate bioluminescence assay Impact of an environmental cleaning intervention on the presence of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci on surfaces in intensive care unit rooms Improving cleaning of the environment surrounding patients in 36 acute care hospitals Antiseptics and disinfectants: activity, action, and resistance Are room decontamination units needed to prevent transmission of environmental pathogens? Gaseous and air decontamination technologies for Clostridium difficile in the healthcare environment Room decontamination with UV radiation Effectiveness of ultraviolet devices and hydrogen peroxide systems for terminal room decontamination: focus on clinical trials Selection of the ideal disinfectant source and prevention of waterborne healthcare-associated infections: a review A hot water supply as the source of Legionella pneumophila in incubators of a neonatology unit First outbreak of nosocomial Legionella infection in term neonates caused by a cold mist ultrasonic humidifier