Definition of Colonization

Colonization is the survival of a microorganism on an internal (gastrointestinal, respiratory, or genitourinary tract) or external (skin) surface of the host without causing disease. Different types of organisms colonize different surfaces. For example, skin and the mucous membranes of the nose may be colonized with gram-positive organisms, including Staphylococcus aureus and coagulase-negative staphylococci [1]. The pharynx is colonized with gram-positive and gram-negative organisms including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis [2]. Gram-negative aerobic and anaerobic organisms commonly found colonizing the gastrointestinal tract include gram-negative aerobic and anaerobic bacteria and gram-positive organisms including Enterococcus and C. difficile.

Hosts encounter microbes on a nearly constant basis from the environment around them. A patient’s own colonizing flora can result in hospital-associated infections when host defenses are compromised by underlying disease, immune compromise, or invasive devices. Alternatively, the healthcare environment can provide a source of pathogens, either by indirect transmission on the hands of healthcare workers (HCWs) or by direct transfer from environmental contamination.

The outcome of human-microbe interactions depends on the complex interplay of host defenses against microbial invasion and microbial virulence factors. If microbes are not killed by the immune system, a commensal relationship between the colonizer and the host may develop; alternatively, this may be the first step in the process of infection, damaging the host as a result of multiplication of the microorganism. Prolonged illness leading to immunodeficiency and breaks in barriers 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].

The Role of Host Flora in Hospital-Acquired Infections

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 methicillin-resistant 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 Role of Environmental Flora in Hospital-Acquired Infections

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.

Surface as a Reservoir

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].

Contact with Contaminated Surfaces or Equipment Contaminating Gloves or Hands of HCWs

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].

Transmission of HAI from Roommates and Associated with Prior Room Occupants

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].

The Role of Identifying Colonization

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.

Active Surveillance Testing (Screening)

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.

AST Samples

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.

AST and Isolation (Screening and Isolation)

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].

AST, Isolation, and Targeted Decolonization Using Mupirocin

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 non-carriage [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. Short-term 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 high-risk 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 short-lived [95, 96]. Mupirocin decolonization has been used specifically to reduce the risk of surgical site infections (SSIs) associated with gram-positive organisms. In a meta-analysis 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 mupirocin-based decolonization in prevention of SSI [99]; this topic as it pertains to cardiac surgery is discussed further in Chap. 11.

Use of Universal Decolonization Strategies: Chlorhexidine Bathing

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].

Digestive and Respiratory Tract Decolonization/Decontamination Strategies

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 meta-analyses 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.

Surgical Site Infections

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 105 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].

Environmental Contamination

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 gram-negative (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.

Legionella and Other Water-Associated Infections

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].

Conclusion

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.