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From the Division of Adult Infectious Diseases, University of Colorado Denver, Aurora, CO, and the Department of Veterans Affairs, Eastern Colorado Healthcare System, Denver, CO.
Abstract
- Objective: To review the published literature on methicillin-resistant Staphylococcus aureus (MRSA) infections among patients recently discharged from hospital, with a focus on possible prevention measures.
- Methods: Literature review.
- Results: MRSA is a major cause of post-discharge infections. Risk factors for post-discharge MRSA include colonization, dependent ambulatory status, duration of hospitalization > 5 days, discharge to a long-term care facility, presence of a central venous catheter (CVC), presence of a non-CVC invasive device, a chronic wound in the post-discharge period, hemodialysis, systemic corticosteroids, and receiving anti-MRSA antimicrobial agents. Potential approaches to control include prevention of incident colonization during hospital stay, removal of nonessential CVCs and other devices, good wound debridement and care, and antimicrobial stewardship. Hand hygiene and environmental cleaning are horizontal measures that are also recommended. Decolonization may be useful in selected cases.
- Conclusion: Post-discharge MRSA infections are an important and underestimated source of morbidity and mortality. The future research agenda should include identification of post-discharge patients who are most likely to benefit from decolonization strategies, and testing those strategies.
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of morbidity and mortality due to infections of the bloodstream, lung, surgical sites, bone, and skin and soft tissues. The mortality associated with S. aureus bloodstream infections is 14% to 45% [1–4]. A bloodstream infection caused by MRSA is associated with a twofold increased mortality as compared to one caused by methicillin-sensitive S. aureus [5]. MRSA pneumonia carries a mortality of 8%, which increases to 39% when bacteremia is also present [6]. S. aureus bloodstream infection also carries a high risk of functional disability, with 65% of patients in a recent series requiring nursing home care in the recovery period [7]. In 2011 there were more than 11,000 deaths due to invasive MRSA infection in the United States [8]. Clearly S. aureus, and particularly MRSA, is a pathogen of major clinical significance.
Methicillin resistance was described in 1961, soon after methicillin became available in the 1950s. Prevalence of MRSA remained low until the 1980s, when it rapidly increased in health care settings. The predominant health care–associated strain in the United States is USA100, a member of clonal complex 5. Community-acquired MRSA infection has garnered much attention since it was recognized in 1996 [9]. The predominant community-associated strain has been USA300, a member of clonal complex 8 [10]. Following its emergence in the community, USA300 became a significant health care–associated pathogen as well [11]. The larger share of MRSA disease remains health care–associated [8]. The most recent data from the Center for Disease Control and Prevention Active Bacterial Core Surveillance system indicate that 77.6% of invasive MRSA infection is health care–associated, resulting in 9127 deaths in 2011 [8].
This article reviews the published literature on MRSA infections among patients recently discharged from hospital, with a focus on possible prevention measures.
MRSA Epidemiologic Categories
Epidemiologic investigations of MRSA categorize infections according to the presumed acquisition site, ie, in the community or in a health care setting. Older literature refers to nosocomial MRSA infection, which is now commonly referred to as hospital-onset health care–associated (HO-HCA) MRSA. A common definition of HO-HCA MRSA infection is an infection with the first positive culture on hospital day 4 or later [12]. Community-onset health care–associated MRSA (CO-HCA MRSA) is defined as infection that is diagnosed in the outpatient setting, or prior to day 4 of hospitalization, in a patient with recent health care exposure, eg, hospitalization within the past year, hemodialysis, surgery, or presence of a central venous catheter at time of presentation to the hospital [12]. Community-associated MRSA (CA-MSRSA) is infection in patients who do not meet criteria for either type of health care associated MRSA. Post-discharge MRSA infections would be included in the CO-HCA MRSA group.
Infection Control Programs
Classic infection control programs, developed in the 1960s, focused on infections that presented more than 48 to 72 hours after admission and prior to discharge from hospital. In that era, the average length of hospital stay was 1 week or more, and there was sufficient time for health care–associated infections to become clinically apparent. In recent years, length of stay has progressively shortened [13]. As hospital stays shortened, the risk that an infection caused by a health care–acquired pathogen would be identified after discharge grew. More recent studies have documented that the majority of HO-HCA infections become apparent after the index hospitalization [8,14].
Data from the Active Bacterial Core Surveillance System quantify the burden of CO-HCA MRSA disease at a national level [8,14]. However, it is not readily detected by many hospital infection surveillance programs. Avery et al studied a database constructed with California state mandated reports of MRSA infection and identified cases with MRSA present on admission. They then searched for a previous admission, within 30 days. If a prior admission was identified, the MRSA case was assigned to the hospital that had recently discharged the patient. Using this approach, they found that the incidence of health care–associated MRSA infection increased from 12.2 cases/10,000 admissions when traditional surveillance methods were used to 35.7/10,000 admissions using the revised method of assignment of health care exposure [15]. These data suggest that post-discharge MRSA disease is underappreciated by hospital infection control programs.
Lessons from Hospital-Onset MRSA
The morbidity and mortality associated with MRSA have led to the development of vigorous infection control programs to reduce the risk of health care–associated MRSA infection [16–18]. Vertical infection control strategies, ie, those focused on MRSA specifically, have included active screening for colonization, and nursing colonized patients in contact precautions. Since colonization is the antecedent to infection in most cases, prevention of transmission of MRSA from patient to patient should prevent most infections. There is ample evidence that colonized patients contaminate their immediate environment with MRSA, creating a reservoir of resistant pathogens that can be transmitted to other patients on the hands and clothing of health care workers [19,20]. Quasi-experimental studies of active screening and isolation strategies have shown decreases in MRSA transmission and infection following implementation [18]. The only randomized comparative trial of active screening and isolation versus usual care did not demonstrate benefit, possibly due to delays in lab confirmation of colonization status [21]. Horizontal infection control strategies are applied to all patients, regardless of colonization with resistant pathogens, in an attempt to decrease health care–associated infections with all pathogens. Examples of horizontal strategies are hand hygiene, environmental cleaning, and the prevention bundles for central line–associated bloodstream infection.
The Burden of Community-Onset MRSA
CO-HCA MRSA represents 60% of the burden of invasive MRSA infection [8]. While this category includes cases that have not been hospitalized, eg, patients on hemodialysis, post-discharge MRSA infection accounts for the majority of cases [15]. Recent data indicate that the incidence of HO-HCA MRSA decreased 54.2% between 2005 and 2011 [8]. This decrease in HO-HCA MRSA infection occurred concurrently with widespread implementation of vigorous horizontal infection control measures, such as bundled prevention strategies for central line–associated bloodstream infection and ventilator-associated pneumonia. The decline in CO-HCA MRSA infection has been much less steep, at 27.7%. The majority of the CO-HCA infections are in post-discharge patients. Furthermore, the incidence of CO-HCA MRSA infection may be underestimated [15].
Post-Discharge MRSA Colonization and Infection
Hospital-associated MRSA infection is reportable in many jurisdictions, but post-discharge MRSA infection is not a specific reportable condition, limiting the available surveillance data. Avery et al [15] studied ICD-9 code data for all hospitals in Orange County, California, and found that 23.5/10,000 hospital admissions were associated with a post-discharge MRSA infection. This nearly tripled the incidence of health care–associated MRSA infection, compared to surveillance that included only hospital-onset cases. Future research should refine these observations, as ICD-9 code data correlate imperfectly with chart reviews and have not yet been well validated for MRSA research.
The CDC estimated that in 2011 there were 48,353 CO-HCA MRSA infections resulting in 10,934 deaths. This estimate is derived from study of the Active Bacterial Core surveillance sample [8]. In that sample, 79% of CO-HCA MRSA infections occurred in patients hospitalized within the last year. Thus, we can estimate that there were 34,249 post-discharge MRSA infections resulting in 8638 deaths in the United States in 2011.
MRSA colonization is the antecedent to infection in the majority of cases [22]. Thus we can assess the health care burden of post-discharge MRSA by analyzing colonization as well as infection. Furthermore, the risk of MRSA colonization of household members can be addressed. Lucet et al evaluated hospital inpatients preparing for discharge to a home health care setting, and found that 12.7% of them were colonized with MRSA at the time of discharge, and 45% of them remained colonized for more than a year [23]. Patients who regained independence in activities of daily living were more likely to become free of MRSA colonization. The study provided no data on the risk of MRSA infection in the colonized patients. 19.1% of household contacts became colonized with MRSA, demonstrating that the burden of MRSA extends beyond the index patient. None of the colonized household contacts developed MRSA infection during the study period.
Risk Factors for Post-Discharge MRSA
Case control studies of patients with post-discharge invasive MRSA have shed light on risk factors for infection. While many risk factors are not modifiable, these studies may provide a road map to development of prevention strategies for the post-discharge setting. A study of hospitals in New York that participated in the Active Bacterial Core surveillance system identified a statistically significant increased risk of MRSA invasive infection among patients with several factors associated with physical disability, including a physical therapy evaluation, dependent ambulatory status, duration of hospitalization > 5 days, and discharge to a long-term care facility. Additional risk factors identified in the bivariate analysis were presence of a central venous catheter, hemodialysis, systemic corticosteroids, and receiving anti-MRSA antimicrobial agents. When subjected to multivariate analysis, however, the most significant and potent risk factor was a previous positive MRSA clinical culture (matched odds ratio 23, P < 0.001). Other significant risk factors in the multivariate analysis were hemodialysis, presence of a central venous catheter in the outpatient setting, and a visit to the emergency department [24]. A second, larger, multistate study also based on data from the Active Bacterial Core surveillance system showed that 5 risk factors were significantly associated with post-discharge invasive MRSA infection: (1) MRSA colonization, (2) a central venous catheter (CVC) present at discharge, (3) presence of a non-CVC invasive device, (4) a chronic wound in the post-discharge period, and (5) discharge to a nursing home. MRSA colonization was associated with a 7.7-fold increased odds of invasive MRSA infection, a much greater increase than any of the other risk factors [25]. Based on these results, strategies to consider include enhanced infection measures for prevention of incident MRSA colonization in the inpatient setting, decolonization therapy for those who become colonized, removal of non-essential medical devices, including central venous catheters, excellent nursing care for essential devices and wounds, hand hygiene, environmental cleaning, and antimicrobial stewardship.
Development of Strategies to Decrease Post-Discharge MRSA
While the epidemiology of post-discharge health care–associated MRSA infections has become a topic of interest to researchers, approaches to control are in their infancy. Few of the approaches have been subjected to rigorous study in the post-discharge environment. Nevertheless, some low risk, common sense strategies may be considered. Furthermore, an outline of research objectives may be constructed.
Prevention of Colonization in the Inpatient Setting
Robust infection control measures must be implemented in inpatient settings to prevent incident MRSA colonization [16,17]. Key recommendations include surveillance and monitoring of MRSA infections, adherence to standard hand hygiene guidance, environmental cleanliness, and use of dedicated equipment for patients who are colonized or infected with MRSA. Active screening for asymptomatic MRSA carriage and isolation of carriers may be implemented if routine measures are not successful.
Decolonization
Despite the best infection control programs, some patients will be colonized with MRSA at the time of hospital discharge. As detailed above, MRSA colonization is a potent risk factor for infection in the post-discharge setting, as well as in hospital inpatients [22]. A logical approach to this would be to attempt to eradicate colonization. There are several strategies for decolonization therapy, which may be used alone or in combination, including nasal mupirocin, nasal povidone-iodine, systemic antistaphylococcal drugs alone or in combination with oral rifampin, chlorhexidine bathing, or bleach baths [26–29].
A preliminary step in approaching the idea of post-discharge decolonization therapy is to show that patients can be successfully decolonized. With those data in hand, randomized trials seeking to demonstrate a decrease in invasive MRSA infections can be planned. Decolonization using nasal mupirocin has an initial success rate of 60% to 100% in a variety of patient populations [30–35]. Poor adherence to the decolonization protocol may limit success in the outpatient setting. Patients are more likely to resolve their MRSA colonization spontaneously when they regain their general health and independence in activities of daily living [23]. Colonization of other household members may provide a reservoir of MRSA leading to recolonization of the index case. Treatment of the household members may be offered, to provide more durable maintenance of the decolonized state [35]. When chronically ill patients who have been decolonized are followed longitudinally, up to 39% become colonized again, most often with the same strain [30,31]. Attempts to maintain a MRSA-free state in nursing home residents using prolonged mupirocin therapy resulted in emergence of mupirocin resistance [31]. Thus decolonization can be achieved, but is difficult to maintain, especially in debilitated, chronically ill patients. Mupirocin resistance can occur, limiting success of decolonization therapies.
Successful decolonization has been proven to reduce the risk of MRSA infection in the perioperative, dialysis, and intensive care unit settings [33,36–38]. In dialysis patients the risk of S. aureus bloodstream infection, including MRSA, can be reduced 59% with the use of mupirocin decolonization of the nares, with or without treatment of dialysis access exit sites [37]. A placebo-controlled trial demonstrated that decolonization of the nares with mupirocin reduced surgical site infections with S. aureus. All S. aureus isolates in the study were methicillin-susceptible. A second randomized controlled trial of nasal mupirocin did not achieve a statistically significant decrease in S. aureus surgical site infections, but it showed that mupirocin decolonization therapy decreased nosocomial S. aureus infections among nasal carriers [33]. 99.2% of isolates in that study et al were methicillin-susceptible. Quasi-experimental studies have shown similar benefits for surgical patients who are colonized with MRSA [39–41]. A more recent randomized trial, in ICU patients, demonstrated decreased incidence of invasive infection in patients treated with nasal mupirocin and chlorhexidine baths [38]. The common themeof these studies is that they enrolled patients who had a short-term condition, eg, surgery or critical illness, placing them at high risk for invasive MRSA infection. This maximizes the potential benefit of decolonization and minimizes the risk of emergence of resistance. Furthermore, adherence to decolonization protocols is likely to be high in the perioperative and ICU settings. To extrapolate the ICU and perioperative data to the post-discharge setting would be imprudent.
In summary, decolonization may be a useful strategy to reduce invasive MRSA infection in post-discharge patients, but more data are needed for most patient populations. The evidence for decolonization therapy is strongest for dialysis patients, in whom implementation of routine decolonization of MRSA colonized nares is a useful intervention [37]. There are not yet clinical trials of decolonization therapy in patients at time of hospital discharge showing a reduction in invasive MRSA infection. Decolonization strategies have important drawbacks, including emergence of resistance to mupirocin, chlorhexidine, and systemic agents. Furthermore, there is a risk of hypersensitivity reactions, Clostridium difficile infection, and potential for negative impacts onthe normal microbiome. The potential for lesser efficacy in a chronically ill outpatient population must also be considered in the post-discharge setting. Randomized controlled trials with invasive infection outcomes should be performed prior to implementing routine decolonization therapy of hospital discharge patients.
Care of Invasive Devices
Discharge with a central venous catheter was associated with a 2.16-fold increased risk of invasive MRSA infection; other invasive devices were associated with a 3.03-fold increased risk [25]. Clinicians must carefully assess patients nearing discharge for any opportunity to remove invasive devices. Idle devices have been reported in inpatient settings [42] and could occur in other settings. Antimicrobial therapy is a common indication for an outpatient central venous catheter and can also be associated with increased risk of invasive MRSA infection [25,43]. Duration and route of administration of antimicrobial agents should be carefully considered, with an eye to switching to oral therapy whenever possible. When a central venous catheter must be utilized, it should be maintained as carefully as in the inpatient setting. Tools for reducing risk of catheter-associated bloodstream infection include keeping the site dry, scrubbing the hub whenever accessing the catheter, aseptic techniques for dressing changes, and chlorhexidine sponges at the insertion site [44,45]. Reporting of central line–associated bloodstream infection rates by home care agencies is an important quality measure.
Wound Care
The presence of a chronic wound in the post-discharge period is associated with a 4.41-fold increased risk of invasive MRSA infection [25]. Although randomized controlled trials are lacking, it is prudent to ensure that wounds are fully debrided to remove devitalized tissue that can be fertile ground for a MRSA infection. The burden of organisms on a chronic wound is often very large, creating high risk of resistance when exposed to antimicrobial agents. Decolonization therapy is not likely to meet with durable success in such cases and should probably be avoided, except in special circumstances, eg, in preparation for cardiothoracic surgery.
Infection Control in Nursing Home Settings
In the Active Bacterial Core cohort, discharge to a nursing home was associated with a 2.1- to 2.65-fold increased risk of invasive MRSA infection [24,25]. It is notable that the authors controlled for the Charlson comorbidity index, suggesting that nursing home care is more than a marker for comorbidity [25]. The tension between the demands of careful infection control and the home-like setting that is desirable for long-term care creates challenges in the prevention of invasive MRSA infection. Nevertheless, careful management of invasive devices and wounds and antimicrobial stewardship are strategies that may reduce the risk of invasive MRSA infection in long-term care settings. Contact precautions for colonized nursing home residents are recommended only during an outbreak [46]. Staff should be trained in proper application of standard precautions, including use of gowns and gloves when handling body fluids. A study of an aggressive program of screening, decolonization with nasal mupirocin and chlorhexidine bathing, enhanced hand hygiene and environmental cleaning demonstrated a significant reduction in MRSA colonization [47]. An increase in mupirocin resistance during the study led to a switch to retapamulin for nasal application. The Association of Practitioners of Infection Control has issued guidance for MRSA prevention in long-term care facilities [48]. The guidance focuses on surveillance for MRSA infection, performing a MRSA risk assessment, hand hygiene, and environmental cleaning.
Antimicrobial Stewardship
Antimicrobial therapy, especially with fluoroquinolones and third- or fourth-generation cephalosporins, is associated with increased risk of MRSA colonization and infection [43,49,50]. Implementation of an antimicrobial stewardship program, coupled with infection control measures, in a region of Scotland resulted in decreased incidence of MRSA infections among hospital inpatients and in the surrounding community [51]. Thus a robust antimicrobial stewardship program is likely to reduce post-discharge MRSA infections.
Role of Hand Hygiene
The importance of hand hygiene in the prevention of infection has been observed for nearly 2 centuries [52]. Multiple quasi-experimental studies have demonstrated a decreased infection rate when hand hygiene practices for health care workers were introduced or strengthened. A randomized trial in a newborn nursery documented a decrease in transmission of S. aureus when nurses washed their hands after handling a colonized infant [53]. In addition to health care providers, patient hand hygiene can reduce health care–associated infections [54]. Traditional handwashing with soap and water will be familiar to most patients and families. Waterless hand hygiene, typically using alcohol-based hand rubs, is more efficacious and convenient for cleaning hands that are not visibly soiled [52]. If products containing emollients are used, it can also reduce skin drying and cracking. Patients and families should be taught to wash their hands before and after manipulating any medical devices and caring for wounds. Education of patients and family members on the techniques and importance of hand hygiene during hospitalization and at the time of discharge is a simple, low-cost strategy to reduce post-discharge MRSA infections. Teaching can be incorporated into the daily care of patients by nursing and medical staff, both verbally and by example. As a horizontal infection control measure, hand hygiene education has the additional benefit of reducing infections due to all pathogens.
Role of Environmental Cleaning in the Home Setting
Multiple studies have found that the immediate environment of patients who are colonized or infected with MRSA is contaminated with the organism, with greater organism burdens associated with infected patients compared to those who are only colonized [55–59]. Greater environmental contamination is observed when MRSA is present in the urine or wounds of patients [59]. This can lead to transmission of MRSA to family members [23,60,61]. Risk factors for transmission include participation in the care of the patient, older age, and being the partner of the case patient. For the patient, there can be transmission to uninfected body sites and a cycle of recolonization and re-infection. Successful decolonization strategies have included frequent laundering of bedclothes and towels, as well as screening and decolonization of family members. While these strategies may succeed in decolonization, there is no consensus on efficacy in preventing infection in patients or family members. More research in this area is needed, particularly for decolonization strategies, which carry risk of resistance. Attention to cleanliness in the home is a basic hygiene measure that can be recommended.
Conclusion
Post-discharge MRSA infections are an important and underestimated source of morbidity and mortality. Strategies for prevention include infection control measures to prevent incident colonization during hospitalization, removal of any nonessential invasive devices, nursing care for essential devices, wound care, avoiding nonessential antimicrobial therapy, hand hygiene for patients and caregivers, and cleaning of the home environment. Decolonization therapies currently play a limited role, particularly in outbreak situations. The future research agenda should include identification of post-discharge patients who are most likely to benefit from decolonization strategies, and testing those strategies.
Corresponding author: Mary Bessesen, MD, InfectiousDiseases (111L), 1055 Clermont St., Denver, CO 80220, [email protected].
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54. Gagne D, Bedard G, Maziade PJ. Systematic patients’ hand disinfection: impact on meticillin-resistant Staphylococcus aureus infection rates in a community hospital. J Hosp Infect 2010;75:269–72.
55. Knelson LP, Williams DA, Gergen MF, et al. A comparison of environmental contamination by patients infected or colonized with methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci: a multicenter study. Infect Control Hosp Epidemiol 2014;35:872–5.
56. Murphy CR, Eells SJ, Quan V, et al. Methicillin-resistant Staphylococcus aureus burden in nursing homes associated with environmental contamination of common areas. J Am Geriatr Soc 2012;60:1012–8.
57. Datta R, Platt R, Yokoe DS, Huang SS. Environmental cleaning intervention and risk of acquiring multidrug-resistant organisms from prior room occupants. Arch Intern Med 2011;171:491–4.
58. Dancer SJ. The role of environmental cleaning in the control of hospital-acquired infection. J Hosp Infect 2009;73:378–85.
59. Boyce JM, Potter-Bynoe G, Chenevert C, King T. Environmental contamination due to methicillin-resistant Staphylococcus aureus: possible infection control implications. Infect Control Hosp Epidemiol 1997;18:622–7.
60. Mollema FP, Richardus JH, Behrendt M, et al. Transmission of methicillin-resistant Staphylococcus aureus to household contacts. J Clin Microbiol 2010;48:202–7.
61. Calfee DP, Durbin LJ, Germanson TP, et al. Spread of methicillin-resistant Staphylococcus aureus (MRSA) among household contacts of individuals with nosocomially acquired MRSA. Infect Control Hosp Epidemiol 2003;24:422–6.
From the Division of Adult Infectious Diseases, University of Colorado Denver, Aurora, CO, and the Department of Veterans Affairs, Eastern Colorado Healthcare System, Denver, CO.
Abstract
- Objective: To review the published literature on methicillin-resistant Staphylococcus aureus (MRSA) infections among patients recently discharged from hospital, with a focus on possible prevention measures.
- Methods: Literature review.
- Results: MRSA is a major cause of post-discharge infections. Risk factors for post-discharge MRSA include colonization, dependent ambulatory status, duration of hospitalization > 5 days, discharge to a long-term care facility, presence of a central venous catheter (CVC), presence of a non-CVC invasive device, a chronic wound in the post-discharge period, hemodialysis, systemic corticosteroids, and receiving anti-MRSA antimicrobial agents. Potential approaches to control include prevention of incident colonization during hospital stay, removal of nonessential CVCs and other devices, good wound debridement and care, and antimicrobial stewardship. Hand hygiene and environmental cleaning are horizontal measures that are also recommended. Decolonization may be useful in selected cases.
- Conclusion: Post-discharge MRSA infections are an important and underestimated source of morbidity and mortality. The future research agenda should include identification of post-discharge patients who are most likely to benefit from decolonization strategies, and testing those strategies.
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of morbidity and mortality due to infections of the bloodstream, lung, surgical sites, bone, and skin and soft tissues. The mortality associated with S. aureus bloodstream infections is 14% to 45% [1–4]. A bloodstream infection caused by MRSA is associated with a twofold increased mortality as compared to one caused by methicillin-sensitive S. aureus [5]. MRSA pneumonia carries a mortality of 8%, which increases to 39% when bacteremia is also present [6]. S. aureus bloodstream infection also carries a high risk of functional disability, with 65% of patients in a recent series requiring nursing home care in the recovery period [7]. In 2011 there were more than 11,000 deaths due to invasive MRSA infection in the United States [8]. Clearly S. aureus, and particularly MRSA, is a pathogen of major clinical significance.
Methicillin resistance was described in 1961, soon after methicillin became available in the 1950s. Prevalence of MRSA remained low until the 1980s, when it rapidly increased in health care settings. The predominant health care–associated strain in the United States is USA100, a member of clonal complex 5. Community-acquired MRSA infection has garnered much attention since it was recognized in 1996 [9]. The predominant community-associated strain has been USA300, a member of clonal complex 8 [10]. Following its emergence in the community, USA300 became a significant health care–associated pathogen as well [11]. The larger share of MRSA disease remains health care–associated [8]. The most recent data from the Center for Disease Control and Prevention Active Bacterial Core Surveillance system indicate that 77.6% of invasive MRSA infection is health care–associated, resulting in 9127 deaths in 2011 [8].
This article reviews the published literature on MRSA infections among patients recently discharged from hospital, with a focus on possible prevention measures.
MRSA Epidemiologic Categories
Epidemiologic investigations of MRSA categorize infections according to the presumed acquisition site, ie, in the community or in a health care setting. Older literature refers to nosocomial MRSA infection, which is now commonly referred to as hospital-onset health care–associated (HO-HCA) MRSA. A common definition of HO-HCA MRSA infection is an infection with the first positive culture on hospital day 4 or later [12]. Community-onset health care–associated MRSA (CO-HCA MRSA) is defined as infection that is diagnosed in the outpatient setting, or prior to day 4 of hospitalization, in a patient with recent health care exposure, eg, hospitalization within the past year, hemodialysis, surgery, or presence of a central venous catheter at time of presentation to the hospital [12]. Community-associated MRSA (CA-MSRSA) is infection in patients who do not meet criteria for either type of health care associated MRSA. Post-discharge MRSA infections would be included in the CO-HCA MRSA group.
Infection Control Programs
Classic infection control programs, developed in the 1960s, focused on infections that presented more than 48 to 72 hours after admission and prior to discharge from hospital. In that era, the average length of hospital stay was 1 week or more, and there was sufficient time for health care–associated infections to become clinically apparent. In recent years, length of stay has progressively shortened [13]. As hospital stays shortened, the risk that an infection caused by a health care–acquired pathogen would be identified after discharge grew. More recent studies have documented that the majority of HO-HCA infections become apparent after the index hospitalization [8,14].
Data from the Active Bacterial Core Surveillance System quantify the burden of CO-HCA MRSA disease at a national level [8,14]. However, it is not readily detected by many hospital infection surveillance programs. Avery et al studied a database constructed with California state mandated reports of MRSA infection and identified cases with MRSA present on admission. They then searched for a previous admission, within 30 days. If a prior admission was identified, the MRSA case was assigned to the hospital that had recently discharged the patient. Using this approach, they found that the incidence of health care–associated MRSA infection increased from 12.2 cases/10,000 admissions when traditional surveillance methods were used to 35.7/10,000 admissions using the revised method of assignment of health care exposure [15]. These data suggest that post-discharge MRSA disease is underappreciated by hospital infection control programs.
Lessons from Hospital-Onset MRSA
The morbidity and mortality associated with MRSA have led to the development of vigorous infection control programs to reduce the risk of health care–associated MRSA infection [16–18]. Vertical infection control strategies, ie, those focused on MRSA specifically, have included active screening for colonization, and nursing colonized patients in contact precautions. Since colonization is the antecedent to infection in most cases, prevention of transmission of MRSA from patient to patient should prevent most infections. There is ample evidence that colonized patients contaminate their immediate environment with MRSA, creating a reservoir of resistant pathogens that can be transmitted to other patients on the hands and clothing of health care workers [19,20]. Quasi-experimental studies of active screening and isolation strategies have shown decreases in MRSA transmission and infection following implementation [18]. The only randomized comparative trial of active screening and isolation versus usual care did not demonstrate benefit, possibly due to delays in lab confirmation of colonization status [21]. Horizontal infection control strategies are applied to all patients, regardless of colonization with resistant pathogens, in an attempt to decrease health care–associated infections with all pathogens. Examples of horizontal strategies are hand hygiene, environmental cleaning, and the prevention bundles for central line–associated bloodstream infection.
The Burden of Community-Onset MRSA
CO-HCA MRSA represents 60% of the burden of invasive MRSA infection [8]. While this category includes cases that have not been hospitalized, eg, patients on hemodialysis, post-discharge MRSA infection accounts for the majority of cases [15]. Recent data indicate that the incidence of HO-HCA MRSA decreased 54.2% between 2005 and 2011 [8]. This decrease in HO-HCA MRSA infection occurred concurrently with widespread implementation of vigorous horizontal infection control measures, such as bundled prevention strategies for central line–associated bloodstream infection and ventilator-associated pneumonia. The decline in CO-HCA MRSA infection has been much less steep, at 27.7%. The majority of the CO-HCA infections are in post-discharge patients. Furthermore, the incidence of CO-HCA MRSA infection may be underestimated [15].
Post-Discharge MRSA Colonization and Infection
Hospital-associated MRSA infection is reportable in many jurisdictions, but post-discharge MRSA infection is not a specific reportable condition, limiting the available surveillance data. Avery et al [15] studied ICD-9 code data for all hospitals in Orange County, California, and found that 23.5/10,000 hospital admissions were associated with a post-discharge MRSA infection. This nearly tripled the incidence of health care–associated MRSA infection, compared to surveillance that included only hospital-onset cases. Future research should refine these observations, as ICD-9 code data correlate imperfectly with chart reviews and have not yet been well validated for MRSA research.
The CDC estimated that in 2011 there were 48,353 CO-HCA MRSA infections resulting in 10,934 deaths. This estimate is derived from study of the Active Bacterial Core surveillance sample [8]. In that sample, 79% of CO-HCA MRSA infections occurred in patients hospitalized within the last year. Thus, we can estimate that there were 34,249 post-discharge MRSA infections resulting in 8638 deaths in the United States in 2011.
MRSA colonization is the antecedent to infection in the majority of cases [22]. Thus we can assess the health care burden of post-discharge MRSA by analyzing colonization as well as infection. Furthermore, the risk of MRSA colonization of household members can be addressed. Lucet et al evaluated hospital inpatients preparing for discharge to a home health care setting, and found that 12.7% of them were colonized with MRSA at the time of discharge, and 45% of them remained colonized for more than a year [23]. Patients who regained independence in activities of daily living were more likely to become free of MRSA colonization. The study provided no data on the risk of MRSA infection in the colonized patients. 19.1% of household contacts became colonized with MRSA, demonstrating that the burden of MRSA extends beyond the index patient. None of the colonized household contacts developed MRSA infection during the study period.
Risk Factors for Post-Discharge MRSA
Case control studies of patients with post-discharge invasive MRSA have shed light on risk factors for infection. While many risk factors are not modifiable, these studies may provide a road map to development of prevention strategies for the post-discharge setting. A study of hospitals in New York that participated in the Active Bacterial Core surveillance system identified a statistically significant increased risk of MRSA invasive infection among patients with several factors associated with physical disability, including a physical therapy evaluation, dependent ambulatory status, duration of hospitalization > 5 days, and discharge to a long-term care facility. Additional risk factors identified in the bivariate analysis were presence of a central venous catheter, hemodialysis, systemic corticosteroids, and receiving anti-MRSA antimicrobial agents. When subjected to multivariate analysis, however, the most significant and potent risk factor was a previous positive MRSA clinical culture (matched odds ratio 23, P < 0.001). Other significant risk factors in the multivariate analysis were hemodialysis, presence of a central venous catheter in the outpatient setting, and a visit to the emergency department [24]. A second, larger, multistate study also based on data from the Active Bacterial Core surveillance system showed that 5 risk factors were significantly associated with post-discharge invasive MRSA infection: (1) MRSA colonization, (2) a central venous catheter (CVC) present at discharge, (3) presence of a non-CVC invasive device, (4) a chronic wound in the post-discharge period, and (5) discharge to a nursing home. MRSA colonization was associated with a 7.7-fold increased odds of invasive MRSA infection, a much greater increase than any of the other risk factors [25]. Based on these results, strategies to consider include enhanced infection measures for prevention of incident MRSA colonization in the inpatient setting, decolonization therapy for those who become colonized, removal of non-essential medical devices, including central venous catheters, excellent nursing care for essential devices and wounds, hand hygiene, environmental cleaning, and antimicrobial stewardship.
Development of Strategies to Decrease Post-Discharge MRSA
While the epidemiology of post-discharge health care–associated MRSA infections has become a topic of interest to researchers, approaches to control are in their infancy. Few of the approaches have been subjected to rigorous study in the post-discharge environment. Nevertheless, some low risk, common sense strategies may be considered. Furthermore, an outline of research objectives may be constructed.
Prevention of Colonization in the Inpatient Setting
Robust infection control measures must be implemented in inpatient settings to prevent incident MRSA colonization [16,17]. Key recommendations include surveillance and monitoring of MRSA infections, adherence to standard hand hygiene guidance, environmental cleanliness, and use of dedicated equipment for patients who are colonized or infected with MRSA. Active screening for asymptomatic MRSA carriage and isolation of carriers may be implemented if routine measures are not successful.
Decolonization
Despite the best infection control programs, some patients will be colonized with MRSA at the time of hospital discharge. As detailed above, MRSA colonization is a potent risk factor for infection in the post-discharge setting, as well as in hospital inpatients [22]. A logical approach to this would be to attempt to eradicate colonization. There are several strategies for decolonization therapy, which may be used alone or in combination, including nasal mupirocin, nasal povidone-iodine, systemic antistaphylococcal drugs alone or in combination with oral rifampin, chlorhexidine bathing, or bleach baths [26–29].
A preliminary step in approaching the idea of post-discharge decolonization therapy is to show that patients can be successfully decolonized. With those data in hand, randomized trials seeking to demonstrate a decrease in invasive MRSA infections can be planned. Decolonization using nasal mupirocin has an initial success rate of 60% to 100% in a variety of patient populations [30–35]. Poor adherence to the decolonization protocol may limit success in the outpatient setting. Patients are more likely to resolve their MRSA colonization spontaneously when they regain their general health and independence in activities of daily living [23]. Colonization of other household members may provide a reservoir of MRSA leading to recolonization of the index case. Treatment of the household members may be offered, to provide more durable maintenance of the decolonized state [35]. When chronically ill patients who have been decolonized are followed longitudinally, up to 39% become colonized again, most often with the same strain [30,31]. Attempts to maintain a MRSA-free state in nursing home residents using prolonged mupirocin therapy resulted in emergence of mupirocin resistance [31]. Thus decolonization can be achieved, but is difficult to maintain, especially in debilitated, chronically ill patients. Mupirocin resistance can occur, limiting success of decolonization therapies.
Successful decolonization has been proven to reduce the risk of MRSA infection in the perioperative, dialysis, and intensive care unit settings [33,36–38]. In dialysis patients the risk of S. aureus bloodstream infection, including MRSA, can be reduced 59% with the use of mupirocin decolonization of the nares, with or without treatment of dialysis access exit sites [37]. A placebo-controlled trial demonstrated that decolonization of the nares with mupirocin reduced surgical site infections with S. aureus. All S. aureus isolates in the study were methicillin-susceptible. A second randomized controlled trial of nasal mupirocin did not achieve a statistically significant decrease in S. aureus surgical site infections, but it showed that mupirocin decolonization therapy decreased nosocomial S. aureus infections among nasal carriers [33]. 99.2% of isolates in that study et al were methicillin-susceptible. Quasi-experimental studies have shown similar benefits for surgical patients who are colonized with MRSA [39–41]. A more recent randomized trial, in ICU patients, demonstrated decreased incidence of invasive infection in patients treated with nasal mupirocin and chlorhexidine baths [38]. The common themeof these studies is that they enrolled patients who had a short-term condition, eg, surgery or critical illness, placing them at high risk for invasive MRSA infection. This maximizes the potential benefit of decolonization and minimizes the risk of emergence of resistance. Furthermore, adherence to decolonization protocols is likely to be high in the perioperative and ICU settings. To extrapolate the ICU and perioperative data to the post-discharge setting would be imprudent.
In summary, decolonization may be a useful strategy to reduce invasive MRSA infection in post-discharge patients, but more data are needed for most patient populations. The evidence for decolonization therapy is strongest for dialysis patients, in whom implementation of routine decolonization of MRSA colonized nares is a useful intervention [37]. There are not yet clinical trials of decolonization therapy in patients at time of hospital discharge showing a reduction in invasive MRSA infection. Decolonization strategies have important drawbacks, including emergence of resistance to mupirocin, chlorhexidine, and systemic agents. Furthermore, there is a risk of hypersensitivity reactions, Clostridium difficile infection, and potential for negative impacts onthe normal microbiome. The potential for lesser efficacy in a chronically ill outpatient population must also be considered in the post-discharge setting. Randomized controlled trials with invasive infection outcomes should be performed prior to implementing routine decolonization therapy of hospital discharge patients.
Care of Invasive Devices
Discharge with a central venous catheter was associated with a 2.16-fold increased risk of invasive MRSA infection; other invasive devices were associated with a 3.03-fold increased risk [25]. Clinicians must carefully assess patients nearing discharge for any opportunity to remove invasive devices. Idle devices have been reported in inpatient settings [42] and could occur in other settings. Antimicrobial therapy is a common indication for an outpatient central venous catheter and can also be associated with increased risk of invasive MRSA infection [25,43]. Duration and route of administration of antimicrobial agents should be carefully considered, with an eye to switching to oral therapy whenever possible. When a central venous catheter must be utilized, it should be maintained as carefully as in the inpatient setting. Tools for reducing risk of catheter-associated bloodstream infection include keeping the site dry, scrubbing the hub whenever accessing the catheter, aseptic techniques for dressing changes, and chlorhexidine sponges at the insertion site [44,45]. Reporting of central line–associated bloodstream infection rates by home care agencies is an important quality measure.
Wound Care
The presence of a chronic wound in the post-discharge period is associated with a 4.41-fold increased risk of invasive MRSA infection [25]. Although randomized controlled trials are lacking, it is prudent to ensure that wounds are fully debrided to remove devitalized tissue that can be fertile ground for a MRSA infection. The burden of organisms on a chronic wound is often very large, creating high risk of resistance when exposed to antimicrobial agents. Decolonization therapy is not likely to meet with durable success in such cases and should probably be avoided, except in special circumstances, eg, in preparation for cardiothoracic surgery.
Infection Control in Nursing Home Settings
In the Active Bacterial Core cohort, discharge to a nursing home was associated with a 2.1- to 2.65-fold increased risk of invasive MRSA infection [24,25]. It is notable that the authors controlled for the Charlson comorbidity index, suggesting that nursing home care is more than a marker for comorbidity [25]. The tension between the demands of careful infection control and the home-like setting that is desirable for long-term care creates challenges in the prevention of invasive MRSA infection. Nevertheless, careful management of invasive devices and wounds and antimicrobial stewardship are strategies that may reduce the risk of invasive MRSA infection in long-term care settings. Contact precautions for colonized nursing home residents are recommended only during an outbreak [46]. Staff should be trained in proper application of standard precautions, including use of gowns and gloves when handling body fluids. A study of an aggressive program of screening, decolonization with nasal mupirocin and chlorhexidine bathing, enhanced hand hygiene and environmental cleaning demonstrated a significant reduction in MRSA colonization [47]. An increase in mupirocin resistance during the study led to a switch to retapamulin for nasal application. The Association of Practitioners of Infection Control has issued guidance for MRSA prevention in long-term care facilities [48]. The guidance focuses on surveillance for MRSA infection, performing a MRSA risk assessment, hand hygiene, and environmental cleaning.
Antimicrobial Stewardship
Antimicrobial therapy, especially with fluoroquinolones and third- or fourth-generation cephalosporins, is associated with increased risk of MRSA colonization and infection [43,49,50]. Implementation of an antimicrobial stewardship program, coupled with infection control measures, in a region of Scotland resulted in decreased incidence of MRSA infections among hospital inpatients and in the surrounding community [51]. Thus a robust antimicrobial stewardship program is likely to reduce post-discharge MRSA infections.
Role of Hand Hygiene
The importance of hand hygiene in the prevention of infection has been observed for nearly 2 centuries [52]. Multiple quasi-experimental studies have demonstrated a decreased infection rate when hand hygiene practices for health care workers were introduced or strengthened. A randomized trial in a newborn nursery documented a decrease in transmission of S. aureus when nurses washed their hands after handling a colonized infant [53]. In addition to health care providers, patient hand hygiene can reduce health care–associated infections [54]. Traditional handwashing with soap and water will be familiar to most patients and families. Waterless hand hygiene, typically using alcohol-based hand rubs, is more efficacious and convenient for cleaning hands that are not visibly soiled [52]. If products containing emollients are used, it can also reduce skin drying and cracking. Patients and families should be taught to wash their hands before and after manipulating any medical devices and caring for wounds. Education of patients and family members on the techniques and importance of hand hygiene during hospitalization and at the time of discharge is a simple, low-cost strategy to reduce post-discharge MRSA infections. Teaching can be incorporated into the daily care of patients by nursing and medical staff, both verbally and by example. As a horizontal infection control measure, hand hygiene education has the additional benefit of reducing infections due to all pathogens.
Role of Environmental Cleaning in the Home Setting
Multiple studies have found that the immediate environment of patients who are colonized or infected with MRSA is contaminated with the organism, with greater organism burdens associated with infected patients compared to those who are only colonized [55–59]. Greater environmental contamination is observed when MRSA is present in the urine or wounds of patients [59]. This can lead to transmission of MRSA to family members [23,60,61]. Risk factors for transmission include participation in the care of the patient, older age, and being the partner of the case patient. For the patient, there can be transmission to uninfected body sites and a cycle of recolonization and re-infection. Successful decolonization strategies have included frequent laundering of bedclothes and towels, as well as screening and decolonization of family members. While these strategies may succeed in decolonization, there is no consensus on efficacy in preventing infection in patients or family members. More research in this area is needed, particularly for decolonization strategies, which carry risk of resistance. Attention to cleanliness in the home is a basic hygiene measure that can be recommended.
Conclusion
Post-discharge MRSA infections are an important and underestimated source of morbidity and mortality. Strategies for prevention include infection control measures to prevent incident colonization during hospitalization, removal of any nonessential invasive devices, nursing care for essential devices, wound care, avoiding nonessential antimicrobial therapy, hand hygiene for patients and caregivers, and cleaning of the home environment. Decolonization therapies currently play a limited role, particularly in outbreak situations. The future research agenda should include identification of post-discharge patients who are most likely to benefit from decolonization strategies, and testing those strategies.
Corresponding author: Mary Bessesen, MD, InfectiousDiseases (111L), 1055 Clermont St., Denver, CO 80220, [email protected].
From the Division of Adult Infectious Diseases, University of Colorado Denver, Aurora, CO, and the Department of Veterans Affairs, Eastern Colorado Healthcare System, Denver, CO.
Abstract
- Objective: To review the published literature on methicillin-resistant Staphylococcus aureus (MRSA) infections among patients recently discharged from hospital, with a focus on possible prevention measures.
- Methods: Literature review.
- Results: MRSA is a major cause of post-discharge infections. Risk factors for post-discharge MRSA include colonization, dependent ambulatory status, duration of hospitalization > 5 days, discharge to a long-term care facility, presence of a central venous catheter (CVC), presence of a non-CVC invasive device, a chronic wound in the post-discharge period, hemodialysis, systemic corticosteroids, and receiving anti-MRSA antimicrobial agents. Potential approaches to control include prevention of incident colonization during hospital stay, removal of nonessential CVCs and other devices, good wound debridement and care, and antimicrobial stewardship. Hand hygiene and environmental cleaning are horizontal measures that are also recommended. Decolonization may be useful in selected cases.
- Conclusion: Post-discharge MRSA infections are an important and underestimated source of morbidity and mortality. The future research agenda should include identification of post-discharge patients who are most likely to benefit from decolonization strategies, and testing those strategies.
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of morbidity and mortality due to infections of the bloodstream, lung, surgical sites, bone, and skin and soft tissues. The mortality associated with S. aureus bloodstream infections is 14% to 45% [1–4]. A bloodstream infection caused by MRSA is associated with a twofold increased mortality as compared to one caused by methicillin-sensitive S. aureus [5]. MRSA pneumonia carries a mortality of 8%, which increases to 39% when bacteremia is also present [6]. S. aureus bloodstream infection also carries a high risk of functional disability, with 65% of patients in a recent series requiring nursing home care in the recovery period [7]. In 2011 there were more than 11,000 deaths due to invasive MRSA infection in the United States [8]. Clearly S. aureus, and particularly MRSA, is a pathogen of major clinical significance.
Methicillin resistance was described in 1961, soon after methicillin became available in the 1950s. Prevalence of MRSA remained low until the 1980s, when it rapidly increased in health care settings. The predominant health care–associated strain in the United States is USA100, a member of clonal complex 5. Community-acquired MRSA infection has garnered much attention since it was recognized in 1996 [9]. The predominant community-associated strain has been USA300, a member of clonal complex 8 [10]. Following its emergence in the community, USA300 became a significant health care–associated pathogen as well [11]. The larger share of MRSA disease remains health care–associated [8]. The most recent data from the Center for Disease Control and Prevention Active Bacterial Core Surveillance system indicate that 77.6% of invasive MRSA infection is health care–associated, resulting in 9127 deaths in 2011 [8].
This article reviews the published literature on MRSA infections among patients recently discharged from hospital, with a focus on possible prevention measures.
MRSA Epidemiologic Categories
Epidemiologic investigations of MRSA categorize infections according to the presumed acquisition site, ie, in the community or in a health care setting. Older literature refers to nosocomial MRSA infection, which is now commonly referred to as hospital-onset health care–associated (HO-HCA) MRSA. A common definition of HO-HCA MRSA infection is an infection with the first positive culture on hospital day 4 or later [12]. Community-onset health care–associated MRSA (CO-HCA MRSA) is defined as infection that is diagnosed in the outpatient setting, or prior to day 4 of hospitalization, in a patient with recent health care exposure, eg, hospitalization within the past year, hemodialysis, surgery, or presence of a central venous catheter at time of presentation to the hospital [12]. Community-associated MRSA (CA-MSRSA) is infection in patients who do not meet criteria for either type of health care associated MRSA. Post-discharge MRSA infections would be included in the CO-HCA MRSA group.
Infection Control Programs
Classic infection control programs, developed in the 1960s, focused on infections that presented more than 48 to 72 hours after admission and prior to discharge from hospital. In that era, the average length of hospital stay was 1 week or more, and there was sufficient time for health care–associated infections to become clinically apparent. In recent years, length of stay has progressively shortened [13]. As hospital stays shortened, the risk that an infection caused by a health care–acquired pathogen would be identified after discharge grew. More recent studies have documented that the majority of HO-HCA infections become apparent after the index hospitalization [8,14].
Data from the Active Bacterial Core Surveillance System quantify the burden of CO-HCA MRSA disease at a national level [8,14]. However, it is not readily detected by many hospital infection surveillance programs. Avery et al studied a database constructed with California state mandated reports of MRSA infection and identified cases with MRSA present on admission. They then searched for a previous admission, within 30 days. If a prior admission was identified, the MRSA case was assigned to the hospital that had recently discharged the patient. Using this approach, they found that the incidence of health care–associated MRSA infection increased from 12.2 cases/10,000 admissions when traditional surveillance methods were used to 35.7/10,000 admissions using the revised method of assignment of health care exposure [15]. These data suggest that post-discharge MRSA disease is underappreciated by hospital infection control programs.
Lessons from Hospital-Onset MRSA
The morbidity and mortality associated with MRSA have led to the development of vigorous infection control programs to reduce the risk of health care–associated MRSA infection [16–18]. Vertical infection control strategies, ie, those focused on MRSA specifically, have included active screening for colonization, and nursing colonized patients in contact precautions. Since colonization is the antecedent to infection in most cases, prevention of transmission of MRSA from patient to patient should prevent most infections. There is ample evidence that colonized patients contaminate their immediate environment with MRSA, creating a reservoir of resistant pathogens that can be transmitted to other patients on the hands and clothing of health care workers [19,20]. Quasi-experimental studies of active screening and isolation strategies have shown decreases in MRSA transmission and infection following implementation [18]. The only randomized comparative trial of active screening and isolation versus usual care did not demonstrate benefit, possibly due to delays in lab confirmation of colonization status [21]. Horizontal infection control strategies are applied to all patients, regardless of colonization with resistant pathogens, in an attempt to decrease health care–associated infections with all pathogens. Examples of horizontal strategies are hand hygiene, environmental cleaning, and the prevention bundles for central line–associated bloodstream infection.
The Burden of Community-Onset MRSA
CO-HCA MRSA represents 60% of the burden of invasive MRSA infection [8]. While this category includes cases that have not been hospitalized, eg, patients on hemodialysis, post-discharge MRSA infection accounts for the majority of cases [15]. Recent data indicate that the incidence of HO-HCA MRSA decreased 54.2% between 2005 and 2011 [8]. This decrease in HO-HCA MRSA infection occurred concurrently with widespread implementation of vigorous horizontal infection control measures, such as bundled prevention strategies for central line–associated bloodstream infection and ventilator-associated pneumonia. The decline in CO-HCA MRSA infection has been much less steep, at 27.7%. The majority of the CO-HCA infections are in post-discharge patients. Furthermore, the incidence of CO-HCA MRSA infection may be underestimated [15].
Post-Discharge MRSA Colonization and Infection
Hospital-associated MRSA infection is reportable in many jurisdictions, but post-discharge MRSA infection is not a specific reportable condition, limiting the available surveillance data. Avery et al [15] studied ICD-9 code data for all hospitals in Orange County, California, and found that 23.5/10,000 hospital admissions were associated with a post-discharge MRSA infection. This nearly tripled the incidence of health care–associated MRSA infection, compared to surveillance that included only hospital-onset cases. Future research should refine these observations, as ICD-9 code data correlate imperfectly with chart reviews and have not yet been well validated for MRSA research.
The CDC estimated that in 2011 there were 48,353 CO-HCA MRSA infections resulting in 10,934 deaths. This estimate is derived from study of the Active Bacterial Core surveillance sample [8]. In that sample, 79% of CO-HCA MRSA infections occurred in patients hospitalized within the last year. Thus, we can estimate that there were 34,249 post-discharge MRSA infections resulting in 8638 deaths in the United States in 2011.
MRSA colonization is the antecedent to infection in the majority of cases [22]. Thus we can assess the health care burden of post-discharge MRSA by analyzing colonization as well as infection. Furthermore, the risk of MRSA colonization of household members can be addressed. Lucet et al evaluated hospital inpatients preparing for discharge to a home health care setting, and found that 12.7% of them were colonized with MRSA at the time of discharge, and 45% of them remained colonized for more than a year [23]. Patients who regained independence in activities of daily living were more likely to become free of MRSA colonization. The study provided no data on the risk of MRSA infection in the colonized patients. 19.1% of household contacts became colonized with MRSA, demonstrating that the burden of MRSA extends beyond the index patient. None of the colonized household contacts developed MRSA infection during the study period.
Risk Factors for Post-Discharge MRSA
Case control studies of patients with post-discharge invasive MRSA have shed light on risk factors for infection. While many risk factors are not modifiable, these studies may provide a road map to development of prevention strategies for the post-discharge setting. A study of hospitals in New York that participated in the Active Bacterial Core surveillance system identified a statistically significant increased risk of MRSA invasive infection among patients with several factors associated with physical disability, including a physical therapy evaluation, dependent ambulatory status, duration of hospitalization > 5 days, and discharge to a long-term care facility. Additional risk factors identified in the bivariate analysis were presence of a central venous catheter, hemodialysis, systemic corticosteroids, and receiving anti-MRSA antimicrobial agents. When subjected to multivariate analysis, however, the most significant and potent risk factor was a previous positive MRSA clinical culture (matched odds ratio 23, P < 0.001). Other significant risk factors in the multivariate analysis were hemodialysis, presence of a central venous catheter in the outpatient setting, and a visit to the emergency department [24]. A second, larger, multistate study also based on data from the Active Bacterial Core surveillance system showed that 5 risk factors were significantly associated with post-discharge invasive MRSA infection: (1) MRSA colonization, (2) a central venous catheter (CVC) present at discharge, (3) presence of a non-CVC invasive device, (4) a chronic wound in the post-discharge period, and (5) discharge to a nursing home. MRSA colonization was associated with a 7.7-fold increased odds of invasive MRSA infection, a much greater increase than any of the other risk factors [25]. Based on these results, strategies to consider include enhanced infection measures for prevention of incident MRSA colonization in the inpatient setting, decolonization therapy for those who become colonized, removal of non-essential medical devices, including central venous catheters, excellent nursing care for essential devices and wounds, hand hygiene, environmental cleaning, and antimicrobial stewardship.
Development of Strategies to Decrease Post-Discharge MRSA
While the epidemiology of post-discharge health care–associated MRSA infections has become a topic of interest to researchers, approaches to control are in their infancy. Few of the approaches have been subjected to rigorous study in the post-discharge environment. Nevertheless, some low risk, common sense strategies may be considered. Furthermore, an outline of research objectives may be constructed.
Prevention of Colonization in the Inpatient Setting
Robust infection control measures must be implemented in inpatient settings to prevent incident MRSA colonization [16,17]. Key recommendations include surveillance and monitoring of MRSA infections, adherence to standard hand hygiene guidance, environmental cleanliness, and use of dedicated equipment for patients who are colonized or infected with MRSA. Active screening for asymptomatic MRSA carriage and isolation of carriers may be implemented if routine measures are not successful.
Decolonization
Despite the best infection control programs, some patients will be colonized with MRSA at the time of hospital discharge. As detailed above, MRSA colonization is a potent risk factor for infection in the post-discharge setting, as well as in hospital inpatients [22]. A logical approach to this would be to attempt to eradicate colonization. There are several strategies for decolonization therapy, which may be used alone or in combination, including nasal mupirocin, nasal povidone-iodine, systemic antistaphylococcal drugs alone or in combination with oral rifampin, chlorhexidine bathing, or bleach baths [26–29].
A preliminary step in approaching the idea of post-discharge decolonization therapy is to show that patients can be successfully decolonized. With those data in hand, randomized trials seeking to demonstrate a decrease in invasive MRSA infections can be planned. Decolonization using nasal mupirocin has an initial success rate of 60% to 100% in a variety of patient populations [30–35]. Poor adherence to the decolonization protocol may limit success in the outpatient setting. Patients are more likely to resolve their MRSA colonization spontaneously when they regain their general health and independence in activities of daily living [23]. Colonization of other household members may provide a reservoir of MRSA leading to recolonization of the index case. Treatment of the household members may be offered, to provide more durable maintenance of the decolonized state [35]. When chronically ill patients who have been decolonized are followed longitudinally, up to 39% become colonized again, most often with the same strain [30,31]. Attempts to maintain a MRSA-free state in nursing home residents using prolonged mupirocin therapy resulted in emergence of mupirocin resistance [31]. Thus decolonization can be achieved, but is difficult to maintain, especially in debilitated, chronically ill patients. Mupirocin resistance can occur, limiting success of decolonization therapies.
Successful decolonization has been proven to reduce the risk of MRSA infection in the perioperative, dialysis, and intensive care unit settings [33,36–38]. In dialysis patients the risk of S. aureus bloodstream infection, including MRSA, can be reduced 59% with the use of mupirocin decolonization of the nares, with or without treatment of dialysis access exit sites [37]. A placebo-controlled trial demonstrated that decolonization of the nares with mupirocin reduced surgical site infections with S. aureus. All S. aureus isolates in the study were methicillin-susceptible. A second randomized controlled trial of nasal mupirocin did not achieve a statistically significant decrease in S. aureus surgical site infections, but it showed that mupirocin decolonization therapy decreased nosocomial S. aureus infections among nasal carriers [33]. 99.2% of isolates in that study et al were methicillin-susceptible. Quasi-experimental studies have shown similar benefits for surgical patients who are colonized with MRSA [39–41]. A more recent randomized trial, in ICU patients, demonstrated decreased incidence of invasive infection in patients treated with nasal mupirocin and chlorhexidine baths [38]. The common themeof these studies is that they enrolled patients who had a short-term condition, eg, surgery or critical illness, placing them at high risk for invasive MRSA infection. This maximizes the potential benefit of decolonization and minimizes the risk of emergence of resistance. Furthermore, adherence to decolonization protocols is likely to be high in the perioperative and ICU settings. To extrapolate the ICU and perioperative data to the post-discharge setting would be imprudent.
In summary, decolonization may be a useful strategy to reduce invasive MRSA infection in post-discharge patients, but more data are needed for most patient populations. The evidence for decolonization therapy is strongest for dialysis patients, in whom implementation of routine decolonization of MRSA colonized nares is a useful intervention [37]. There are not yet clinical trials of decolonization therapy in patients at time of hospital discharge showing a reduction in invasive MRSA infection. Decolonization strategies have important drawbacks, including emergence of resistance to mupirocin, chlorhexidine, and systemic agents. Furthermore, there is a risk of hypersensitivity reactions, Clostridium difficile infection, and potential for negative impacts onthe normal microbiome. The potential for lesser efficacy in a chronically ill outpatient population must also be considered in the post-discharge setting. Randomized controlled trials with invasive infection outcomes should be performed prior to implementing routine decolonization therapy of hospital discharge patients.
Care of Invasive Devices
Discharge with a central venous catheter was associated with a 2.16-fold increased risk of invasive MRSA infection; other invasive devices were associated with a 3.03-fold increased risk [25]. Clinicians must carefully assess patients nearing discharge for any opportunity to remove invasive devices. Idle devices have been reported in inpatient settings [42] and could occur in other settings. Antimicrobial therapy is a common indication for an outpatient central venous catheter and can also be associated with increased risk of invasive MRSA infection [25,43]. Duration and route of administration of antimicrobial agents should be carefully considered, with an eye to switching to oral therapy whenever possible. When a central venous catheter must be utilized, it should be maintained as carefully as in the inpatient setting. Tools for reducing risk of catheter-associated bloodstream infection include keeping the site dry, scrubbing the hub whenever accessing the catheter, aseptic techniques for dressing changes, and chlorhexidine sponges at the insertion site [44,45]. Reporting of central line–associated bloodstream infection rates by home care agencies is an important quality measure.
Wound Care
The presence of a chronic wound in the post-discharge period is associated with a 4.41-fold increased risk of invasive MRSA infection [25]. Although randomized controlled trials are lacking, it is prudent to ensure that wounds are fully debrided to remove devitalized tissue that can be fertile ground for a MRSA infection. The burden of organisms on a chronic wound is often very large, creating high risk of resistance when exposed to antimicrobial agents. Decolonization therapy is not likely to meet with durable success in such cases and should probably be avoided, except in special circumstances, eg, in preparation for cardiothoracic surgery.
Infection Control in Nursing Home Settings
In the Active Bacterial Core cohort, discharge to a nursing home was associated with a 2.1- to 2.65-fold increased risk of invasive MRSA infection [24,25]. It is notable that the authors controlled for the Charlson comorbidity index, suggesting that nursing home care is more than a marker for comorbidity [25]. The tension between the demands of careful infection control and the home-like setting that is desirable for long-term care creates challenges in the prevention of invasive MRSA infection. Nevertheless, careful management of invasive devices and wounds and antimicrobial stewardship are strategies that may reduce the risk of invasive MRSA infection in long-term care settings. Contact precautions for colonized nursing home residents are recommended only during an outbreak [46]. Staff should be trained in proper application of standard precautions, including use of gowns and gloves when handling body fluids. A study of an aggressive program of screening, decolonization with nasal mupirocin and chlorhexidine bathing, enhanced hand hygiene and environmental cleaning demonstrated a significant reduction in MRSA colonization [47]. An increase in mupirocin resistance during the study led to a switch to retapamulin for nasal application. The Association of Practitioners of Infection Control has issued guidance for MRSA prevention in long-term care facilities [48]. The guidance focuses on surveillance for MRSA infection, performing a MRSA risk assessment, hand hygiene, and environmental cleaning.
Antimicrobial Stewardship
Antimicrobial therapy, especially with fluoroquinolones and third- or fourth-generation cephalosporins, is associated with increased risk of MRSA colonization and infection [43,49,50]. Implementation of an antimicrobial stewardship program, coupled with infection control measures, in a region of Scotland resulted in decreased incidence of MRSA infections among hospital inpatients and in the surrounding community [51]. Thus a robust antimicrobial stewardship program is likely to reduce post-discharge MRSA infections.
Role of Hand Hygiene
The importance of hand hygiene in the prevention of infection has been observed for nearly 2 centuries [52]. Multiple quasi-experimental studies have demonstrated a decreased infection rate when hand hygiene practices for health care workers were introduced or strengthened. A randomized trial in a newborn nursery documented a decrease in transmission of S. aureus when nurses washed their hands after handling a colonized infant [53]. In addition to health care providers, patient hand hygiene can reduce health care–associated infections [54]. Traditional handwashing with soap and water will be familiar to most patients and families. Waterless hand hygiene, typically using alcohol-based hand rubs, is more efficacious and convenient for cleaning hands that are not visibly soiled [52]. If products containing emollients are used, it can also reduce skin drying and cracking. Patients and families should be taught to wash their hands before and after manipulating any medical devices and caring for wounds. Education of patients and family members on the techniques and importance of hand hygiene during hospitalization and at the time of discharge is a simple, low-cost strategy to reduce post-discharge MRSA infections. Teaching can be incorporated into the daily care of patients by nursing and medical staff, both verbally and by example. As a horizontal infection control measure, hand hygiene education has the additional benefit of reducing infections due to all pathogens.
Role of Environmental Cleaning in the Home Setting
Multiple studies have found that the immediate environment of patients who are colonized or infected with MRSA is contaminated with the organism, with greater organism burdens associated with infected patients compared to those who are only colonized [55–59]. Greater environmental contamination is observed when MRSA is present in the urine or wounds of patients [59]. This can lead to transmission of MRSA to family members [23,60,61]. Risk factors for transmission include participation in the care of the patient, older age, and being the partner of the case patient. For the patient, there can be transmission to uninfected body sites and a cycle of recolonization and re-infection. Successful decolonization strategies have included frequent laundering of bedclothes and towels, as well as screening and decolonization of family members. While these strategies may succeed in decolonization, there is no consensus on efficacy in preventing infection in patients or family members. More research in this area is needed, particularly for decolonization strategies, which carry risk of resistance. Attention to cleanliness in the home is a basic hygiene measure that can be recommended.
Conclusion
Post-discharge MRSA infections are an important and underestimated source of morbidity and mortality. Strategies for prevention include infection control measures to prevent incident colonization during hospitalization, removal of any nonessential invasive devices, nursing care for essential devices, wound care, avoiding nonessential antimicrobial therapy, hand hygiene for patients and caregivers, and cleaning of the home environment. Decolonization therapies currently play a limited role, particularly in outbreak situations. The future research agenda should include identification of post-discharge patients who are most likely to benefit from decolonization strategies, and testing those strategies.
Corresponding author: Mary Bessesen, MD, InfectiousDiseases (111L), 1055 Clermont St., Denver, CO 80220, [email protected].
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1. Chen SY, Wang JT, Chen TH et al. Impact of traditional hospital strain of methicillin-resistant Staphylococcus aureus (MRSA) and community strain of MRSA on mortality in patients with community-onset S aureus bacteremia. Medicine 2010;89:285–94.
2. Lahey T, Shah R, Gittzus J,et al. Infectious diseases consultation lowers mortality from Staphylococcus aureus bacteremia. Medicine 2009;88:263–7.
3. Chang FY, MacDonald BB, Peacock JE Jr, et al. A prospective multicenter study of Staphylococcus aureus bacteremia: incidence of endocarditis, risk factors for mortality, and clinical impact of methicillin resistance. Medicine 2003;82:322–32.
4. Blot SI, Vandewoude KH, Hoste EA, Colardyn FA. Outcome and attributable mortality in critically Ill patients with bacteremia involving methicillin-susceptible and methicillin-resistant Staphylococcus aureus. Arch Intern Med 2002;162:2229–35.
5. Cosgrove SE, Sakoulas G, Perencevich EN, et al. Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis 2003;36:53–9.
6. Schreiber MP, Chan CM, Shorr AF. Bacteremia in Staphylococcus aureus pneumonia: outcomes and epidemiology. J Crit Care 2011;26:395–401.
7. Malani PN, Rana MM, Banerjee M, Bradley SF. Staphylococcus aureus bloodstream infections: the association between age and mortality and functional status. J Am Geriatr Soc 2008;56:1485–9.
8. Dantes RM, Mu YP, Belflower RR, et al. National burden of invasive methicillin-resistant Staphylococcus aureus infections, United States, 2011. JAMA Intern Med 2013;173:1970–8.
9. Centers for Disease Control and Prevention (CDC). Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus - Minnesota and North Dakota, 1997-1999. MMWR Morb Mortal Wkly Rep 1999;48:707–10.
10. Diep BA, Carleton HA, Chang RF, et al. Roles of 34 virulence genes in the evolution of hospital- and community-associated strains of methicillin-resistant Staphylococcus aureus. J Infect Dis 2006;193:1495–503.
11. Jenkins TC, McCollister BD, Sharma R, et al. Epidemiology of healthcare-associated bloodstream infection caused by USA300 strains of methicillin-resistant Staphylococcus aureus in 3 affiliated hospitals. Infect Control Hosp Epidemiol 2009;30:233–41.
12. Kallen AJ, Mu Y, Bulens S, et al. Health care-associated invasive MRSA infections, 2005-2008. JAMA 2010;304:641–8.
13. Bueno H, Ross JS, Wang Y, et al. Trends in length of stay and short-term outcomes among Medicare patients hospitalized for heart failure, 1993-2006. JAMA 2010;303:2141–7.
14. Klevens RM, Edwards JR, Tenover FC, et al. Changes in the epidemiology of methicillin-resistant Staphylococcus aureus in intensive care units in US hospitals, 1992-2003. Clin Infect Dis 2006;42:389–91.
15. Avery TR, Kleinman KP, Klompas M, et al. Inclusion of 30-day postdischarge detection triples the incidence of hospital-onset methicillin-resistant Staphylococcus aureus. Infect Control Hosp Epidemiol 2012;33:114–21.
16. Calfee DP, Salgado CD, Classen D, et al. Strategies to prevent transmission of methicillin-resistant Staphylococcus aureus in acute care hospitals. Infect Control Hosp Epidemiol 2008;29:Suppl 80.
17. Yokoe DS, Anderson DJ, Berenholtz SM, et al. A compendium of strategies to prevent healthcare-associated infections in acute care hospitals: 2014 updates. Infect Control Hosp Epidemiol 2014;35:967–77.
18. Jain R, Kralovic SM, Evans ME, et al. Veterans Affairs initiative to prevent methicillin-resistant Staphylococcus aureus infections. N Engl J Med 2011;364:1419–30.
19. Stiefel U, Cadnum JL, Eckstein BC, et al. Contamination of hands with methicillin-resistant Staphylococcus aureus after contact with environmental surfaces and after contact with the skin of colonized patients. Infect Control Hosp Epidemiol 2011;32:185–7.
20. Chang S, Sethi AK, Eckstein BC, et al. Skin and environmental contamination with methicillin-resistant Staphylococcus aureus among carriers identified clinically versus through active surveillance. Clin Infect Dis 2009;48:1423–8.
21. Huskins WC, Huckabee CM, O’Grady NP, et al. Intervention to reduce transmission of resistant bacteria in intensive care. N Engl J Med 2011;364:1407–18.
22. Wertheim HF, Vos MC, Ott A, et al. Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus non-carriers. Lancet 2004;364:703–5.
23. Lucet JC, Paoletti X, Demontpion C, et al. Carriage of methicillin-resistant Staphylococcus aureus in home care settings: prevalence, duration, and transmission to household members. Arch Intern Med 2009;169:1372–8.
24. Duffy J, Dumyati G, Bulens S, et al. Community-onset invasive methicillin-resistant Staphylococcus aureus infections following hospital discharge. Am J Infect Control 2013;41:782–6.
25. Epstein L, Mu Y, Belflower R, et al. Risk factors for invasive methicillin-resistant Staphylococcus aureus infection after recent discharge from an acute-care hospitalization, 2011-2013. Clin Infect Dis 2016;62:45–52.
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