From the Department of Medicine, Infectious Disease Practice and Innovations, The Medical City, Pasig City, Philippines (Dr. Abad), the Division of Emergency Medicine, University of Wisconsin Medical School, Madison, WI (Dr. Pulia), University of Wisconsin Hospital and Clinics, Madison, WI (Ms. Krupp), and the Willam S. Middleton Memorial Veterans Affairs Hospital, Madison, WI (Dr. Safdar).
Patients in intensive care units (ICUs) are at greatly increased risk of developing health care-associated infections (HAIs) [1]. More than 70% of the bacteria that cause HAIs are resistant to at least one of the antimicrobials commonly used to treat these infections [2]. Two such pathogens, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) are responsible for a considerable proportion of ICU infections that are associated with increased morbidity, mortality, and costs [3–5]. In this review, we discuss the epidemiology of colonization and infection by MRSA and VRE and provide an update on practices for prevention of transmission and infection by MRSA and VRE in the ICU.
EPIDEMIOLOGY AND MECHANISMS OF RESISTANCE
MRSA is the major cause of HAIs worldwide [6]. Among ICUs in the United States, the proportion of methicillin resistance among S. aureus isolates increased from 35.9% in 1992 to 64.4% in 2003 [4]. Approximately 8% of patients are colonized with MRSA upon admission, and an average of 5% will acquire MRSA colonization in the ICU [7,8]. A comparison study of academic tertiary care facilities found medical ICUs had higher MRSA admission prevalence rates than surgical ICUs, whereas surgical ICUs had a higher incidence rate [7]. Enteroccoccus is the third most common pathogen associated with HAIs, with 33% resistant to vancomycin [9]. VRE infection is associated with increased ICU cost and increased length of stay [10]. Incidence of ICU-acquired VRE varies among regions and countries. For example, in the United States, Warren et al [11] reported a VRE incidence of 27 cases per 1000 patient ICU days, whereas Kohlenberg et al [12] reported a mean incidence of 0.29 cases per 1000 patient ICU days in Germany.
Understanding the mechanisms that allow development of resistant strains of S. aureus and Enterococcus species is important to devise preventive strategies. Methicillin resistance in MRSA is determined by the staphylococcal cassette chromosome mec (SCC mec), a mobile genetic element that carries the mecA gene. The mecA gene codes for an additional penicillin-binding protein (PBP) that has a reduced affinity towards methicillin (PBP2a/PBP2'). This results in a reduced ability to bind to the bacterial cell wall and inhibit synthesis [13,14]. Study of molecular epidemiology has identified MRSA as originating from 8 major variants of the mecA gene [15]. The majority of MRSA infections are caused by strains belonging to a few internationally disseminated clones [14]. The first identified strains were associated with infections in hospitalized patients (hospital-associated MRSA), but community-associated MRSA strains have since emerged and have become established globally, including in health care institutions [16].
Community-acquired MRSA can cause severe infections in health hosts [17]; possible explanations include increased CA-MRSA virulence due to the acquisition of mobile genetic elements, namely those containing Panton-Valentine leukocidin (PVL) [18] or increased expression of core genome-encoded virulence genes, such as phenol-soluble modulin (PSM) cytolysins, α-toxin, and other virulence determinants [19].