Regardless of whether MRSA colonization precedes admission or occurs due to nosocomial spread, it is associated with increased risk of developing a HAI [46–49]. In 2 large prospective observational cohort studies, the hazard ratios of MRSA colonization developing into S. aureus infections during the ICU stay were 3.84 and 4.70, respectively [50,51]. High levels of concordance between MRSA colonization strains and HAI strains have also been reported [52]. Nasal colonization with S. aureus has also been identified as an independent risk factor for developing ventilator-associated pneumonia (VAP) and bacteremia [53,54]. A case series of ICU patients with S. aureus nasal colonization who developed lower respiratory tract infections demonstrated genetically identical nasal and bronchial strains in 15/16 cases [55]. This finding strongly suggests that nasopharyngeal colonization with S. aureus contaminates oral secretions that are aspirated by critically ill patients, resulting in subsequent pneumonia. In a long-term outcomes study among a matched cohort of veterans, MRSA colonization was associated with an increased risk of infection-related readmission and mortality [56]. These findings reflect the critically important nature of measures designed to curb nosocomial transmission and acquisition of MRSA, especially among the vulnerable ICU population.
VRE
As with MRSA, risk factors associated with VRE colonization include both patient-level and ICU-level (or environmental) factors [57]. Examples of patient-level factors include previous antimicrobial exposure [58–62], underlying medical illnesses such as chronic renal failure requiring hemodialysis [11,63], length of hospital or ICU stay [11,59,64,65], and recent exposure to health care facilities. ICU-level factors of relevance are the prevalence of VRE in the unit, with high levels of endemicity leading to higher risk of colonization and transmission.
Antibiotic use is a major risk factor for VRE acquisition, although the type and class of antibiotic varies considerably across studies; the most frequently identified antibiotics are broad-spectrum cephalosporins, vancomycin, and anti-anaerobic agents [58,62,64]. Patients with chronic liver disease and post-transplantation are at exceedingly high risk for VRE acquisition [59]. In a recent study by Pan [66], for example, the authors found that the incidence of newly acquired VRE was 21.9 per 1000 patient-days in an ICU setting. On multivariate analysis, the authors found that, similar to other reports [11,59,67], length of stay in the ICU was associated with increased risk of VRE acquisition, with each additional day of stay increasing risk of VRE by 1.03 times. Warren et al undertook a prospective cohort study involving 519 patients admitted to the ICU for more than 48 hours [11]. Seventy-four (21%) of 352 patients were subsequently colonized with VRE. The median time to development of a positive VRE culture after ICU admission was 6 days. Increased mean APACHE II score on ICU admission ( P = 0.002), sucralfate use ( P = 0.003), vasopressor use ( P = 0.01), tracheostomy in the ICU ( P = 0.02), and C. difficile diarrhea ( P = 0.002) appeared to be associated with VRE acquisition.
It appears that VRE acquisition is often associated with the sick subgroup of patients, and risk factors generally associated with VRE colonization and infection co-relate with disease chronicity and severity of illness. Length of hospitalization, ICU stay, hemodialysis, or transplantation may all be markers of disease severity. A summary of risk factors for VRE acquisition is shown in Table 2 .
