During the 2-year cohort period (January 1, 2002–December 31, 2003), 3,090 patients were admitted to the MICU or SICU for a >5-hour stay. Of these, 2,440 patients (79.0%) had both anterior nares and perirectal admission cultures collected. Sixty-five patients (2.7%) were co-colonized with VRE and MRSA, 247 patients (10.1%) were colonized with VRE alone, and 175 patients (7.2%) were colonized with MRSA alone. Of the 57 MRSA/VRE co-colonized patients with perirectal samples available for additional analysis, 23 patients (40.4%) were perirectally colonized with MRSA in addition to perirectal VRE and MRSA nasal colonization. Results of the bivariable analyses for VRE/MRSA co-colonization are displayed in Table 1. Because of space constraints, bivariable results for colonization by MRSA or VRE alone are not shown. These results suggest that patients colonized with VRE, MRSA, or both were significantly more likely to have been admitted to the MICU, have had previous hospital admissions, and have antimicrobial exposures within 1 year of current admission (p<0.05 for all). Among co-colonized patients, 58% had been admitted to the index hospital in the previous year, and 51% had received antimicrobial drugs during an admission in the previous year. In addition, ≈48% of MRSA/VRE co-colonized patients had a previous positive culture (clinical or surveillance) for MRSA before the study period, and ≈28% had a previous positive culture for VRE.

Independent risk factors identified with logistic regression for the different colonization states (co-colonization, VRE only, or MRSA only) were markedly different (Table 2). Table 3 displays clinical outcomes of VRE/MRSA co-colonized patients. Approximately 25% percent of co-colonized patients died during the current admission; however, mortality was not significantly higher compared to non–co-colonized patients (p = 0.15). Three percent of co-colonized patients had MRSA-positive clinical cultures, and 3% of co-colonized patients had VRE-positive clinical cultures on the current or subsequent admissions (within 6 months). None of the co-colonized patients had clinical cultures positive for both organisms. Thirty-two percent of VRE/MRSA co-colonized patients were transferred to another hospital upon discharge from the index hospital compared with 15% of non–co-colonized patients (p<0.01).

Increasing VRSA prevalence in the healthcare setting could result in considerable illness and death (21). To our knowledge, we present the first estimates of the prevalence, risk factors, and clinical outcomes of patients with VRE and MRSA co-colonization. As has been previously reported, co-colonization with VRE and MRSA has always preceded VRSA colonization or infection, and patients admitted to ICUs are likely a high-risk population (11–13,15). We show that among patients who had admission cultures taken, 4.6% admitted to the MICU and 1.2% admitted to the SICU of a tertiary-care facility during a 2-year period were co-colonized with MRSA and VRE, with an overall co-colonization proportion of 3% in both ICUs together. In addition, the observation that ≈40% of MRSA/VRE co-colonized patients were perirectally colonized with both organisms suggests the potential risk for the exchange of genetic material, which could result in the emergence of VRSA.

None of the 65 VRE/MRSA–co-colonized patients had positive clinical cultures for both VRE and MRSA on current or subsequent admissions to the index hospital. Thus, none would have been identified as co-colonized without the active surveillance culturing program in place at our institution. As has been suggested by previously reported cases of VRSA, early identification of these patients is recommended to minimize antimicrobial selective pressure and enhance infection control efforts to reduce the potential for patient-to-patient transmission (5,7).

In this study, <25% of co-colonized patients died, and nearly 35% were discharged to other hospitals or rehabilitation facilities, where the risk of transmitting these organisms to other patients is substantial. Considering the potential for colonization, infection, and transmission of VRSA, treating physicians, hospital staff, and infection control personnel at receiving institutions must be adequately prepared to isolate and treat these patients (22,23). Previous studies of transmission from vancomycin-intermediate S. aureus (VISA)- or VRSA-colonized or infected patients show that these organisms can be transmitted to close contacts or other hospitalized patients (7,21,24).

Previous studies have also shown that carriage of VRE or MRSA may be persistent, which would increase the potential for co-colonized patients to transmit either or both of these organisms to other patients (25,26). A mathematical model of the transmission dynamics of VRE has suggested that persistent colonization is the most important factor for increasing the endemic prevalence of this organism in the hospital (26). Furthermore, the potential for prolonged co-colonization could increase the likelihood that these patients would experience sufficient selective pressure for emergence of VRSA.

Recent reviews by Reuf, Fridkin, and Cosgrove et al. have summarized risk factors associated with clinical culture positivity for VRSA and VISA (4,22,23). However, with only 3 reported cases of VRSA and ≈20 reported cases of VISA, the precision of statistical associations has been limited. Recent exposure to vancomycin and recent isolation of MRSA were identified as risk factors for VISA in addition to concurrent colonization or infection with VRE and MRSA. Among co-colonized patients in this study, ≈21% received vancomycin, 26% received piperacillin-tazobactam, and 17% received a fluoroquinolone before culture results.

This study is the first to report the prevalence, risk factors, and clinical outcomes of patients with VRE/MRSA co-colonization upon admission to the ICU. We report several risk-factors for co-colonization, including that the odds of co-colonization for patients admitted to the MICU were >4 times greater than those of patients admitted to the SICU and that patients who received antimicrobial drugs within 1 year of admission had 3 times the odds of co-colonization as patients who had not received antimicrobial drugs during a previous admission.

Ray et al. assessed the prevalence of gastrointestinal S. aureus colonization among a convenience sample of 37 patients colonized with VRE and reported that 20 (54.1%) of these patients were also colonized with MRSA (27). However, comparing these results to those presented here is difficult, given the stark differences between patient groups. The study by Ray et al. included only hospitalized patients from whom a minimum of 3 stool samples (collected weekly) were obtained (i.e., inpatients with extended lengths of stay). We believe that ICU patients co-colonized with VRE and MRSA are at risk of acquiring and transmitting VRSA because they generally are exposed to greater antimicrobial selective pressure, have extended lengths of stay, greater likelihood of indwelling devices, greater severity of illness, and are more likely to have a history of previous hospitalization and related exposures than patients admitted to general medical wards. Despite these differences, perirectal colonization of both organisms was similar between the patients in the study by Ray et al. and this study (54.1% vs. 40.3%, respectively). Other studies have also suggested a prevalence of VRE/MRSA co-colonization or co-infection ranging from 9.5% to 28.6%; however, these studies relied upon clinical cultures to provide these estimates (14,15).

A limitation of this study is that investigators were unable to determine the species of the VRE isolates. Historically, Enterococcus faecalis has been more likely to be associated with conjugation events and subsequent VRSA colonization or infection compared with E. faecium (7,28). However, only 3 VRSA cases are known, and we are not aware of any biologic explanation for why E. faecium would be less likely to be involved in transmission of vancomycin resistance to MRSA compared with E. faecalis. Still, these data would have been useful and informative. A previous, hospitalwide study at UMMC suggested that among isolated VRE, the prevalence of E. faecium and E. faecalis were 87%, and 13%, respectively (29).

In summary, these data describe a high prevalence of patients co-colonized with VRE and MRSA on admission to an ICU at a tertiary-care hospital, none of whom would have been detected by clinical culture. Risk factors for VRE and MRSA co-colonization are also described. Given that many of these patients were discharged to other institutions, treating physicians and infection control personnel must be cognizant of the risks for VRSA colonization and infection and use appropriate precautions. Appropriate methods to rapidly detect co-colonized patients must be identified to suppress the emergence of VRSA; limit patient-to-patient transmission of MRSA, VRE, and VRSA; and prevent endemic VRSA colonization in healthcare institutions.