From March 1, 2007, through May 31, 2008, 1,674 children were admitted to the Johns Hopkins Hospital PICU. The median age was 5 years (IQR 1–12 years), and 55% of patients were male. Only 53 patients (3.2%) had an institutional history of MRSA colonization or infection. Screening cultures were performed on nasal swabs from 1,210 children (72%) obtained at the time of PICU admission. When patients that were screened were compared with those that were not screened, screened patients were more likely to have been hospitalized in the previous 12 months (29% vs. 22%, p<0.01). No other significant differences in demographic or clinical characteristics were found between those patients screened for MRSA colonization and those not screened (Table 1).

At the time of admission to PICU, 72 (6.0%) patients were colonized with MRSA: 68 patients (94%) identified by results of nasal screening cultures and 4 patients whose clinical culture grew MRSA within 3 days of PICU admission. Characteristics of patients colonized with MRSA at the time of admission (group 1, currently colonized) were compared with those of patients not colonized with MRSA and never known to be colonized (group 2, never colonized) and patients not colonized with MRSA at admission but who had an institutional history of prior colonization or infection (group 3, previously colonized) (Table 2). Compared with never-colonized patients, MRSA-colonized patients tended to be younger (median age 3 years vs. 5 years, p = 0.02), to be African American (54% vs. 32%; p<0.001), and to have been hospitalized in the previous 12 months (p<0.001). MRSA-colonized patients had a longer stay in the PICU (3 days vs. 2 days, p<0.001) and a longer stay in the hospital (8 days vs. 5 days; p<0.01). MRSA-colonized patients tended to be younger than previously colonized patients (median age 3 years vs. 10.5 years; p<0.01), but these 2 groups were otherwise similar.

Of the 72 MRSA colonized patients, 54 (75%) were newly identified MRSA carriers (51 by screening cultures and 3 by clinical cultures). Of the 51 patients newly identified by screening cultures, 8 (16%) had a subsequent clinical culture grow MRSA during their PICU stay. Therefore, 43 (60%) of 72 MRSA-colonized patients would have gone undetected had admission screening cultures not been performed. Most MRSA-colonized patients were <6 years of age (71%) and African American (54%). Eighteen percent were admitted from an in-patient unit, and in the previous 12 months, 58% had been hospitalized and 43% had been admitted to the PICU.

Figure

Figure. Dendrogram of methicillin-resistant Staphylococcus aureus strains that colonized children admitted to the pediatric intensive care unit, The Johns Hopkins Hospital, Baltimore, MD, USA, 2007–2008. Isolates were characterized by pulsed-field gel electrophoresis...

MRSA isolates from 66 (92%) of 72 patients colonized with MRSA at the time of admission were analyzed by PFGE; 14 distinct strains were identified (Figure). Forty (61%) isolates were CA-MRSA strains, including those identical to or related to PFGE types USA300 (n = 39) and USA400 (n = 1). Twenty-six isolates (39%) were HA-MRSA strains related to USA100 (n = 11), USA200 (n = 1), USA700 (n = 1), and 8 other strains had unique PFGE fingerprints (n = 13). Many isolates did not have identical band patterns, but they did have <3 band differences and were considered related strains (3).

Patients colonized with CA-MRSA were compared with those colonized with HA-MRSA (Table 3). Patients colonized with CA-MRSA strains were less likely to have been admitted to the PICU within the previous 12 months (OR 0.31; 95% CI 0.11–0.84). No significant differences were found between the 2 groups in other demographic, clinical, or outcome characteristics, including median age, sex, number of newly identified MRSA carriers, length of stay in the hospital before PICU admission, admission from home or patient care unit, admission to a medical or surgical service, PICU length of stay, or hospital length of stay.

To identify patients who became colonized with MRSA while in the PICU, MRSA screening cultures from nares specimens were sent weekly, and clinical cultures from patients in the PICU for >3 days were monitored. During the study period, 8 incident MRSA cases were identified (Table 4), an incidence density of 1.01 cases per 1,000 patient days at risk. No correlation was shown between monthly colonization prevalence at time of admission and incident MRSA cases (p = 0.09). Six (75%) of 8 incident cases were identified by a screening culture. Of these 6 patients, 2 had subsequent clinical cultures grow MRSA. If weekly MRSA screening cultures were not performed, only 4 (50%) of 8 incident MRSA cases would have been identified. Patients with incident MRSA cases were in the PICU for a median of 6 days (range 5–24 days) before acquiring MRSA and had a median age of 6 years (range 1–11 years). Seven (88%) of 8 MRSA isolates were available for PFGE analysis. Four (57%) of 7 isolates were identical to or related to PFGE-type USA300, documenting healthcare-associated transmission of CA-MRSA strains. Six (75%) of 8 patients with incident cases were admitted to a surgical service. Of the patients who became colonized with MRSA, 3 (38%) acquired a subsequent MRSA infection during their stay in the PICU (1 central-line–associated bloodstream infection, 1 case of ventilator-associated pneumonia, 1 case of ventilator-associated tracheitis). Both respiratory infections were caused by PFGE strain A, a strain that was not associated with colonization of any patients at the time of PICU admission. The only HA-MRSA bloodstream infection was caused by a USA300-related strain.

These data describe the prevalence of MRSA colonization in patients admitted to the PICU and suggest that CA-MRSA strains may be becoming endemic in hospitalized children. We found that 6.0% of patients screened at the time of admission to the PICU were colonized with MRSA. Most (60%) MRSA-colonized patients would not have been recognized if admission screening cultures had not been performed. Sixty-one percent of MRSA colonized patients harbored CA-MRSA strains, mostly USA300. Our data show that epidemic CA-MRSA strains are endemic to the PICU. These strains can be transmitted to children in the hospital and can cause invasive hospital-acquired infections, including bacteremia.

Aside from how to manage an MRSA outbreak, little research has attempted to characterize the epidemiology of MRSA colonization and transmission in the PICU. The lack of research in PICU patients is surprising, given the abundance of published articles that have characterized the epidemiology of MRSA in adult ICU patients (24,25). Our findings agree with those of studies of adult patients: screening cultures detect a large reservoir of MRSA-colonized patients, cases that would otherwise go undetected (18,24). Most (75%) patients colonized at the time of PICU admission had no institutional history of MRSA colonization or infection. MRSA-colonized patients serve as a reservoir for contamination of healthcare workers’ hands and subsequent MRSA transmission to patients. Active detection and isolation of MRSA carriers can reduce MRSA transmission in hospitals (26,27). Given the risk to patients for MRSA acquisition and subsequent infection (28), many hospitals screen high-risk populations to identify MRSA carriers. In an attempt to curb the spread of MRSA in healthcare facilities, some states have passed legislation mandating MRSA screening.

As the community prevalence of MRSA has risen (9), more children infected with MRSA have been admitted to hospitals (10,11). Our data suggest that these patients represent a small fraction of the patients colonized with CA-MRSA strains who enter the hospital. We found that 61% of children colonized with MRSA at the time of PICU admission harbored a CA-MRSA strain. Findings from a previous cohort showed a lower percentage of colonization with CA-MRSA strains (29). Among patients >13 years of age who were admitted to an urban hospital in Atlanta, 7.3% were colonized with MRSA, and 30% of those were colonized with CA-MRSA strains (29).

Several factors may explain the high prevalence of colonization with CA-MRSA strains in our cohort. First, the community prevalence of MRSA colonization in children is increasing nationwide and in Baltimore (30–32), largely the result of spread of CA-MRSA strains. Second, children generally have less exposure to healthcare settings where they would be exposed to traditional HA-MRSA strains. Third, children frequently are in settings of close personal contact where opportunities for hygiene may be limited, such as day care, schools, and sports teams, settings postulated as high-risk environments for MRSA transmission.

Notably, children in this study who were colonized with MRSA at the time of admission to PICU were more likely to be younger and African American. Our finding of younger age is consistent with data from the 2003–2004 Centers for Disease Control and Prevention National Health and Nutrition Examination Survey Nasal Swab survey, which found that children 1–5 years of age had the second highest MRSA colonization rates, behind adults >60 years of age (R. Gorwitz, pers. comm.). Similarly, we found that children with previous, but not current, MRSA colonization tended to be older. Why colonization prevalence is different in various pediatric age groups remains unknown. Previous studies have found racial disparities in rates of invasive MRSA disease (6,33). In a 2007 report by Klevens et al., incidence rates of invasive MRSA disease were more than twice as high for African Americans than for whites, and mortality rates were 80% higher for African Americans (7). The reason for these racial disparities is unknown. MRSA colonization is a known risk factor for invasive MRSA, so higher colonization rates in African Americans may in part explain higher rates of invasive disease.

CA-MRSA strains are changing the landscape of MRSA infection prevention and control in hospitals. We found that CA-MRSA strain USA300 was the most commonly acquired MRSA strain identified in the PICU. All patients who acquired MRSA had negative nares swab cultures at the time of PICU admission, and all subsequently exhibited MRSA nasal colonization. Of 8 patients, 3 (38%) had subsequent MRSA infection during their PICU stay. We were unable to monitor these patients after PICU discharge and likely have underestimated their long-term risk for subsequent MRSA infection. CA-MRSA strains, with the potential to spread rapidly and cause severe disease, have now been shown to cause hospital-acquired infections and hospital outbreaks (7,13–15). Hospital outbreaks confirm that CA-MRSA strains can be transmitted and acquired in the healthcare setting. The role of CA-MRSA strains in endemic MRSA transmission has not been elucidated. The extent to which endemic CA-MRSA strains will affect the epidemiology of HA-MRSA transmission and infections remains unknown. Our data suggest that this topic requires further study.

As CA-MRSA strains become more prevalent in hospitals, the importance of distinguishing between MRSA strains remains unclear. However, CA-MRSA strains appear to be highly transmissible and may have increased virulence (33–35). When attempting to distinguish between patients colonized with CA-MRSA strains and those colonized with non–CA-MRSA strains, we found that patients colonized with HA-MRSA strains were 3× more likely to have been admitted to an ICU within the previous 12 months. Other demographic characteristics did not differ between the groups. Overall, our findings agree with those of other studies that have shown that demographic data and risk factors may not reliably distinguish between patients colonized or those infected with various MRSA strains (14,36).

Our study has several limitations. First, only nares cultures were performed to identify asymptomatic MRSA carriers at the time of admission to the PICU. Recent studies have shown that screening extranasal sites or subtances, such as throat, axilla, perineum, or stool can increase the detection of MRSA carriers (37,38), especially those colonized with CA-MRSA strains. However, the best sites to detect MRSA, in combination with nasal culture, remain unclear (38). Nares cultures, if poorly carried out, can have false-negative results. Therefore, if we misclassified MRSA carriers with negative nasal screening cultures, we may have underestimated the MRSA prevalence. Sensitive, yet cost-effective, methods of screening for MRSA colonization are still needed.

The second limitation is that admission screening cultures were instituted in March 2007, and compliance with screening was only 72%. Our PICU did not have admission order sets, and in the absence of a physician’s written order, cultures were not always performed. Compliance improved over time with initiation of a patient order entry system, a visual reminder to perform screening cultures on the front of the patient’s chart, and frequent compliance auditing by the nurse manager. However, given the similarities between screened and unscreened patients, we expect that our measured prevalence was representative of the entire cohort. Third, our PICU has low MRSA incidence rates and may have a low prevalence of MRSA colonization at the time of admission compared with other PICUs. These conditions may limit how our findings can be generalized to other institutions.

Overall, we found that epidemic CA-MRSA strains are likely endemic to PICUs. These virulent and transmissible strains are entering the PICU through infected or colonized patients, they are being transmitted to children, and they are responsible for hospital-onset MRSA infections. CA-MRSA strains often colonize children without healthcare-associated risk factors. Traditional infection-control strategies, in which risk factors are used to target high-risk patients for screening and intervention, may prove insufficient for MRSA. Future studies to determine optimal approaches to control MRSA transmission in hospitalized children are needed. As CA-MRSA strains enter the hospital environment, the increased frequency of methicillin resistance and the coexistence of multiple strain types may lead to the selection of novel MRSA strains with enhanced capacity for transmission and infection. These conditions would be especially concerning with regard to children, for whom a more restricted antimicrobial drug arsenal is available. Sound epidemiologic investigation and feasible interventions are needed to control MRSA and protect hospitalized children.