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The incidence of and outcomes associated with methicillin-resistant Staphylococcus aureus (MRSA) infection in hospitalized children have been incompletely characterized.We performed a retrospective, observational study using the Pediatric Health Information System, a database of clinical and financial data from >40 freestanding US children's hospitals. Using discharge coding data, we characterized S. aureus infections in children <18 years of age who were hospitalized during the period from 1 January 2002 through 31 December 2007.During this 6-year study period, we identified 57,794 children with S. aureus infection, 29,309 (51%) of whom had MRSA infection. The median age of patients with S. aureus infection was 3.1 years (interquartile range, 0.8-11.2 years), and less than one-third of these patients had complex, chronic medical conditions. Over time, there was a significant increase in cases of MRSA infection (from 6.7 cases per 1000 admissions in 2002 to 21.1 cases per 1000 admissions in 2007; P=.02, by test for trend), whereas the incidence of methicillin-susceptible S. aureus infection remained stable (14.1 cases per 1000 patient-days in 2002 to 14.7 cases per 1000 patient-days in 2007; P=.85, by test for trend). Of the 38,123 patients whose type of infection was identified, 23,280 (61%) had skin and soft-tissue infections. The incidences of skin and soft-tissue infection, pneumonia, osteomyelitis, and bacteremia that were caused by S. aureus increased over time, and these increases were due exclusively to MRSA. The mortality rate for hospitalized children with MRSA infection was 1% (360 of 29,309 children).There has been a recent increase in the number of hospitalized children with MRSA infection. This increase is largely driven by, but is not limited to, an increase in skin and soft-tissue infections. The mortality rate for hospitalized children with MRSA infection is low.