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The aim of this study was to evaluate diagnostic practices for suspected community-acquired central nervous system (CNS) infection in an urban pediatric population.This is an observational, retrospective single-center review of cerebrospinal fluid (CSF) studies in children, 1 month to 21 years old, evaluated for suspected CNS infection from 2004 to 2014. Cases of suspected nosocomial meningitis were excluded. The frequency of N-methyl-D-aspartate receptor antibody (NMDAR ab) encephalitis was analyzed from 2010 to 2014.A total of 940 unique patient visits with CSF studies were included in the final analysis. There were 940 bacterial cultures sent; 4 (0.42%) grew suspected CSF bacterial pathogens, and 18 (1.9%) grew organisms that were suspected contaminants. Bacterial pathogens included late-onset group B Streptococcus in 3 infants younger than 3 months and Streptococcus pneumoniae in an unvaccinated 9-year-old child. Viral CNS infection was 7.5 times more frequent than bacterial infection. Enterovirus was the only virus isolated. Five cases positive for NMDAR ab were identified since 2010.Bacterial studies were performed more frequently than viral and other studies. Cerebrospinal fluid bacterial culture was nearly 5 times more likely to yield a contaminant than a pathogen. The frequency of viral infection was likely underestimated as only 20% were tested, mainly by culture, which is suboptimal. These data suggest diagnostic practices for the evaluation of suspected community-acquired CNS infections in children need to be modified to reflect current epidemiology and highlight the need for greater accessibility to polymerase chain reaction for viral diagnostics. Furthermore, NMDAR ab–mediated encephalitis should be considered early in children presenting with suggestive symptoms.