Background.There are few data comparing the clinical features, management and outcome of penicillin-nonsusceptibleStreptococcus pneumoniae(PNSP) meningitis patients with penicillin-susceptibleS. pneumoniae(PSSP) meningitis patients.Methods.We performed a retrospective, nested case-control study comparing cases with PNSP meningitis with controls with PSSP meningitis obtained from the Immunization Monitoring Program, Active (IMPACT) cross-Canada surveillance study of invasiveS. pneumoniaeinfections.Results.There were 30 PNSP meningitis cases (10.1% of total) and 45 PSSP meningitis controls from 6 centers obtained from 297 meningitis cases in the IMPACT database from 1991 through 1999. Vancomycin was used for empiric therapy in no cases and controls in 1991 to 1993 and in all cases in 1999. A third generation cephalosporin was used in 93.3% of confirmed PNSP cases, and 70.0% also received vancomycin and/or rifampin. Penicillin was used in 66.7% of confirmed PSSP cases. PNSP cases were more likely than PSSP controls to have a second lumbar puncture (odds ratio, 4.1;P= 0.01). PNSP cases were treated with intravenous antibiotics for an average of 15.6 days compared with 12.3 days for controls (P= 0.04). Among PNSP cases, those patients who did not receive empiric vancomycin were treated with intravenous antibiotics for an average of 18.5 days compared with 12.0 days for those who did receive empiric vancomycin (P= 0.04). The overall mortality was 5.3%, and 36.6% of survivors had ≥1 neurologic sequelae, including 19.7% with hearing loss. In multivariate statistical models, PNSP was not a risk factor for intensive care unit admission or neurologic sequelae.Conclusions.Management of suspected bacterial meningitis and confirmedS. pneumoniaemeningitis in Canadian children changed in the past decade. Treatment of PNSP meningitis is significantly different from that for PSSP meningitis. These changes have occurred in response to the emergence of PNSP in Canada. Neurologic sequelae remain common afterS. pneumoniaemeningitis, but there are no differences between PNSP cases and PSSP cases.