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It is important to monitor β-lactam antimicrobial nonsusceptibility trends for Streptococcus pneumoniae to inform empirical treatment guidelines. In this study, we describe penicillin and ceftriaxone susceptibility trends using national laboratory-based pneumococcal surveillance data from 2003 to 2010. A sentinel enhanced-site patient subset (2009 to 2010) contributed to the risk factor and mortality analyses. We included 9,218 invasive pneumococcal disease (IPD) cases for trend analyses and 2,854 IPD cases for risk factor and mortality analyses. Overall, we detected no significant changes in penicillin (patients &lt;5 years of age, P = 0.50; patients ≥ 5 years of age, P = 0.05) or ceftriaxone nonsusceptibility rates (patients &lt;5 years of age, P = 0.21; patients ≥ 5 years of age, P = 0.60). Factors associated with ceftriaxone nonsusceptibility on multivariate analysis were an age of &lt;5 years (&lt;1 year of age: adjusted odds ratio [aOR], 2.87; 95% confidence interval [CI], 1.70 to 4.86; 1 to 4 years of age: aOR, 2.58; 95% CI, 1.53 to 4.35, versus 25 to 44 years of age), province (Gauteng [aOR, 2.46; 95% CI, 1.26 to 4.84], and Northern Cape [aOR, 4.52; 95% CI, 1.95 to 10.52] versus KwaZulu-Natal), β-lactam use within 24 h preceding admission (aOR, 2.52; 95% CI, 1.41 to 4.53), and 13-valent vaccine serotypes (aOR, 51.64; 95% CI, 7.18 to 371.71). Among patients ≥ 5 years of age with meningitis who were treated according to current guidelines, HIV-infected patients (aOR, 2.94; 95% CI, 1.32 to 6.54) and patients infected with ceftriaxone-nonsusceptible isolates (aOR, 3.17; 95% CI, 1.27 to 7.89) had increased mortality rates. Among children &lt;5 years of age with meningitis, mortality was increased in HIV-infected patients (aOR, 3.04; 95% CI, 1.40 to 6.56) but not in those with ceftriaxone-nonsusceptible isolates. Penicillin and ceftriaxone nonsusceptibility remained stable over the study period. Ceftriaxone nonsusceptibility was associated with increased mortality among patients ≥5 years of age with meningitis. The introduction of a pneumococcal conjugate vaccine may reduce ceftriaxone-nonsusceptible meningitis.

Factors Associated with Ceftriaxone Nonsusceptibility of Streptococcus pneumoniae: Analysis of South African National Surveillance Data, 2003 to 2010