Increased antimicrobial resistance among nonvaccine serotypes of Streptococcus pneumoniae in the pediatric population after the introduction of 7-valent pneumococcal vaccine in the United States

Background: The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in the United States in February 2000. The PROTEKT US study evaluated serotype distribution, PCV7 coverage and antimicrobial susceptibility among Streptococcus pneumoniae isolates collected from children aged 0 to 14 years in 2000 through 2001 (year 1; n = 2033), 2002 through 2003 (year 3; n = 1740) and 2003 through 2004 (year 4; n = 1591). Methods: Serotyping was performed by Neufeld Quellung reaction. Antimicrobial susceptibilities were determined centrally according to Clinical Laboratory Standards Institute methodology and interpretive breakpoints. Results: The proportion of isolates covered by PCV7 (vaccine serotypes) decreased from 65.5% (year 1) to 34.7% (year 3) and to 27.0% (year 4) (P < 0.0001) with similar changes seen at regional and state levels. The most common serotypes in year 4 were nonvaccine serotypes (NVS) 19A (19.0% of all isolates), 6A (7.8%), 3 (7.6%), 15 (6.3%) and 35B (5.8%) and vaccine serotype 19F (12.7%). NVS 19A increased relative to vaccine serotype 19F among isolates expressing the erm(B) + mef(A) macrolide-resistant genotype (P < 0.0001) between year 1 (7.8% [19A] versus 86.7% [19F]) and year 4 (45.5% [19A] versus 51.7% [19F]). Antimicrobial resistance rates (year 1 versus year 4) among NVS from nonblood (respiratory tract) sources increased for penicillin (resistant: 12.7-16.1% [P = 0.0857]; intermediate susceptibility: 20.1-31.5% [P < 0.0001]), erythromycin (21.2-31.6% [P < 0.0001]), amoxicillin-clavulanate (1.4-5.8% [P < 0.0001]) and multidrug resistance (resistance to >= 2 antimicrobial classes) (24.6-31.6% [P = 0.0034]). Conclusions: The proportion of S. pneumoniae isolates from U.S. pediatric patients covered by PCV7 decreased substantially in the 4 years after vaccine introduction. However, resistance to commonly used antimicrobials, including beta-lactams and macrolides, as well as multidrug-resistant strains increased significantly among respiratory tract isolates of NVS.