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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

Farrell, David J. PhD*; Klugman, Keith P. MD†; Pichichero, Michael MD‡

Pediatric Infectious Disease Journal:
doi: 10.1097/01.inf.0000253059.84602.c3
Original Studies

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 β-lactams and macrolides, as well as multidrug-resistant strains increased significantly among respiratory tract isolates of NVS.

Author Information

From the *G. R. Micro Ltd, London, U.K.; †Hubert Department of Global Health, Rollins School of Public Health and Division of Infectious Diseases, School of Medicine, Emory University, Atlanta, GA; and the ‡University of Rochester, Rochester, NY.

Accepted for publication November 6, 2006.

Dr. Farrell has been a consultant to sanofi-aventis and Pfizer and has received funding from sanofi-aventis, Pfizer, Theravance and Bayer. Dr. Pichichero has received honoraria for speaking and consulting, and has received research grants from sanofi-aventis. Dr. Klugman has been a consultant to sanofi-aventis and Bayer and has received research support from sanofi-aventis.

Address for correspondence: David J. Farrell, PhD, G. R. Micro Ltd., 7–9 William Road, London NW1 3ER, U.K. E-mail:

© 2007 Lippincott Williams & Wilkins, Inc.