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Antimicrobial Agents and Chemotherapy, August 2004, p. 3016-3023, Vol. 48, No. 8
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.8.3016-3023.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Emergence of Streptococcus pneumoniae with Very-High-Level Resistance to Penicillin

Stephanie J. Schrag,1* Lesley McGee,1,2 Cynthia G. Whitney,1 Bernard Beall,1 Allen S. Craig,3 Miriam E. Choate,2 James H. Jorgensen,4 Richard R. Facklam,1 Keith P. Klugman,1,2 and the Active Bacterial Core Surveillance Team{dagger}

Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention,1 Department of International Health, Rollins School of Public Health, and Division of Infectious Diseases, School of Medicine, Emory University, Atlanta, Georgia,2 Tennessee Department of Health, Nashville, Tennessee,3 Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, Texas4

Received 29 January 2004/ Returned for modification 5 April 2004/ Accepted 26 April 2004

Penicillin resistance threatens the treatment of pneumococcal infections. We used sentinel hospital surveillance (1978 to 2001) and population-based surveillance (1995 to 2001) in seven states in the Active Bacterial Core surveillance of the Emerging Infections Program Network to document the emergence in the United States of invasive pneumococcal isolates with very-high-level penicillin resistance (MIC ≥ 8 µg/ml). Very-high-level penicillin resistance was first detected in 1995 in multiple pneumococcal serotypes in three regions of the United States. The prevalence increased from 0.56% (14 of 2,507) of isolates in 1995 to 0.87% in 2001 (P = 0.03), with peaks in 1996 and 2000 associated with epidemics in Georgia and Maryland. For a majority of the strains the MICs of amoxicillin (91%), cefuroxime (100%), and cefotaxime (68%), were ≥8 µg/ml and all were resistant to at least one other drug class. Pneumonia (50%) and bacteremia (36%) were the most common clinical presentations. Factors associated with very highly resistant infections included residence in Tennessee, age of <5 or ≥65 years, and resistance to at least three drug classes. Hospitalization and case fatality rates were not higher than those of other pneumococcal infection patients; length of hospital stay was longer, controlling for age. Among the strains from 2000 and 2001, 39% were related to Tennessee23F-4 and 35% were related to England14-9. After the introduction of the pneumococcal conjugate vaccine, the incidence of highly penicillin resistant infections decreased by 50% among children <5 years of age. The emergence, clonality, and association of very-high-level penicillin resistance with multiple drug resistance requires further monitoring and highlights the need for novel agents active against the pneumococcus.

* Corresponding author. Mailing address: Mailstop C-23, Centers for Disease Control and Prevention, 1600 Clifton Rd., Atlanta, GA 30333. Phone: (404) 639-4646. Fax: (404) 639-3970. E-mail: zha6{at}cdc.gov.

{dagger} Contributing members of the Active Bacterial Core Surveillance Team are listed in Acknowledgments.

Antimicrobial Agents and Chemotherapy, August 2004, p. 3016-3023, Vol. 48, No. 8
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.8.3016-3023.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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