Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli has become widespread in healthcare settings. These organisms are not only resistant to most beta-lactams but also fluoroquinolones and aminoglycosides. ESBL producers have typically been regarded as a problem confined to hospitals. However, reports are emerging worldwide of isolation of ESBL-producing E. coli from patients in the community who previously had no contact to the healthcare system. The ESBL type associated with such infection is known as CTX-M. It is increasing recognized overseas that a particular clone of ESBL-producing E. coli, defined by phylogenetic group B2, serotype O25:H4, multilocus sequence typing (MLST) profile ST131 and production of CTX-M-15, is responsible for the majority of community-associated infections. The extent of this problem in the United States is not well defined. Spread of ESBL-producing E. coli into the community has significant clinical implications in that empiric management of common infections such as complicated urinary tract infection may no longer be effective.
The specific aims addressed in this proposal are: 1. to conduct surveillance for community-associated infections caused by ESBL-producing E. coli at multiple geographic areas in the United States. 2. To determine the clonal group of community-associated, ESBL-producing E. coli isolates from different geographic areas in the United States. The proposed study consists of clinical and microbiologic parts. The clinical study is purely observational and will be performed to identify community-associated infections caused by ESBL-producing E. coli at the participating sites. Susceptibility testing, PCR and sequencing of ESBL genes, pulsed-field gel electrophoresis, MLST, phylotyping, serotyping and plasmid analysis will then be performed at the central laboratory. The overarching goal of this project is to obtain sentinel clinical and microbiologic data on community- associated infections caused by ESBL-producing E. coli in the United States. This would provide a platform from which to build more extensive nationwide surveillance.

Public Health Relevance

Escherichia coli that produce extended-spectrum beta-lactamase (ESBL) tend to be resistant to many classes of antibiotics. Spread of these multidrug-resistant strains of E. coli in the community may lead to treatment failures of common infections such as urinary tract infection. The proposed study intends to collect data on the occurrence of such infections across the United States.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
1R03AI079296-01A1
Application #
7737686
Study Section
Drug Discovery and Mechanisms of Antimicrobial Resistance Study Section (DDR)
Program Officer
Korpela, Jukka K
Project Start
2009-09-12
Project End
2011-08-31
Budget Start
2009-09-12
Budget End
2010-08-31
Support Year
1
Fiscal Year
2009
Total Cost
$91,476
Indirect Cost
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Bogdanovich, Tatiana; Adams-Haduch, Jennifer M; Tian, Guo-Bao et al. (2011) Colistin-resistant, Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae belonging to the international epidemic clone ST258. Clin Infect Dis 53:373-6

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