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Virulence Determinants in S Aureus Bacteremia

This study is ongoing, but not recruiting participants.

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00319826
  Purpose

The purpose of this study is to investigate why some people develop life-threatening infections caused by the bacteria Staphylococcus aureus, while other people do not. It is possible that the infectious ability of the bacteria can determine whether an infection develops and its severity. The investigators will look at old blood and nasal specimens collected from 1000 adults who had S. aureus infections and who were hospitalized at Duke University Medical Center. Previously collected health information regarding these patients and the specific bacterial traits in the samples will be studied. Eventually this information may be used to help treat and prevent S. aureus infection.


Condition
S. Aureus Bacteremia

U.S. FDA Resources

Study Type:   Observational
Study Design:   Retrospective
Official Title:   Virulence Determinants in Staphylococcus Aureus Bacteremia

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment:   1000
Study Start Date:   March 2004
Estimated Study Completion Date:   February 2008

Detailed Description:

The purpose of this study is to more thoroughly investigate the impact of bacterial genetic characteristics on the outcome of patients with S. aureus bacteremia (SAB). The investigators will address salient aspects of bacterial virulence using strong collaborative relationships with authorities in bacterial genetics and genomics. The overall hypothesis of this investigation is that distinct bacterial virulence determinants influence the severity of S. aureus infection. The specific hypothesis is that virulence determinants associated with clinical outcome of S. aureus infection segregate into clonal groups, identified by Multilocus Sequence Typing (MLST), and can be localized in the genome by comparative genetic hybridization (CGH). The investigators have established the following aims to pursue this hypothesis. Specific Aim 1: Define the allelic diversity of S. aureus bloodstream isolates using MSLT. Allelic profiles among the 1000 isolates will be compared using the program BURST (Based Upon Related Sequence Type), and relatedness of lineages in the overall collection will be defined. Specific Aim 2: Define the genomic diversity of S. aureus bloodstream isolates using CGH. Using MLST results, a subset of 200 isolates will be selected to undergo further study. These ~200 isolates will form a unique collection hereafter referred to as the SAGA (S. aureus genomic analysis) collection. The genomic diversity of the SAGA subset will be defined using CGH. Specific Aim 3: Correlate MLST and CGH results, MLST and clinical outcome, and CGH, and clinical outcome, and make SAGA isolates available to the scientific community. In this Specific Aim, the discriminate ability of MLST and CGH will be compared among the SAGA subset isolates undergoing both assays. The association between bacterial clonality and clinical outcome will be considered among 1000 S. aureus isolates collected from adults at Duke University Medical Center who had S. aureus infections undergoing MLST. The association between clinical outcome and the presence or absence of virulence factors and pathogenicity islands in the S. aureus genome will also be considered among the 200 SAGA subset isolates undergoing CGH. The products of this study will include an increased understanding of genetic diversity in S. aureus and the role of this genetic diversity on determining the severity of infections caused by S. aureus. The full value of the current proposal also includes the potential future benefit to the research community as a whole if associations between pathogen genotype and clinical outcome, only possible to identify using such a large and clinically well-characterized collection of isolates, can be defined. To amplify these potential downstream dividends, the final goal of Specific Aim 3 will be to make SAGA subset isolates, corresponding MLST types, and CGH profiles available to the scientific community through the repository maintained by the Network for Antimicrobial Resistance in S. aureus (NARSA). The long-term objectives of this project are to: (1) identify bacterial genes contributing to the severity of infection in isolates from a large cohort of patients with SAB; and (2) ultimately use these genes to identify novel interventions for the control of S. aureus pathogenesis by investigating genes that govern the virulence of this emerging pathogen. Culture-confirmed SAB nasal carriage isolates and/or bloodstream bacterial isolates previously collected from 1000 inpatient adults at Duke University Medical Center will be used in this study.

  Eligibility
Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

Inclusion Criteria:

  1. Adults (>= 18 years) with culture-confirmed Staphylococcus aureus bacteremia (SAB). Patients with SAB transferred to Duke University Medical Center are eligible if speculation and antibiotic susceptibilities are confirmed by the Duke Clinical Microbiology Laboratory.
  2. Absolute neutrophil count of > 1000 cells/cubic millimeter at the time that the initial positive blood culture is obtained.
  3. Patient or patient's representative provides signed informed consent allowing study participation.

Exclusion Criteria:

  1. Prior enrollment of patient in this investigation (to ensure statistical independence of observations).
  2. Staphylococcus aureus bacteremia (SAB) that is not confirmed by culture and speciation at the Duke Clinical Microbiology Laboratory.
  3. Outpatient status.
  4. Isolation of any pathogen other than S. aureus from bloodstream.
  5. Inability of patient or patient's representative to provide written informed consent.
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00319826

Locations
United States, North Carolina
Duke University Medical Center    
      Durham, North Carolina, United States, 27710

Sponsors and Collaborators
  More Information


Study ID Numbers:   04-087
First Received:   April 27, 2006
Last Updated:   January 31, 2008
ClinicalTrials.gov Identifier:   NCT00319826
Health Authority:   Unspecified

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Staphylococcus aureus, S. aureus, bacteremia  

Study placed in the following topic categories:
Systemic Inflammatory Response Syndrome
Bacterial Infections
Sepsis
Bacteremia
Inflammation

Additional relevant MeSH terms:
Pathologic Processes
Infection

ClinicalTrials.gov processed this record on October 06, 2008




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