Host Factors in Invasive and Recurrent Staphylococcus Aureus Infection

NCT ID: NCT00911430

Last Updated: 2019-12-17

Basic Information

• Recruitment Status: TERMINATED
• Total Enrollment: 22 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-05-28
• Study Completion Date: 2014-09-17

Brief Summary

The incidence of community-associated (CA) staphylococcal infections, especially those caused by methicillin-resistant Staphylococcus aureus (MRSA), has increased dramatically in recent years. Although the majority of these infections are limited to the skin and soft tissue and thus not life threatening, the number of invasive cases in otherwise healthy individuals is increasing and some are fatal. As a first step toward understanding pathogenesis, there has been significant focus on elucidating the key CA-MRSA virulence factors. The relative significance of these factors is still being delineated. By comparison, there has been little focus on host factors associated with these invasive infections. In this protocol, we will recruit 100 otherwise healthy subjects with invasive staphylococcal infection, 50 otherwise healthy subjects with recurrent staphylococcal infections, and obtain samples from 150 unidentified healthy controls from the blood bank to investigate host immunologic factors predisposing people to staphylococcal infection. Subjects will receive standard of care treatment for acute or recurrent staphylococcal infections. The primary objective of this research is to identify host genetic factors that contribute to susceptibility or severity of community acquired staphylococcal diseases. We will use three experimental approaches to complete this objective: 1) expression microarray analyses of study population s (subjects and controls) white cells (neutrophils and peripheral blood mononuclear cells) at rest and stimulated with staphylococci, 2) evaluation of toll-like receptor (TLR) pathways in the study population s cells, and 3) evaluation of Th17 cells. The proposed research will address a key area of staphylococcal pathogenesis for which there is a striking lack of information. We fully anticipate that the research also will provide critical new information directly relevant to vaccine, diagnostics, and therapeutics development.

Detailed Description

The incidence of community-associated (CA) staphylococcal infections, especially those caused by methicillin-resistant Staphylococcus aureus (MRSA), has increased dramatically in recent years. Although the majority of these infections are limited to the skin and soft tissue and thus not life threatening, the number of invasive cases in otherwise healthy individuals is increasing and some are fatal. As a first step toward understanding pathogenesis, there has been significant focus on elucidating the key CA-MRSA virulence factors. The relative significance of these factors is still being delineated. By comparison, there has been little focus on host factors associated with these invasive infections. In this protocol, we will recruit 100 otherwise healthy subjects with invasive staphylococcal infection, 50 otherwise healthy subjects with recurrent staphylococcal infections, and obtain samples from 150 unidentified healthy controls from the blood bank to investigate host immunologic factors predisposing people to staphylococcal infection. Subjects will receive standard of care treatment for acute or recurrent staphylococcal infections. The primary objective of this research is to identify host genetic factors that contribute to susceptibility or severity of community acquired staphylococcal diseases. We will use three experimental approaches to complete this objective: 1) expression microarray analyses of study population s (subjects and controls) white cells (neutrophils and peripheral blood mononuclear cells) at rest and stimulated with staphylococci, 2) evaluation of toll-like receptor (TLR) pathways in the study population s cells, and 3) evaluation of Th17 cells. The proposed research will address a key area of staphylococcal pathogenesis for which there is a striking lack of information. We fully anticipate that the research also will provide critical new information directly relevant to vaccine, diagnostics, and therapeutics development.

Conditions

Staphylococcal Aureus Infection; Recurrent Staphylococcal Infection; Invasive Staphylococcal Infection

Keywords

Staphylococcus Aureus (S. Areus); Recurrent Staphylococcal Infection; Atopic Dermatitis; Immunodeficiency; Community Associated Staphylococcal Infection; Staphylococcal Infection; Invasive Staphylococcal Infection; Staph Infection

Study Design

• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

1. Age greater than or equal to 2 years.

2. Current or past S. aureus infection, either invasive or soft tissue.

3. Willingness to allow storage of blood and tissue samples for future use.

4. Subjects will be eligible without regard to race, gender, or ethnic origin.

Exclusion Criteria

1. Infection with known HIV-1, HIV-2 as demonstrated by ELISA and Western blot or viral load testing.

2. Evidence of intravenous drug abuse in the year prior to the first (or only) S. aureus infection.

3. Previously known immunodeficiency syndrome.

4. Evidence of active malignancy.

5. Any condition that the investigators judge would compromise the results of the study.

6. Diabetes mellitus.

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Principal Investigators

Steven M Holland, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Allergy and Infectious Diseases (NIAID)

Locations

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States

Countries

United States

References

Diekema DJ, Pfaller MA, Schmitz FJ, Smayevsky J, Bell J, Jones RN, Beach M; SENTRY Partcipants Group. Survey of infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997-1999. Clin Infect Dis. 2001 May 15;32 Suppl 2:S114-32. doi: 10.1086/320184.

Reference Type: BACKGROUND

PMID: 11320452 (View on PubMed)

Zetola N, Francis JS, Nuermberger EL, Bishai WR. Community-acquired meticillin-resistant Staphylococcus aureus: an emerging threat. Lancet Infect Dis. 2005 May;5(5):275-86. doi: 10.1016/S1473-3099(05)70112-2.

Reference Type: BACKGROUND

PMID: 15854883 (View on PubMed)

Naimi TS, LeDell KH, Como-Sabetti K, Borchardt SM, Boxrud DJ, Etienne J, Johnson SK, Vandenesch F, Fridkin S, O'Boyle C, Danila RN, Lynfield R. Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection. JAMA. 2003 Dec 10;290(22):2976-84. doi: 10.1001/jama.290.22.2976.

Reference Type: BACKGROUND

PMID: 14665659 (View on PubMed)

Other Identifiers

09-I-0157

Identifier Type: -

Identifier Source: secondary_id

090157

Identifier Type: -

Identifier Source: org_study_id