Host Factors in Invasive and Recurrent Staphylococcus Aureus Infection

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.

Study Overview

• Status: Terminated
• Conditions: Staphylococcal Aureus Infection; Recurrent Staphylococcal Infection; Invasive Staphylococcal Infection

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.

• Study Type: Observational
• Enrollment (Actual): 22

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• 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.
7. Evidence of healthcare-associated infection invasive device, history of surgery with implantation of artificial device in previous 12 months, history of surgery without device implantation in previous 12 month, or dialysis, hospitalization, or residence in long-term care facility in previous 12 months. An exception to these exclusion criteria is hospitalization for the acute S. aureus infection at the time of enrollment.

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: May 28, 2009
• Study Completion: September 17, 2014

Study Registration Dates

• First Submitted: May 29, 2009
• First Submitted That Met QC Criteria: May 29, 2009
• First Posted (Estimate): June 2, 2009

Study Record Updates

• Last Update Posted (Actual): December 17, 2019
• Last Update Submitted That Met QC Criteria: December 14, 2019
• Last Verified: September 17, 2014

More Information

Terms related to this study

• Keywords: Immunodeficiency; Atopic Dermatitis; Staphylococcus Aureus (S. Areus); Recurrent Staphylococcal Infection; Community Associated Staphylococcal Infection; Staphylococcal Infection; Invasive Staphylococcal Infection; Staph Infection
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Recurrence; Staphylococcal Infections
• Other Study ID Numbers: 090157; 09-I-0157