At the MRSA Research Center, we are investigating the following research questions:

• How does MRSA spread? By touching another person? By sharing personal items? How easily does MRSA spread?
• Can you get infected from MRSA by touching a surface or object? If so, how long can MRSA last on a surface or object?
• How do you best treat a MRSA infection?
• Why do some people get really sick from MRSA and others don’t?
• Why is MRSA so resistant to antibiotics?
• Can we prevent MRSA infection with a vaccine?
• Why is community-associated MRSA spreading so quickly?

Modeling MRSA in the Community

Diane Lauderdale, PhD, Epidemiologist
University of Chicago

Charles Macal, PhD, Computer Modeling Specialist
Argonne National Laboratory

The goal of this project is to create a new agent-based model of MRSA that includes theoretically based and empirically derived variables representing behavioral features of the population (e.g., social networks) and healthcare system.  We will develop a flexible agent-based model scaling up in stages to the population of the Chicago metropolitan area, the first of which will include a corridor across the south side of Chicago and adjoining suburbs.  We will use high-performance computing capabilities at the University of Chicago and Argonne National Laboratory to run individual model configurations thousands of times.

For more information on Models of Infectious Disease Agent Study (MIDAS), visit:
http://www.nigms.nih.gov/Initiatives/MIDAS/

 

Grant Healthcare: New antibiotics to treat MRSA

The goal of this project is to validate new targets for MRSA-specific antimicrobials based on comparative genomics and microarray transcriptional profiling of resistant versus susceptible (or mutant) MRSA.

 

Recurrent MRSA Infections: Risk Factors and Molecular Epidemiology

MRSA infections often recur in patients, but it is not known which patients are at highest risk for recurrence nor whether CA- or HA-strains are more likely to cause recurrence. In the era of CA-MRSA, it is not known if patients with persistent carriage of MRSA are at elevated risk of recurrent MRSA infections. There are interventions that may decrease the likelihood of recurrent MRSA infections in an individual: decolonization protocols, cleaning of fomites, antibiotic therapies, and vaccines are all potentially relevant avenues for the future control of MRSA in the community. Each of these modalities will require further study to assess its efficacy and safety. Patients with recurrent MRSA disease are likely to benefit from such interventions, and the control of MRSA infections in this population may be critical to stemming the dissemination of CA-MRSA in the U.S. In this a two-part study, using a collection of >13,800 stored clinical S. aureus strains, obtained through surveillance at the University of Chicago Medical Center (UCMC), I will attempt to define risk factors for recurrent MRSA infections. First, using existing surveillance data from UCMC in 2003-9, in a case-control study treating those with multiple infections as the cases and those with a single infection as controls, I will examine the following as risk factors for re-infection:  anatomic site of first infection, genotype of first and subsequent infecting MRSA strains including CA- and HA-MRSA strain characteristics, patient demographic characteristics, previous exposures to the health care system, and patient comorbidities. Second, nesting a prospective cohort study of recurrent MRSA infections in surveillance at UCMC, I will enroll 400 patients with incident MRSA infections and monitor them for two years. I will determine how frequently these patients have recurrent MRSA infections, how commonly they seek medical attention for the infections, the presence of the risk factors for re-infection listed above, and the genotypes of MRSA strains associated with infections and any identified asymptomatic colonization to assess the role of chronic colonization in the recurrence of MRSA infections.

Colonization, 'New' Risk Factors, and Genetics of Patients with Skin and Soft Tissue Infections

The goals of this project are to identify anatomic sites of CA-MRSA isolates, human genetic markers predisposing to S. aureus infection, and risk factors for CA-MRSA.

MRSA Surveillance

The MRSA Research Center Lab collaborates with the University of Chicago Medical Center Clinical Microbiology Lab to obtain all MRSA strains isolated from patients on a daily basis. Upon receipt, the MRSA Research Center Lab subcultures the isolates, stores them in a freezer, and warehouses molecular and clinical information from these isolates in a database. The MRSA Research Center Lab analyzes the clinical and demographic characteristics of patients from whom the isolates were recovered, as well as the isolates' genetic characteristics and antimicrobial resistance profiles.

Spread of Community-Associated MRSA among Household Contacts ("Household Contacts Study")

NIH-funded study to prospectively define colonization and infection rates among household contacts of index patients with CA-MRSA infection and to assess rates of environmental contamination in these households.

Randomized, Double Blind Trial of Clindamycin, Trimethoprim-Sulfamethoxazole, or Placebo for Uncomplicated Skin and Soft Tissue Infections Caused by Community-Associated Methicillin-Resistant Staphylococcus aureus ("Treatment Study")

NIAID-funded study to determine the optimal management of uncomplicated skin and soft tissue infections in the setting of epidemic CA-MRSA in both children and adults in areas where CA-MRSA is prevalent.

More more information on this clinical trial visit:
http://clinicaltrials.gov/ct2/show/NCT00730028?term=07+0051&rank=1

Epidemic CA-MRSA: Human Genomics

National Human Genome Research Institute-funded study coordinated with the Treatment Study whose aim is to identify human genetic markers predisposing to S. aureus infection.

MRSA Colonization and Control in the Dallas County Jail ("Jail Study")

CDC-funded study to determine: 1) the frequency of environmental contamination in the Dallas County Jail; 2) which objects are most commonly contaminated and which MRSA strains are on them; 3) the number of detainees at the Jail who carry MRSA in their noses or on their skin and how many become infected or colonized with MRSA; 4) the specific strains of MRSA that come from the nose and skin in detainees with and without skin infections; and 5) the efficacy of bathing with chlorhexidine wipes in decreasing the prevalence of MRSA colonization and transmission.

Role of Signal Transduction in Resistance to Cell-Wall Antimicrobials in MRSA

Research seeking to gain better insight into antibiotic resistance mechanisms in MRSA strains and to find new therapeutic strategies to combat MRSA infection.

Molecular Pathophysiology of MRSA Infection

Why are we experiencing a MRSA epidemic in the United States? This study aims to investigate the appearance and dominance of the so-called USA300 MRSA clone. The investigation combines cloning of candidate virulence genes and assessing their in vitro expression as well as their virulence in several models of human CA-MRSA disease.

Randomized, Investigator-Blinded, Comparative Study of Daptomycin vs. Standard of Care in the Treatment of Complicated Skin Infections in Pediatric Patients

Cubist Pharmaceuticals-funded multi-center study to look at the safety, efficacy, and pharmacokinetics (distribution, breakdown, and removal) of daptomycin in patients aged 7 to 17 years who have complicated skin or skin structure infections that are caused by a specific group of bacteria (called Gram-positive bacteria).  This research is being done because while the Food and Drug Administration (FDA) has approved daptomycin for use in the United States to treat skin infections caused by these types of bacteria in adults, daptomycin is not approved by the FDA to treat children.

More more information on this clinical trial visit:
http://clinicaltrials.gov/ct2/results?term=DAP+PEDS+07+03

Systems for Studying the Mobility of the SCCmec Element in MRSA

This is an NIAID-funded collaboration between the Drs. Daum/Boyle-Vavra and Dr. Rice groups to understand, at a molecular level, the mobility of the SCCmec element. Insertion of this DNA element into host chromosome turns garden-variety S. aureus into MRSA. The initial phase of this project will develop: 1) an in vitro system for studying the relevant SCCmec-encoded DNA recombinases with purified components, and 2) in vivo systems for studying these proteins in S. aureus and E. coli strains. The long-term goals are to understand the mechanism and regulation of these recombinases at the atomic level, leverage this knowledge to understand the horizontal transmission of SCCmec, and devise ways to stop its spread into new strains and/or trigger its excision and loss from the MRSA genome.