Atlanta Universities Support MRSA Studies at Children's and Grady

Participant in the MRSA Treatment Study on a follow-up visit at Hughes Spalding with (back row) Kevin Thornton, Research Assistant, (front row LtoR) Lilly Immergluck, MD, T'khia Rivers (9 years old), Study Participant, and Shelley Mays, Research Assistant

In MRSA (methicillin resistant Staphylococcus aureus) research one critical question remains – determining what is the best evidence-based treatment for patients (especially children). An Atlanta Clinical & Translational Science Institute-supported researcher is attempting to answer this question through three clinical trials taking place at Children’s Healthcare of Atlanta and Grady Memorial Hospital. These studies are also raising awareness of how to prevent the spread of antibiotic resistance in the Atlanta medical community.

The Atlanta Clinical & Translational Science Institute (ACTSI) is an inter-institutional magnet that concentrates basic, translational, and clinical researchers, community clinicians, professional societies, and industry collaborators in dynamic clinical and translational research projects throughout Atlanta. Emory engaged two of its close academic partners in metropolitan Atlanta – Morehouse School of Medicine (MSM) and Georgia Institute of Technology (Georgia Tech) – to form the ACTSI in 2007. An important initiative of the ACTSI is to enhance efficiency, breakdown administrative barriers, and accelerate the pace of quality science, and collaboration among ACTSI institutions and Atlanta partners.

ACTSI-supported research investigator Lilly Immergluck, MD, FAAP, Associate Professor of Pediatrics and Assistant Professor of Microbiology/Biochemistry/Immunology at MSM, Adjunct Assistant Professor of Clinical Pediatrics, Department of Pediatrics, Division of Infectious Diseases, Emory, and Pediatric Infectious Disease Specialist at Children's Healthcare of Atlanta, is conducting three clinical trials to better understand the antibiotic resistant bacterium, community-associated methicillin resistantStaphylococcus aureus (also known as CA-MRSA) using multiple ACTSI Clinical Research Sites, ACTSI funding, ACTSI collaborative investigators, ACTSI-secured partner reciprocity, and ACTSI collaborative services.

“As a general pediatrician and pediatric infectious disease specialist, I’ve seen so many children and families impacted by this pathogen over the past 15 years. MRSA originated from the community and not from the hospital. However, its presence has become so prevalent; it is now also a hospital-acquired source of infection,” said Immergluck. “I see families in despair whose child is critically ill from severe infections and also those who struggle with recurrent MRSA infections. It is their stories which continue to fuel my passion to make some impact on decreasing the circulation of this antibiotic resistant staph.”

The Role of the ACTSI

Over the last six years, the ACTSI achieved expanded institutional review board (IRB) reciprocity across all ACTSI partner institutions and worked to ensure Material Transfer Agreements, Intellectual Property agreements, and other cooperative agreements among Emory, MSM, Georgia Tech, the U.S. Department of Veterans Affairs, and Children’s Healthcare of Atlanta (Children’s). IRB reciprocity makes work like Immergluck’s multi-centered trials possible. An institutional review board is an ethical review board that approves, monitors, and reviews biomedical and behavioral research involving humans. When a reciprocity agreement is reached between research partners, investigators have fewer steps to complete when partnering with other institutions and more time and resources to focus on finding a cure or new treatment option. “These trials required us to navigate among the various IRB's,” said Immergluck. “Moreover, these studies have required the collaboration of researchers from Emory, MSM, Georgia Tech, and Children’s across different clinical disciplines, the engagement and reciprocity of the various IRBs, and the development of a memorandum of understanding between ACTSI and Hughes Spalding, Inc.”

The multi-site Clinical Research Network (CRN) of the ACTSI includes sites at Emory University Hospital, Emory Midtown, Grady Memorial Hospital, the Ponce Infectious Diseases Clinic, the Hope Clinic, Wesley Woods Health Center, the MSM Clinical Research Center, and Kaiser Permanente of Georgia. An efficient, flexible, and geographically distributed CRN is in place to meet the needs of translational and clinical investigators from Emory, MSM, and Georgia Tech. The sites offer research nursing support and sample processing and storage to complete translational science trials approved by the CRN Scientific Advisory Council at little or no cost to the research team. Immergluck is using multiple CRN Clinical Research Sites for patient enrollment such as, Grady Memorial Hospital and Children's Healthcare of Atlanta at Egleston, Scottish Rite, and Hughes Spalding campuses.

The ACTSI also offers consultative services in biostatistics, research design, biomedical informatics, ethics, and community engagement. Immergluck’s work required assistance from the ACTSI’s Biostatistics, Epidemiology, & Research Design (BERD) program at Emory’s Rollins School of Public Health and MSM’s biostatistics core. This support is also free to Emory, MSM, and Georgia Tech investigators as time and expertise allow. Immergluck also partnered with Georgia Tech researchers to develop novel approaches to better understand social determinants tied with health disparities seen with CA-MRSA infections using electronic health records.

“My ACTSI pilot grant funding allowed me to generate pilot data and findings, which sparked the interest of other research investigators who are in my same field and allowed me the opportunity to collaborate with Emory and Children's investigators interested in this topic. Consequently, it did lead me to these clinical trial opportunities,” said Immergluck.

Finally, Dr. Immergluck is a recipient of funding received as a participant of the ACTSI MSM Master of Science in Clinical Research/CRECD Faculty Scholars Program and received funding through the MSM Research Center in Minority Institutions, part of the NIH, National Institute of Minority Health and Health Disparities. She benefitted from the educational workshops/courses on community-based participatory research (CBPR) presented by the ACTSI’s Community Engagement Research Program (CERP). Her CBPR training led to a successful grant application for the American Academy of Pediatrics' Community Access to Child Health Planning Grant. “Dr. Immergluck's career is characterized by compassion, perseverance, and excellent science. We are fortunate to have her as a member of the ACTSI family,” said Daniel Blumenthal, MD, CERP program director, professor, Department of Community Health and Preventive Medicine and associate dean for community health,
Morehouse School of Medicine.

Three ACTSI Multi-Centered MRSA Trials

Currently, the MRSA guidelines and treatment practice vary depending on physician type – internal medicine, general pediatrician, pediatric or adult infectious disease specialist, family medicine, emergency medicine physicians, etc. "Our findings will define practice and guide all types of physicians as to what is the best way to treat these types of antibiotic resistant infections effectively while minimizing the spread of developing further antibiotic resistance,” explains Immergluck.

The MRSA treatment study titled, The Randomized, Double-Blind Trial of Clindamycin, Trimethorprim-Sulfamethoxazole, or Placebo for Uncomplicated Skin and Soft Tissue Infections Caused by Community-Associated Methicillin-Resistant Staphylococcus aureus, uses multiple collaborations managed through agreements between MSM, Emory, and Children's in order to effectively carry out screening of over 900 patients, and subsequent enrollments and follow-up visits. Follow-up participant visits and specimen testing are carried out through the ACTSI Clinical Research Sites at Egleston, Hughes Spalding, the Grady Clinical Research Site, and the Children’s Clinical Microbiology Laboratory.

This is a multi-center study occurring at six different Clinical and Translational Science Award (CTSA) sites (University of California San Francisco, University of Chicago, University of California Los Angeles, Vanderbilt University, Washington University in St. Louis, and the ACTSI) and is funded by the National Institutes of Health’s National Institute of Allergy and Infectious Diseases. Team science leads to faster, more well-disseminated cures through resource and expertise sharing. The CTSA works to remove or bypass significant bottlenecks that can occur in working with other institutions and promotes team science for the betterment of the country’s health. “Our research team has truly benefited from the ACTSI resources and it is through the CTSA consortium that we have forged much collaboration across institutions and disciplines. We promote the judicious use of antibiotics simply by our presence in the emergency rooms and raising the awareness of CA-MRSA. This NIH study provides close follow-up so we have many opportunities to also educate the patient/participant about MRSA and how to prevent recurrence of infections,” said Immergluck.

For the Asymptomatic Colonization with S. aureus after Therapy with Linezolid or Clindamycin for Acute S. aureus Skin and Skin Structure Infections in Patients with Comorbid Conditions:  A Randomized Trial and Colonization, New Risk Factors, and Genetics of Patients with Skin and Soft Tissue Infections Study screening, enrollment, and follow-up visits are carried out at Grady Emergency Department and ACTSI’s Grady Clinical Research Site. This study is being conducted to determine the prevalence of asymptomatic carriage of S. aureus in patients with acute bacterial skin and soft tissue infections after therapy with linezolid or clindamycin at 40 days after completion of therapy for patients with a co-morbid condition.

For the trial Identification of Immune Markers Associated with CA-MRSA Infections in Adults – Steps towards a vaccine for community acquired-methicillin resistant Staphylococcus aureus (CA-MRSA) screening, enrollment, and follow-up visits are also carried out at Grady Emergency Department and ACTSI’s Grady Clinical Research Site, with cooperation between basic science immunology laboratories between CTSA institutions. This study is being conducted to help understand why some individuals have a minor skin infection with S. aureus and others have a serious infection. Through the three trials, the goal is to develop more effective strategies for prevention and control of staphylococcal disease and identify potential common and cross-reactive bacteria targets for a sub-unit vaccine against S. aureus.

“Dr. Immergluck is the local leader for this important NIH-funded multicenter trial evaluating the appropriate management of CA-MRSA. She was able to unite efforts between Children's, Emory, Grady, and MSM to perform the trials, a feat that fits perfectly with the ACTSI mission and will help set the stage for a number of future inter-institutional clinical trials in adults and children,” said Paul Spearman, MD, chief research officer, Children’s Healthcare of Atlanta, Nahmias-Schinazi Research Professor and vice chair for research, Department of Pediatrics, Emory University.

The ACTSI is a city-wide partnership between Emory University, Morehouse School of Medicine, and Georgia Institute of Technology and is one of a national consortium striving to improve the way biomedical research is conducted across the country. The consortium, funded through the National Center for Advancing Translational Sciences, part of the National Institutes of Health’s CTSA, shares a common vision to translate laboratory discoveries into treatments for patients, engage communities in clinical research efforts, and train the next generation of clinical investigators.