URMC Leads International Consortium to Fight Deadly Bone Infections

Apr. 16, 2012
Stephen L. Kates, M.D.

Serious, drug-resistant staph infections are a growing problem in health care in the United States and across the globe. In a coordinated effort to stop these superbugs, investigators from the University of Rochester Medical Center have been selected to lead an ambitious, five-year project, with an emphasis on infections from complex orthopedic surgeries such as joint replacement, fracture repair, or trauma.

AOTrauma, part of the Switzerland-based AO Foundation, awarded $3 million to a team led by Stephen L. Kates, M.D., professor of Orthopaedics at URMC. Kates will oversee eight research projects involving 21 medical centers. In summary they plan to:

1)       identify the best ways to prevent infection and create an education template for medical providers everywhere;

2)      develop a diagnostic test to demonstrate a patient’s immunity to Staphylococcus infections;

3)      develop a novel, MRSA passive immunization (vaccine) to prevent MRSA infections during total joint replacement;

4)      use animal models to study the best ways to deliver antibiotics to deep wounds and to study a possible vaccine against staph;

5)      analyze all current treatment protocols for patients suffering from severe bone and joint infections;

6)      create an international infection registry to help with the study and treatment of infections in a standardized manner;

7)      Disseminate study results and discoveries about best clinical practices in a six-part educational series to be available through the AO Trauma Foundation.

“Only with such a comprehensive approach and many talented people working together, can we get at the root of this problem and solve it,” Kates said. “I am grateful that AO Trauma chose to make this the new Clinical Priority Program and we are highly motivated to find ways to make game-changing improvements in the prevention, diagnosis and treatment of orthopaedic infections.” 

Methicillin–Resistant Staphylococcus Aureus (MRSA) is so pervasive that in 2008 it surpassed HIV as the leading cause of infectious death in the U.S. MRSA is rampant in most communities – it is common in sports settings and can be passed from household pets to humans, for example – and also can be acquired in health care settings. Many people carry staph without ever experiencing symptoms, and others become symptomatic when their immune system is weakened. Obesity and diabetes also increase the likelihood of a person developing an infection.

In the context of orthopaedic surgery, staph infections are rare, occurring in only 1 percent to 5 percent of cases. (In trauma cases, however, the infection rate can be as high as 40 percent.) When infections do occur they are serious, costly, and often result in lifelong or life-threatening health issues for the patient. Failure rates to repair surgery-related bacterial infections approach 50 percent.

The URMC has been studying ways to combat MRSA for several years. Edward M. Schwarz, Ph.D., a co-investigator on the AOTrauma project, the Burton Professor of Orthopaedics, and director of the URMC Center for Musculoskeletal Research, is leading the development of a vaccine to prevent MRSA infections following bone and joint surgery.

One key component of the AOTrauma project is the use of existing resources and data from Schwarz’s ongoing research, at the Center for Musculoskeletal Research, to continue testing the vaccine approach in various models that reflect the clinical situation. The vaccine targets an enzyme that functions as a zipper during staph cell division, and thus breaks through the bacteria’s unique armor. By disrupting the bacteria’s growth, the vaccine approach is different than antibiotic treatments, many of which are no longer effective against resistant staph.

The consortium includes trauma surgeons, infectious disease specialists, and translational scientists. Each research or clinical project was designed to use existing resources at the URMC, the University of Giessen’s laboratories and clinics in Germany, and the AO Clinical Investigation and Documentation facilities for data management in Zurich, Switzerland. Other institutions involved are: Yale University, Johns Hopkins University, Harvard University, New Jersey Medical School, Geisinger Medical Center, University of Colorado, Innsbruck University Hospital, Basel University Hospital, University of Calgary, University of Missouri, Aarhus University, Hong Kong University, Chinese University of Hong Kong, Kyoto University, University of Sao Paolo, Cairo University, Hokkaido University Hospital, and University of Tokushima.

Kates is the principal investigator and Schwarz is a co-investigator along with Volker Alt., M.D., Ph.D., of the University of Giessen. Philipp Buescher, at AOTrauma, is serving as program manager.

AO (Arbeitsgemeinschaft für Osteosynthesefragen), was founded in 1958 as a non-profit by five visionary Swiss surgeons who invented the first modern implants used in fracture-repair surgery. Their mission was to study, practice and teach advancements in the field of fracture care, which today involves a network of more than 10,000 specialists. The AO Foundation was formed in the 1980s to take responsibility for research and development, education, and international affairs.

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