DETROIT— Infections caused by vancomycin-resistant Enterococcus faecium (VREfm) bacteria can often be serious and life threatening. These drug-resistant bacterial pathogens are one of the most problematic in the hospital setting, especially in immune system deficient patients, and constitute an emerging local and global health crisis. The development of new anti-infective drugs has largely diminished in the past decade, complicating treatment options for these infections and creating a critical need to maximize the effectiveness of currently available drug treatments.

Michael Rybak, Pharm. D., M.P.H., professor of pharmacy practice in Wayne State University’s Eugene Applebaum College of Pharmacy and Health Sciences and adjunct professor of medicine in WSU’s School of Medicine, recently received a five-year, $1.9 million grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. His research project aims to further explore treatment of these problematic bacteria in the hospital setting. This project, “A Pharmacologic Approach to Prevent Daptomycin Resistance in VRE,” will explore various dosing regimens of daptomycin (DAP), a lipopeptide antibiotic, for VREfm.

According to Rybak, enterococcal organisms such as Enterococcus faecium (Efm) are highly problematic pathogens in the hospital setting and are responsible for life-threatening infections, including intra-abdominal infections, urinary tract infections, endocarditis, bloodstream infections, and infections transmitted by medical devices.  Vancomycin is a powerful antibiotic that treats enterococcal infections, but many Efm infections are now resistant even to vancomycin, leaving few options that will treat this illness and save the lives of many of these patients.

“Daptomycin (DAP) has demonstrated bactericidal activity against VREfm in vitro, but the development of resistance during therapy has threatened its viability for future use,” said Rybak. “Our research will evaluate several dosing regimens of DAP against VREfm strains in the DAP ‘susceptible’ minimum inhibitory concentration range with genetically proven proclivity for DAP resistance development. We will also evaluate several beta-lactam antibiotics in combination with DAP at optimized dosing regimens to determine the optimal beta-lactam antibiotic to use with DAP against VREfm, lowering the necessary dose exposures of DAP for clinical success, and successfully prevent the emergence of DAP resistance.”

Rybak and his research team hope that the knowledge gained from this research will help preserve DAP for future use and ultimately improve patient outcomes in VREfm infections.

“Dr. Rybak is superbly qualified and well-positioned to conduct this important work,” said Brian Crabtree, Pharm.D., BCPP, chair of the Department of Pharmacy Practice at Wayne State.  “Dr. Rybak’s work – along with his many current and previous research fellows and that of other faculty who are deeply involved in infectious diseases research, teaching, and service in our department and beyond – makes us world-class in the area of infectious diseases antibiotic therapy.  I am gratified at how extraordinary individual talent and the synergy of teamwork advance our strategic goals and our mission and vision to improve health.”

Co-investigators that will be collaborating with Rybak are Drs. Cesar Arias and Barbara Murray, international experts in this area from the University of Texas Health Science Center of Houston.

The project number for this NIH-funded award is R01AI121400-01.


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