Contacts:
University of Nebraska Medical Center: Vicky Cerino, (402) 559-5190, vcerino@unmc.edu
Duke University Medical Center: Lauren Shaftel, (919) 824-1647, shaft001@mc.duke.edu
University of Nebraska Medical Center researchers participated in an international clinical study led by Duke University Medical Center, which demonstrated the effectiveness and safety of a new drug for treating bloodstream and heart infections caused by staphylococcus aureus (S. aureus) bacteria, a major cause of sickness and death worldwide.
The article appears in the Aug. 17 issue of the New England Journal of Medicine.
Based on the study, the Food and Drug Administration already has approved the drug — daptomycin — for treating heart infections like endocarditis, and bacteremia, also known as bloodstream infection or blood poisoning, caused by S. aureus, said Vance Fowler Jr., M.D., Duke University Medical Center associate professor of infectious diseases, who participated in the study.
"This is the first new drug the FDA has approved in two decades for treating these types of potentially life-threatening infections," Dr. Fowler said. "This advance adds a new weapon to our dwindling arsenal of antibiotics against these difficult-to-treat infections."
Mark Rupp, M.D., UNMC professor of infectious diseases, headed the research team at UNMC, and is one of the co-authors of the paper. The research study was funded by Cubist Pharmaceuticals, the maker of daptomycin (Cubicin™).
“This is the first study in several decades that has really looked at the sickest patients, those with bacteremia and endocarditis,” Dr. Rupp said. “One of the most feared complications of a staphylococcal infection is when it gains access to your bloodstream and causes endocarditis, a disease associated with quite significant mortality — 20 to 50 percent,” he said.
Daptomycin was approved by the FDA in 2003 for treating skin infections caused by S. aureus. But until now, Fowler said, no one knew definitively whether the drug would be effective against the more serious bloodstream and heart infections.
S. aureus bacteria are common in the environment. People whose immune systems have been weakened by disease or certain medical treatments, including surgery or receiving intravenous catheters, are at greater risk of infection. For patients in hospitals, S. aureus is a leading cause of bloodstream infection and infection at surgical sites.
S. aureus now causes up to 2 million infections and 90,000 deaths per year worldwide, most of them in health care settings, Fowler said.
Treating S. aureus infections is difficult because many strains have developed resistance to all penicillin-related antibiotics. For these highly resistant strains — called methicillin-resistant S. aureus, or MRSA — the drug vancomycin has been the only consistently reliable treatment alternative. Recently, however, MRSA strains with resistance to vancomycin have appeared.
In the study, the research team tested daptomycin’s ability to combat two specific types of infection caused by S. aureus, including MRSA strains, bacteremia, or bloodstream infection, and infective endocarditis. Endocarditis due to S. aureus is a particularly severe form of the infection. It can involve either the tricuspid, mitral, or aortic valves and often occurs in patients with pre-existing heart disease.
The randomized, controlled trial enrolled 246 patients with bacteremia, with or without endocarditis, from 44 centers in four countries. Patients were randomly assigned to one of two treatment groups. One group received six milligrams of daptomycin per kilogram of body weight, administered intravenously once daily. The other group received standard antibiotic therapy, which consisted of an initial four-day course of the antibiotic gentamicin plus a full course of either an antistaphylococcal penicillin or vancomycin, depending on bacterial susceptibilities.
The researchers evaluated patients during antibiotic treatment until discharge. In addition, because up to 10 percent of S. aureus infections can reoccur after antibiotics are stopped, all patients were evaluated again six weeks after treatment ended.
The results showed daptomycin was as effective as standard therapy, Fowler said. Daptomycin was more successful at eliminating drug-resistant S. aureus, at 44.4 percent success versus 31.8 percent. However, the standard therapy slightly outperformed daptomycin for S. aureus without drug resistance, at 48.6 percent success versus 44.6 percent. Neither of these differences was statistically significant, Fowler said. Both types of treatment took roughly the same amount of time — eight or nine days — to clear an MRSA infection.
“We desperately need alternatives to existing drugs to treat these most resistant organisms and these most severe clinical entities,” Dr. Rupp said. “This study will move that frontier as it shows that we have an effective new drug to treat these organisms.”
He said the study was important for a variety of factors. “First, we studied a unique antibiotic – daptomycin, which is a new class of antibiotics. Unfortunately, there are very few new antibiotic classes in development. Secondly, we helped develop an alternative to treat these resistant organisms. And third, this study has shed new light on staphylococcus.
Other institutions involved in the study included Johns Hopkins University School of Medicine, Cleveland Clinic Foundation, Tufts New England Medical Center, Harbor-University of California Los Angeles Medical Center and institutions in Belgium, France and Germany.
Dr. Rupp said UNMC was one of the lead institutions in designing the study, patient enrollment and dissemination of data.
“UNMC is a leader in research related to staphylococci both at the lab bench and at the patient bedside. We are exploring novel approaches to prevention and treatment of staphylococcal disease and we’re working today, on how we can treat these patients … developing these new tools, these new antibiotics, to treat these most feared infections.”