Antibiotic study shows promise in treating infections

by Vicky Cerino, UNMC public affairs | August 17, 2006

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Mark Rupp, M.D.
UNMC researchers are part of an international team whose study results offer the medical world another drug - daptomycin -- to treat the growing threat of methicillin-resistant staphylococcus aureus (MRSA).

The article appears in the Aug. 17 issue of the New England Journal of Medicine. Mark Rupp, M.D., professor of infectious diseases headed the research team at UNMC, and is one of the co-authors of the paper. The research study, led by Duke University, was funded by the maker of daptomycin (Cubicin), Cubist Pharmaceuticals.

"This is the first study in several decades that has really looked at the sickest patients - those with bacteremia (bacteria in the bloodstream) and endocarditis (an infection of the heart valves)," Dr. Rupp said. "It's the first antibiotic to come along to really test itself where we need new antibiotics the most, which is in our sickest patients with the most resistant pathogens."

He said one of the most feared complications of a staphylococcal infection is when it gains access to the bloodstream (bacteremia) and causes an infection involving the heart valves (endocarditis). Endocarditis is associated with a 20 percent to 50 percent mortality rate.

Daptomycin, approved by the U.S. Food and Drug Administration (FDA) for treatment of skin and soft tissue infections, was approved for treatment of bacteriemia and endocarditis on the strength of the research team's data. "This will be the first time we've published the data in a format such that practitioners can examine it and decide for themselves what it means in their practice," Dr. Rupp said.

UNMC collaborated with institutions including Duke University Medical Center, 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.

The 44-center study involved 246 patients in four countries with Staphylococcus aureus (S. aureus) bacteremia and endocarditis and found that daptomycin, a relatively new class of antibiotic, is safe and as effective as the best standard therapy.

Vancomycin currently is the most common drug used to treat S. aureus infections, particularly those strains of staphylococci known as methicillin-resistant S. aureus (MRSA) that are resistant to multiple standard antibiotics.

"The problem is that vancomycin, although broadly covering nearly all staphylococci, is not as potent as the penicillins. Unfortunately, the penicillins don't cover the resistant staphylococci. Therefore, the medical community has been very interested in finding alternative antistaphylococcal antibiotics that offers both broad coverage and potent activity. Daptomycin appears to offer that combination of traits," Dr. Rupp said.

In addition, he said there's a lot of concern about MRSA, which used to be confined to persons in close contact with the health care system - hospitalized persons, dialysis patients and nursing home residents. More recently, MRSA is infecting individuals in the community.

"There are numerous descriptions of outbreaks on sports teams, in jail inmates, in various populations - including normal healthy folks without risk factors for infection," he said.

Unfortunately, many of the common antibiotics used to treat staphylococcal infections are not active against MRSA, he said. Doctors are having to change the way they think and the way they treat patients with these types of infections.

S. aureus usually gains access to the bloodstream through the skin. S. aureus is a very well-armed pathogen, and once in the bloodstream, has the ability to adhere to various human tissues and membranes and cause infections of the heart valves, bones, joints and abscesses in just about any organ. Tens of thousands of people are hospitalized each year due to staphylococcal infections and they are responsible for thousands of deaths.

Dr. Rupp 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 that are in the development pipeline. Secondly, we helped develop an alternative to treat these resistant organisms causing these severe infections. And third, this study shed some new light on an old pathogen - the staphylococcus.

"This is a study that has helped to move the frontier of our knowledge base," Dr. Rupp said. "We should all express our gratitude to the patients who volunteered for this study. This is how medical science advances. Without these clinical studies there would not be any new developments."

Antibiotic resistance is considered to be an urgent priority in public health. Infectious disease specialists and researchers say antibiotic resistance is responsible for increasing death rates, health care costs and the severity of disease. Many infectious disease experts believe the spread of staphylococcus is a public health crisis and new solutions must soon be found.

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," he said. "We are exploring novel approaches to prevention and treatment of staphylococcal disease as well as investigating the basic biology of the staphylococcus. We're working today on how to develop these new tools and antibiotics to treat the most feared infections."