New Antibiotic may Help Patients for Whom Existing Antibiotics are No Longer Effective

Duke University Medical Center
Tuesday, 19 September 2000

In the continuing race to stay ahead of the ever-changing microbial world, researchers from Duke University Medical Center believe that a new class of antibiotics may prove effective against life-threatening infections that fail to respond to vancomycin, the antibiotic of last resort for an increasing number of bacterial infections.

The researchers are encouraged that the results of a retrospective study of a small number of hospitalized patients with severe antibiotic-resistant bacterial infections are strong enough to support the initiation of a large multi-center prospective trial.

The antibiotic, known as quinupristin/dalfopristin (Q/D), successfully treated infections in more than 75 percent of the 54 patients who were given the drug on a compassionate use basis after all other therapies failed.

"Since the number of infections that are becoming resistant to our best medicines continues to rise, we need new antibiotics to help these patients," said Dr. Vance Fowler, an infectious disease specialist at Duke and lead investigator of the study.

"The results of this study support the hypothesis that this newer class of agents can play an important role in taking care of patients with life-threatening infections," Fowler continued. "We feel that a large, multi-center trial should be conducted to determine how these new agents should be used."

Fowler prepared the results of his study for presentation Sept. 19 at the 40th annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy. Q/D is manufactured by Aventis Pharmaceuticals, Parsippany, N.J., who supported the research.

Most of the patients in the trial had bloodstream infections caused by Methicillin-Resistant Staphylococcus aureus (MRSA), one of the most commonly encountered bacteria in a growing number of hospitals. For these patients, the treatment of choice is the antibiotic vancomycin.

"Vancomycin is a good drug and is still the treatment of choice for MRSA, but we need an alternative when it doesn't work or the patient can't tolerate it," Fowler said.

Currently, there are only two approved new agents - Q/D being one of them - that have shown any effectiveness in treating patients in whom vancomycin therapy has failed. The other agent is Linezolid (Zyvox), a drug produced by Pharmacia and Upjohn.

Fowler emphasizes that while the results of his analysis are promising, there are a number of reasons why a larger study should be conducted before he would recommend widespread use of the drug for this difficult-to-treat patient population. He cited the small number of patients, the retrospective nature of his analysis and the fact it was not possible to follow the patients over time to see if their infections returned at a later date.

"While the number of patients was small, this study still represents the largest group of patients to date who failed vancomycin therapy and were treated with Q/D," Fowler said. "The results offer a reasonable first step in the design of the definitive trial."

To test Q/D's effectiveness, the researchers went to an international database of more than 6,000 patients who had been treated with Q/D. They then searched for those treated in the United States, whose medical records were available and who failed vancomycin therapy, and ended up with 54 patients. To be eligible for review, the patients had to be hospitalized for at least one of the four most difficult-to-treat sources of infection: bone and joint infections, catheter-related infections, infective endocarditis and skin infections.

About 30 percent of the patients with endocarditis showed improvement; in the other three groups, greater than 80 percent of patients improved after being treated with Q/D.

Fowler said it is ironic that the greatest source of these infections is the hospital setting.

"These bugs are a product of our medical successes," Fowler said. "The tools that we use to treat people and save lives - like invasive procedures, intravenous lines and intubations - are the things that put people at the greatest risk for these infections."

The Centers for Disease Control and Prevention estimates that more than 2 million Americans each year acquire these in-hospital infections, and between 60,000 and 80,000 die. The culprit in the majority of the cases is S. aureus, which typically enters patients through surgical wounds and intravenous line sites, and can be passed very easily from person to person.

Researchers warn that when antibiotics are used indiscriminately, bacteria with mild resistance can develop and pass this resistance to other bacteria, creating newer strains that become increasingly resistant to the antibiotic.

An example of how much bacteria can change in response to medicine is provided by penicillin, the first effective antibiotic. When it was first introduced in the 1940s, it was effective against almost all S. aureus strains; today, about 99 percent of S. aureus is resistant to penicillin.

Joining Fowler in the study were, from Duke, Richard Drew, Dr. John Perfect and Dr. Scott Palmer; and from Aventis Pharmaceuticals, Dr. Bruce Lavin.

For more information, or to contact Duke University Medical Center, see their website at: www.mc.duke.edu