New Antibiotic may Help Patients for Whom Existing Antibiotics are No Longer Effective
September 19, 2000
TORONTO - 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
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 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
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
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
"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
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
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.