For three decades, vancomycin
has been the powerhouse therapy for certain life-threatening bacteria.
Research now shows that with the widespread use of vancomycin,
vancomycin-resistant organisms have emerged. Data from the Synercid as an
Alternative to Vancomycin in Staph (S.A.V.S.) study presented today at the
40th annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Toronto shows that Synercid®
(quinupristin/dalfopristin) I.V., the world's only injectable streptogramin,
is a potential alternative in cases where patients with a staphylococcal
infection were unable to tolerate vancomycin's side effects, and where
vancomycin did not eradicate the bacteria.
"Quinupristin/dalfopristin offers a potential therapeutic alternative for
patients with staphylococcal infections failing or intolerant of vancomycin
therapy," said Vance Fowler, M.D., of Duke University Medical Center and a
lead investigator of the study. "Prospective trials are needed to further
define the role of quinupristin/dalfopristin in the management of patients
with these difficult to treat infections."
Nearly two million Americans contract serious hospital-acquired infections
each year, resulting in approximately 90,000 deaths. Staphylococci commonly
cause hospital-acquired infections such as pneumonia, skin and skin structure
infections and bloodstream infections. For years, vancomycin had been the
only effective antibiotic in controlling these bacteria. Recently, S. aureus
strains with reduced susceptibility to vancomycin have emerged in Japan,
Europe, and the United States.
S.A.V.S. examined Synercid activity in a retrospective analysis, funded by
Aventis Pharmaceuticals, of patients receiving Synercid through an emergency-
use program in the U.S. The study included 54 clinically and/or
microbiologically evaluable patients who failed vancomycin therapy - defined
as suspected or confirmed treatment failure with clinically appropriate
antibiotics, including vancomycin -- and 113 clinically and/or
microbiologically evaluable patients who were intolerant to vancomycin
-- defined as adverse events and toxicities judged by the investigator to be
related to vancomycin and requiring discontinuation of treatment. The
inclusion criteria of the study required that each participant have a
confirmed staphylococcal infection, including methicillin-susceptible
Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, or
coagulase-negative staphylococci. Each patient was required to have one of
the following: complicated skin and skin structure infections,
catheter-related bacteremia, bone and joint infections or infective
S.A.V.S. Study Results
In cases of patients failing vancomycin therapy, patients responded to
Synercid in 74 percent of all cases evaluated (37 of 50 clinically evaluable
patients). This number included 70 percent of methicillin-resistant
Staphylococcus aureus cases evaluated (26 of 37 patients), 100 percent of
methicillin-susceptible Staphylococcus aureus cases (3 of 3 patients), and 80
percent of coagulase-negative staphylococci cases (8 of 10 patients).
Synercid's activity against infections caused by staphylococci was 78
percent for complicated skin and skin structure infections (7 of 9 patients),
75 percent for catheter-related bacteremia (6 of 8 patients), 75 percent for
bone and joint infections (18 of 24 patients) and 67 percent for infective
endocarditis (6 of 9 patients).
Among patients who were intolerant to vancomycin, patients responded to
Synercid in 89 percent of the cases evaluated (93 of 105 clinically evaluable
patients). Symptoms of vancomycin intolerance in study participants included
systemic hypersensitivity reaction, severe rash, hematologic (related to blood
and blood forming tissues) abnormalities, hearing impairment, renal toxicity
and fever. Patients responded favorably to Synercid in 88 percent of
methicillin-resistant Staphylococcus aureus cases treated (67 of 76 patients),
100 percent of methicillin-susceptible Staphylococcus aureus cases (3 of 3
patients), and 88 percent of coagulase-negative staphylococci cases (23 of 26
Synercid's activity against staphylococci related infections measured in
the evaluation included 97 percent among complicated skin and skin structure
infections (30 of 31 patients), 91 percent for catheter-related bacteremia (20
of 22 patients), 88 for bone and joint infections (37 of 42 patients) and 60
percent for infective endocarditis (6 of 10 patients).
Adverse events, possibly or probably related to Synercid, were reported in
6 percent of patients failing vancomycin therapy (arthralgia, anemia, and
hematoma) and in 2 percent of patients intolerant to vancomycin (weakness and
arthralgia, wound dehiscence, and burning at infusion site).
Synercid® (quinupristin/dalfopristin) I.V., the world's first injectable
antibiotic in a distinct class of antibacterials known as streptogramins, was
approved by the U.S. Food and Drug Administration (FDA) to treat bloodstream
infections due to vancomycin-resistant Enterococcus faecium (VREF) and skin
and skin structure infections (SSTI) caused by methicillin-susceptible
Staphylococcus aureus or Streptococcus pyogenes.
Synercid also is approved in the European Union (Austria, Belgium,
Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg,
Netherlands, Portugal, Spain and Sweden), Canada and Australia.
Synercid is the first antibiotic to be indicated for the treatment of
patients with serious or life-threatening infections associated with
vancomycin-resistant Enterococcus faecium bacteremia. Certain strains of
Enterococcus faecium have proven to be resistant to virtually all available
antibiotics -- until now. Synercid is active against these strains, although
several cases of emerging resistance occurred in VREF trials. The FDA also
approved Synercid to treat patients with complicated skin and skin structure
infections caused by methicillin-susceptible Staphylococcus aureus or
One of Synercid's approved indications is for the treatment of patients
with serious or life-threatening infections associated with
vancomycin-resistant Enterococcus faecium (VREF) bacteremia. Synercid has
been approved for marketing in the United States for this indication under
FDA's accelerated approval regulations that allow marketing of products for
use in life-threatening conditions when other therapies are not available.
Approval of drugs for marketing under these regulations is based upon a
demonstrated effect on a surrogate endpoint that is likely to predict clinical
The two distinct antibiotic agents that form Synercid, quinupristin and
dalfopristin, work synergistically to inhibit or destroy susceptible bacteria
through a two-pronged attack on protein synthesis in bacterial cells. Without
the ability to manufacture new proteins, the bacterial cells are inactivated
The most common adverse drug reactions in comparative trials were
inflammation at the infusion site (42.0%) and pain at the infusion site
(40.0%). In three non-comparative trials, the most common adverse drug
reactions were arthralgia (7.8%, 5.2%, and 4.3%), myalgia (5.1%, 0.95%, and
3.1%), both arthralgia and myalgia (7.4%, 3.3%, and 6.8%) and nausea (3.8%,
2.8%, and 4.9%).
P450 3A4 substrates (e.g., cyclosporine A, midazolam, nifedipine, and
terfenadine) should be used with caution and monitored when co-administered
with Synercid. Those drugs used concomitantly that may prolong the QTc
interval should be avoided.