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Back To Vidyya Therapeutic Alternative To Vancomycin For Staphylococcal Infections Needed

Study Examines Drug That Shows Activity Against Staphylococcal Infections In Cases of Vancomycin Failure and Intolerance

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.

About S.A.V.S.

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 endocarditis.

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 patients).

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).

About Synercid

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 Streptococcus pyogenes.

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 benefit.

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 or die.

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.


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Editor: Susan K. Boyer, RN
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