January 3, 2003
DURHAM, NC -- In the first large-scale trial of its kind, researchers have shown caspofungin, a new type of antifungal drug, to be as effective and less toxic than amphotericin B, the current standard treatment for candidiasis.
Candidiasis is the fourth most common bloodstream infection detected in hospitalized patients, and causes death in 30 to 40 percent of cases.
“Echinocandins,” including caspofungin, are a new class of medication that will treat fungal infections by directly targeting the structure of the fungal cell wall. On the other hand, amphotericin B is a member of the “polyene” class of treatments, which function by binding to the chemical ergosterol on fungal cell membranes, ultimately causing the fungal cells to die, but potentially damaging human cells as well.
“This study represents the first comprehensive trial comparing echinocandin and polyene treatments for invasive fungal infections,” said John Perfect, M.D., professor of medicine at Duke University Medical Center and senior author of the study published in today’s (December 19, 2002) New England Journal of Medicine. “I consider the results of this trial to be an advance that may help change the way physicians approach the treatment of candidiasis. Caspofungin is a safe and effective treatment for a variety of candida species which frequently infect hospitalized patients.”
Candidiasis is a bloodstream and tissue infection caused by an overabundance of candida, a fungus that occurs naturally in the human body. In most people, candida is suppressed by naturally occurring bacteria and other processes. However, many patients with serious medical conditions require treatment with broad-spectrum antibacterial medications that reduce bacterial levels in the body, allowing candida to flourish and leaving the patients at risk for developing candidiasis.
“Infections like candidiasis are often the price we pay for medical progress,” said Perfect. “Medical professionals today are able to treat a wide range of conditions that historically would have proven fatal; the down side of this progress is that patients with existing diseases who are taking powerful medications, or whose treatments require insertion of tubes and other foreign objects into their bodies, become at risk for these opportunistic infections such as candidiasis. The ability to have a safer, effective treatment to control this infection will be an advance in medical management.”
The study was funded by Merck & Co., Inc., the manufacturer of caspofungin, and conducted at 56 institutions in 20 countries between November 1997 and June 2001.
Since 1957, amphotericin B has been the “gold standard” treatment for candidiasis. Although the drug is considered the best available treatment for a wide range of invasive candida infections, amphotericin B has proven to have serious side effects including fever, chills, muscle aches, kidney toxicity and interactions with other medications.
The new study compared the efficacy and toxicity of amphotericin B with caspofungin. Because echinocandin treatments (including caspofungin) target the fungal cell wall and therefore do not act against other parts of the human body, they do not cause the range of side effects associated with amphotericin B.
“Although amphotericin B has historically been the most effective treatment for candida infections, its side effects are often so severe that at times we are unable to prescribe the optimal dose for treatment of these infections,” said Perfect.
In the study, hospitalized patients who tested positive for either tissue or bloodstream candida infections were treated intravenously with either caspofungin or amphotericin B.
Candidiasis was successfully treated in 61.7 percent of patients who received amphotericin B, and in 73.4 percent of patients who received caspofungin. The study was designed to ensure even distribution of seriously ill and severely immune compromised patients between the two treatments -- to compare the effectiveness of the drugs in treating a wide range of patients.
Amphotericin B treatment caused moderate or severe infusion-related side effects in 32 percent of patients, while only 0.9 percent of caspofungin-treated patients reported such effects. A significantly greater number of amphotericin B treated-patients developed kidney problems or other severe side effects than did caspofungin-treated patients.
“This study establishes the potential of caspofungin and possibly other echinocandin treatments to become a significant part of the therapeutic armamentarium against serious candida infections,” said Perfect. “We’re hopeful that the results of this study will help physicians make efficient treatment decisions that will have a direct impact on patient health and quality of life. It definitely increases the available therapeutic options, which is good for both patients and their physicians.”
Perfect has served as a paid consultant to and has received speaking honoraria and research grants from Merck & Co., Inc. He holds no financial interests in Merck.
Joining Perfect in reporting this study were Jorge Mora-Duarte, M.D., of Neeman-ICIC and Hospital Mexico, C.C.S.S., San Jose, Costa Rica; Robert Betts, M.D., of the University of Rochester, NY; Coleman Rotstein, M.D., of McMaster University, Hamilton, Canada; Arnaldo Lopes Colombo, M.D., of Escola Paulista de Medicina-UNIFESP, Sao Paulo, Brazil; Luis Thompson-Moya, M.D., of Clinica Santa Maria, Santiago, Chile; Juanita Smietana, Robert Lupinacci, Carole Sable, M.D., and Nicholas Kartsonis, M.D., of Merck Research Labs, West Point, PA.
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