Dr Perfect is Professor of Medicine and Associate Professor of Microbiology at Duke University Medical Center, and has been on the Duke University faculty since 1982. He is director of the Duke University Mycology Research Unit, which is committed to the study of fungal diseases at the basic and clinical science level, and is a member of the National Institute of Allergy and Infectious Diseases Mycoses Study Group. Dr Perfect has made outstanding contributions to the understanding of fungal pathogens and pathogenesis, in particular with regard to his pioneering studies on the pathogenic basidiomycete Cryptococcus neoformans as a model fungal pathogen. He was an investigator and author of the clinical study comparing caspofungin vs amphotericin B for the treatment of invasive candidiasis, which can be found on page S22 of this issue.|
The Advanced Studies in Medicine (ASiM) Clinical Editor interviewed Dr Perfect about the implications of the clinical study as they relate to the current available armamentarium against invasive candidiasis.
AsiM: What are the implications of the caspofungin study for choice of initial therapy for proven invasive candidiasis?
Dr Perfect: The study shows that caspofungin is not inferior to amphotericin B in the treatment of invasive candidiasis. In all respects, caspofungin performed as well as amphotericin but was less toxic. Other groups, such as the US Food and Drug Administration (FDA) and the pharmaceutical sponsor, will need to evaluate this study to determine if caspofungin should be indicated for initial therapy of invasive candidiasis.
AsiM: Caspofungin appears to have become an additional first-line choice for therapy, along with fluconazole and amphotericin B. How should one choose among them?
Dr Perfect: Caspofungin has not yet received FDA approval for management of invasive candidiasis, and it was not compared with fluconazole. Therefore, it is premature for me to recommend it as a first-line choice. However, I believe this study has displayed very encouraging results for caspofungin with its breadth of anti-Candida activity as well as its safety profile.
AsiM: What are the limitations of caspofungin?
Dr Perfect: Caspofungin appears to have few limitations in the treatment of candidiasis. One limitation is that the drug has only an intravenous formulation, but the design of the present study shows that many patients can be converted to oral fluconazole to finish a 2-week course after first receiving intravenous caspofungin. Although not examined in this study, a second limitation may be its ability to treat Candida urinary tract infections. It is not certain that this will be a problem, but the pharmacokinetics are not encouraging.
AsiM: What are the side effects of caspofungin?
Dr Perfect: In this study, there were few side effects directly attributable to caspofungin and, except for some early concern about interaction with cyclosporine, there has yet to be any specific toxicity noted with this drug.
AsiM: Are there any particular contraindications to the use of caspofungin?
Dr Perfect: Caspofungin is indicated for use in refractory aspergillosis and esophageal candidiasis. Its use in invasive candidiasis should be evaluated in the context of clinical studies and the patient’s clinical condition. It remains unclear whether there is a clinical benefit of caspofungin in combination with other antifungal agents–this will require further study.
AsiM: How is caspofungin dosed, and under what circumstances should the dose be adjusted?
Dr Perfect: Presently, caspofungin is dosed with an initial load of 70 mg, followed by 50 mg daily, which is the dose used in the study. Patients with moderate-to-severe liver disease are suggested to have the dose lowered to 35 mg daily. It will be interesting to see the safety profile of higher doses, which are not yet available. There is always the possibility of developing new dosing regimens.
AsiM: Is antifungal susceptibility testing useful or needed for caspofungin?
Dr Perfect: Presently, caspofungin susceptibility testing has not been predictive of outcome. There is continued work in the field to improve susceptibility testing methods for caspofungin. This is important because we should always have a method to be a ‘watch guard’ for the development of drug resistance.
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|| Clinician Interview
with John R. Perfect, MD
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Volume 3, Number 1A - January 2003
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