Combination therapy for invasive mycoses: evaluation of past clinical trial designs.
BACKGROUND
Despite the availability of new antifungals, single-agent therapy frequently falls short of high cure rates. Combination therapy offers potentially higher cure rates, especially for resistant organisms. In vitro studies and experimental animal models have provided conflicting data.


METHODS
Retrospective, randomized, controlled clinical studies were reviewed.


RESULTS
Results indicate a clear advantage for polyene and flucytosine combination therapy in cryptococcal meningitis and a possible advantage for combination amphotericin B and fluconazole for candidemia. Unfortunately, the few studies published have been flawed by design problems that have compromised the determination of outcome. Study review allows investigators the opportunity to design future studies to ensure optimal evaluation of efficacy.


CONCLUSIONS
Combination antifungal therapy is advantageous in cryptococcal diseases and may have a role in the treatment of invasive candidiasis. The greatest potential exists for combination therapy against aspergillosis and resistant fungi in patients with refractory mycotic disease who experience failure of monotherapy.
Sobel
Jack D
JD
Department of Internal Medicine, Division of Infectious Diseases, Wayne State University School of Medicine, Detroit, Michigan, USA. jsobel@intmed.wayne.edu
D000935:Antifungal Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000379:methods*; D004359:Drug Therapy, Combination; D006801:Humans; D015201:Meta-Analysis as Topic; D009181:Mycoses / Q000188:drug therapy; D012107:Research Design
D000935:Antifungal Agents