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.

CONCLUSION

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.