Role of new antifungal agents in prophylaxis of mycoses in high risk patients

Abstract

Purpose of review: For pancreas, liver, and hematopoietic stem cell transplant recipients, no antifungal prophylaxis led to a high rate of and high morbidity from fungal infection. With the use of fluconazole as prophylaxis since the early 1990s, there have been shifts in the types of infecting fungal pathogens, documentation of resistance among fungal organisms, and changes in transplant practices. The aim of this article is to review recent clinical trials regarding antifungal chemoprophylaxis among several populations of high risk patients.

Recent findings: Itraconazole, micafungin, and posaconazole have been studied as alternatives to fluconazole prophylaxis. Itraconazole showed no dramatic improvement over fluconazole as prophylaxis during liver and hematopoietic stem cell transplantation, primarily due to gastrointestinal side effects. In addition, detrimental changes to cyclophosphamide metabolism were noted for hematopoietic stem cell transplant recipients. Micafungin was superior to fluconazole during the pre-engraftment period of hematopoietic stem cell transplantation, because it was able to prevent mold infections, required less switches to empirical antifungal therapy, and functioned as well as fluconazole in preventing yeast infections. Posaconazole was compared to fluconazole during a 16-week prophylaxis period during graft-versus-host disease, but results of this study are still forthcoming. Aerosolized amphotericin products appear to be safe for lung transplant recipients.

Summary: Fluconazole remains the standard agent for prophylaxis against invasive fungal infections for pancreas, liver, and hematopoietic stem cell transplant recipients. Micafungin is superior to fluconazole with minimal toxicity for use in the pre-engraftment period of hematopoietic stem cell transplantation. The optimal agent for prophylaxis later following transplant, if mold coverage is desired during prolonged immunosuppression, has not been determined.