Prophylaxis against Aspergillus is not perfect: problems and perils in stem cell transplantation

Availability of newer, well tolerated anti-Aspergillus drugs at a time of rising prevalence of invasive aspergillosis has sparked enthusiasm for chemoprophylaxis against Aspergillus in allogeneic stem cell recipients. Such a drug-oriented approach however is associated with problems. In the azole class, itraconazole has been shown to be effective, but hepatotoxicity and gastrointestinal intolerability have made the drug less attractive. Posaconazole, approved for prophylaxis in allogeneic stem cell recipients with graft versus host disease and in those with acute leukemia, is of promise but has a limitation relating to its oral bioavailability. Preliminary data do not show any survival advantage with voriconazole over fluconazole; also, emergence of resistant organisms, high frequency of drug interactions and liver function abnormalities with voriconazole are drawbacks. Whether serum levels of azoles need to be monitored for optimal outcome remain controversial. Reports of emergence of azole-resistant Aspergillus (e.g., A. ustus, A. nidulans, A. fumigatus) in azole-exposed and unexposed patients, though rare, raise concern. Echinocandins have static activity against Aspergillus, not orally administrable and have been associated with breakthrough aspergillosis. Polyenes (amphotericin B and its lipid forms) are shunned in view of their nephrotoxicity; inhalational (aerosol) form may be of promise, more data are needed. As our screening tests to detect early presence of aspergillosis prove more reliable and user-friendly, the need for universal chemoprophylaxis may diminish and a preemptive strategy may evolve to become the preferred approach.