Invasive mycoses in organ transplant recipients: controversies in prophylaxis and management.

Organ transplant recipients are a growing and increasingly important group of immunocompromised hosts in whom invasive mycoses remain one of the most significant infectious complications. 1–3 Although candida infections occur more frequently, the highest mortality rate associated with fungal infections in transplant recipients is for Aspergillus spp. infections. 4 The last decade has witnessed the emergence of diverse mycelial fungi, including dematiaceous moulds, as significant pathogens in transplant patients. 5 Trends in invasive fungal infections in the post-transplant setting have also been notable for a rise in non-albicans Candida spp. 6 Given the high mortality associated with invasive mycoses in transplant recipients, effective prophylaxis for such infections is a worthy goal: an optimal approach has not, however, been devised. Uncertainty and controversy abound regarding the choice of antifungal agent, mode of drug delivery and types of patients who should receive anti-fungal prophylaxis. The lipid formulations of amphotericin B represent a significant advance in drug delivery of ampho-tericin B. 7 Although the potential for reduced nephro-toxicity with lipid preparations of amphotericin B has been amply demonstrated, a frequent dilemma pertaining to the use of such agents is whether their high acquisition cost is justifiable in the transplant setting and whether there are data supportive of their superior efficacy as compared with amphotericin B deoxycholate. Finally, a growing body of evidence suggests a potential role for immunomodulatory agents in the treatment of invasive fungal infections. 2,8–10 This review focuses on: (i) optimizing the approach to antifungal prophylaxis in organ transplant recipients; (ii) treatment of invasive mycoses; (iii) the role of adjunctive therapies, e.g. immunomodulation; and (iv) surgery in the management of invasive mycoses in organ transplant recipients. Antifungal prophylaxis Itraconazole, being orally administered and highly active in vitro against Aspergillus and Candida spp., would appear to be an attractive prophylactic agent in transplant recipients. However, the erratic absorption and poor bioavail-ability of itraconazole capsules make it difficult to achieve adequate serum concentrations. Studies documenting the efficacy of itraconazole capsules as prophylaxis in transplant recipients have been largely uncontrolled, with the incidence of invasive aspergillosis in historical controls being far higher than would now be expected for the type of transplant. Itraconazole cyclodextrin preparation in oral solution has significantly improved bioavailability. 13 To date, however , no randomized, controlled trials have demonstrated the efficacy of itraconazole cyclodextrin as prophylaxis against invasive aspergillosis in solid organ transplant recipients. In liver transplant recipients given an …