Variables influencing the risk of dissemination and outcome of Cryptococcus neoformans infection were assessed in 111 organ transplant recipients with cryptococcosis in a prospective, multicenter, international study. Sixty-one percent (68/111) of the patients had disseminated infection. The risk of disseminated cryptococcosis was significantly higher for liver transplant recipients (adjusted hazard ratio [HR], 6.65; P=.048). The overall mortality rate at 90 days was 14% (16/111). The mortality rate was higher in patients with abnormal mental status (P=.023), renal failure at baseline (P=.028), fungemia (P=.006), and disseminated infection (P=.035) and was lower in those receiving a calcineurin-inhibitor agent (P=.003). In a multivariable analysis, the receipt of a calcineurin-inhibitor agent was independently associated with a lower mortality (adjusted HR, 0.21; P=.008), and renal failure at baseline with a higher mortality rate (adjusted HR, 3.14; P=.037). Thus, outcome in transplant recipients with cryptococcosis appears to be influenced by the type of immunosuppressive agent employed. Additionally, discerning the basis for transplant type-specific differences in disease severity has implications relevant for yielding further insights into the pathogenesis of C. neoformans infection in transplant recipients.

To determine the spectrum and impact of mycelial fungal infections, particularly those due to non-Aspergillus molds, 53 liver and heart transplant recipients with invasive mycelial infections were prospectively identified in a multicenter study. Invasive mycelial infections were due to Aspergillus species in 69.8% of patients, to non-Aspergillus hyalohyphomycetes in 9.4%, to phaeohyphomycetes in 9.4%, to zygomycetes in 5.7%, and to other causes in 5.7%. Infections due to mycelial fungi other than Aspergillus species were significantly more likely to be associated with disseminated (P=.005) and central nervous system (P=.07) infection than were those due to Aspergillus species. Overall mortality at 90 days was 54.7%. The associated mortality rate was 100% for zygomycosis, 80% for non-Aspergillus hyalohyphomycosis, 54% for aspergillosis, and 20% for phaeohyphomycosis. Thus, non-Aspergillus molds have emerged as significant pathogens in organ transplant recipients. These molds are more likely to be associated with disseminated infections and to be associated with poorer outcomes than is aspergillosis.

The risks identified for zygomycosis and for disseminated disease, including those that were previously unrecognized, have implications for further elucidating the biologic basis and for optimizing outcomes in SOT recipients with zygomycosis.

: Combination of voriconazole and caspofungin might be considered preferable therapy for subsets of organ transplant recipients with invasive aspergillosis, such as those with renal failure or A. fumigatus infection.

This study demonstrated that an IRS-like entity occurs in organ transplant recipients with C. neoformans infection. Furthermore, this entity may be misconstrued as a failure of therapy. Immunomodulatory agents may have a role as adjunctive therapy in such cases.