Voriconazole in the Treatment of Invasive Mold Infections in Transplant Recipients

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Abstract
Mortality due to invasive mold infections in solid organ transplant recipients is very high despite therapy with amphotericin B, including lipid formulations. Voriconazole is a triazole with a good activity against molds, including Aspergillus spp. and Scedosporium spp. Experience with voriconazole is limited, but preliminary results in patients with these infections are promising. Reported here is the experience with voriconazole administered on a compassionate-use basis to five patients with invasive mold infections: four solid organ recipients and one patient with an autoimmune disorder. Four patients had invasive Aspergillus fumigatus infection (3 lung infections, 1 abdominal infection) and one had invasive ocular Scedosporium apiospermum infection. The MIC of voriconazole was ≤1 µg/ml for all isolates (NCCLS performance standards for microdilution assay, proposed standard M38-P). Voriconazole was administered as primary therapy in a patient with Scedosporium infection and, in patients with Aspergillus infections, after persistence of positive culture despite a cumulative dose of 3 g of a lipid formulation of amphotericin B. Voriconazole was administered for a median time of 80 days (range, 60–90 days). No visual disturbances were observed, but one patient presented a moderate increase in liver enzymes. An increase in the levels of immunosuppressive drugs (tacrolimus or cyclosporine) was detected in all patients during coadministration with voriconazole. A clinical response was observed in all patients (complete response, n=3; partial response, n=2), and a microbiological response was observed in all but one patient. Furthermore, a good relationship between the MIC of voriconazole and outcome was observed. Voriconazole is an effective and safe therapy for treatment of invasive mold infections in solid organ recipients. To avoid toxicity with this drug, however, the dosing of immunosuppressive drugs must be reduced.