Breakthrough Zygomycosis during Empirical Voriconazole Therapy in Febrile Patients with Neutropenia

Sir—Voriconazole, a novel, wide-spectrum triazole, is considered to be superior to amphotericin B in the treatment of infections caused by Aspergillus species [1] and to be equally as effective as amphotericin B in empirical antifungal therapy in cases of febrile neutropenia [2]. Nevertheless, because of its high cost, it is not widely used in Israel. During the late fall of 2003, there was a temporary shortage in the supply of amphotericin B deoxycholate in Israel that lasted for several weeks. During this period, voriconazole was used for empirical antifungal treatment in high-risk cases involving neutropenic patients in our medical center (Rambam Medical Center; Haifa, Israel). We report 2 patients with cases of invasive zygomycosis diagnosed in our hematology ward during this period who received this treatment. The first patient was a 65-year-old man who was admitted for chemotherapy treatment for high-grade lymphoma (stage IV) on 16 November 2003. He was febrile and neutropenic at admission, and therapy with broad-spectrum antibiotics was started. On 24 November, voriconazole was added to his regimen as empirical antifungal treatment for persistent fever unresponsive to broad-spectrum antibiotics. On 2 December, right maxillary sinusitis was diagnosed, and a culture from the sinus grew Mucor species. Therapy with liposomal amphotericin B was started, but the patient died on 6 December.