Zygomycete infection following voriconazole prophylaxis

Abstract

A 14-year-old boy was treated with chemotherapy for T-cell acute lymphoblastic leukaemia. Trimethoprimsulfamethoxazole and itraconazole were given for infection prophylaxis. In the course of this treatment he developed aplastic anaemia that required dose reduction of chemotherapy. During chemotherapy he developed bilateral upper lobe pneumonia. He was treated with meropenem; amphotericin B was added after 48 hours due to lack of improvement. A computed tomography scan showed lesions suspect for fungal infection. After 2 days, the patient remained febrile, and we switched amphotericin B to voriconazole. The lesions resolved almost completely in 10 days, suggesting an infection with Aspergillus spp. We continued voriconazole as prophylaxis instead of itraconazole. 6 months later, while still on voriconazole, he again developed pneumonia, refractory to meropenem, and was treated with amphotericin B. Culture and histology findings of bronchoalveolar lavage fluid disclosed no microbial pathogens. Persisting fever led to resection of the infected lobe and discontinuation of chemotherapy. Microscopy of pulmonary tissue showed necrosis and broad hyphae suspect for zygomycetes. The dose of amphotericin B was doubled but nonetheless the infection disseminated. He suffered from convulsions, spondylodiscitis, and a thromboembolic mass in his left cardiac ventricle. Because of cardiac decompensation and high risk of embolism, the mass was resected. Cultures of the thrombus showed growth of Rhizopus microsporus (figure), susceptible in vitro to amphotericin B and posaconazole, an experimental triazole agent. The thrombus reappeared and posaconazole was added to the amphotericin B treatment. Unfortunately, the boy died of progressive cardiac obstruction. Voriconazole, a broad-spectrum triazole antifungal, is increasingly used as prophylaxis in patients with haematological malignancies. As this case illustrates, prolonged use of this agent may lead to an increase of infections with zygomycetes, all resistant to voriconazole.