Pulmonary Mucormycosis (Zygomycosis) in a Lung Transplant Recipient: Recovery after Posaconazole Therapy

Mucormycosis is a rare opportunistic infection with high mortality in solid transplant recipients (1). Mucormycosis or zygomycosis are the names given to the diseases caused by fungi of the order Mucorales, including Absidia spp. (2). We describe the case of a lung transplant (LT) recipient with pulmonary mucormycosis cured with posaconazole administered as a salvage therapy, after failure of liposomal amphotericin B. A 46-year-old woman with idiopathic pulmonary fibrosis underwent a double LT in February 2004. The immediate postoperative course was complicated by an ischemia-reperfusion injury resolutive within a few days. Immunosuppression included ciclosporine, azathioprine, and methylprednisolone (0.5 mg/kg/day), associated with antithymocyte globulins (1.5 mg/kg/day during the 3 first postoperative days [POD]). Within the days following the extubation (POD 10), respiratory condition worsened again and a tracheostomy was performed on POD 16 to allow regular bronchial aspiration and ventilator support as needed. By POD 16, respiratory specimens (including repeated bronchial aspiration and bronchoalveolar lavage) and pleural aspiration fluid all grew Absidia spp. Computed tomography (CT) scan of the lungs showed nonspecific small nodular infiltrates. On POD 18, bronchoscopy revealed a right main bronchus with multiple ulcers covered with a dark necrotic material, plugging the lumen distal to the anastomotic site. The bronchial involvement was thought to be due both to a postischemic bronchitis and to the possible invasion of the fungus into the bronchial wall. Transbronchial biopsies (TBB) performed in the right lung revealed hyphal forms suggestive of mucorales. CT scan of the brain and sinus were normal. Pulmonary mucormycosis was diagnosed and the patient was started on intravenous liposomal amphotericin B on POD 18 (10 mg/kg/day). She had recurrent bronchial obstruction due to the debris from necrotic and pseudomembranous material requiring daily bronchoscopy (Fig. 1A). All cultures of respiratory specimens (bronchial aspiration [n=19] and bronchoalveolar lavage [n=2], from POD 16 to POD 48) still grew Absidia spp. Because the patient failed to respond clinically and mycologically to liposomal amphotericin B and also because of renal failure, the treatment was switched to oral posaconazole (800 mg/24h; 200 mg q.i.d.) on POD 48. Posaconazole was used because its in vitro activity against the clinical isolate of Absidia spp. was higher than those of other azoles, including voriconazole. Under posaconasole therapy, the patient's respiratory condition dramatically improved and she was able to stroll about in room air on POD 68. After 5 days of posaconazole, no further culture of respiratory specimens (repeated tracheal aspiration and BAL) grew Absidia spp. Control TBB did not show any fungal forms. Repeated bronchoscopies showed progressive healing of the bronchial mucosa by POD 95 (Fig. 1B). New CT scan showed regression of nodules on POD 102. No adverse effect was observed.FIGURE 1.: (A) Pseudomembranous material in the right main bronchus, anastomotic site (POD 41). (B) Progressive healing of the anastomotic site in the right main bronchus (POD 128).The patient was discharged at home on POD 143 with posaconazole. On POD 212, she suddenly died at home from a cataclysmic hemoptysis. No autopsy was performed. We made the hypothesis of bleeding from a bronchial artery due to a systemic hypervascularisation process linked to the previous ischemic bronchitis. Another hypothesis of a direct fistula between the right anastomotic site and the right pulmonary artery seems much less probable because of: 1) the prior macroscopic healing of the bronchial tree; and 2) the mycologic, radiographic, and clinical cure of the patient with posaconazole. The investigational triazole posaconazole has shown to be promising in vitro, in an immunosuppressed mouse model of zygomycosis, and in clinical experiences (3–6), but available clinical data are still scant. In our LT recipient with pulmonary mucormycosis, a salvage therapy with posaconazole resulted in a prompt mycologic and clinical cure. This case suggests that posaconazole may be considered as an alternate treatment in patient with invasive mucormycosis.

Topic: Infectious Diseases and Mycology
Subfield: Small Animals
Field: Veterinary
Domain: Health Sciences