Treatment of chronic pulmonary blastomycosis with caspofungin

Abstract

Current practice guidelines recommend that pulmonary blastomycosis be treated with antifungal agents such as amphotericin B and itraconazole. Echinocandins are not recommended because of poor in vitro activity against Blastomyces dermatitidis and lack of supporting clinical data. We report a case of chronic pulmonary blastomycosis treated successfully with caspofungin. Case reportA 32-year-old male with no prior history of disease and working in construction presented with an insidious onset of right thoracic pain in November 2008. He was living in proximity of the St. Lawrence River, and had recently been exposed to a flooded soil environment. He did not take any medication and had a 42 pack-years smoking history. His chest pain was later followed by haemoptysis and exacerbation of a chronic cough. The patient denied any dyspnoea or expectorations and did not report any constitutional symptoms except for occasional nocturnal diaphoresis. The systems inquiry and physical examination were otherwise unremarkable.Laboratory testing revealed a white blood cell count of 11.2610 9 cells l 21 and an erythrocyte sedimentation rate slightly elevated at 24 mm h 21 . Biochemistry results were in the normal range. A chest X-ray on admission showed discrete opacities in the right paratracheal area. HIV, p-ANCA and c-ANCA testing were negative. In December 2008, a thoracic computed tomography (CT) scan demonstrated a right upper lobe parenchymal consolidation of 47661 mm with occlusion of the left superior lobe bronchus. Bronchocentric nodular opacities and infracentimetric mediastinal lymph nodes were also visualized (Fig. 1a). Bronchoscopy confirmed the presence of an obstructive polypoid mass in the left superior bronchus. An endobronchial biopsy revealed non-necrotizing granulomatous inflammation with several multinucleated giant cells without micro-organisms, neoplasm or vasculitis.In February 2009, further investigation was undertaken because the pulmonary mass had remained identical on control CT scan. A transthoracic needle biopsy demonstrated a fibroinflammatory reaction with multinucleated giant cells and a suppurative infiltrate containing a few 10 mm spherical micro-organisms with a thick wall and broad-based budding consistent with Blastomyces dermatitidis (Fig. 2). Despite negative cultures, histopathology was sufficient to confirm definite diagnosis of blastomycosis (De Pauw et al., 2008).In March 2009, the working diagnosis was chronic pulmonary blastomycosis in an immunocompetent host without evidence of dissemination. Because of the absence of spontaneous resolution at least 3 months after presentation, we decided to initiate antifungal therapy. The patient first received amphotericin B deoxycholate (Fungizone; BristolMyers Squibb) for 4 days but developed acute renal failure (serum creatinine rapidly increased from 70 to 225 mmol l 21 ). Treatment was switched to liposomal amphotericin B (AmBisome; Astellas Pharma) for 5 days with no improvement of renal function. The total administered cumulative dose of ...

New Developments in Blastomycosis

“…The authors do not advocate this strategy because of the minimal amount of drug target, β-(1,3)-glucan, in the cell wall of B. dermatitidis. 72,157 Adjunctive Therapy…”

Role of <I>FKS</I> Gene in the Susceptibility of Pathogenic Fungi to Echinocandins

“…However, there have been no clinical studies that have demonstrated the inferiority of echinocandins compared to other antifungals for the treatment of C. parapsilosis infections 99) . For treatment of blastomycosis 100) , coccidioidomycosis 101) , and Pneumocystis pneumonia 79, 80) (type 3), though not approved nor recommended, it has been reported that echinocandins, alone or in combination, was effective. For therapy of mucormycosis (type 4), combination of lipid formulations of amphotericin B and echinocandins, though its mechanism is unknown, has often been used [102][103][104] and recommended as first-line or salvage therapy in some guidelines 97,105) .…”

Endemic mycoses – are we making progress in management?

“…Thus, isavuconazole and posaconazole can be considered alternative agents for blastomycosis. Lastly, echinocandins should not be used due to poor in vitro activity and rare reported use with mixed results resulting in clinical failure [35,68,69].…”