isavuconazole and Cystic-Fibrosis

The genus Blastobotrys consists of at least 20 species. Disease in humans has been reported with B adeninivorans, B raffinosifermentans, B proliferans and B serpentis, mostly in immunocompromised patients and those with cystic fibrosis.. We report a lung infection secondary to B raffinosifermentans in a cystic fibrosis patient successfully treated with isavuconazole and review the literature of invasive infections caused this genus. We also evaluated clinical isolates in our laboratory for species identification and antifungal susceptibility.. Phylogenetic analysis was performed on a collection of 22 Blastobotrys isolates in our reference laboratory, and antifungal susceptibility patterns were determined for nine clinically available antifungals against 19 of these isolates.. By phylogenetic analysis, 21 of the 22 isolates in our collection were identified as B raffinosifermentans and only 1 as B adeninivorans. Most were cultured from the respiratory tract, although others were recovered from other sources, including CSF and blood. Isavuconazole, caspofungin and micafungin demonstrated the most potent in vitro activity, followed by amphotericin B. In contrast, fluconazole demonstrated poor activity. The patient in this case responded to isavuconazole treatment for breakthrough infection due to B raffinosifermentans that was cultured from pleural fluid while on posaconazole prophylaxis post-bilateral lung transplantation for cystic fibrosis.. Blastobotrys species are rare causes of infections in humans and primarily occur in immunocompromised hosts. In our collection, the majority of isolates were identified as B raffinosifermentans. To our knowledge, this is the first report of successful treatment of such an infection with isavuconazole.

Topics: Adult; Amphotericin B; Antifungal Agents; Cystic Fibrosis; Female; Fluconazole; Genes, Fungal; Humans; Immunosuppression Therapy; Microbial Sensitivity Tests; Mycoses; Nitriles; Phylogeny; Pneumonia; Pyridines; Saccharomycetales; Triazoles

Topics: Aminophenols; Aminopyridines; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Benzodioxoles; Cystic Fibrosis; Female; Humans; Male; Nitriles; Pyridines; Quinolones; Triazoles

Topics: Amphotericin B; Antifungal Agents; Cystic Fibrosis; Disease Progression; Exophiala; Humans; Interferon-gamma; Interleukin-17; Lung Diseases, Fungal; Male; Monitoring, Immunologic; Nitriles; Pyridines; Recombinant Proteins; Respiratory Function Tests; Sputum; Treatment Outcome; Triazoles; Young Adult

Previous studies of patients with cystic fibrosis (CF) treated with azole antifungals have shown altered pharmacokinetics relative to healthy patients. Data regarding the pharmacokinetic profile of isavuconazole in patients with CF undergoing lung transplantation are currently not available. Serum trough concentrations assessed in a single CF patient following transplant revealed significantly lower values relative to available literature. Larger studies are required to validate CF population pharmacokinetics of isavuconazole.

Topics: Adult; Antifungal Agents; Cystic Fibrosis; Drug Monitoring; Female; Humans; Immunosuppressive Agents; Lung Transplantation; Nitriles; Pyridines; Triazoles; Young Adult

A 22-year-old woman with cystic fibrosis developed QTc interval prolongation following lung transplantation in the setting of voriconazole therapy. After the discontinuation of voriconazole and initiation of isavuconazole, her QTc interval normalized. This case highlights the unique property of QTc interval shortening by isavuconazole among the triazole antifungals.

Topics: Antifungal Agents; Cystic Fibrosis; Female; Humans; Long QT Syndrome; Lung Transplantation; Nitriles; Pyridines; Triazoles; Voriconazole; Young Adult