Successful isavuconazole salvage therapy in a patient with invasive mucormycosis

Abstract

A 45-year-old male with rhinocerebral mucormycosis (Rhizopus oryzae), refractory to liposomal amphotericin B and posaconazole, received isavuconazole salvage therapy. Initial isavuconazole plasma and tissue levels were 0.76-0.86 μg/mL and 1.09-1.38 μg/g. Plasma levels increased to 1.3-3.24 μg/mL with reduced comedication. Isavuconazole was well tolerated, and the patient has remained disease-free 24 months post-antifungal therapy.

Breaking the Mold

“…Follow-up biopsies obtained up to 1 year post-isavuconazole therapy gave negative results for filamentous fungal elements. 46 Only 1 trial has prospectively studied the effectiveness of a triazole antifungal agent as initial treatment of invasive mucormycosis. An open-label noncomparative trial evaluated the safety and efficacy of isavuconazole in 37 patients with probable or proven mucormycosis.…”

Comparison of the EUCAST and CLSI Broth Microdilution Methods for Testing Isavuconazole, Posaconazole, and Amphotericin B against Molecularly Identified Mucorales Species

“…Primary antifungal therapies for mucormycosis are amphotericin B (AMB) lipid formulations, whereas open-label salvage studies suggest posaconazole (POS) as an option for patients who are refractory to or intolerant of polyenes (10, 11). Furthermore, recent data also demonstrated the activity of isavuconazole (ISAV), which was approved by the U.S. Food and Drug Administration on 6 March 2015 for the primary treatment of invasive aspergillosis and mucormycosis, against Mucorales in vitro and in vivo, adding a second triazole antifungal for the therapy of patients with mucormycosis (12)(13)(14). Different species of Mucorales show differences in their in vitro susceptibilities to AMB, POS, and voriconazole (VRC) (15-17).…”

Isavuconazole Treatment of a Patient with Disseminated Mucormycosis

“…His brain disease subsequently progressed possibly due to low posaconazole levels which can be associated with poor oral intake due to mucositis (7), reduced central nervous system penetration of posaconazole as suggested in prior reported cases with very low to undetectable posaconazole levels in cerebrospinal fluid (8,9), or antifungal resistance. Ervens and colleagues also found very low levels of posaconazole in plasma and in sampled soft tissue of their patient after 24 days of posaconazole treatment (6). Although our patient's disease stabilized again after resuming LAmB, the patient was unable to go home due to profound amphotericin-related potassium and magnesium wasting.…”

“…Our patient's isavuconazole levels were lower than initially targeted on the first week of treatment. This led us to reload the patient and use higher isavuconazole doses transiently, but 200 mg/day of isavuconazole maintenance treatment was sufficient to keep plasma levels above 1,000 ng/ml, and the levels remained stable over several months of periodic monitoring, similarly to what Ervens and colleagues observed (6).…”