Isavuconazole in the treatment of invasive aspergillosis and mucormycosis infections

Abstract

We have a limited arsenal with which to treat invasive fungal infections caused by Aspergillus and Mucorales. The morbidity and mortality for both pathogens remains high. A triazole antifungal, isavuconazole, was recently granted approval by the US Food and Drug Administration and the European Medicines Agency for the treatment of invasive aspergillosis and mucormycosis. A randomized double-blind comparison trial for the treatment of invasive aspergillosis found isavuconazole noninferior to voriconazole. A separate, open-label study evaluating the efficacy of isavuconazole in the treatment of mucormycosis found comparable response rates to amphotericin B and posaconazole treated historical controls. The prodrug isavuconazonium sulfate is commercially available in both an oral and intravenous formulation and is generally well tolerated. Isavuconazole’s broad spectrum of activity, limited side effect profile, and favorable pharmacokinetics will likely solidify its place in therapy.

Reduced Multidrug Susceptibility Profile Is a Common Feature of Opportunistic Fusarium Species: Fusarium Multi-Drug Resistant Pattern

“…A randomized, double-blind comparison trial for the treatment of invasive aspergillosis found ISV noninferior to voriconazole. Evaluating the efficacy of ISV in the treatment of mucormycosis revealed comparable response rates to AmB and POS [ 69 , 70 ]. ISV MICs were reported for 7 cases ( Table 2 ) with a range of 4– > 16 µg/mL; there is no controlled trial on the use of ISV in invasive fusariosis, but the MIC values reported for these cases are not encouraging.…”

Successful Treatment of Recurrent Pulmonary Mucormycosis in a Renal Transplant Patient: A Case Report and Literature Review

“…The current gold standard for mucormycosis is IV liposomal amphotericin B, surgical debridement, and, if possible, modification of risk factors [8, 10, 11]. Previous case reports have demonstrated the use of posaconazole for salvage therapy.…”

“…However, the use of amphotericin B usually results in renal injury and concomitant loss of the renal allograft. Use of posaconazole has been proposed in several studies; however it has not shown to be as effective as amphotericin B [11]. Thus, emerging treatment strategies have included extended spectrum azoles with specific activity against Mucorales with improved side effect profiles [12, 13].…”

An immunosuppressed man with an isolated necrotic plaque on the chest

“…1 It is a first-line treatment for aspergillosis, for which it shows better efficacy, improved survival, and fewer side effects than amphotericin B. 5 Caspofungin – Incorrect. Caspofungin is ineffective against mucormycosis.…”

“…In addition to surgical excision, intravenous amphotericin B is the drug of choice for initial therapy. 1 , 3 , 5 Posaconazole – Incorrect. Oral posaconazole and isavuconazole are commonly used as step-down therapy several weeks after patients have responded to amphotericin B. Posaconazole and isavuconazole can also be used as salvage therapy for patients who do not respond to or cannot tolerate amphotericin B.…”