Isavuconazole 200mg powder for solution for infusion vials

Mucormycosis is an opportunistic fungal infection which is associated with poor prognosis. Only a few antifungals are available in the arsenal against mucormycosis. The global guidelines for diagnosing and managing mucormycosis recommend high doses of liposomal amphotericin B (LAmB) as the first-line treatment. Isavuconazole is another potential treatment option for mucormycosis. This systematic review aims to consolidate and analyse existing evidence concerning the efficacy and safety of isavuconazole in treating mucormycosis alone or in combination with LAmB. For data aggregation, comprehensive searches were conducted across various electronic databases, such as PubMed, Science Direct, Trip, Google Scholar, the Cochrane Library, and Open-Gray. Furthermore, we explored the gray literature, employing tailored keywords. The reference lists of the selected articles were scrutinized to identify additional pertinent publications. Articles reporting any studies, case series, or case reports on any form of mucormycosis exclusively involving human subjects published in English were included. There were no time restrictions involved. We extracted crucial data, such as publication year, country, disease form, isavuconazole dosage, frequency, duration, overall outcomes, and reported adverse effects. A total of 31 articles, which included four case series, 24 case reports, one open-label trial, one randomized controlled trial, and one non-interventional registry study, were included in the final analysis. 135 adult patients and 14 children were treated with isavuconazole as primary monotherapy, primary combination therapy, nonprimary monotherapy, or nonprimary combination therapy. The mortality rate following LAmB monotherapy, amphotericin B plus azole, amphotericin B followed with azole, posaconazole only and isavuconazole only was 32%, 6.6%, 13.7%, 17.2% and 24.6%, respectively. The heterogeneity of the studies did not allow for a comparison of the different treatment strategies (primary mono- vs. primary combination, etc.). The use of isavuconazole in combination therapies during the acute phase via intravenous administration alongside LAmB or other triazoles, followed by long-term monotherapy via the oral route, has yielded promising recovery rates. Adverse events associated with the use of isavuconazole are infrequently reported.

Abstract licence: CC BY-NC-ND

Management of pulmonary mucormycosis includes intravenous liposomal amphotericin-B (L-AmB), followed by posaconazole or isavuconazole. We aimed to determine the optimal L-AmB duration before switching to triazole therapy. Using data from a retrospective study in France, we performed an emulated trial evaluating stopping L-AmB after 14 days (short treatment) versus continuing L-AmB (long treatment). The benefit of combination L-AmB therapy was also investigated. A cloning, censoring, and weighting approach was used to account for immortal time and indication biases. Ninety-four cases of pulmonary mucormycosis were included, of which 35% had dissemination. Eighty-nine patients received L-AmB first-line therapy for a median of 25 (IQR: 12-54) days, including 18 patients as combination therapy. L-AmB was discontinued for adverse events in 16/89 patients (18%). Treatment was switched to posaconazole (n = 38) or isavuconazole (n = 9) in 47 cases and was switched back to L-AmB due to disease progression in 11/47 (23%) cases. Overall, the 180-day mortality was 54%. Diagnosis in the ICU, dyspnea at diagnosis, disseminated disease, and ground-glass opacities on chest CT scan were associated with increased mortality. No difference in 180-day survival was found between patients receiving short or long L-AmB treatment (HR=0.80, 95% CI [0.29-1.99]) and between patients receiving L-AmB alone or in combination (HR=1.14, 95% CI [0.56-2.32]) in emulated trials, although confidence intervals were wide. Switching to triazole therapy after 14 days of L-AmB treatment was as effective as longer durations while reducing L-AmB side effects. Combination therapy did not improve prognosis. These results could inform randomized clinical trials assessing different first-line therapeutic strategies for pulmonary mucormycosis.

Abstract licence: CC BY