Risk for Breakthrough Invasive Fungal Infections With Isavuconazole: More Data Needed

While isavuconazole is an important therapeutic option in the management of invasive fungal infections, the epidemiology and microbiology of breakthrough infections on this agent are not well understood.

Isavuconazole is an important therapeutic option for managing invasive fungal infections (IFIs), but more information is needed regarding the risk for breakthrough infections with this agent, say the authors of a letter published in Clinical Infectious Diseases.

A broad-spectrum triazole antifungal agent, isavuconazole received approval by the US Food and Drug Administration in 2015 for the treatment of invasive aspergillosis and mucormycosis. Clinical trials evaluating the use of this agent as a prophylactic measure in immunocompromised hosts are ongoing, but it is already being used in a number of clinical settings.

However, the letter authors note that the risk for breakthrough IFI with isavuconazole has not been well studied, particularly in the real-world setting. 

In their institution, isavuconazole has been used selectively as primary or secondary prophylaxis in patients for whom voriconazole or posaconazole are contraindicated. In their letter, they report 5 cases of breakthrough IFI among patients with high-risk hematologic malignancy and patients who underwent organ transplant and received isavuconazole for prophylaxis and treatment.

All patients had pneumonia caused by Aspergillus nigri (2 cases), Rhizopus spp, Scedosporium apiospermum, and A fumigatus. Patients were treated with escalation to liposomal amphotericin B with or without a second antifungal agent (triazole or echinocandin). However, the risk for mortality with breakthrough IFI remained high, with 3 of the 5 patients dying as a result of the infection.

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The epidemiology and microbiology of breakthrough infections on this agent are not well understood, the authors conclude. “To help guide optimal empirical management in these difficult cases, additional studies are needed to systematically evaluate breakthrough IFIs on isavuconazole, given concern for azole-resistant or emerging fungal pathogens.”


Fung M, Schwartz BS, Doernberg SB, et al. Breakthrough invasive fungal infections on isavuconazole prophylaxis and treatment: what is happening in the real-world setting? [published online March 31, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy260